03216nas a2200445 4500008004100000022001400041245008600055210006900141260001600210300001200226490000800238520200500246653000902251653001502260653002802275653003302303653001502336653001502351653001402366653001102380653002202391653003102413653001102444653001102455653002002466653000902486653001402495653002602509653001402535653000902549100002402558700002002582700001602602700002002618700002402638700002002662700002402682700002902706856003502735 2005 eng d a1533-440600aCystatin C and the risk of death and cardiovascular events among elderly persons.0 aCystatin C and the risk of death and cardiovascular events among c2005 May 19 a2049-600 v3523 a
BACKGROUND: Cystatin C is a serum measure of renal function that appears to be independent of age, sex, and lean muscle mass. We compared creatinine and cystatin C levels as predictors of mortality from cardiovascular causes and from all causes in the Cardiovascular Health Study, a cohort study of elderly persons living in the community.
METHODS: Creatinine and cystatin C were measured in serum samples collected from 4637 participants at the study visit in 1992 or 1993; follow-up continued until June 30, 2001. For each measure, the study population was divided into quintiles, with the fifth quintile subdivided into thirds (designated 5a, 5b, and 5c).
RESULTS: Higher cystatin C levels were directly associated, in a dose-response manner, with a higher risk of death from all causes. As compared with the first quintile, the hazard ratios (and 95 percent confidence intervals) for death were as follows: second quintile, 1.08 (0.86 to 1.35); third quintile, 1.23 (1.00 to 1.53); fourth quintile, 1.34 (1.09 to 1.66); quintile 5a, 1.77 (1.34 to 2.26); 5b, 2.18 (1.72 to 2.78); and 5c, 2.58 (2.03 to 3.27). In contrast, the association of creatinine categories with mortality from all causes appeared to be J-shaped. As compared with the two lowest quintiles combined (cystatin C level, < or =0.99 mg per liter), the highest quintile of cystatin C (> or =1.29 mg per liter) was associated with a significantly elevated risk of death from cardiovascular causes (hazard ratio, 2.27 [1.73 to 2.97]), myocardial infarction (hazard ratio, 1.48 [1.08 to 2.02]), and stroke (hazard ratio, 1.47 [ 1.09 to 1.96]) after multivariate adjustment. The fifth quintile of creatinine, as compared with the first quintile, was not independently associated with any of these three outcomes.
CONCLUSIONS: Cystatin C, a serum measure of renal function, is a stronger predictor of the risk of death and cardiovascular events in elderly persons than is creatinine.
10aAged10aBiomarkers10aCardiovascular Diseases10aCerebrospinal Fluid Proteins10aCreatinine10aCystatin C10aCystatins10aFemale10aFollow-Up Studies10aGlomerular Filtration Rate10aHumans10aKidney10aKidney Diseases10aMale10aMortality10aMultivariate Analysis10aPrognosis10aRisk1 aShlipak, Michael, G1 aSarnak, Mark, J1 aKatz, Ronit1 aFried, Linda, F1 aSeliger, Stephen, L1 aNewman, Anne, B1 aSiscovick, David, S1 aStehman-Breen, Catherine uhttps://chs-nhlbi.org/node/84003555nas a2200445 4500008004100000022001400041245008100055210006900136260001600205300001200221490000800233520234700241653000902588653001502597653001502612653001502627653001402642653001102656653002202667653003102689653001802720653001102738653001402749653001102763653002602774653000902800653001702809653001802826100002002844700001602864700003202880700002002912700002502932700002002957700002002977700002102997700002403018710003203042856003503074 2005 eng d a1539-370400aCystatin C concentration as a risk factor for heart failure in older adults.0 aCystatin C concentration as a risk factor for heart failure in o c2005 Apr 05 a497-5050 v1423 aBACKGROUND: Previous studies that evaluated the association of kidney function with incident heart failure may be limited by the insensitivity of serum creatinine concentration for detecting abnormal kidney function.
OBJECTIVE: To compare serum concentrations of cystatin C (a novel marker of kidney function) and creatinine as predictors of incident heart failure.
DESIGN: Observational study based on measurement of serum cystatin C from frozen sera obtained at the 1992-1993 visit of the Cardiovascular Health Study. Follow-up occurred every 6 months.
SETTING: Adults 65 years of age or older from 4 communities in the United States.
PARTICIPANTS: 4384 persons without previous heart failure who had measurements of serum cystatin C and serum creatinine.
MEASUREMENTS: Incident heart failure.
RESULTS: The mean (+/-SD) serum concentrations of cystatin C and creatinine were 82 +/- 25 nmol/L (1.10 +/- 0.33 mg/L) and 89 +/- 34 micromol/L (1.01 +/- 0.39 mg/dL), respectively. During a median follow-up of 8.3 years (maximum, 9.1 years), 763 (17%) participants developed heart failure. After adjustment for demographic factors, traditional and novel cardiovascular risk factors, cardiovascular disease status, and medication use, sequential quintiles of cystatin C concentration were associated with a stepwise increased risk for heart failure in Cox proportional hazards models (hazard ratios, 1.0 [reference], 1.30 [95% CI, 0.96 to 1.75], 1.44 [CI, 1.07 to 1.94], 1.58 [CI, 1.18 to 2.12], and 2.16 [CI, 1.61 to 2.91]). In contrast, quintiles of serum creatinine concentration were not associated with risk for heart failure in adjusted analysis (hazard ratios, 1.0 [reference], 0.77 [CI, 0.59 to 1.01], 0.85 [CI, 0.64 to 1.13], 0.97 [CI, 0.72 to 1.29], and 1.14 [CI, 0.87 to 1.49]).
LIMITATIONS: The mechanism by which cystatin C concentration predicts risk for heart failure remains unclear.
CONCLUSIONS: The cystatin C concentration is an independent risk factor for heart failure in older adults and appears to provide a better measure of risk assessment than the serum creatinine concentration. *For a full list of participating Cardiovascular Health Study investigators and institutions, see http://www.chs-nhlbi.org.
10aAged10aBiomarkers10aCreatinine10aCystatin C10aCystatins10aFemale10aFollow-Up Studies10aGlomerular Filtration Rate10aHeart Failure10aHumans10aIncidence10aKidney10aKidney Function Tests10aMale10aRisk Factors10aUnited States1 aSarnak, Mark, J1 aKatz, Ronit1 aStehman-Breen, Catherine, O1 aFried, Linda, F1 aJenny, Nancy, Swords1 aPsaty, Bruce, M1 aNewman, Anne, B1 aSiscovick, David1 aShlipak, Michael, G1 aCardiovascular Health Study uhttps://chs-nhlbi.org/node/82702928nas a2200433 4500008004100000022001400041245006700055210006500122260001300187300000900200490000800209520175900217653001601976653000901992653001502001653002302016653002802039653001502067653001402082653001102096653001502107653003102122653001102153653002002164653000902184653003002193653003202223100002402255700001602279700001802295700002002313700002902333700002002362700002102382700002202403700001702425700001702442856003502459 2005 eng d a1555-716200aCystatin-C and inflammatory markers in the ambulatory elderly.0 aCystatinC and inflammatory markers in the ambulatory elderly c2005 Dec a14160 v1183 aPURPOSE: Inflammatory factors are elevated in persons with severe renal dysfunction, but their association across all levels of renal function is unclear. We compared cystatin-C, a novel marker of renal function, with creatinine and estimated glomerular filtration rate (eGFR) as predictors of C-reactive protein and fibrinogen levels.
METHODS: This study is a cross-sectional analysis to evaluate cystatin-C, creatinine, and eGFR as predictors of the inflammatory markers C-reactive protein and fibrinogen. Participants included 4637 ambulatory elderly patients from the Cardiovascular Health Study. Multivariate linear regression was used to determine the independent associations of each renal function measurement with the inflammatory marker outcomes.
RESULTS: After adjustment for confounding factors, cystatin-C was correlated with both C-reactive protein (coefficient = 0.13; 95% confidence interval: 0.10-1.16, P <.0001) and fibrinogen levels (0.15; 0.13-0.18, P <.0001). Associations were larger than those for creatinine and C-reactive protein (0.05; 0.02-0.07, P = .003) or fibrinogen (0.07; 0.04-0.10, P <.0001). Adjusted levels of C-reactive protein increased incrementally across quintiles of cystatin-C, from a median of 2.2 mg/L in quintile 1 to 3.7 mg/L in quintile 5. In contrast, both C-reactive protein and fibrinogen had U-shaped associations with quintiles of creatinine and eGFR, because the inflammatory markers were equivalently elevated in quintiles 1 and 5.
CONCLUSIONS: The finding of a significant linear association of cystatin-C and inflammation markers suggests that even small reductions in renal function may be associated with adverse pathophysiologic consequences.
10aAge Factors10aAged10aBiomarkers10aC-Reactive Protein10aCross-Sectional Studies10aCystatin C10aCystatins10aFemale10aFibrinogen10aGlomerular Filtration Rate10aHumans10aKidney Diseases10aMale10aPredictive Value of Tests10aSensitivity and Specificity1 aShlipak, Michael, G1 aKatz, Ronit1 aCushman, Mary1 aSarnak, Mark, J1 aStehman-Breen, Catherine1 aPsaty, Bruce, M1 aSiscovick, David1 aTracy, Russell, P1 aNewman, Anne1 aFried, Linda uhttps://chs-nhlbi.org/node/87602720nas a2200433 4500008004100000022001400041245006800055210006600123260001600189300001100205490000700216520154600223653001601769653000901785653002201794653001501816653001501831653001401846653001101860653002201871653003101893653001801924653001101942653000901953653001901962653003001981653002002011653002202031100002402053700001602077700002002093700002502113700003202138700002002170700002102190700002002211700002002231856003502251 2005 eng d a0735-109700aCystatin-C and mortality in elderly persons with heart failure.0 aCystatinC and mortality in elderly persons with heart failure c2005 Jan 18 a268-710 v453 aOBJECTIVES: We sought to evaluate cystatin-C, a novel measure of renal function, as a predictor of mortality in elderly persons with heart failure (HF) and to compare it with creatinine.
BACKGROUND: Renal function is an important prognostic factor in patients with HF, but creatinine levels, which partly reflect muscle mass, may be insensitive for detecting renal insufficiency.
METHODS: A total of 279 Cardiovascular Health Study participants with prevalent HF and measures of serum cystatin-C and creatinine were followed for mortality outcomes over a median of 6.5 years.
RESULTS: Median creatinine and cystatin-C levels were 1.05 mg/dl and 1.26 mg/l. Each standard deviation increase in cystatin-C (0.35 mg/l) was associated with a 31% greater adjusted mortality risk (95% confidence interval [CI] 20% to 43%, p < 0.001), whereas each standard deviation increase in creatinine (0.39 mg/dl) was associated with a 17% greater adjusted mortality risk (95% CI 1% to 36%, p = 0.04). When both measures were combined in a single adjusted model, cystatin-C remained associated with elevated mortality risk (hazard ratio 1.60, 95% CI 1.32 to 1.94), whereas creatinine levels appeared associated with lower risk (hazard ratio 0.73, 95% CI 0.57 to 0.95).
CONCLUSIONS: Cystatin-C is a stronger predictor of mortality than creatinine in elderly persons with HF. If confirmed in future studies, this new marker of renal function could improve risk stratification in patients with HF.
10aAge Factors10aAged10aAged, 80 and over10aCreatinine10aCystatin C10aCystatins10aFemale10aFollow-Up Studies10aGlomerular Filtration Rate10aHeart Failure10aHumans10aMale10aPilot Projects10aPredictive Value of Tests10aRisk Assessment10aSurvival Analysis1 aShlipak, Michael, G1 aKatz, Ronit1 aFried, Linda, F1 aJenny, Nancy, Swords1 aStehman-Breen, Catherine, O1 aNewman, Anne, B1 aSiscovick, David1 aPsaty, Bruce, M1 aSarnak, Mark, J uhttps://chs-nhlbi.org/node/81603317nas a2200553 4500008004100000022001400041245006700055210006600122260001300188300001200201490000700213520179100220653001602011653000902027653002202036653002802058653001902086653001902105653002502124653001502149653001502164653001402179653001102193653003102204653001102235653002802246653002602274653002502300653000902325653001602334653003202350653002002382653003002402653002202432653001802454100002002472700001602492700002002508700002402528700002302552700002502575700002902600700001602629700002302645700001902668700002102687700002002708856003502728 2005 eng d a1046-667300aKidney function as a predictor of noncardiovascular mortality.0 aKidney function as a predictor of noncardiovascular mortality c2005 Dec a3728-350 v163 aChronic kidney disease is associated with a higher risk for cardiovascular mortality, as well as all-cause mortality. Whether chronic kidney disease is a predictor of noncardiovascular mortality is less clear. To further explore the latter, the association of kidney function with total noncardiovascular mortality and cause-specific mortality was assessed in the Cardiovascular Health Study, a community-based cohort of older individuals. Kidney disease was assessed using cystatin C and estimated GFR in 4637 participants in 1992 to 1993. Participants were followed until June 30, 2001. Deaths were adjudicated as cardiovascular or noncardiovascular disease by committee, and an underlying cause of death was assigned. The associations of kidney function with total noncardiovascular mortality and cause-specific mortality were analyzed by proportional hazards regression. Noncardiovascular mortality rates increased with higher cystatin C quartiles (16.8, 17.1, 21.6, and 50.0 per 1000 person-years). The association of cystatin C with noncardiovascular mortality persisted after adjustment for demographic factors; the presence of diabetes, C-reactive protein, hemoglobin, and prevalent cardiovascular disease; and measures of atherosclerosis (hazard ratio 1.69; 95% confidence interval 1.33 to 2.15, for the fourth quartile versus the first quartile). Results for estimated GFR were similar. The risk for noncardiac deaths attributed to pulmonary disease, infection, cancer, and other causes was similarly associated with cystatin C levels. Kidney function predicts noncardiovascular mortality from multiple causes in the elderly. Further research is needed to understand the mechanisms and evaluate interventions to reduce the high mortality rate in chronic kidney disease.
10aAge Factors10aAged10aAged, 80 and over10aCardiovascular Diseases10aCause of Death10aCohort Studies10aConfidence Intervals10aCreatinine10aCystatin C10aCystatins10aFemale10aGlomerular Filtration Rate10aHumans10aKidney Failure, Chronic10aKidney Function Tests10aLongitudinal Studies10aMale10aProbability10aProportional Hazards Models10aRisk Assessment10aSeverity of Illness Index10aSurvival Analysis10aUnited States1 aFried, Linda, F1 aKatz, Ronit1 aSarnak, Mark, J1 aShlipak, Michael, G1 aChaves, Paulo, H M1 aJenny, Nancy, Swords1 aStehman-Breen, Catherine1 aGillen, Dan1 aBleyer, Anthony, J1 aHirsch, Calvin1 aSiscovick, David1 aNewman, Anne, B uhttps://chs-nhlbi.org/node/86504065nas a2200433 4500008004100000022001400041245011900055210006900174260001600243300001100259490000800270520281000278653000903088653001503097653002803112653001503140653001503155653001403170653003103184653001103215653001103226653002503237653001403262653003203276653003303308653001703341100002403358700001603382700002003398700002003418700002003438700002903458700002403487700002203511700001703533700002203550700002403572856003503596 2006 eng d a1539-370400aCystatin C and prognosis for cardiovascular and kidney outcomes in elderly persons without chronic kidney disease.0 aCystatin C and prognosis for cardiovascular and kidney outcomes c2006 Aug 15 a237-460 v1453 aBACKGROUND: Cystatin C is an alternative measure of kidney function that may have prognostic importance among elderly persons who do not meet standard criteria for chronic kidney disease (estimated glomerular filtration rate [GFR] > or =60 mL/min per 1.73 m2).
OBJECTIVE: To evaluate cystatin C as a prognostic biomarker for death, cardiovascular disease, and incident chronic kidney disease among elderly persons without chronic kidney disease.
DESIGN: Cohort study.
SETTING: The Cardiovascular Health Study, a population-based cohort recruited from 4 communities in the United States.
PARTICIPANTS: 4663 elderly persons.
MEASUREMENTS: Measures of kidney function were creatinine-based estimated GFR by using the Modification of Diet in Renal Disease equation and cystatin C concentration. Outcomes were death, cardiovascular death, noncardiovascular death, heart failure, stroke, myocardial infarction, and incident chronic kidney disease during follow-up (median, 9.3 years).
RESULTS: At baseline, 78% of participants did not have chronic kidney disease (estimated GFR > or =60 mL/min per 1.73 m2) and mean cystatin C concentration, creatinine concentration, and estimated GFR were 1.0 mg/L, 79.6 micromol/L (0.9 mg/dL), and 83 mL/min per 1.73 m2, respectively. Cystatin C concentrations (per SD, 0.18 mg/L) had strong associations with death (hazard ratio, 1.33 [95% CI, 1.25 to 1.40]), cardiovascular death (hazard ratio, 1.42 [CI, 1.30 to 1.54]), noncardiovascular death (hazard ratio, 1.26 [CI, 1.17 to 1.36]), incident heart failure (hazard ratio, 1.28 [CI, 1.17 to 1.40]), stroke (hazard ratio, 1.22 [CI, 1.08 to 1.38]), and myocardial infarction (hazard ratio, 1.20 [CI, 1.06 to 1.36]) among these participants. Serum creatinine concentrations had much weaker associations with each outcome and only predicted cardiovascular death. Participants without chronic kidney disease who had elevated cystatin C concentrations (> or =1.0 mg/L) had a 4-fold risk for progressing to chronic kidney disease after 4 years of follow-up compared with those with cystatin C concentrations less than 1.0 mg/L.
LIMITATIONS: Because this study did not directly measure GFR or albuminuria, the extent to which cystatin C may be influenced by nonrenal factors was not determined and participants with albuminuria might have been misclassified as having no kidney disease.
CONCLUSIONS: Among elderly persons without chronic kidney disease, cystatin C is a prognostic biomarker of risk for death, cardiovascular disease, and chronic kidney disease. In this setting, cystatin C seems to identify a "preclinical" state of kidney dysfunction that is not detected with serum creatinine or estimated GFR.
10aAged10aBiomarkers10aCardiovascular Diseases10aCreatinine10aCystatin C10aCystatins10aGlomerular Filtration Rate10aHumans10aKidney10aLongitudinal Studies10aPrognosis10aProportional Hazards Models10aRenal Insufficiency, Chronic10aRisk Factors1 aShlipak, Michael, G1 aKatz, Ronit1 aSarnak, Mark, J1 aFried, Linda, F1 aNewman, Anne, B1 aStehman-Breen, Catherine1 aSeliger, Stephen, L1 aKestenbaum, Brian1 aPsaty, Bruce1 aTracy, Russell, P1 aSiscovick, David, S uhttps://chs-nhlbi.org/node/91202852nas a2200421 4500008004100000022001400041245009800055210006900153260001300222300001000235490000600245520167800251653000901929653002201938653002401960653002801984653002002012653002102032653002402053653001102077653001102088653001102099653002002110653000902130653002002139100002202159700002002181700002402201700002002225700002002245700001602265700002002281700002102301700002902322700002002351700002402371856003502395 2007 eng d a1555-905X00aKidney function, electrocardiographic findings, and cardiovascular events among older adults.0 aKidney function electrocardiographic findings and cardiovascular c2007 May a501-80 v23 aChronic kidney disease (CKD) is associated with cardiovascular (CV) disease and mortality. It is not known whether cardiac rhythm disturbances are more prevalent among individuals with CKD or whether resting electrocardiogram findings predict future CV events in the CKD setting. Data were obtained from the Cardiovascular Health Study, a community-based study of adults aged >/=65 yr. After exclusions for prevalent heart disease, atrial fibrillation, implantable pacemaker, or antiarrhythmic medication use, 3238 participants were analyzed. CKD was defined by an estimated GFR <60 ml/min per 1.73 m(2). Outcomes were adjudicated incident heart failure (HF), incident coronary heart disease (CHD), and mortality. Participants with CKD had longer PR and corrected QT intervals compared with those without CKD; however, differences in electrocardiographic markers were explained by traditional CV risk factors and CV medication use. After adjustment for known risk factors, each 10-ms increase in the QRS interval was associated with a 15% greater risk for incident HF (95% confidence interval [CI] 1.04 to 1.27), a 13% greater risk for CHD (95% CI 1.04 to 1.24), and a 17% greater risk for mortality (95% CI 1.09, 1.25) among CKD participants. Each 5% increase in QTI was associated with a 42% (95% CI 1.23 to 1.65), 22% (95% CI 1.07 to 1.40), and 10% (95% CI 0.98 to 1.22) greater risk for HF, CHD, and mortality, respectively. Associations seemed stronger for participants with CKD; however, no significant interactions were detected. Resting electrocardiographic abnormalities are common in CKD and independently predict future clinical CV events in this setting.
10aAged10aAged, 80 and over10aCardiac Output, Low10aCardiovascular Diseases10aChronic Disease10aCoronary Disease10aElectrocardiography10aFemale10aHumans10aKidney10aKidney Diseases10aMale10aRisk Assessment1 aKestenbaum, Bryan1 aRudser, Kyle, D1 aShlipak, Michael, G1 aFried, Linda, F1 aNewman, Anne, B1 aKatz, Ronit1 aSarnak, Mark, J1 aSeliger, Stephen1 aStehman-Breen, Catherine1 aPrineas, Ronald1 aSiscovick, David, S uhttps://chs-nhlbi.org/node/97502989nas a2200385 4500008004100000022001400041245006600055210006500121260001300186300001100199490000700210520194000217653000902157653002202166653001902188653002802207653002402235653001102259653003102270653001102301653002002312653000902332653002402341653001402365100002102379700002402400700001602424700002002440700002002460700002402480700002202504700002202526700002002548856003502568 2007 eng d a1523-683800aRelationship of uric acid with progression of kidney disease.0 aRelationship of uric acid with progression of kidney disease c2007 Aug a239-470 v503 aBACKGROUND: Uric acid levels are increased in patients with kidney dysfunction. We tested the hypothesis that uric acid may be associated with kidney disease progression.
STUDY DESIGN: Cohort study.
SETTING & PARTICIPANTS: 5,808 participants of the Cardiovascular Health Study.
PREDICTOR: Uric acid levels.
OUTCOMES & MEASUREMENTS: Kidney disease progression was defined as a decrease in estimated glomerular filtration rate (GFR) of 3 mL/min/1.73 m(2) per year or greater (>or=0.05 mL/s) and as incident chronic kidney disease (CKD). Measures of kidney function were estimated GFR using the Modification of Diet in Renal Disease Study equation.
RESULTS: Higher quintiles of uric acid levels were associated with greater prevalences of estimated GFR less than 60 mL/min/1.73 m(2) (<1.00 mL/s) of 7%, 14%, 12%, 25%, and 42% for quintiles 1 (
LIMITATIONS: Measurements of albuminuria were not available.
CONCLUSIONS: Uric acid levels are associated strongly with prevalent CKD. In comparison, greater uric acid levels had a significant, but much weaker, association with progression of kidney disease.
10aAged10aAged, 80 and over10aCohort Studies10aCross-Sectional Studies10aDisease Progression10aFemale10aGlomerular Filtration Rate10aHumans10aKidney Diseases10aMale10aProspective Studies10aUric Acid1 aChonchol, Michel1 aShlipak, Michael, G1 aKatz, Ronit1 aSarnak, Mark, J1 aNewman, Anne, B1 aSiscovick, David, S1 aKestenbaum, Bryan1 aCarney, Jan, Kirk1 aFried, Linda, F uhttps://chs-nhlbi.org/node/97202997nas a2200409 4500008004100000022001400041245003400055210003300089260001600122300001100138490000800149520198900157653000902146653001002155653001502165653001502180653001502195653001402210653001102224653002202235653003102257653001102288653001102299653000902310100002002319700001602339700002002355700002102375700002202396700002102418700001702439700001902456700002002475700002402495710003202519856003602551 2008 eng d a0003-992600aCystatin C and aging success.0 aCystatin C and aging success c2008 Jan 28 a147-530 v1683 aBACKGROUND: To our knowledge, the effect of kidney function on successful aging has not been examined.
METHODS: We evaluated the relationship between cystatin C and aging success during a 6-year follow-up in the Cardiovascular Health Study, a community-based cohort of older adults (aged >or= 65 years). Successful aging was defined as remaining free of cardiovascular disease, cancer, and chronic obstructive pulmonary disease and having intact physical and cognitive functioning. In adjusted analysis, an accelerated failure time model was used to evaluate the percentage reduction in successful years by level of cystatin C. A separate Cox proportional hazards model evaluated whether cystatin C was related to incident physical and cognitive disability.
RESULTS: A total of 2140 participants had cystatin C measured and were free of the previously mentioned conditions at baseline. Their mean age was 74 years. The mean cystatin C level, creatinine level, and estimated glomerular filtration rate were 1.06 mg/L, 0.93 mg/dL, and 78 mL/min/1.73 m(2), respectively (to convert cystatin C to nanomoles per liter, multiply by 75; and to convert creatinine to micromoles per liter, multiply by 88.4). A total of 873 participants reached a first event in follow-up, 138 because of cognitive disability, 238 because of physical disability, 34 because of chronic obstructive pulmonary disease, 146 because of cancer, and 317 because of cardiovascular disease. The adjusted percentage reduction in successful life years in the highest vs the lowest quartile of cystatin C was 27% (95% confidence interval, 11%-39%). The highest vs lowest quartile of cystatin C also was independently associated with incident cognitive or physical disability (hazard ratio, 1.39; 95% confidence interval, 1.00-1.98).
CONCLUSION: A higher cystatin C level, even within a range of relatively normal kidney function, was associated with unsuccessful aging.
10aAged10aAging10aBiomarkers10aCreatinine10aCystatin C10aCystatins10aFemale10aFollow-Up Studies10aGlomerular Filtration Rate10aHumans10aKidney10aMale1 aSarnak, Mark, J1 aKatz, Ronit1 aFried, Linda, F1 aSiscovick, David1 aKestenbaum, Brian1 aSeliger, Stephen1 aRifkin, Dena1 aTracy, Russell1 aNewman, Anne, B1 aShlipak, Michael, G1 aCardiovascular Health Study uhttps://chs-nhlbi.org/node/101302801nas a2200505 4500008004100000022001400041245008500055210006900140260001300209300001000222490000700232520138800239653000901627653002201636653001501658653001901673653002501692653001501717653001401732653002101746653001101767653002901778653002801807653001101835653002501846653000901871653003001880653001601910653003201926653002001958653003201978653001802010653002202028100001802050700001602068700002202084700002002106700002002126700002402146700001702170700002402187700002402211700002402235856003602259 2008 eng d a1532-841400aCystatin C concentration as a predictor of systolic and diastolic heart failure.0 aCystatin C concentration as a predictor of systolic and diastoli c2008 Feb a19-260 v143 aBACKGROUND: Risk factors for heart failure (HF) may differ according to ejection fraction (EF). Higher cystatin C, a marker of kidney dysfunction, is associated with incident HF, but previous studies did not determine EF at diagnosis. We hypothesized that kidney dysfunction would predict diastolic HF (DHF) better than systolic HF (SHF) in the Cardiovascular Health Study.
METHODS AND RESULTS: Cystatin C was measured in 4453 participants without HF at baseline. Incident HF was categorized as DHF (EF > or = 50%) or SHF (EF < 50%). We compared the association of cystatin C with the risk for DHF and SHF, after adjustment for age, sex, race, medications, and HF risk factors. During 8 years of follow-up, 167 participants developed DHF and 206 participants developed SHF. After adjustment, sequentially higher quartiles of cystatin C were associated with risk for SHF (competing risks hazard ratios 1.0 [reference], 1.99 [95% confidence interval 1.14-3.48], 2.32 [1.32-4.07], 3.17 [1.82-5.50], P for trend < .001). The risk for DHF was apparent only at the highest cystatin C quartile (hazard ratios 1.0 [reference], 1.09 [0.62-1.89], 1.08 [0.61-1.93], and 1.83 [1.07-3.11]).
CONCLUSIONS: Cystatin C levels are linearly associated with the incidence of systolic HF, whereas only the highest concentrations of cystatin C predict diastolic HF.
10aAged10aAged, 80 and over10aBiomarkers10aCohort Studies10aConfidence Intervals10aCystatin C10aCystatins10aEchocardiography10aFemale10aHeart Failure, Diastolic10aHeart Failure, Systolic10aHumans10aLongitudinal Studies10aMale10aPredictive Value of Tests10aProbability10aProportional Hazards Models10aRisk Assessment10aSensitivity and Specificity10aStroke Volume10aSurvival Analysis1 aMoran, Andrew1 aKatz, Ronit1 aSmith, Nicolas, L1 aFried, Linda, F1 aSarnak, Mark, J1 aSeliger, Stephen, L1 aPsaty, Bruce1 aSiscovick, David, S1 aGottdiener, John, S1 aShlipak, Michael, G uhttps://chs-nhlbi.org/node/101202916nas a2200349 4500008004100000022001400041245007000055210006900125260001600194300001100210490000800221520198600229653000902215653002802224653001502252653001402267653001102281653003102292653001102323653001102334653000902345653001402354100002002368700002402388700001602412700002002428700002102448700002102469700002002490700002002510856003602530 2008 eng d a1538-367900aRapid kidney function decline and mortality risk in older adults.0 aRapid kidney function decline and mortality risk in older adults c2008 Nov 10 a2212-80 v1683 aBACKGROUND: Impaired kidney function is associated with increased mortality risk in older adults. It remains unknown, however, whether longitudinal declines in kidney function are independently associated with increased cardiovascular and all-cause mortality in older adults.
METHODS: The Cardiovascular Health Study evaluated a cohort of community-dwelling older adults enrolled from 1989 to 1993 in 4 US communities with follow-up through 2005. Among 4380 participants, the slope of annual decline in estimated glomerular filtration rate (eGFR) was estimated using both serum creatinine (eGFR(creat)) and cystatin C (eGFR(cys)) rates, which were measured at baseline, year 3, and year 7 of follow-up. Rapid decline in eGFR was defined as a loss greater than 3 mL/min/1.73 m(2) per year, and cardiovascular and all-cause mortality were assessed over a mean of 9.9 years of follow-up.
RESULTS: Mean (SD) levels of creatinine and cystatin C were 0.93 (0.30) mg/dL and 1.03 (0.25) mg/L, respectively; mean (SD) eGFR(creat) and eGFR(cys) were 79 (23) mL/min/1.73 m(2) and 79 (19) mL/min/1.73 m(2), respectively. Individuals with rapid decline measured by eGFR(creat) (n = 714; 16%) had increased risk of cardiovascular (adjusted hazard ratio [AHR], 1.70; 95% confidence interval [CI], 1.40-2.06) and all-cause (AHR, 1.73; 95% CI, 1.54-1.94) mortality. Individuals with rapid decline measured by eGFR(cys) (n = 1083; 25%) also had increased risk of cardiovascular (AHR, 1.53; 95% CI, 1.29-1.80) and all-cause (AHR, 1.53; 95% CI, 1.38-1.69) mortality. The association of rapid decline in eGFR with elevated mortality risk did not differ across subgroups based on baseline kidney function, age, sex, race, or prevalent coronary heart disease.
CONCLUSION: Rapid decline in eGFR is associated with an increased risk of cardiovascular and all-cause mortality in older adults, independent of baseline eGFR and other demographic variables.
10aAged10aCardiovascular Diseases10aCreatinine10aCystatins10aFemale10aGlomerular Filtration Rate10aHumans10aKidney10aMale10aMortality1 aRifkin, Dena, E1 aShlipak, Michael, G1 aKatz, Ronit1 aFried, Linda, F1 aSiscovick, David1 aChonchol, Michel1 aNewman, Anne, B1 aSarnak, Mark, J uhttps://chs-nhlbi.org/node/106203049nas a2200433 4500008004100000022001400041245012300055210006900178260001600247300001200263490000700275520179800282653000902080653002202089653002502111653002302136653002802159653002002187653001902207653002802226653001102254653003102265653001102296653002002307653001102327653000902338653001702347100001902364700001602383700002002399700002502419700002402444700002402468700002002492700002002512700002402532700002302556856003602579 2009 eng d a1558-359700aAssociation of chronic kidney disease with the spectrum of ankle brachial index the CHS (Cardiovascular Health Study).0 aAssociation of chronic kidney disease with the spectrum of ankle c2009 Sep 22 a1176-840 v543 aOBJECTIVES: This study sought to determine the association of chronic kidney disease (CKD) with high ankle brachial index (ABI) measurement and to compare its strength with that of CKD with a low ABI.
BACKGROUND: CKD is an important risk factor for cardiovascular disease (CVD) events. A high ABI, a marker of lower extremity arterial stiffness, is associated with CVD events and mortality. The association between CKD and high ABI is unknown.
METHODS: The CHS (Cardiovascular Health Study) enrolled community-living people >65 years of age and measured kidney function and ABI. Glomerular filtration rate (GFR) was estimated using equations that incorporated either cystatin C or creatinine, and CKD was defined by estimated GFR <60 ml/min/1.73 m(2). The ABI was categorized as low (<0.90), low-normal (0.90 to 1.09), normal (1.10 to 1.40), and high (>1.40 or incompressible). Multinomial logistic regression was used to evaluate the associations of CKD with ABI categories.
RESULTS: Among 4,513 participants, 23% had CKD, 13% had a low ABI, and 3% had a high ABI. In models adjusted for age, sex, race, hypertension, diabetes, smoking, body mass index, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and C-reactive protein, cystatin C-based CKD was associated with both low ABI (relative risk [RR]: 2.0; 95% confidence interval [CI]: 1.6 to 2.5; p <0.001) and high ABI (RR: 1.6; 95% CI: 1.0 to 2.3; p = 0.03). Results were similar when CKD was defined by creatinine.
CONCLUSIONS: CKD is associated with both the high and the low extremes of ABI in community-living older people. Future studies should evaluate whether arterial stiffness is an important mechanism leading to CVD in people with CKD.
10aAged10aAged, 80 and over10aAnkle Brachial Index10aC-Reactive Protein10aCardiovascular Diseases10aChronic Disease10aCohort Studies10aCross-Sectional Studies10aFemale10aGlomerular Filtration Rate10aHumans10aKidney Diseases10aLipids10aMale10aRisk Factors1 aIx, Joachim, H1 aKatz, Ronit1 ade Boer, Ian, H1 aKestenbaum, Brian, R1 aAllison, Matthew, A1 aSiscovick, David, S1 aNewman, Anne, B1 aSarnak, Mark, J1 aShlipak, Michael, G1 aCriqui, Michael, H uhttps://chs-nhlbi.org/node/113003044nas a2200445 4500008004100000022001400041245009600055210006900151260001300220300001200233490000800245520184200253653001602095653000902111653002002120653002802140653001502168653001502183653001102198653003102209653001802240653001102258653001102269653002002280653001802300653002502318653000902343653001502352653002002367653001702387653001702404653001802421100002402439700001602463700002202479700002002501700002102521700002002542856003602562 2009 eng d a1879-148400aClinical and subclinical cardiovascular disease and kidney function decline in the elderly.0 aClinical and subclinical cardiovascular disease and kidney funct c2009 May a298-3030 v2043 aOBJECTIVE: Kidney function decline in elderly persons may be the result of microvascular atherosclerosis. As a proxy for the renovascular system, we evaluated the association of clinical and subclinical cardiovascular disease (CVD) with kidney function decline.
METHODS: This study included 4380 subjects from the Cardiovascular Health Study, a longitudinal, community-based cohort of persons aged >or=65 from 4 U.S. communities. Creatinine and cystatin C were measured at baseline, year 3, and year 7; eligible subjects had at least two measures. Creatinine-based estimated glomerular filtration rate (eGFR(creat)) was calculated using the MDRD equation. Rapid kidney function decline was defined as an annual eGFR loss >3 mL/min/1.73 m(2). Predictors of rapid kidney decline included prevalent and subclinical measures of CVD.
RESULTS: Mean decline in eGFR(creat) was 0.4+/-2.6/year; 714 (16%) had rapid progression. In multivariate models adjusted for demographics, cardiovascular risk factors, and inflammation, prevalent stroke (OR, 95% CI: 1.55, 1.16-2.08) and heart failure (OR, 95% CI: 1.80, 1.40-2.31) were independent predictors of rapid kidney decline. Among persons without clinical CV, the subclinical disease measures ankle-arm index <0.9 (OR, 95% CI: 1.67, 1.25-2.24), common carotid intima-media thickness (>or=1.14 mm) (OR, 95% CI: 1.52, 1.12-2.06) and internal carotid intima-media thickness (>1.82 mm) (OR, 95% CI: 1.50, 1.12-2.02) had independent associations with rapid kidney function decline. Results were similar using cystatin C.
CONCLUSION: Clinical atherosclerosis and heart failure and subclinical measures of CVD have independent associations with kidney function decline progression in the elderly, suggesting an underlying role of renal atherosclerosis.
10aAge Factors10aAged10aAtherosclerosis10aCardiovascular Diseases10aCreatinine10aCystatin C10aFemale10aGlomerular Filtration Rate10aHeart Failure10aHumans10aKidney10aKidney Diseases10aLinear Models10aLongitudinal Studies10aMale10aOdds Ratio10aRisk Assessment10aRisk Factors10aTime Factors10aUnited States1 aShlipak, Michael, G1 aKatz, Ronit1 aKestenbaum, Bryan1 aFried, Linda, F1 aSiscovick, David1 aSarnak, Mark, J uhttps://chs-nhlbi.org/node/105702856nas a2200397 4500008004100000022001400041245007700055210006900132260001300201300001100214490000700225520178700232653000902019653002202028653001602050653001502066653001502081653002202096653001102118653003102129653001102160653002602171653000902197653001702206100002002223700001602243700001602259700002002275700002202295700001702317700002002334700002002354700002402374700002402398856003602422 2009 eng d a1935-554800aCystatin C, albuminuria, and mortality among older adults with diabetes.0 aCystatin C albuminuria and mortality among older adults with dia c2009 Oct a1833-80 v323 aOBJECTIVE: Albuminuria and impaired glomerular filtration rate (GFR) are each associated with poor health outcomes among individuals with diabetes. Joint associations of albuminuria and impaired GFR with mortality have not been comprehensively evaluated in this population.
RESEARCH DESIGN AND METHODS: This is a cohort study among Cardiovascular Health Study participants with diabetes, mean age 78 years. GFR was estimated using serum cystatin C and serum creatinine. Albumin-to-creatinine ratio (ACR) was measured in single-voided urine samples.
RESULTS: Of 691 participants, 378 died over 10 years of follow-up. Cystatin C-estimated GFR <60 ml/min per 1.73 m(2), creatinine-based estimated GFR <60 ml/min per 1.73 m(2), and urine ACR > or =30 mg/g were each associated with increased mortality risk with hazard ratios of 1.73 (95% CI 1.37-2.18), 1.54 (1.21-1.97), and 1.73 (1.39-2.17), respectively, adjusting for age, sex, race, diabetes duration, hypoglycemic medications, hypertension, BMI, smoking, cholesterol, lipid-lowering medications, prevalent cardiovascular disease (CVD), and prevalent heart failure. Cystatin C-estimated GFR and urine ACR were additive in terms of mortality risk. Cystatin C-estimated GFR predicted mortality more strongly than creatinine-based estimated GFR.
CONCLUSIONS: Albuminuria and impaired GFR were independent, additive risk factors for mortality among older adults with diabetes. These findings support current recommendations to regularly assess both albuminuria and GFR in the clinical care of patients with diabetes; a focus on interventions to prevent or treat CVD in the presence of albuminuria, impaired GFR, or both; and further consideration of cystatin C use in clinical care.
10aAged10aAged, 80 and over10aAlbuminuria10aCreatinine10aCystatin C10aDiabetes Mellitus10aFemale10aGlomerular Filtration Rate10aHumans10aKidney Function Tests10aMale10aRisk Factors1 ade Boer, Ian, H1 aKatz, Ronit1 aCao, Jie, J1 aFried, Linda, F1 aKestenbaum, Bryan1 aMukamal, Ken1 aRifkin, Dena, E1 aSarnak, Mark, J1 aShlipak, Michael, G1 aSiscovick, David, S uhttps://chs-nhlbi.org/node/111003050nas a2200445 4500008004100000022001400041245006000055210005900115260001300174300001200187490000700199520190000206653000902106653001002115653002102125653002002146653002002166653001902186653001502205653001502220653001102235653003102246653001102277653001102288653002002299653002502319653000902344653001202353653001702365100002002382700001602402700002002418700001902438700002102457700002002478700002402498700002402522700002202546856003602568 2009 eng d a1523-683800aObesity and change in estimated GFR among older adults.0 aObesity and change in estimated GFR among older adults c2009 Dec a1043-510 v543 aBACKGROUND: The prevalence of chronic kidney disease is growing most rapidly among older adults; however, determinants of impaired kidney function in this population are not well understood. Obesity assessed in midlife has been associated with chronic kidney disease.
STUDY DESIGN: Cohort study.
SETTING & PARTICIPANTS: 4,295 participants in the community-based Cardiovascular Health Study, aged >or= 65 years.
PREDICTORS: Body mass index, waist circumference, and fat mass measured using bioelectrical impedance.
OUTCOME: Change in glomerular filtration rate (GFR) during 7 years of follow-up.
MEASUREMENTS: Longitudinal estimates of GFR calculated using the 4-variable Modification of Diet in Renal Disease (MDRD) Study equation.
RESULTS: Estimated GFR decreased by an average of 0.4 +/- 3.6 mL/min/1.73 m(2)/y, and rapid GFR loss (>3 mL/min/1.73 m(2)/y) occurred in 693 participants (16%). Baseline body mass index, waist circumference, and fat mass were each associated with increased risk of rapid GFR loss: ORs, 1.19 (95% CI, 1.09-1.30) per 5 kg/m(2), 1.25 (95% CI, 1.16-1.36) per 12 cm, and 1.14 (95% CI, 1.05-1.24) per 10 kg after adjustment for age, sex, race, and smoking. The magnitude of increased risk was larger for participants with estimated GFR < 60 mL/min/1.73 m(2) at baseline (P for interaction < 0.05). Associations were substantially attenuated by further adjustment for diabetes, hypertension, and C-reactive protein level. Obesity measurements were not associated with change in GFR estimated using serum cystatin C level.
LIMITATIONS: Few participants with advanced chronic kidney disease at baseline, no direct GFR measurements.
CONCLUSION: Obesity may be a modifiable risk factor for the development and progression of kidney disease in older adults.
10aAged10aAging10aBody Composition10aBody Mass Index10aChronic Disease10aCohort Studies10aCreatinine10aCystatin C10aFemale10aGlomerular Filtration Rate10aHumans10aKidney10aKidney Diseases10aLongitudinal Studies10aMale10aObesity10aRisk Factors1 ade Boer, Ian, H1 aKatz, Ronit1 aFried, Linda, F1 aIx, Joachim, H1 aLuchsinger, Jose1 aSarnak, Mark, J1 aShlipak, Michael, G1 aSiscovick, David, S1 aKestenbaum, Bryan uhttps://chs-nhlbi.org/node/113102675nas a2200445 4500008004100000022001400041245008300055210006900138260001300207300001200220490000700232520145100239653000901690653002201699653002801721653001501749653001501764653001101779653003101790653001801821653001101839653002501850653000901875653002601884653003301910653003301943653001701976653001101993653001702004653001802021100002402039700001602063700002202079700002102101700001702122700001702139700001702156700002002173856003602193 2009 eng d a1533-345000aRapid decline of kidney function increases cardiovascular risk in the elderly.0 aRapid decline of kidney function increases cardiovascular risk i c2009 Dec a2625-300 v203 aChronic kidney disease (CKD), defined at a specific time point, is an important risk factor for cardiovascular disease. Whether the rate of kidney function decline contributes additional cardiovascular risk is unknown. In the Cardiovascular Health Study, we compared the associations of changes in kidney function during the first 7 yr with the incidence of heart failure (HF), myocardial infarction (MI), stroke, and peripheral arterial disease (PAD) during the subsequent 8 yr. We defined a rapid decline in cystatin C-based estimated GFR as >3 ml/min per 1.73 m(2)/yr, on the basis of determination at baseline, year 3, and year 7. Among eligible participants, 1083 (24%) had rapid kidney decline. The incidence of each type of cardiovascular event was significantly higher among patients with rapid decline (all P < 0.001). After multivariate adjustment for demographics, cardiovascular disease risk factors, and baseline kidney function, rapid kidney function decline was significantly associated with HF (adjusted hazard ratio [HR] 1.32; 95% confidence interval [CI] 1.13 to 1.53), MI (HR 1.48; 95% CI 1.21 to 1.83), and PAD (HR 1.67; 95% CI 1.02 to 2.75) but not with stroke (HR 1.19; 95% CI 0.97 to 1.45). The association of rapid decline with each outcome did not differ by the presence or absence of CKD. In conclusion, declining kidney function associates with higher risk for HF, MI, and PAD among patients with or without CKD.
10aAged10aAged, 80 and over10aCardiovascular Diseases10aCreatinine10aCystatin C10aFemale10aGlomerular Filtration Rate10aHeart Failure10aHumans10aLongitudinal Studies10aMale10aMyocardial Infarction10aPeripheral Vascular Diseases10aRenal Insufficiency, Chronic10aRisk Factors10aStroke10aTime Factors10aUnited States1 aShlipak, Michael, G1 aKatz, Ronit1 aKestenbaum, Bryan1 aSiscovick, David1 aFried, Linda1 aNewman, Anne1 aRifkin, Dena1 aSarnak, Mark, J uhttps://chs-nhlbi.org/node/114402550nas a2200373 4500008004100000022001400041245009900055210006900154260000900223300001000232490000700242520153600249653001601785653000901801653001501810653001501825653002401840653001101864653003101875653001101906653001101917653002001928653000901948653001701957100002401974700001601998700002202014700002002036700002002056700002402076700002002100700002002120856003602140 2009 eng d a1421-967000aRate of kidney function decline in older adults: a comparison using creatinine and cystatin C.0 aRate of kidney function decline in older adults a comparison usi c2009 a171-80 v303 aBACKGROUND/AIMS: The aim of this study was to determine the decline in the estimated glomerular filtration rate (eGFR) in elderly persons and to compare estimates based on creatinine and cystatin C.
METHODS: In the Cardiovascular Health Study, GFR changes in an elderly cohort were estimated from serum creatinine and cystatin C measured at baseline, year 3 and year 7 in 4,380 participants (age 72 +/- 5 years at entry). Outcomes were mean eGFR decline, incident chronic kidney disease (CKD) and rapid decline in eGFR (annual loss >3 ml/min/1.73 m(2)).
RESULTS: Mean annual eGFR loss as estimated from creatinine was 0.4 +/- 3.6 ml/min/1.73 m(2), with 16% of the participants experiencing a rapid decline. Mean eGFR loss as estimated from cystatin C was 1.8 +/- 2.6, with 25% of the participants experiencing a rapid decline (p < 0.001 for both). Among participants without baseline CKD, incident CKD was detected at year 7 in 10% (n = 263) using creatinine and 19% (n = 544) using cystatin C (p < 0.001). Increasing age was the strongest predictor of rapid decline; adjusted odds ratios were 1.38 (1.16-1.65), 1.62 (1.31-1.99) and 2.96 (2.28-3.84) for participants aged 70-74, 75-79 and 80+ at baseline, compared with those aged 65-69.
CONCLUSION: In elderly persons, cystatin C estimated substantially larger declines in kidney function than creatinine did. Defining the optimal measurement of kidney function in elderly persons should be a high priority for future research.
10aAge Factors10aAged10aCreatinine10aCystatin C10aDisease Progression10aFemale10aGlomerular Filtration Rate10aHumans10aKidney10aKidney Diseases10aMale10aRisk Factors1 aShlipak, Michael, G1 aKatz, Ronit1 aKestenbaum, Bryan1 aFried, Linda, F1 aNewman, Anne, B1 aSiscovick, David, S1 aStevens, Lesley1 aSarnak, Mark, J uhttps://chs-nhlbi.org/node/108902733nas a2200385 4500008004100000022001400041245006500055210006300120260001300183300001000196490000700206520170400213653001001917653000901927653002201936653002801958653001501986653001102001653001102012653001602023653002102039100002302060700001802083700002302101700002502124700001602149700002002165700002002185700002202205700001902227700002002246700002102266700002402287856003602311 2010 eng d a1460-238500aAge and cystatin C in healthy adults: a collaborative study.0 aAge and cystatin C in healthy adults a collaborative study c2010 Feb a463-90 v253 aBACKGROUND: Kidney function declines with age, but a substantial portion of this decline has been attributed to the higher prevalence of risk factors for kidney disease at older ages. The effect of age on kidney function has not been well described in a healthy population across a wide age spectrum.
METHODS: The authors pooled individual-level cross-sectional data from 18 253 persons aged 28-100 years in four studies: the Cardiovascular Health Study; the Health, Aging and Body Composition Study; the Multi-Ethnic Study of Atherosclerosis and the Prevention of Renal and Vascular End-Stage Disease cohort. Kidney function was measured by cystatin C. Clinical risk factors for kidney disease included diabetes, hypertension, obesity, smoking, coronary heart disease, cerebrovascular disease, peripheral arterial disease and heart failure.
RESULTS: Across the age range, there was a strong, non-linear association of age with cystatin C concentration. This association was substantial, even among participants free of clinical risk factors for kidney disease; mean cystatin C levels were 46% higher in participants 80 and older compared with those <40 years (1.06 versus 0.72 mg/L, P < 0.001). Participants with one or more risk factors had higher cystatin C concentrations for a given age, and the age association was slightly stronger (P < 0.001 for age and risk factor interaction).
CONCLUSIONS: There is a strong, non-linear association of age with kidney function, even in healthy individuals. An important area for research will be to investigate the mechanisms that lead to deterioration of kidney function in apparently healthy persons.
10aAdult10aAged10aAged, 80 and over10aCross-Sectional Studies10aCystatin C10aHumans10aKidney10aMiddle Aged10aReference Values1 aOdden, Michelle, C1 aTager, Ira, B1 aGansevoort, Ron, T1 aBakker, Stephan, J L1 aKatz, Ronit1 aFried, Linda, F1 aNewman, Anne, B1 aCanada, Robert, B1 aHarris, Tamara1 aSarnak, Mark, J1 aSiscovick, David1 aShlipak, Michael, G uhttps://chs-nhlbi.org/node/112802881nas a2200385 4500008004100000022001400041245009900055210006900154260001300223300001100236490000700247520182100254653000902075653001602084653002802100653001502128653001502143653001102158653003102169653001802200653001102218653000902229653002602238653001702264100002002281700001602301700002102317700002002338700001302358700002002371700002402391700002402415700002002439856003602459 2010 eng d a1460-238500aAlbuminuria, impaired kidney function and cardiovascular outcomes or mortality in the elderly.0 aAlbuminuria impaired kidney function and cardiovascular outcomes c2010 May a1560-70 v253 aBACKGROUND: Kidney disease is a risk factor for mortality and cardiovascular disease in older adults, but the separate and combined effects of albuminuria and cystatin C, a novel marker of glomerular filtration, are not known.
METHODS: We examined associations of these markers with mortality and cardiovascular outcomes during a median follow-up of 8.3 years in 3291 older adults in the Cardiovascular Health Study. Kidney disease was assessed using urinary albumin/creatinine ratio (ACR), cystatin C and Modification of Diet in Renal Disease estimated glomerular filtration rate (eGFR). We defined subgroups based on presence of microalbuminuria (MA, ACR > 30 mg/g) and categories of normal kidney function (cystatin C < 1.0 mg/L and eGFR > 60 mL/min/1.73 m(2)); preclinical kidney disease (cystatin C level > 1.0 mg/l but eGFR > 60 mL/min/1.73 m(2)); and chronic kidney disease (CKD) (eGFR < 60 mL/min/1.73 m(2)). Cox proportional hazards models were used to examine associations between these six subgroups and all-cause or cardiovascular mortality, myocardial infarction and heart failure.
RESULTS: One thousand one hundred fifty (34.9%) had normal kidney function (12.2% with MA), 1518 (46.1%) had preclinical kidney disease (17.9% with MA) and 622 (18.9%) had CKD (47% with MA). After adjustment, the presence of either preclinical kidney disease or MA was associated with an over 50% increase in mortality risk; the presence of both was associated with a 2.4-fold mortality risk. Those with CKD and MA were at highest risk, with a nearly 4-fold mortality risk.
CONCLUSION: Elevated cystatin C and albuminuria are common, identify different subsets of the older population, and are independent, graded risk factors for cardiovascular disease and mortality.
10aAged10aAlbuminuria10aCardiovascular Diseases10aCreatinine10aCystatin C10aFemale10aGlomerular Filtration Rate10aHeart Failure10aHumans10aMale10aMyocardial Infarction10aRisk Factors1 aRifkin, Dena, E1 aKatz, Ronit1 aChonchol, Michel1 aFried, Linda, F1 aCao, Jie1 ade Boer, Ian, H1 aSiscovick, David, S1 aShlipak, Michael, G1 aSarnak, Mark, J uhttps://chs-nhlbi.org/node/114902802nas a2200373 4500008004100000022001400041245009600055210006900151260001300220300001100233490000700244520178400251653000902035653001002044653002102054653001902075653001502094653001102109653003102120653001102151653001102162653002002173653000902193653002402202100001902226700001602245700002102261700002202282700002002304700002402324700002002348700002402368856003602392 2010 eng d a1460-238500aAlcohol consumption and kidney function decline in the elderly: alcohol and kidney disease.0 aAlcohol consumption and kidney function decline in the elderly a c2010 Oct a3301-70 v253 aBACKGROUND: Alcohol consumption appears to be protective for cardiovascular disease; however, its relationship with kidney disease is unclear.
METHODS: This prospective cohort study included 4343 subjects from the Cardiovascular Health Study, a longitudinal, community-based cohort of persons aged ≥65 from four US communities. We used previously defined categories based on weekly alcohol consumption: none, former, <1 drink, 1-6 drinks, 7-13 drinks and ≥14 drinks. Cystatin C was measured at baseline, year 3 and year 7; eligible subjects had at least two measures. Estimated GFR(cys) was calculated from cystatin C. The primary outcome was rapid kidney function as an annual estimated GFR (eGFR(cys)) loss >3 mL/min/1.73 m(2)/year.
RESULTS: Eight percent of the cohort reported former alcohol use and 52% reported current alcohol consumption. During a mean follow-up of 5.6 years, 1075 (25%) participants had rapid kidney function decline. In adjusted logistic regression models, there was no association between alcohol use and kidney function decline (odds ratio, 95% confidence interval: none = reference; former = 1.18, 0.89-1.56; <1 drink = 1.20, 0.99-1.47; 1-6 = 1.18, 0.95-1.45; 7-13 = 1.10, 0.80-1.53; >14 = 0.89, 0.61-1.13). Results were similar with kidney function decline as a continuous outcome.
CONCLUSIONS: Our results suggest that moderate alcohol consumption has neither adverse nor beneficial effects on kidney function. Although clinicians will need to consider the potential deleterious effects associated with alcohol consumption, there does not appear to be a basis for recommending that older adults discontinue or initiate light to moderate alcohol consumption to protect against kidney disease.
10aAged10aAging10aAlcohol Drinking10aCohort Studies10aCystatin C10aFemale10aGlomerular Filtration Rate10aHumans10aKidney10aKidney Diseases10aMale10aProspective Studies1 aMenon, Vandana1 aKatz, Ronit1 aMukamal, Kenneth1 aKestenbaum, Bryan1 ade Boer, Ian, H1 aSiscovick, David, S1 aSarnak, Mark, J1 aShlipak, Michael, G uhttps://chs-nhlbi.org/node/118602789nas a2200409 4500008004100000022001400041245011600055210006900171260000900240300001200249490000800261520159600269653000901865653001501874653002301889653002801912653001901940653002801959653001101987653002201998653003102020653001102051653002602062653002502088653000902113653003002122100002002152700001602172700002002188700002202208700002502230700002002255700002402275700002402299700002002323856003602343 2010 eng d a1660-211000aAssociation between baseline kidney function and change in CRP: an analysis of the cardiovascular health study.0 aAssociation between baseline kidney function and change in CRP a c2010 ac114-210 v1153 aBACKGROUND: In cross-sectional analyses, C-reactive protein (CRP) levels are inversely related to levels of kidney function. The relationship between kidney function and subsequent changes in CRP is unknown.
METHODS: We studied 4,364 individuals from the Cardiovascular Health Study, a longitudinal cohort of community-dwelling older adults. Baseline eGFRcys was estimated using cystatin C. CRP was measured at baseline and after 3 and 7 years of follow-up; slopes of change in CRP were calculated.
RESULTS: The mean (SD) age of the cohort was 72 (5.2) years; mean (SD) eGFRcys was 78.9 (18.4) ml/min/1.73 m(2). The median (interquartile range IQR) baseline CRP was 2.39 (1.22, 4.33) mg/l; the median (IQR) yearly change in CRP was -0.0051 (-0.020 to 0.27) mg/l/year. After adjustment for demographic characteristics and the initial level of CRP, each standard deviation lower baseline eGFR was associated with a small and non-significant yearly increase in CRP (0.032 mg/l/year; 95% CI: -0.005 to 0.070, p = 0.094).
CONCLUSIONS: We did not find a relationship between eGFR and subsequent changes in CRP. The association between kidney function and CRP in cross-sectional analyses may reflect unmeasured confounding by atherosclerosis; alternatively, the burden of comorbidity and interval mortality in this population may have masked a stronger longitudinal association between kidney function and change in CRP. Further study in younger populations may clarify whether impaired kidney function leads to change in inflammation over time.
10aAged10aBiomarkers10aC-Reactive Protein10aCardiovascular Diseases10aCohort Studies10aCross-Sectional Studies10aFemale10aFollow-Up Studies10aGlomerular Filtration Rate10aHumans10aKidney Function Tests10aLongitudinal Studies10aMale10aResidence Characteristics1 aRifkin, Dena, E1 aKatz, Ronit1 aFried, Linda, F1 aKestenbaum, Bryan1 aJenny, Nancy, Swords1 aNewman, Anne, B1 aSiscovick, David, S1 aShlipak, Michael, G1 aSarnak, Mark, J uhttps://chs-nhlbi.org/node/119003253nas a2200493 4500008004100000022001400041245006100055210006000116260001300176300001100189490000600200520194500206653001602151653000902167653001502176653002802191653001502219653001502234653002702249653001102276653003102287653001102318653001402329653002002343653002502363653000902388653003202397653002002429653001702449653001702466653001802483653001802501100001502519700002202534700001602556700002002572700002002592700002102612700002202633700002002655700002402675700002402699856003602723 2010 eng d a1941-770500aCystatin C and sudden cardiac death risk in the elderly.0 aCystatin C and sudden cardiac death risk in the elderly c2010 Mar a159-640 v33 aBACKGROUND: Recent studies have demonstrated an association between moderate kidney dysfunction and sudden cardiac death in people with cardiovascular disease.
METHODS AND RESULTS: The study was a longitudinal analysis among 4465 participants from the Cardiovascular Health Study without prevalent cardiovascular disease at baseline. Cystatin C and creatinine were measured from baseline sera. Sudden cardiac death (SCD) was defined as a sudden pulseless condition from a cardiac origin in a previously stable individual that occurred out of the hospital or in the emergency room. The association between cystatin C tertiles and SCD was determined with multivariate Cox proportional hazards. A similar analysis compared SCD incidence across creatinine-based estimated glomerular filtration rate (eGFR) tertiles. Over a median follow-up of 11.2 years, 91 adjudicated SCD events occurred. The annual incidence of SCD events increased across cystatin C tertiles: 10 events per 10 000 person years in tertile 1, 25 events per 10 000 person years in tertile 2, and 32 events per 10 000 person-years in the highest cystatin C tertile. These associations persisted after multivariate adjustment: hazards ratio=2.72; 95% confidence interval, 1.44 to 5.16 in tertile 2 and hazards ratio=2.67; 95% confidence interval, 1.33 to 5.35 in tertile 3. After multivariate adjustment, the rate of SCD also increased in a linear distribution across creatinine-based eGFR tertiles: 15 events per 10 000 person-years in tertile 1, 22 events per 10 000 person-years in tertile 2, and 27 events per 10 000 person-years in tertile 3. No significant associations, however, remained between creatinine-based eGFR and SCD after multivariable adjustment.
CONCLUSIONS: Impaired kidney function, as measured by cystatin C, has an independent association with SCD risk among elderly persons without clinical cardiovascular disease.
10aAge Factors10aAged10aBiomarkers10aChi-Square Distribution10aCreatinine10aCystatin C10aDeath, Sudden, Cardiac10aFemale10aGlomerular Filtration Rate10aHumans10aIncidence10aKidney Diseases10aLongitudinal Studies10aMale10aProportional Hazards Models10aRisk Assessment10aRisk Factors10aTime Factors10aUnited States10aUp-Regulation1 aDeo, Rajat1 aSotoodehnia, Nona1 aKatz, Ronit1 aSarnak, Mark, J1 aFried, Linda, F1 aChonchol, Michel1 aKestenbaum, Bryan1 aPsaty, Bruce, M1 aSiscovick, David, S1 aShlipak, Michael, G uhttps://chs-nhlbi.org/node/117704031nas a2200733 4500008004100000022001400041245014700055210006900202260001600271490000600287520185700293653001002150653000902160653004002169653001102209653003402220653001102254653001402265653000902279653001602288653003602304653001402340653001102354100002002365700002602385700002002411700002202431700002102453700002602474700002002500700002102520700002102541700002202562700002202584700001602606700001902622700001902641700001602660700001802676700001902694700001902713700002002732700002202752700001802774700001802792700002202810700001802832700001902850700002002869700002202889700002802911700002602939700002002965700002302985700002003008700003003028700002403058700002403082700002103106700001903127710004803146710006703194856003603261 2010 eng d a1553-740400aGenome-wide association studies of serum magnesium, potassium, and sodium concentrations identify six Loci influencing serum magnesium levels.0 aGenomewide association studies of serum magnesium potassium and c2010 Aug 050 v63 aMagnesium, potassium, and sodium, cations commonly measured in serum, are involved in many physiological processes including energy metabolism, nerve and muscle function, signal transduction, and fluid and blood pressure regulation. To evaluate the contribution of common genetic variation to normal physiologic variation in serum concentrations of these cations, we conducted genome-wide association studies of serum magnesium, potassium, and sodium concentrations using approximately 2.5 million genotyped and imputed common single nucleotide polymorphisms (SNPs) in 15,366 participants of European descent from the international CHARGE Consortium. Study-specific results were combined using fixed-effects inverse-variance weighted meta-analysis. SNPs demonstrating genome-wide significant (p<5 x 10(-8)) or suggestive associations (p<4 x 10(-7)) were evaluated for replication in an additional 8,463 subjects of European descent. The association of common variants at six genomic regions (in or near MUC1, ATP2B1, DCDC5, TRPM6, SHROOM3, and MDS1) with serum magnesium levels was genome-wide significant when meta-analyzed with the replication dataset. All initially significant SNPs from the CHARGE Consortium showed nominal association with clinically defined hypomagnesemia, two showed association with kidney function, two with bone mineral density, and one of these also associated with fasting glucose levels. Common variants in CNNM2, a magnesium transporter studied only in model systems to date, as well as in CNNM3 and CNNM4, were also associated with magnesium concentrations in this study. We observed no associations with serum sodium or potassium levels exceeding p<4 x 10(-7). Follow-up studies of newly implicated genomic loci may provide additional insights into the regulation and homeostasis of human serum magnesium levels.
10aAdult10aAged10aEuropean Continental Ancestry Group10aFemale10aGenome-Wide Association Study10aHumans10aMagnesium10aMale10aMiddle Aged10aPolymorphism, Single Nucleotide10aPotassium10aSodium1 aMeyer, Tamra, E1 aVerwoert, Germaine, C1 aHwang, Shih-Jen1 aGlazer, Nicole, L1 aSmith, Albert, V1 avan Rooij, Frank, J A1 aEhret, Georg, B1 aBoerwinkle, Eric1 aFelix, Janine, F1 aLeak, Tennille, S1 aHarris, Tamara, B1 aYang, Qiong1 aDehghan, Abbas1 aAspelund, Thor1 aKatz, Ronit1 aHomuth, Georg1 aKocher, Thomas1 aRettig, Rainer1 aRied, Janina, S1 aGieger, Christian1 aPrucha, Hanna1 aPfeufer, Arne1 aMeitinger, Thomas1 aCoresh, Josef1 aHofman, Albert1 aSarnak, Mark, J1 aChen, Yii-Der Ida1 aUitterlinden, André, G1 aChakravarti, Aravinda1 aPsaty, Bruce, M1 aDuijn, Cornelia, M1 aKao, Linda, W H1 aWitteman, Jacqueline, C M1 aGudnason, Vilmundur1 aSiscovick, David, S1 aFox, Caroline, S1 aKöttgen, Anna1 aGenetic Factors for Osteoporosis Consortium1 aMeta Analysis of Glucose and Insulin Related Traits Consortium uhttps://chs-nhlbi.org/node/122302681nas a2200385 4500008004100000022001400041245007400055210006900129260001300198300001000211490000700221520162500228653001601853653000901869653002201878653002401900653001901924653002801943653001101971653002201982653003102004653001102035653002002046653002602066653000902092100001502101700001602116700002202132700001702154700002002171700002002191700002402211700002402235856003602259 2010 eng d a1532-841400aImpaired kidney function and atrial fibrillation in elderly subjects.0 aImpaired kidney function and atrial fibrillation in elderly subj c2010 Jan a55-600 v163 aBACKGROUND: Impaired kidney function is associated with increased risk for cardiovascular events. We evaluated whether kidney function is associated with atrial fibrillation (AF) risk in elderly persons.
METHODS AND RESULTS: Subjects were participants in the Cardiovascular Health Study (CHS), a population-based cohort of ambulatory elderly. Measures of kidney function were cystatin C and creatinine-based estimated glomerular filtration rate (eGFR). Among the 4663 participants, 342 (7%) had AF at baseline and 579 (13%) developed incident AF during follow-up (mean 7.4 years). In unadjusted analyses, cystatin C quartiles were strongly associated with prevalent AF with a nearly 3-fold odds in the highest quartile compared with the lowest (HR=1.19, 95% CI [0.80-1.76] in quartile 2; HR=2.00, 95% CI [1.38-2.88] in quartile 3; and HR=2.87, 95% CI [2.03-4.07] in quartile 4). This increased risk for prevalent AF remained significant after multivariate adjustment. The risk for incident AF increased across cystatin C quartiles in the unadjusted analysis (HR=1.37, 95% CI [1.07-1.75] in quartile 2; HR=1.43, 95% CI [1.11-1.84] in quartile 3; and HR=1.88, 95% CI [1.47-2.41] in quartile 4); however, after multivariate adjustment, these findings were no longer significant. An estimated GFR <60 mL.min.1.73m(2) was associated with prevalent and incident AF in unadjusted, but not multivariate analyses.
CONCLUSIONS: Impaired kidney function, as measured by cystatin C, is an independent marker of prevalent AF; however, neither cystatin C nor eGFR are predictors of incident AF.
10aAge Factors10aAged10aAged, 80 and over10aAtrial Fibrillation10aCohort Studies10aCross-Sectional Studies10aFemale10aFollow-Up Studies10aGlomerular Filtration Rate10aHumans10aKidney Diseases10aKidney Function Tests10aMale1 aDeo, Rajat1 aKatz, Ronit1 aKestenbaum, Bryan1 aFried, Linda1 aSarnak, Mark, J1 aPsaty, Bruce, M1 aSiscovick, David, S1 aShlipak, Michael, G uhttps://chs-nhlbi.org/node/116603047nas a2200433 4500008004100000022001400041245010800055210006900163260001300232300001100245490000700256520184200263653000902105653001502114653002302129653001902152653001502171653001102186653003102197653001102228653001702239653003802256653001802294653001102312653002002323653002502343653000902368653002402377653001802401100002402419700001602443700002002459700002002479700002202499700001802521700002402539710001402563856003602577 2010 eng d a1460-238500aInflammatory biomarkers and decline in kidney function in the elderly: the Cardiovascular Health Study.0 aInflammatory biomarkers and decline in kidney function in the el c2010 Jan a119-240 v253 aBACKGROUND: Cross-sectional studies have demonstrated a consistent and linear association between circulating inflammatory markers and kidney function. The objective of this study was to determine whether elevated markers of inflammation are independently associated with longitudinal kidney function decline.
METHODS: This study included 4128 subjects from the Cardiovascular Health Study. Cystatin C was measured at baseline, 3 years later and 7 years later; eligible subjects had at least two measures. Cystatin C-based estimated glomerular filtration rate (eGFR(cysC)) was estimated, and rapid kidney function decline was defined as an annual loss of eGFR(cysC) >3 mL/min/1.73 m(2). Predictors included ten inflammatory and procoagulant biomarkers: C-reactive protein, interleukin-6, intercellular adhesion molecule-1, white blood cell count, fibrinogen, factor VII, factor VIII, D-dimer, plasmin-antiplasmin complex and serum albumin.
RESULTS: During the study, 1059 subjects (26%) had a rapid decline in kidney function. In contrast to the other nine inflammatory or procoagulant biomarkers, serum albumin had a consistent and inverse association with rapid kidney function decline [final adjusted logistic regression model: 1.14-fold increased odds (95% CI 1.06-1.23) of rapid decline per standard deviation lower albumin]. The lowest quartile of albumin had an odds ratio of 1.55 (95% CI 1.23-1.96) for rapid decline compared with the highest quartile. These associations persisted after adjusting the albumin models for CRP, IL-6 and fibrinogen.
CONCLUSIONS: In contrast to nine other inflammatory and procoagulant markers, only lower baseline levels of serum albumin were consistently associated with a rapid decline in kidney function, as measured by cystatin C-based eGFR.
10aAged10aBiomarkers10aC-Reactive Protein10aCohort Studies10aCystatin C10aFemale10aGlomerular Filtration Rate10aHumans10aInflammation10aIntercellular Adhesion Molecule-110aInterleukin-610aKidney10aLogistic Models10aLongitudinal Studies10aMale10aProspective Studies10aSerum Albumin1 aKeller, Christopher1 aKatz, Ronit1 aSarnak, Mark, J1 aFried, Linda, F1 aKestenbaum, Bryan1 aCushman, Mary1 aShlipak, Michael, G1 aCHS study uhttps://chs-nhlbi.org/node/112702817nas a2200385 4500008004100000022001400041245012300055210006900178260000900247300001500256490000600271520169500277653000901972653002801981653001502009653003702024653001102061653003102072653001102103653001702114653001102131653002502142653000902167653002402176100002302200700001802223700002602241700002502267700002302292700001602315700002002331700002002351700002402371856003602395 2011 eng d a1557-467900aAntihypertensive medication use and change in kidney function in elderly adults: a marginal structural model analysis.0 aAntihypertensive medication use and change in kidney function in c2011 aArticle 340 v73 aBACKGROUND: The evidence for the effectiveness of antihypertensive medication use for slowing decline in kidney function in older persons is sparse. We addressed this research question by the application of novel methods in a marginal structural model.
METHODS: Change in kidney function was measured by two or more measures of cystatin C in 1,576 hypertensive participants in the Cardiovascular Health Study over 7 years of follow-up (1989-1997 in four U.S. communities). The exposure of interest was antihypertensive medication use. We used a novel estimator in a marginal structural model to account for bias due to confounding and informative censoring.
RESULTS: The mean annual decline in eGFR was 2.41 ± 4.91 mL/min/1.73 m(2). In unadjusted analysis, antihypertensive medication use was not associated with annual change in kidney function. Traditional multivariable regression did not substantially change these estimates. Based on a marginal structural analysis, persons on antihypertensives had slower declines in kidney function; participants had an estimated 0.88 (0.13, 1.63) ml/min/1.73 m(2) per year slower decline in eGFR compared with persons on no treatment. In a model that also accounted for bias due to informative censoring, the estimate for the treatment effect was 2.23 (-0.13, 4.59) ml/min/1.73 m(2) per year slower decline in eGFR.
CONCLUSION: In summary, estimates from a marginal structural model suggested that antihypertensive therapy was associated with preserved kidney function in hypertensive elderly adults. Confirmatory studies may provide power to determine the strength and validity of the findings.
10aAged10aAntihypertensive Agents10aCystatin C10aData Interpretation, Statistical10aFemale10aGlomerular Filtration Rate10aHumans10aHypertension10aKidney10aLongitudinal Studies10aMale10aModels, Statistical1 aOdden, Michelle, C1 aTager, Ira, B1 avan der Laan, Mark, J1 aDelaney, Joseph, A C1 aPeralta, Carmen, A1 aKatz, Ronit1 aSarnak, Mark, J1 aPsaty, Bruce, M1 aShlipak, Michael, G uhttps://chs-nhlbi.org/node/134802962nas a2200421 4500008004100000022001400041245008100055210006900136260001300205300001100218490000700229520178200236653000902018653002202027653001902049653001902068653001102087653002202098653001102120653002802131653002502159653000902184653002402193653003302217653001702250653002202267100002502289700001602314700002202330700002402352700002002376700002902396700002102425700002102446700002002467700001702487856003602504 2011 eng d a1525-149700aChronic kidney disease and the risk of end-stage renal disease versus death.0 aChronic kidney disease and the risk of endstage renal disease ve c2011 Apr a379-850 v263 aBACKGROUND: Among older adults with chronic kidney disease (CKD), the comparative event rates of end-stage renal disease (ESRD) and cause-specific death are unknown.
OBJECTIVE: To compare the rates of ESRD, cardiovascular and non-cardiovascular death and examine risk factors for ESRD and all-cause mortality in Cardiovascular Health Study (CHS) participants.
DESIGN: The CHS is a longitudinal cohort study of community-dwelling adults aged 65 years and older.
PARTICIPANTS: 1,268 participants with an estimated glomerular filtration rate (eGFR) < 60 ml/min per 1.73 m(2) were followed until the time of first event (ESRD, cardiovascular or non-cardiovascular death) or until March 31, 2003.
MAIN MEASURES: The outcomes were ESRD, cardiovascular- and non-cardiovascular death. Rates of each event were calculated, and a Cox Proportional Hazards Model with a competing risk framework was used to examine risk factors for ESRD as compared with death. Predictors included age, gender, race, BMI, hypertension, diabetes, cardiovascular disease, heart failure, tobacco use, eGFR, and total cholesterol.
KEY RESULTS: During 9.7 years of follow-up, 5% of the cohort progressed to ESRD, and 61% of the cohort died. The rate (per 100 person-years) was 0.5 for ESRD and 6.8 for all-cause mortality (3.0 for cardiovascular and 3.8 for non-cardiovascular mortality). In the competing risk framework, lower eGFR, male gender, African-American race, and higher BMI were associated with an increased risk of ESRD.
CONCLUSIONS: Older adults with CKD are 13-fold more likely to die from any cause than progress to ESRD and are 6-fold more likely to die from cardiovascular causes than develop ESRD.
10aAged10aAged, 80 and over10aCause of Death10aCohort Studies10aFemale10aFollow-Up Studies10aHumans10aKidney Failure, Chronic10aLongitudinal Studies10aMale10aProspective Studies10aRenal Insufficiency, Chronic10aRisk Factors10aTreatment Outcome1 aDalrymple, Lorien, S1 aKatz, Ronit1 aKestenbaum, Bryan1 aShlipak, Michael, G1 aSarnak, Mark, J1 aStehman-Breen, Catherine1 aSeliger, Stephen1 aSiscovick, David1 aNewman, Anne, B1 aFried, Linda uhttps://chs-nhlbi.org/node/123003030nas a2200505 4500008004100000022001400041245004500055210004400100260001300144300001100157490000600168520171200174653001601886653002201902653002501924653001501949653002801964653002801992653002002020653001502040653002802055653001502083653002202098653001102120653003102131653001102162653001102173653002002184653002002204653000902224653002302233653001502256653002002271653001702291653001802308100001902326700002302345700001602368700002002384700002002404700002402424700002002448700002002468856003602488 2011 eng d a1555-905X00aChronic kidney disease in octogenarians.0 aChronic kidney disease in octogenarians c2011 Jun a1410-70 v63 aBACKGROUND AND OBJECTIVES: There are limited data on the prevalence of chronic kidney disease (CKD) and its clinical importance in the very old. We examined the prevalence of CKD in octogenarians and its association with cardiovascular disease (CVD).
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In a cross-sectional analysis of 1028 participants from the Cardiovascular Health Study All Stars, we evaluated association of prevalent CKD with CVD using multivariable logistic regression. CKD was defined as eGFR of <60 ml/min per 1.73 m(2). GFR was estimated using CKD-Epi creatinine and cystatin C equations that incorporate coefficients for age, gender, and race (eGFR(EPI), eGFR(CYS3var)) and the one-variable cystatin C equation (eGFR(CYS1var)). Prevalent CVD was defined as a composite of coronary heart disease, heart failure, and stroke.
RESULTS: Mean age was 86 years, 64% were women, 86% were Caucasians, 14% had diabetes, and 39% had prevalent CVD. Mean eGFR(EPI), eGFR(CYS3var), and eGFR(CYS1var) were 59, 62, and 70 ml/min per 1.73 m(2), and 51%, 46%, and 33% had CKD, respectively. Associations of CKD with CVD varied by equation in adjusted analyses: CKD(EPI) (OR, 1.53; 95% CI, 1.15 to 2.03), CKD(CYS3var) (OR, 1.67; 95% CI, 1.25, 2.23), and CKD(CYS1var) (OR, 2.09; 95% CI, 1.55, 2.83).
CONCLUSIONS: Reduced eGFR is highly prevalent in octogenarians, and the eGFR(CYS1var) equation yielded the lowest prevalence of CKD but the strongest association with prevalent CVD. Because there are no validated estimating equations in the elderly, estimation of kidney function on the basis of on any one equation should be interpreted with caution.
10aAge Factors10aAged, 80 and over10aAnalysis of Variance10aBiomarkers10aCardiovascular Diseases10aChi-Square Distribution10aChronic Disease10aCreatinine10aCross-Sectional Studies10aCystatin C10aDiabetes Mellitus10aFemale10aGlomerular Filtration Rate10aHumans10aKidney10aKidney Diseases10aLogistic Models10aMale10aModels, Biological10aPrevalence10aRisk Assessment10aRisk Factors10aUnited States1 aShastri, Shani1 aTighiouart, Hocine1 aKatz, Ronit1 aRifkin, Dena, E1 aFried, Linda, F1 aShlipak, Michael, G1 aNewman, Anne, B1 aSarnak, Mark, J uhttps://chs-nhlbi.org/node/128602955nas a2200481 4500008004100000022001400041245009200055210006900147260001300216300001100229490000700240520162800247653000901875653002201884653001501906653002801921653002001949653001501969653001501984653002401999653001102023653003102034653001802065653001102083653002002094653002802114653000902142653001602151653003002167653002602197653001702223100002302240700001602263700002002279700001602299700002002315700001702335700001902352700002102371700002102392700002402413856003602437 2011 eng d a1533-345000aCystatin C identifies chronic kidney disease patients at higher risk for complications.0 aCystatin C identifies chronic kidney disease patients at higher c2011 Jan a147-550 v223 aAlthough cystatin C is a stronger predictor of clinical outcomes associated with CKD than creatinine, the clinical role for cystatin C is unclear. We included 11,909 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) and the Cardiovascular Health Study (CHS) and assessed risks for death, cardiovascular events, heart failure, and ESRD among persons categorized into mutually exclusive groups on the basis of the biomarkers that supported a diagnosis of CKD (eGFR <60 ml/min per 1.73 m(2)): creatinine only, cystatin C only, both, or neither. We used CKD-EPI equations to estimate GFR from these biomarkers. In MESA, 9% had CKD by the creatinine-based equation only, 2% had CKD by the cystatin C-based equation only, and 4% had CKD by both equations; in CHS, these percentages were 12, 4, and 13%, respectively. Compared with those without CKD, the adjusted hazard ratios (HR) for mortality in MESA were: 0.80 (95% CI 0.50 to 1.26) for CKD by creatinine only; 3.23 (95% CI 1.84 to 5.67) for CKD by cystatin C only; and 1.93 (95% CI 1.27 to 2.92) for CKD by both; in CHS, the adjusted HR were 1.09 (95% CI 0.98 to 1.21), 1.78 (95% CI 1.53 to 2.08), and 1.74 (95% CI 1.58 to 1.93), respectively. The pattern was similar for cardiovascular disease (CVD), heart failure, and kidney failure outcomes. In conclusion, among adults diagnosed with CKD using the creatinine-based CKD-EPI equation, the adverse prognosis is limited to the subset who also have CKD according to the cystatin C-based equation. Cystatin C may have a role in identifying persons with CKD who have the highest risk for complications.
10aAged10aAged, 80 and over10aBiomarkers10aCardiovascular Diseases10aChronic Disease10aCreatinine10aCystatin C10aDisease Progression10aFemale10aGlomerular Filtration Rate10aHeart Failure10aHumans10aKidney Diseases10aKidney Failure, Chronic10aMale10aMiddle Aged10aPredictive Value of Tests10aRetrospective Studies10aRisk Factors1 aPeralta, Carmen, A1 aKatz, Ronit1 aSarnak, Mark, J1 aIx, Joachim1 aFried, Linda, F1 ade Boer, Ian1 aPalmas, Walter1 aSiscovick, David1 aLevey, Andrew, S1 aShlipak, Michael, G uhttps://chs-nhlbi.org/node/125602897nas a2200397 4500008004100000022001400041245013200055210006900187260001300256300001100269490000600280520175800286653002402044653000902068653002002077653001902097653001602116653001502132653001102147653002202158653003102180653001102211653002002222653002502242653000902267100001902276700002402295700002102319700001602340700002302356700002002379700002002399700002002419700002402439856003602463 2011 eng d a1555-905X00aLongitudinal association of depressive symptoms with rapid kidney function decline and adverse clinical renal disease outcomes.0 aLongitudinal association of depressive symptoms with rapid kidne c2011 Apr a834-440 v63 aBACKGROUND AND OBJECTIVES: Depression is a risk indicator for adverse outcomes in dialysis patients, but its prognostic impact in individuals who are not yet on dialysis is unknown. This study examines whether depressive symptoms are longitudinally associated with renal function decline, new-onset chronic kidney disease (CKD), ESRD, or hospitalization with acute kidney injury (AKI).
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Depressive symptoms were measured in a longitudinal cohort study with the 10-item Centers for Epidemiologic Studies Depression scale using a previously validated cut-off value (≥8). CKD at study entry and during follow-up was defined as an estimated GFR (eGFR) < 60 ml/min per m(2). Outcomes were rapid decline in eGFR (>3 ml/min per m(2) per year), new-onset CKD, ESRD (U.S. Renal Data System-based), and AKI (based on adjudicated medical record review). The median follow-up duration was 10.5 years.
RESULTS: Depressed participants (21.2%) showed a higher prevalence of CKD at baseline compared with nondepressed participants in multivariable analysis. Depression was associated with a subsequent risk of rapid decline in eGFR, incident ESRD, and AKI, but not incident CKD in unadjusted models. In multivariable analyses, only associations of depressive symptoms with AKI remained significant.
CONCLUSIONS: Elevated depressive symptoms are associated with subsequent adverse renal disease outcomes. The depression-related elevated risk of AKI was independent of traditional renal disease risk factors and may in part be explained by the predictive value of depression for acute coronary syndromes and heart failure hospitalizations that can be complicated by AKI.
10aAcute Kidney Injury10aAged10aChronic Disease10aCohort Studies10aComorbidity10aDepression10aFemale10aFollow-Up Studies10aGlomerular Filtration Rate10aHumans10aKidney Diseases10aLongitudinal Studies10aMale1 aKop, Willem, J1 aSeliger, Stephen, L1 aFink, Jeffrey, C1 aKatz, Ronit1 aOdden, Michelle, C1 aFried, Linda, F1 aRifkin, Dena, E1 aSarnak, Mark, J1 aGottdiener, John, S uhttps://chs-nhlbi.org/node/127702896nas a2200361 4500008004100000022001400041245010300055210006900158260001300227300001200240490000700252520185800259653000902117653002802126653002402154653001702178653001102195653002102206653002902227653002102256653002002277653001702297100001902314700002002333700001702353700002402370700001802394700002202412700002002434700002202454700002202476856003602498 2011 eng d a1524-462800aRetinal microvascular signs and functional loss in older persons: the cardiovascular health study.0 aRetinal microvascular signs and functional loss in older persons c2011 Jun a1589-950 v423 aBACKGROUND AND PURPOSE: We hypothesized that retinal microvascular signs are associated with executive dysfunction, slow gait, and depressive mood, which are characteristic features of microvascular disease affecting frontal subcortical regions of the brain.
METHODS: In the Cardiovascular Health Study, 1744 participants (mean age, 78) free of stroke had retinal photographs and carotid ultrasound during the 1997 to 1998 visit. We examined the cross-sectional association of retinal signs with the digit-symbol substitution test (DSST) score, gait speed, the Center for Epidemiologic Studies-Depression score, and depressive mood, defined as Center for Epidemiologic Studies-Depression score >9 or antidepressant use.
RESULTS: After adjusting for potential confounders, retinal signs were associated with lower DSST score (generalized arteriolar narrowing and arteriovenous nicking), slower gait (retinopathy), and depressive mood (generalized arteriolar narrowing). A higher number of retinal signs was associated with lower DSST score (-0.76 and -2.79 points for 1 sign and ≥2 signs versus none; P<0.001) and slower gait (-0.009 and -0.083 m/s; P=0.047), but not with the square root of Center for Epidemiologic Studies-Depression score (0.079 and -0.208; P=0.072). In addition, coexistence of retinal signs (generalized arteriolar narrowing and arteriovenous nicking) and carotid atherosclerosis was associated with lower DSST score compared with either process alone (P for interaction <0.01). Notably, further adjustment for ventricular size, white matter disease, and infarcts on MRI did not attenuate the association.
CONCLUSIONS: Retinal signs are associated with executive dysfunction and slow gait, and possibly with depressive mood, suggesting a common process involving small vessels.
10aAged10aCardiovascular Diseases10aDepressive Disorder10aFrontal Lobe10aHumans10aMicrocirculation10aNeuropsychological Tests10aRetinal Diseases10aRetinal Vessels10aRisk Factors1 aKim, Dae, Hyun1 aNewman, Anne, B1 aHajjar, Ihab1 aStrotmeyer, Elsa, S1 aKlein, Ronald1 aNewton, Elizabeth1 aSarnak, Mark, J1 aBurke, Gregory, L1 aLipsitz, Lewis, A uhttps://chs-nhlbi.org/node/128302601nas a2200325 4500008004100000022001400041245008200055210006900137260001300206300001100219490000600230520170800236653000901944653001101953653003101964653001101995653002002006653000902026653002402035653001402059100002002073700001602093700002102109700001902130700002002149700002402169700002402193700002202217856003602239 2011 eng d a1555-905X00aSerum 25-hydroxyvitamin D and change in estimated glomerular filtration rate.0 aSerum 25hydroxyvitamin D and change in estimated glomerular filt c2011 Sep a2141-90 v63 aBACKGROUND AND OBJECTIVES: Mounting evidence suggests that 1,25-dihydroxyvitamin D prevents the progression of chronic kidney disease (CKD). It is not clear whether "nutritional" forms of vitamin D affect GFR.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We tested whether serum 25-hydroxyvitamin D concentration (25(OH)D), a measure of total vitamin D intake from cutaneous synthesis and dietary consumption, is associated with loss of estimated GFR among 1705 older adults with predominantly normal baseline kidney function participating in the Cardiovascular Health Study. Baseline 25(OH)D was measured by HPLC-tandem mass spectrometry. GFR was estimated at baseline and 4 years later using the CKD-EPI formula, with rapid GFR loss defined as 12 ml/min per 1.73 m(2) or more over 4 years.
RESULTS: Rapid GFR loss was observed for 207 participants (12%). Each 10 ng/ml lower 25(OH)D was associated with a 25% greater risk of rapid GFR loss (95% confidence interval [CI] 5%, 49%, P = 0.01), adjusting for potential confounding characteristics. Compared with 25(OH)D ≥30 ng/ml, 25(OH)D concentrations 15 to 29 ng/ml and <15 ng/ml were associated with 29% (95% CI -13%, 91%) and 68% (95% CI 1%, 177%) greater adjusted risks of rapid GFR loss, respectively. Magnitudes of association were largest among participants with diabetes.
RESULTS: were similar evaluating a composite outcome of rapid GFR loss, end stage renal disease, and death. Conclusions Insufficient 25(OH)D may be a modifiable risk factor for early GFR loss. We recommend clinical trials to determine whether vitamin D supplementation prevents the development and progression of CKD.
10aAged10aFemale10aGlomerular Filtration Rate10aHumans10aKidney Diseases10aMale10aProspective Studies10aVitamin D1 ade Boer, Ian, H1 aKatz, Ronit1 aChonchol, Michel1 aIx, Joachim, H1 aSarnak, Mark, J1 aShlipak, Michael, G1 aSiscovick, David, S1 aKestenbaum, Bryan uhttps://chs-nhlbi.org/node/131202894nas a2200385 4500008004100000022001400041245008200055210006900137260001600206300001200222490000700234520184400241653001602085653000902101653002202110653001502132653002802147653001902175653001102194653002202205653001102227653000902238653002402247653002402271653001402295100002202309700001602331700001702347700002002364700002002384700002402404700002002428700002402448856003602472 2011 eng d a1558-359700aVitamin D, parathyroid hormone, and cardiovascular events among older adults.0 aVitamin D parathyroid hormone and cardiovascular events among ol c2011 Sep 27 a1433-410 v583 aOBJECTIVES: The aim of this study was to evaluate associations of 25-hydroxyvitamin D (25-OHD) and parathyroid hormone (PTH) concentrations separately and in combination with incident cardiovascular events and mortality during 14 years of follow-up in the CHS (Cardiovascular Health Study).
BACKGROUND: Vitamin D deficiency and PTH excess are common in older adults and may adversely affect cardiovascular health.
METHODS: A total of 2,312 participants who were free of cardiovascular disease at baseline were studied. Vitamin D and intact PTH were measured from previously frozen serum using mass spectrometry and a 2-site immunoassay. Outcomes were adjudicated cases of myocardial infarction, heart failure, cardiovascular death, and all-cause mortality.
RESULTS: There were 384 participants (17%) with serum 25-OHD concentrations <15 ng/ml and 570 (25%) with serum PTH concentrations ≥ 65 pg/ml. After adjustment, each 10 ng/ml lower 25-OHD concentration was associated with a 9% greater (95% confidence interval [CI]: 2% to 17% greater) relative hazard of mortality and a 25% greater (95% CI: 8% to 44% greater) relative hazard of myocardial infarction. Serum 25-OHD concentrations <15 ng/ml were associated with a 29% greater (95% CI: 5% to 55% greater) risk for mortality. Serum PTH concentrations ≥ 65 pg/ml were associated with a 30% greater risk for heart failure (95% CI: 6% to 61% greater) but not other outcomes. There was no evidence of an interaction between serum 25-OHD and PTH concentrations and cardiovascular events.
CONCLUSIONS: Among older adults, 25-OHD deficiency is associated with myocardial infarction and mortality; PTH excess is associated with heart failure. Vitamin D and PTH might influence cardiovascular risk through divergent pathways.
10aAge Factors10aAged10aAged, 80 and over10aBiomarkers10aCardiovascular Diseases10aCohort Studies10aFemale10aFollow-Up Studies10aHumans10aMale10aParathyroid Hormone10aProspective Studies10aVitamin D1 aKestenbaum, Bryan1 aKatz, Ronit1 ade Boer, Ian1 aHoofnagle, Andy1 aSarnak, Mark, J1 aShlipak, Michael, G1 aJenny, Nancy, S1 aSiscovick, David, S uhttps://chs-nhlbi.org/node/132903030nas a2200517 4500008004100000022001400041245010800055210006900163260001300232300001100245490000700256520161100263653000901874653002801883653001601911653002701927653002201954653001101976653002201987653001102009653001702020653001402037653001102051653000902062653001602071653001302087653002402100653003202124653001702156653002602173653001802199653001402217100001502231700001602246700002402262700002202286700002002308700002002328700002002348700002102368700002002389700002402409700002102433700002202454856003602476 2011 eng d a1524-456300aVitamin D, parathyroid hormone, and sudden cardiac death: results from the Cardiovascular Health Study.0 aVitamin D parathyroid hormone and sudden cardiac death results f c2011 Dec a1021-80 v583 aRecent studies have demonstrated greater risks of cardiovascular events and mortality among persons who have lower 25-hydroxyvitamin D (25-OHD) and higher parathyroid hormone (PTH) levels. We sought to evaluate the association between markers of mineral metabolism and sudden cardiac death (SCD) among the 2312 participants from the Cardiovascular Health Study who were free of clinical cardiovascular disease at baseline. We estimated associations of baseline 25-OHD and PTH concentrations individually and in combination with SCD using Cox proportional hazards models after adjustment for demographics, cardiovascular risk factors, and kidney function. During a median follow-up of 14 years, there were 73 adjudicated SCD events. The annual incidence of SCD was greater among subjects who had lower 25-OHD concentrations, 2 events per 1000 for 25-OHD ≥20 ng/mL and 4 events per 1000 for 25-OHD <20 ng/mL. Similarly, SCD incidence was greater among subjects who had higher PTH concentrations, 2 events per 1000 for PTH <65 pg/mL and 4 events per 1000 for PTH ≥65 pg/mL. Multivariate adjustment attenuated associations of 25-OHD and PTH with SCD. Finally, 267 participants (11.7% of the cohort) had high PTH and low 25-OHD concentrations. This combination was associated with a >2-fold risk of SCD after adjustment (hazard ratio: 2.19 [95% CI: 1.17-4.10]; P=0.017) compared with participants with normal levels of PTH and 25-OHD. The combination of lower 25-OHD and higher PTH concentrations appears to be associated independently with SCD risk among older adults without cardiovascular disease.
10aAged10aCardiovascular Diseases10aComorbidity10aDeath, Sudden, Cardiac10aDiabetes Mellitus10aFemale10aFollow-Up Studies10aHumans10aHypertension10aIncidence10aKidney10aMale10aMiddle Aged10aMinerals10aParathyroid Hormone10aProportional Hazards Models10aRisk Factors10aSocioeconomic Factors10aUnited States10aVitamin D1 aDeo, Rajat1 aKatz, Ronit1 aShlipak, Michael, G1 aSotoodehnia, Nona1 aPsaty, Bruce, M1 aSarnak, Mark, J1 aFried, Linda, F1 aChonchol, Michel1 ade Boer, Ian, H1 aEnquobahrie, Daniel1 aSiscovick, David1 aKestenbaum, Bryan uhttps://chs-nhlbi.org/node/135002904nas a2200457 4500008004100000022001400041245005800055210005700113260001300170300001100183490000700194520167600201653000901877653002201886653001201908653002201920653002501942653001501967653002801982653001502010653002402025653004002049653001102089653001902100653001302119653003102132653001102163653001102174653000902185653001502194653003302209653001702242100003002259700001602289700002002305700002102325700002402346700002002370700002002390856003602410 2012 eng d a0301-043000aApolipoprotein E and kidney function in older adults.0 aApolipoprotein E and kidney function in older adults c2012 Sep a174-800 v783 aBACKGROUND: Previous studies suggest that the ε4 and ε2 alleles of apolipoprotein E (APOE) may be associated with decreased and increased risks of CKD, respectively, but there are limited data in older adults. We evaluated the associations of apolipoprotein E alleles with kidney function among older adults in the cardiovascular health study (CHS).
METHODS: Caucasian participants had APOE allelic analysis and serum creatinine and cystatin C measured at baseline (n = 3,844 for cross sectional analysis) and in follow up (n = 3,226 for longitudinal analysis). APOE variation was evaluated as an additive model with number of ε2, ε3 and ε4 alleles. GFR was estimated using the CKD epidemiology equation (eGFRcreat) and the cystatin C demographic equation (eGFRcys). The primary outcome was CKD defined by eGFR < 60 ml/min/1.73 m2. The secondary outcome was rapid progression defined by annual loss of eGFR > 3 ml/min/1.73 m2.
RESULTS: Mean eGFRcreat was 72 ml/min/1.73 m2 (25% CKD). Compared with the ε3 allele, the APOE ε4 allele was associated with reduced risk of CKD by eGFRcreat: unadjusted odds ratio (OR) and 95% confidence interval (CI) 0.79 (0.67 - 0.93) per allele, fully adjusted OR (95% CI) 0.80 (0.68 - 0.96) per allele. Results were consistent using eGFRcys. There was no association of the ε2 allele with CKD or between the apolipoprotein E gene with rapid progression.
CONCLUSIONS: The apolipoprotein ε4 allele was associated with lower odds of CKD in elderly Caucasian individuals. Future research should confirm these findings in other races and explore mechanisms to explain these results.
10aAged10aAged, 80 and over10aAlleles10aApolipoproteins E10aConfidence Intervals10aCreatinine10aCross-Sectional Studies10aCystatin C10aDisease Progression10aEuropean Continental Ancestry Group10aFemale10aGene Frequency10aGenotype10aGlomerular Filtration Rate10aHumans10aKidney10aMale10aOdds Ratio10aRenal Insufficiency, Chronic10aRisk Factors1 aSeshasai, Rebecca, Kurnik1 aKatz, Ronit1 ade Boer, Ian, H1 aSiscovick, David1 aShlipak, Michael, G1 aRifkin, Dena, E1 aSarnak, Mark, J uhttps://chs-nhlbi.org/node/586203302nas a2200397 4500008004100000022001400041245015200055210006900207260001600276300001000292490000700302520213300309653000902442653002202451653001502473653001102488653003002499653001802529653001102547653002602558653000902584653001402593653003302607653001802640100001902658700001602677700002502693700002002718700002102738700002402759700001702783700002402800700002002824700002402844856003602868 2012 eng d a1558-359700aFibroblast growth factor-23 and death, heart failure, and cardiovascular events in community-living individuals: CHS (Cardiovascular Health Study).0 aFibroblast growth factor23 and death heart failure and cardiovas c2012 Jul 17 a200-70 v603 aOBJECTIVES: This study sought to determine the association of fibroblast growth factor (FGF)-23 with death, heart failure (HF), and cardiovascular disease (CVD) in the general population, as well as the influence of chronic kidney disease (CKD) in this setting.
BACKGROUND: FGF-23 increases renal phosphorus excretion and inhibits vitamin D activation. In end-stage renal disease, high FGF-23 levels are associated with mortality. The association of FGF-23 with death, HF, and CVD in the general population, and the influence of CKD in this setting, are unknown.
METHODS: Plasma FGF-23 was measured in 3,107 community-living persons ≥ 65 years of age in 1996 and 1997, and participants were followed through 2008. HF and CVD events were adjudicated by a panel of experts. Associations of FGF-23 with each outcome were evaluated using Cox proportional hazards models, and we tested whether associations differed by CKD status.
RESULTS: Both lower estimated glomerular filtration rate and higher urine albumin to creatinine ratios were associated with high FGF-23 at baseline. During 10.5 years (median) follow-up, there were 1,730 deaths, 697 incident HF events, and 797 incident CVD events. Although high FGF-23 concentrations were associated with each outcome in combined analyses, the associations were consistently stronger for those with CKD (p interactions all <0.006). In the CKD group (n = 1,128), the highest FGF-23 quartile had adjusted hazards ratios (HR) of 1.87 (95% confidence interval [CI]: 1.47 to 2.38) for all-cause death, 1.94 (95% CI: 1.32 to 2.83) for incident HF, and 1.49 (95% CI: 1.02 to 2.18) for incident CVD events compared with the lowest quartile. Corresponding HRs in those without CKD (n = 1,979) were 1.29 (95% CI: 1.05 to 1.59), 1.37 (95% CI: 0.99 to 1.89), and 1.07 (95% CI: 0.79 to 1.45).
CONCLUSIONS: FGF-23, a hormone involved in phosphorous and vitamin D homeostasis, is independently associated with all-cause death and incident HF in community-living older persons. These associations appear stronger in persons with CKD.
10aAged10aAged, 80 and over10aBiomarkers10aFemale10aFibroblast Growth Factors10aHeart Failure10aHumans10aKidney Function Tests10aMale10aMortality10aRenal Insufficiency, Chronic10aUnited States1 aIx, Joachim, H1 aKatz, Ronit1 aKestenbaum, Bryan, R1 ade Boer, Ian, H1 aChonchol, Michel1 aMukamal, Kenneth, J1 aRifkin, Dena1 aSiscovick, David, S1 aSarnak, Mark, J1 aShlipak, Michael, G uhttps://chs-nhlbi.org/node/139203458nas a2200481 4500008004100000022001400041245009100055210006900146260001300215300001100228490000700239520210500246653002202351653002502373653002802398653002802426653001502454653001502469653002202484653001102506653003102517653001102548653001702559653002002576653000902596653001502605653003202620653002602652653001702678653001802695100001902713700001602732700002002748700002002768700002302788700002302811700002102834700002102855700002402876700002002900700002002920856003602940 2012 eng d a1532-541500aKidney function and mortality in octogenarians: Cardiovascular Health Study All Stars.0 aKidney function and mortality in octogenarians Cardiovascular He c2012 Jul a1201-70 v603 aOBJECTIVES: To examine the association between kidney function and all-cause mortality in octogenarians.
DESIGN: Retrospective analysis of prospectively collected data.
SETTING: Community.
PARTICIPANTS: Serum creatinine and cystatin C were measured in 1,053 Cardiovascular Health Study (CHS) All Stars participants.
MEASUREMENTS: Estimated glomerular filtration rate (eGFR) was determined using the Chronic Kidney Disease Epidemiology Collaboration creatinine (eGFR(CR) ) and cystatin C one-variable (eGFR(CYS) ) equations. The association between quintiles of kidney function and all-cause mortality was analyzed using unadjusted and adjusted Cox proportional hazards models.
RESULTS: Mean age of the participants was 85, 64% were female, 66% had hypertension, 14% had diabetes mellitus, and 39% had prevalent cardiovascular disease. There were 154 deaths over a median follow-up of 2.6 years. The association between eGFR(CR) and all-cause mortality was U-shaped. In comparison with the reference quintile (64-75 mL/min per 1.73 m(2) ), the highest (≥ 75 mL/min per 1.73 m(2) ) and lowest (≤ 43 mL/min per 1.73 m(2) ) quintiles of eGFR(CR) were independently associated with mortality (hazard ratio (HR) = 2.49, 95% confidence interval (CI) = 1.36-4.55; HR = 2.28, 95% CI = 1.26-4.10, respectively). The association between eGFR(CYS) and all-cause mortality was linear in those with eGFR(CYS) of less than 60 mL/min per 1.73 m(2) , and in the multivariate analyses, the lowest quintile of eGFR(CYS) (<52 mL/min per 1.73 m(2) ) was significantly associated with mortality (HR = 2.04, 95% CI = 1.12-3.71) compared with the highest quintile (>0.88 mL/min per 1.73 m(2) ).
CONCLUSION: Moderate reduction in kidney function is a risk factor for all-cause mortality in octogenarians. The association between eGFR(CR) and all-cause mortality differed from that observed with eGFR(CYS) ; the relationship was U-shaped for eGFR(CR) , whereas the risk was primarily present in the lowest quintile for eGFR(CYS) .
10aAged, 80 and over10aAnalysis of Variance10aCardiovascular Diseases10aChi-Square Distribution10aCreatinine10aCystatin C10aDiabetes Mellitus10aFemale10aGlomerular Filtration Rate10aHumans10aHypertension10aKidney Diseases10aMale10aPrevalence10aProportional Hazards Models10aRetrospective Studies10aRisk Factors10aUnited States1 aShastri, Shani1 aKatz, Ronit1 aRifkin, Dena, E1 aFried, Linda, F1 aOdden, Michelle, C1 aPeralta, Carmen, A1 aChonchol, Michel1 aSiscovick, David1 aShlipak, Michael, G1 aNewman, Anne, B1 aSarnak, Mark, J uhttps://chs-nhlbi.org/node/139503074nas a2200481 4500008004100000022001400041245011600055210006900171260001300240300001000253490000700263520173100270653000902001653002202010653001002032653002302042653002802065653001402093653001902107653002802126653001102154653001102165653001702176653002702193653001802220653002502238653000902263653001702272653001202289100002002301700002102321700002102342700002402363700001802387700002302405700002002428700002002448700002802468700002002496700002002516700002002536856003602556 2012 eng d a1758-535X00aLong-term assessment of inflammation and healthy aging in late life: the Cardiovascular Health Study All Stars.0 aLongterm assessment of inflammation and healthy aging in late li c2012 Sep a970-60 v673 aBACKGROUND: Associations of inflammation with age-related pathologies are documented; however, it is not understood how changes in inflammation over time impact healthy aging.
METHODS: We examined associations of long-term change in C-reactive protein (CRP) and interleukin-6 (IL-6) with concurrent onset of physical and cognitive impairment, subsequent cardiovascular disease (CVD), and mortality in 1,051 participants in the Cardiovascular Health Study All Stars Study. Biomarkers were measured in 1996-1997 and 2005-2006.
RESULTS: In 2005-2006, median age was 84.9 years, 63% were women and 17% non-white; 21% had at least a doubling in CRP over time and 23% had at least a doubling in IL-6. Adjusting for demographics, CVD risk factors, and 1996-1997 CRP level, each doubling in CRP change over 9 years was associated with higher risk of physical or cognitive impairment (odds ratio 1.29; 95% confidence interval 1.15, 1.45). Results were similar for IL-6 (1.45; 1.20, 1.76). A doubling in IL-6 change over time, but not CRP, was associated with incident CVD events; hazard ratio (95% confidence interval) 1.34 (1.03, 1.75). Doubling in change in each biomarker was individually associated with mortality (CRP: 1.12 [1.03, 1.22]; IL-6 1.39 [1.16, 1.65]). In models containing both change and 2005-2006 level, only level was associated with CVD events and mortality.
CONCLUSIONS: Although increases in inflammation markers over 9 years were associated with higher concurrent risk of functional impairment and subsequent CVD events and mortality, final levels of each biomarker appeared to be more important in determining risk of subsequent events than change over time.
10aAged10aAged, 80 and over10aAging10aC-Reactive Protein10aCardiovascular Diseases10aCognition10aCohort Studies10aCross-Sectional Studies10aFemale10aHumans10aInflammation10aInflammation Mediators10aInterleukin-610aLongitudinal Studies10aMale10aRisk Factors10aVermont1 aJenny, Nancy, S1 aFrench, Benjamin1 aArnold, Alice, M1 aStrotmeyer, Elsa, S1 aCushman, Mary1 aChaves, Paulo, H M1 aDing, Jingzhong1 aFried, Linda, P1 aKritchevsky, Stephen, B1 aRifkin, Dena, E1 aSarnak, Mark, J1 aNewman, Anne, B uhttps://chs-nhlbi.org/node/136603128nas a2200469 4500008004100000022001400041245008300055210006900138260001300207300001000220490000800230520178800238653003102026653000902057653002802066653002402094653004402118653002602162653002202188653001102210653001702221653001402238653002602252653002102278653003002299653001502329653001402344653002402358653002102382653001702403653001202420100001902432700002302451700002002474700001802494700002002512700002202532700002402554700002202578700002202600856003602622 2012 eng d a1538-360100aRetinal microvascular signs and disability in the Cardiovascular Health Study.0 aRetinal microvascular signs and disability in the Cardiovascular c2012 Mar a350-60 v1303 aOBJECTIVE: To study the associations of retinal microvascular changes, which are associated with systemic conditions and cognitive decline, with disability in performing activities of daily living (ADL).
DESIGN: Prospective cohort study of 1487 community-dwelling participants in the Cardiovascular Health Study (mean age, 78 years) who were free of ADL disability and had available data on retinal signs and carotid intima-media thickness at the 1998-1999 visit. Main outcome measures were incident ADL disability, defined as self-reported difficulty in performing any ADL, by the presence of retinal signs and advanced carotid atherosclerosis, defined by carotid intima-media thickness in the 80th percentile or more or 25% or more stenosis, and potential mediation by cerebral microvascular disease on brain imaging or by executive dysfunction, slow gait, and depressive mood, which are symptoms of frontal subcortical dysfunction.
RESULTS: During the median follow-up of 3.1 years (maximum, 7.8 years), participants with 2 or more retinal signs had a higher rate of disability than those with fewer than 2 retinal signs (10.1% vs 7.1%; adjusted hazard ratio, 1.45; 95% confidence interval, 1.24-1.69; P < .001). There was no evidence of interaction by advanced carotid atherosclerosis (P > .10). The association seemed to be partially mediated by executive dysfunction, slow gait, and depressive symptoms but not by cerebral microvascular disease on brain imaging.
CONCLUSIONS: These results provide further support for the pathophysiologic and prognostic significance of microvascular disease in age-related disability. However, it remains to be determined how to best use retinal photography in clinical risk prediction.
10aActivities of Daily Living10aAged10aCarotid Artery Diseases10aCognition Disorders10aDiagnostic Techniques, Ophthalmological10aDisability Evaluation10aFollow-Up Studies10aHumans10aHypertension10aIncidence10aKaplan-Meier Estimate10aMicrocirculation10aPredictive Value of Tests10aPrevalence10aPrognosis10aProspective Studies10aRetinal Diseases10aRisk Factors10aSmoking1 aKim, Dae, Hyun1 aChaves, Paulo, H M1 aNewman, Anne, B1 aKlein, Ronald1 aSarnak, Mark, J1 aNewton, Elizabeth1 aStrotmeyer, Elsa, S1 aBurke, Gregory, L1 aLipsitz, Lewis, A uhttps://chs-nhlbi.org/node/135102611nas a2200337 4500008004100000022001400041245008200055210006900137260001300206300001100219490000700230520170400237653000901941653001901950653001101969653003101980653002002011653001102031653001402042653001102056653000902067653001702076100002502093700001602118700002202134700002002156700001702176700002002193700002402213856003602237 2012 eng d a1523-683800aThe risk of infection-related hospitalization with decreased kidney function.0 arisk of infectionrelated hospitalization with decreased kidney f c2012 Mar a356-630 v593 aBACKGROUND: Moderate kidney disease may predispose to infection. We sought to determine whether decreased kidney function, estimated by serum cystatin C level, was associated with the risk of infection-related hospitalization in older individuals.
STUDY DESIGN: Cohort study.
SETTING & PARTICIPANTS: 5,142 Cardiovascular Health Study (CHS) participants with measured serum creatinine and cystatin C and without estimated glomerular filtration rate (eGFR) <15 mL/min/1.73 m(2) at enrollment.
PREDICTOR: The primary exposure of interest was eGFR using serum cystatin C level (eGFR(SCysC)).
OUTCOME: Infection-related hospitalizations during a median follow-up of 11.5 years.
RESULTS: In adjusted analyses, eGFR(SCysC) categories of 60-89, 45-59, and 15-44 mL/min/1.73 m(2) were associated with 16%, 37%, and 64% greater risk of all-cause infection-related hospitalization, respectively, compared with eGFR(SCysC) ≥90 mL/min/1.73 m(2). When cause-specific infection was examined, eGFR(SCysC) of 15-44 mL/min/1.73 m(2) was associated with an 80% greater risk of pulmonary and 160% greater risk of genitourinary infection compared with eGFR(SCysC) ≥90 mL/min/1.73 m(2).
LIMITATIONS: No measures of urinary protein, study limited to principal discharge diagnosis.
CONCLUSIONS: Lower kidney function, estimated using cystatin C level, was associated with a linear and graded risk of infection-related hospitalization. These findings highlight that even moderate degrees of decreased kidney function are associated with clinically significant higher risks of serious infection in older individuals.
10aAged10aCohort Studies10aFemale10aGlomerular Filtration Rate10aHospitalization10aHumans10aInfection10aKidney10aMale10aRisk Factors1 aDalrymple, Lorien, S1 aKatz, Ronit1 aKestenbaum, Bryan1 ade Boer, Ian, H1 aFried, Linda1 aSarnak, Mark, J1 aShlipak, Michael, G uhttps://chs-nhlbi.org/node/132202921nas a2200433 4500008004100000022001400041245012800055210006900183260001300252300001200265490000700277520170100284653000901985653001901994653001902013653001502032653001302047653002402060653001102084653003102095653001102126653001702137653002002154653002502174653000902199653001002208653003302218653001202251100002002263700001602283700002102299700002402320700002002344700002002364700002002384700002402404700002302428856003602451 2013 eng d a1941-722500aBlood pressure components and decline in kidney function in community-living older adults: the Cardiovascular Health Study.0 aBlood pressure components and decline in kidney function in comm c2013 Aug a1037-440 v263 aBACKGROUND: Although hypertension contributes to kidney dysfunction in the general population, the contributions of elevated systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure (PP) to kidney function decline in community-dwelling older adults are unknown.
METHODS: We used linear and logistic regression to examine the separate and combined associations of SBP, DBP, and PP at baseline with kidney function decline among 4,365 older adults in the Cardiovascular Health Study. We used cystatin C to estimate glomerular filtration rate on 3 occasions over 7 years of follow-up. We defined rapid decline ≥ 3ml/min/year.
RESULTS: Average age was 72.2 and mean (standard deviation) SBP, DBP, and PP were 135 (21), 71 (11), and 65 (18) mm Hg, respectively. SBP and PP, rather than DBP, were most significantly associated with kidney function decline. In adjusted linear models, each 10-mm Hg increment in SBP and PP was associated with 0.13ml/min/year (-0.19, -0.08, P < 0.001) and 0.15-ml/min/year faster decline (-0.21, -0.09, P < 0.001), respectively. Each 10-mm Hg increment in DBP was associated with a nonsignificant 0.10-ml/min/year faster decline (95% confidence interval, -0.20, 0.01). In adjusted logistic models, SBP had the strongest associations with rapid decline, with 14% increased hazard of rapid decline (95% confidence interval, 10% to 17%, P < 0.01) per 10mm Hg. In models combining BP components, only SBP consistently had independent associations with rapid decline.
CONCLUSIONS: Our findings suggest that elevated BP, particularly SBP, contributes to declining kidney function in older adults.
10aAged10aBlood Pressure10aCohort Studies10aCystatin C10aDiastole10aDisease Progression10aFemale10aGlomerular Filtration Rate10aHumans10aHypertension10aLogistic Models10aLongitudinal Studies10aMale10aPulse10aRenal Insufficiency, Chronic10aSystole1 aRifkin, Dena, E1 aKatz, Ronit1 aChonchol, Michel1 aShlipak, Michael, G1 aSarnak, Mark, J1 aFried, Linda, F1 aNewman, Anne, B1 aSiscovick, David, S1 aPeralta, Carmen, A uhttps://chs-nhlbi.org/node/599903326nas a2200409 4500008004100000022001400041245007900055210006900134260001600203300001100219490000800230520214100238653001502379653001502394653003102409653001102440653002802451653002602479653002402505653003302529653000902562653002002571100002402591700002502615700001902640700002102659700001602680700002702696700002702723700002002750700001902770700001802789700002102807700002302828710002902851856003602880 2013 eng d a1533-440600aCystatin C versus creatinine in determining risk based on kidney function.0 aCystatin C versus creatinine in determining risk based on kidney c2013 Sep 05 a932-430 v3693 aBACKGROUND: Adding the measurement of cystatin C to that of serum creatinine to determine the estimated glomerular filtration rate (eGFR) improves accuracy, but the effect on detection, staging, and risk classification of chronic kidney disease across diverse populations has not been determined.
METHODS: We performed a meta-analysis of 11 general-population studies (with 90,750 participants) and 5 studies of cohorts with chronic kidney disease (2960 participants) for whom standardized measurements of serum creatinine and cystatin C were available. We compared the association of the eGFR, as calculated by the measurement of creatinine or cystatin C alone or in combination with creatinine, with the rates of death (13,202 deaths in 15 cohorts), death from cardiovascular causes (3471 in 12 cohorts), and end-stage renal disease (1654 cases in 7 cohorts) and assessed improvement in reclassification with the use of cystatin C.
RESULTS: In the general-population cohorts, the prevalence of an eGFR of less than 60 ml per minute per 1.73 m(2) of body-surface area was higher with the cystatin C-based eGFR than with the creatinine-based eGFR (13.7% vs. 9.7%). Across all eGFR categories, the reclassification of the eGFR to a higher value with the measurement of cystatin C, as compared with creatinine, was associated with a reduced risk of all three study outcomes, and reclassification to a lower eGFR was associated with an increased risk. The net reclassification improvement with the measurement of cystatin C, as compared with creatinine, was 0.23 (95% confidence interval [CI], 0.18 to 0.28) for death and 0.10 (95% CI, 0.00 to 0.21) for end-stage renal disease. Results were generally similar for the five cohorts with chronic kidney disease and when both creatinine and cystatin C were used to calculate the eGFR.
CONCLUSIONS: The use of cystatin C alone or in combination with creatinine strengthens the association between the eGFR and the risks of death and end-stage renal disease across diverse populations. (Funded by the National Kidney Foundation and others.).
10aCreatinine10aCystatin C10aGlomerular Filtration Rate10aHumans10aKidney Failure, Chronic10aKidney Function Tests10aReference Standards10aRenal Insufficiency, Chronic10aRisk10aRisk Assessment1 aShlipak, Michael, G1 aMatsushita, Kunihiro1 aArnlöv, Johan1 aInker, Lesley, A1 aKatz, Ronit1 aPolkinghorne, Kevan, R1 aRothenbacher, Dietrich1 aSarnak, Mark, J1 aAstor, Brad, C1 aCoresh, Josef1 aLevey, Andrew, S1 aGansevoort, Ron, T1 aCKD Prognosis Consortium uhttps://chs-nhlbi.org/node/737703095nas a2200553 4500008004100000022001400041245013400055210006900189260001300258300001100271490000700282520158200289653001001871653001601881653000901897653002201906653001001928653001401938653002101952653001901973653001601992653002802008653001502036653001102051653001102062653001702073653002602090653000902116653001602125653001202141653001502153653003302168653001702201653001202218653001802230100002302248700001802271700002302289700002502312700002002337700002002357700001602377700002502393700002202418700002002440700002102460700002402481856003602505 2013 eng d a1873-258500aHypertension and low HDL cholesterol were associated with reduced kidney function across the age spectrum: a collaborative study.0 aHypertension and low HDL cholesterol were associated with reduce c2013 Mar a106-110 v233 aPURPOSE: To determine if the associations among established risk factors and reduced kidney function vary by age.
METHODS: We pooled cross-sectional data from 14,788 nondiabetics aged 40 to 100 years in 4 studies: Cardiovascular Health Study, Health, Aging, and Body Composition Study, Multi-Ethnic Study of Atherosclerosis, and Prevention of Renal and Vascular End-Stage Disease cohort.
RESULTS: Hypertension and low high-density lipoprotein (HDL) cholesterol were associated with reduced cystatin C-based estimated glomerular filtration rate (eGFR) across the age spectrum. In adjusted analyses, hypertension was associated with a 2.3 (95% confidence interval [CI], 0.1, 4.4), 5.1 (95% CI, 4.1, 6.1), and 6.9 (95% CI, 3.0, 10.4) mL/min/1.73 m(2) lower eGFR in participants 40 to 59, 60 to 79, and at least 80 years, respectively (P for interaction < .001). The association of low HDL cholesterol with reduced kidney function was also greater in the older age groups: 4.9 (95% CI, 3.5, 6.3), 7.1 (95% CI, 6.0, 8.3), 8.9 (95% CI, 5.4, 11.9) mL/min/1.73 m(2) (P for interaction < .001). Smoking and obesity were associated with reduced kidney function in participants under 80 years. All estimates of the potential population impact of the risk factors were modest.
CONCLUSIONS: Hypertension, obesity, smoking, and low HDL cholesterol are modestly associated with reduced kidney function in nondiabetics. The associations of hypertension and HDL cholesterol with reduced kidney function seem to be stronger in older adults.
10aAdult10aAge Factors10aAged10aAged, 80 and over10aAging10aCausality10aCholesterol, LDL10aCohort Studies10aComorbidity10aCross-Sectional Studies10aCystatin C10aFemale10aHumans10aHypertension10aKidney Function Tests10aMale10aNetherlands10aObesity10aPrevalence10aRenal Insufficiency, Chronic10aRisk Factors10aSmoking10aUnited States1 aOdden, Michelle, C1 aTager, Ira, B1 aGansevoort, Ron, T1 aBakker, Stephan, J L1 aFried, Linda, F1 aNewman, Anne, B1 aKatz, Ronit1 aSatterfield, Suzanne1 aHarris, Tamara, B1 aSarnak, Mark, J1 aSiscovick, David1 aShlipak, Michael, G uhttps://chs-nhlbi.org/node/585403866nas a2200613 4500008004100000022001400041245005600055210005500111260001300166300001100179490000600190520229500196653001602491653000902507653002202516653001002538653001502548653001502563653002802578653001502606653001202621653001102633653001802644653002502662653003102687653001102718653001402729653002302743653001102766653002002777653002002797653000902817653001902826653002602845653002002871653001502891653001402906653001502920653002402935653001702959653001702976653001802993653001603011100002503027700001603052700002003068700002103088700002003109700002003129700002003149700002303169700002403192856003603216 2013 eng d a1555-905X00aKidney function and prevalent and incident frailty.0 aKidney function and prevalent and incident frailty c2013 Dec a2091-90 v83 aBACKGROUND AND OBJECTIVES: Kidney disease is associated with physiologic changes that may predispose to frailty. This study sought to investigate whether lower levels of kidney function were associated with prevalent or incident frailty in Cardiovascular Health Study (CHS) participants.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: CHS enrolled community-dwelling adults age ≥65 years between 1989-1990 and 1992-1993. To examine prevalent frailty, included were 4150 participants without stroke, Parkinson disease, prescribed medications for Alzheimer disease or depression, or severely impaired cognition. To examine incident frailty, included were a subset of 3459 participants without baseline frailty or development of exclusion criteria during follow-up. The primary predictor was estimated GFR (eGFR) calculated using serum cystatin C (eGFR(cys)). Secondary analyses examined eGFR using serum creatinine (eGFR(SCr)). Outcomes were prevalent frailty and incident frailty at 4 years of follow-up. Frailty was ascertained on the basis of weight loss, exhaustion, weakness, slowness, and low physical activity.
RESULTS: The mean age was 75 years and the median eGFR(cys) was 73 ml/min per 1.73 m(2). Among participants with an eGFR(cys) <45 ml/min per 1.73 m(2), 24% had prevalent frailty. In multivariable analysis and compared with eGFR(cys) ≥90 ml/min per 1.73 m(2), eGFR(cys) categories of 45-59 (odds ratio [OR], 1.80; 95% confidence interval [CI], 1.17 to 2.75) and 15-44 (OR, 2.87; 95% CI, 1.72 to 4.77) were associated with higher odds of frailty, whereas 60-75 (OR, 1.14; 95% CI, 0.76 to 1.70) was not. In multivariable analysis, eGFR(cys) categories of 60-75 (incidence rate ratio [IRR], 1.72; 95% CI, 1.07 to 2.75) and 15-44 (IRR, 2.28; 95% CI, 1.23 to 4.22) were associated with higher incidence of frailty whereas 45-59 (IRR, 1.53; 95% CI, 0.90 to 2.60) was not. Lower levels of eGFR(SCr) were not associated with higher risk of prevalent or incident frailty.
CONCLUSIONS: In community-dwelling elders, lower eGFR(cys) was associated with a higher risk of prevalent and incident frailty whereas lower eGFR(SCr) was not. These findings highlight the importance of considering non-GFR determinants of kidney function.
10aAge Factors10aAged10aAged, 80 and over10aAging10aBiomarkers10aCreatinine10aCross-Sectional Studies10aCystatin C10aFatigue10aFemale10aFrail Elderly10aGeriatric Assessment10aGlomerular Filtration Rate10aHumans10aIncidence10aIndependent Living10aKidney10aKidney Diseases10aLogistic Models10aMale10aMotor Activity10aMultivariate Analysis10aMuscle Weakness10aOdds Ratio10aPhenotype10aPrevalence10aProspective Studies10aRisk Factors10aTime Factors10aUnited States10aWeight Loss1 aDalrymple, Lorien, S1 aKatz, Ronit1 aRifkin, Dena, E1 aSiscovick, David1 aNewman, Anne, B1 aFried, Linda, F1 aSarnak, Mark, J1 aOdden, Michelle, C1 aShlipak, Michael, G uhttps://chs-nhlbi.org/node/613602957nas a2200373 4500008004100000022001400041245013400055210006900189260001300258300000900271490000800280520182700288653000902115653002502124653002802149653002802177653003002205653001102235653001402246653003202260653001702292100002502309700001902334700001602353700002402369700002502393700002002418700002402438700001902462700002202481700002402503700002002527856003602547 2014 eng d a1879-148400aFibroblast growth factor 23, the ankle-brachial index, and incident peripheral artery disease in the Cardiovascular Health Study.0 aFibroblast growth factor 23 the anklebrachial index and incident c2014 Mar a91-60 v2333 aBACKGROUND: Fibroblast growth factor 23 (FGF23) has emerged as a novel risk factor for mortality and cardiovascular events. Its association with the ankle-brachial index (ABI) and clinical peripheral artery disease (PAD) is less known.
METHODS: Using data (N = 3143) from the Cardiovascular Health Study (CHS), a cohort of community dwelling adults >65 years of age, we analyzed the cross-sectional association of FGF23 with ABI and its association with incident clinical PAD events during 9.8 years of follow up using multinomial logistic regression and Cox proportional hazards models respectively.
RESULTS: The prevalence of cardiovascular disease (CVD) and traditional risk factors like diabetes, coronary artery disease, and heart failure increased across higher quartiles of FGF23. Compared to those with ABI of 1.1-1.4, FGF23 per doubling at baseline was associated with prevalent PAD (ABI < 0.9) although this association was attenuated after adjusting for CVD risk factors, and kidney function (OR 0.91, 95% CI 0.76-1.08). FGF23 was not associated with high ABI (>1.4) (OR 1.06, 95% CI 0.75-1.51). Higher FGF23 was associated with incidence of PAD events in unadjusted, demographic adjusted, and CVD risk factor adjusted models (HR 2.26, 95% CI 1.28-3.98; highest versus lowest quartile). The addition of estimated glomerular filtration and urine albumin to creatinine ratio to the model however, attenuated these findings (HR 1.46, 95% CI, 0.79-2.70).
CONCLUSIONS: In community dwelling older adults, FGF23 was not associated with baseline low or high ABI or incident PAD events after adjusting for confounding variables. These results suggest that FGF23 may primarily be associated with adverse cardiovascular outcomes through non atherosclerotic mechanisms.
10aAged10aAnkle Brachial Index10aCardiovascular Diseases10aCross-Sectional Studies10aFibroblast Growth Factors10aHumans10aIncidence10aPeripheral Arterial Disease10aRisk Factors1 aGarimella, Pranav, S1 aIx, Joachim, H1 aKatz, Ronit1 aChonchol, Michel, B1 aKestenbaum, Bryan, R1 ade Boer, Ian, H1 aSiscovick, David, S1 aShastri, Shani1 aHiramoto, Jade, S1 aShlipak, Michael, G1 aSarnak, Mark, J uhttps://chs-nhlbi.org/node/623903491nas a2200493 4500008004100000022001400041245012600055210006900181260001300250300001100263490000600274520211000280653002402390653001602414653000902430653002202439653001602461653001502477653001502492653001502507653001102522653003002533653003102563653002002594653001102614653002302625653001102648653002502659653000902684653001402693653003202707653002402739653001702763653001702780100002302797700001602820700001902836700002002855700002402875700002102899700002102920700002002941856003602961 2014 eng d a1555-905X00aFibroblast growth factor-23 and the long-term risk of hospital-associated AKI among community-dwelling older individuals.0 aFibroblast growth factor23 and the longterm risk of hospitalasso c2014 Feb a239-460 v93 aBACKGROUND AND OBJECTIVES: AKI occurs frequently in older persons. Elevated circulating fibroblast growth factor-23 (FGF-23), a known marker of impaired mineral metabolism, may also reflect tubular dysfunction and risk of AKI. This study evaluated FGF-23 as well as traditional markers of kidney disease, namely urine albumin-to-creatinine ratio (UACR) and creatinine-cystatin C estimated GFR (eGFRCrCyC), as risk factors for AKI in elderly individuals.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Plasma FGF-23, UACR, and eGFRCrCyC were measured in 3241 community-dwelling elderly individuals in the Cardiovascular Health Study. Hospitalization for AKI was defined by International Classification of Diseases, Ninth Revision, Clinical Modification codes. Associations of each biomarker with AKI were evaluated using Cox proportional hazards models adjusted for demographics, cardiovascular risk factors, and biomarkers of kidney function.
RESULTS: The mean participant age was 78 years; 60% of participants were women and 16% were African American. The median (interquartile range) values of biomarkers were as follows: FGF-23, 70 RU/ml (53, 99); UACR, 8.88 mg/g (4.71, 20.47); and eGFRCrCyC, 71 ml/min per 1.73 m(2) (59, 83). Hospitalized AKI occurred in 119 participants over 10.0 years of median follow-up. In fully adjusted analyses, compared with the lowest quartiles, the highest quartiles of FGF-23 (≥100 RU/ml) and UACR (≥20.9 mg/g) were associated with AKI (FGF-23: hazard ratio [HR], 1.99; 95% confidence interval [95% CI], 1.04 to 3.80; and UACR: HR, 3.35; 95% CI, 1.83 to 6.13). Compared with the highest quartile, the lowest quartile of eGFRCrCyC (<57 ml/min per 1.73 m(2)) was associated with AKI with an HR of 2.15 (95% CI, 1.21 to 3.82).
CONCLUSIONS: FGF-23 adjusted for albuminuria, cardiovascular disease risk factors, and baseline eGFR is independently associated with a higher risk of AKI hospitalizations in community-dwelling elderly individuals. Further studies to understand the nature of this association are warranted.
10aAcute Kidney Injury10aAge Factors10aAged10aAged, 80 and over10aAlbuminuria10aBiomarkers10aCreatinine10aCystatin C10aFemale10aFibroblast Growth Factors10aGlomerular Filtration Rate10aHospitalization10aHumans10aIndependent Living10aKidney10aLongitudinal Studies10aMale10aPrognosis10aProportional Hazards Models10aProspective Studies10aRisk Factors10aTime Factors1 aBrown, Jeremiah, R1 aKatz, Ronit1 aIx, Joachim, H1 ade Boer, Ian, H1 aSiscovick, David, S1 aGrams, Morgan, E1 aShlipak, Michael1 aSarnak, Mark, J uhttps://chs-nhlbi.org/node/630802589nas a2200361 4500008004100000022001400041245009100055210006900146260001600215300001000231490000800241520158100249653000901830653002801839653001401867653002401881653001501905653001101920653003101931653001801962653001101980653001101991653002002002653000902022653002902031100002002060700002402080700002002104700001602124700002802140700002302168856003602191 2014 eng d a1476-625600aKidney function and cognitive health in older adults: the Cardiovascular Health Study.0 aKidney function and cognitive health in older adults the Cardiov c2014 Jul 01 a68-750 v1803 aRecent evidence has demonstrated the importance of kidney function in healthy aging. We examined the association between kidney function and change in cognitive function in 3,907 participants in the Cardiovascular Health Study who were recruited from 4 US communities and studied from 1992 to 1999. Kidney function was measured by cystatin C-based estimated glomerular filtration rate (eGFRcys). Cognitive function was assessed using the Modified Mini-Mental State Examination and the Digit Symbol Substitution Test, which were administered up to 7 times during annual visits. There was an association between eGFRcys and change in cognitive function after adjustment for confounders; persons with an eGFRcys of less than 60 mL/minute/1.73 m(2) had a 0.64 (95% confidence interval: 0.51, 0.77) points/year faster decline in Modified Mini-Mental State Examination score and a 0.42 (95% confidence interval: 0.28, 0.56) points/year faster decline in Digit Symbol Substitution Test score compared with persons with an eGFRcys of 90 or more mL/minute/1.73 m(2). Additional adjustment for intermediate cardiovascular events modestly affected these associations. Participants with an eGFRcys of less than 60 mL/minute/1.73 m(2) had fewer cognitive impairment-free life-years on average compared with those with eGFRcys of 90 or more mL/minute/1.73 m(2), independent of confounders and mediating cardiovascular events (mean difference = -0.44, 95% confidence interval: -0.62, -0.26). Older adults with lower kidney function are at higher risk of worsening cognitive function.
10aAged10aCardiovascular Diseases10aCognition10aCognition Disorders10aCystatin C10aFemale10aGlomerular Filtration Rate10aHealth Status10aHumans10aKidney10aKidney Diseases10aMale10aNeuropsychological Tests1 aDarsie, Brendan1 aShlipak, Michael, G1 aSarnak, Mark, J1 aKatz, Ronit1 aFitzpatrick, Annette, L1 aOdden, Michelle, C uhttps://chs-nhlbi.org/node/636403265nas a2200457 4500008004100000022001400041245012300055210006900178260001300247300001300260490000700273520196100280653000902241653002202250653001002272653002502282653002602307653002402333653001102357653002202368653001602390653001102406653002002417653003102437653000902468653002102477653001402498653002402512653001702536653002702553100001902580700002402599700002002623700002302643700002302666700001802689700002002707700002202727700002202749856003602771 2014 eng d a1758-535X00aPrognostic implications of microvascular and macrovascular abnormalities in older adults: cardiovascular health study.0 aPrognostic implications of microvascular and macrovascular abnor c2014 Dec a1495-5020 v693 aBACKGROUND: Microvascular and macrovascular abnormalities are frequently found on noninvasive tests performed in older adults. Their prognostic implications on disability and life expectancy have not been collectively assessed.
METHODS: This prospective study included 2,452 adults (mean age: 79.5 years) with available measures of microvascular (brain, retina, kidney) and macrovascular abnormalities (brain, carotid, coronary, peripheral artery) in the Cardiovascular Health Study. The burden of microvascular and macrovascular abnormalities was examined in relation to total, activity-of-daily-living disability-free, and severe disability-free life expectancies in the next 10 years (1999-2009).
RESULTS: At 75 years, individuals with low burden of both abnormalities lived, on average, 8.71 years (95% confidence interval: 8.29, 9.12) of which 7.67 years (7.16, 8.17) were without disability. In comparison, individuals with high burden of both abnormalities had shortest total life expectancy (6.95 years [6.52, 7.37]; p < .001) and disability-free life expectancy (5.60 years [5.10, 6.11]; p < .001). Although total life expectancy was similarly reduced for those with high burden of either type of abnormalities (microvascular: 7.96 years [7.50, 8.42] vs macrovascular: 8.25 years [7.80, 8.70]; p = .10), microvascular abnormalities seemed to have larger impact than macrovascular abnormalities on disability-free life expectancy (6.45 years [5.90, 6.99] vs 6.96 years [6.43, 7.48]; p = .016). These results were consistent for severe disability-free life expectancy and in individuals without clinical cardiovascular disease.
CONCLUSIONS: Considering both microvascular and macrovascular abnormalities from multiple noninvasive tests may provide additional prognostic information on how older adults spend their remaining life. Optimal clinical use of this information remains to be determined.
10aAged10aAged, 80 and over10aAging10aAnkle Brachial Index10aDisability Evaluation10aElectrocardiography10aFemale10aFollow-Up Studies10aForecasting10aHumans10aLife Expectancy10aMagnetic Resonance Imaging10aMale10aMicrocirculation10aPrognosis10aProspective Studies10aRisk Factors10aVascular Malformations1 aKim, Dae, Hyun1 aGrodstein, Francine1 aNewman, Anne, B1 aChaves, Paulo, H M1 aOdden, Michelle, C1 aKlein, Ronald1 aSarnak, Mark, J1 aPatel, Kushang, V1 aLipsitz, Lewis, A uhttps://chs-nhlbi.org/node/636303245nas a2200517 4500008004100000022001400041245011100055210006900166260001300235300001100248490000800259520180600267653000902073653002202082653001902104653002302123653002802146653002102174653002102195653002702216653002202243653001102265653001102276653001702287653001102304653002002315653001102335653000902346653003102355653001202386653002202398653001702420100002302437700002402460700002402484700001602508700002502524700002102549700001902570700002002589700002402609700001802633700002002651700002002671856003602691 2014 eng d a1879-148400aRisk factors for cardiovascular disease across the spectrum of older age: the Cardiovascular Health Study.0 aRisk factors for cardiovascular disease across the spectrum of o c2014 Nov a336-420 v2373 aOBJECTIVE: The associations of some risk factors with cardiovascular disease (CVD) are attenuated in older age; whereas others appear robust. The present study aimed to compare CVD risk factors across older age.
METHODS: Participants (n = 4883) in the Cardiovascular Health Study free of prevalent CVD, were stratified into three age groups: 65-74, 75-84, 85+ years. Traditional risk factors included systolic blood pressure (BP), LDL-cholesterol, HDL-cholesterol, obesity, and diabetes. Novel risk factors included kidney function, C-reactive protein (CRP), and N-terminal pro-B-type natriuretic peptide (NT pro-BNP).
RESULTS: There were 1498 composite CVD events (stroke, myocardial infarction, and cardiovascular death) over 5 years. The associations of high systolic BP and diabetes appeared strongest, though both were attenuated with age (p-values for interaction = 0.01 and 0.002, respectively). The demographic-adjusted hazard ratios (HR) for elevated systolic BP were 1.79 (95% confidence interval: 1.49, 2.15), 1.59 (1.37, 1.85) and 1.10 (0.86, 1.41) in participants aged 65-74, 75-84, 85+, and for diabetes, 2.36 (1.89, 2.95), 1.55 (1.27, 1.89), 1.51 (1.10, 2.09). The novel risk factors had consistent associations with the outcome across the age spectrum; low kidney function: 1.69 (1.31, 2.19), 1.61 (1.36, 1.90), and 1.57 (1.16, 2.14) for 65-74, 75-84, and 85+ years, respectively; elevated CRP: 1.54 (1.28, 1.87), 1.33 (1.13, 1.55), and 1.51 (1.15, 1.97); elevated NT pro-BNP: 2.67 (1.96, 3.64), 2.71 (2.25, 3.27), and 2.18 (1.43, 3.45).
CONCLUSIONS: The associations of most traditional risk factors with CVD were minimal in the oldest old, whereas diabetes, eGFR, CRP, and NT pro-BNP were associated with CVD across older age.
10aAged10aAged, 80 and over10aBlood Pressure10aC-Reactive Protein10aCardiovascular Diseases10aCholesterol, HDL10aCholesterol, LDL10aDiabetes Complications10aDiabetes Mellitus10aFemale10aHumans10aInflammation10aKidney10aKidney Diseases10aLipids10aMale10aNatriuretic Peptide, Brain10aObesity10aPeptide Fragments10aRisk Factors1 aOdden, Michelle, C1 aShlipak, Michael, G1 aWhitson, Heather, E1 aKatz, Ronit1 aKearney, Patricia, M1 adeFilippi, Chris1 aShastri, Shani1 aSarnak, Mark, J1 aSiscovick, David, S1 aCushman, Mary1 aPsaty, Bruce, M1 aNewman, Anne, B uhttps://chs-nhlbi.org/node/658803702nas a2200529 4500008004100000022001400041245011600055210006900171260001500240300001100255490000700266520220700273653001602480653000902496653002202505653001602527653003402543653001502577653002202592653001102614653003102625653001802656653001102674653000902685653003202694653002402726653003302750653001702783653001602800653001202816653001102828100001802839700001602857700002002873700002302893700002002916700002402936700002002960700001902980700002402999700002203023700002803045700002003073700002403093700001903117856003603136 2015 eng d a1555-905X00aDevelopment and validation of a model to predict 5-year risk of death without ESRD among older adults with CKD.0 aDevelopment and validation of a model to predict 5year risk of d c2015 Mar 6 a363-710 v103 aBACKGROUND AND OBJECTIVES: CKD is associated with mortality. Accurate prediction tools for mortality may guide clinical decision-making, particularly among elderly persons with CKD.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A prediction equation was developed for 5-year risk of mortality among participants with CKD in the Cardiovascular Health Study. Sixteen candidate predictor variables were explored, which included demographics, physical examination measures, comorbidity, medication use, and kidney function measures (eGFR calculated from serum creatinine and the CKD Epidemiology Collaboration equation and the urine albumin-to-creatinine ratio). Models were developed using Cox regression and evaluated using c statistics. A final parsimonious model was externally validated in an independent cohort of community-living elders with CKD in the Health, Aging, and Body Composition Study.
RESULTS: The development cohort included 828 participants who had a mean age of 80 (±5.6) years and an eGFR of 47 (±11) ml/min per 1.73 m(2), and median albumin-to-creatinine ratio of 13 (interquartile range 6-51) mg/g. The validation cohort included 789 participants who had a mean age of 74 (±2.8) years and an eGFR of 50 (±9) ml/min per 1.73 m(2), and median albumin-to-creatinine ratio of 13 (interquartile range 6-42) mg/g. The final model for 5-year mortality risk included age, sex, race, eGFR, urine albumin-to-creatinine ratio, smoking, diabetes mellitus, and history of heart failure and stroke (c statistic=0.72; 95% confidence interval, 0.68 to 0.74). When a point-based system was assigned for each of nine variables in the equation, the estimated risk of death within 5 years ranged from 3.8% among participants with the lowest scores to 83.6% among participants with nine points. The model performed fair in external validation (c statistic=0.69; 95% confidence interval, 0.64 to 0.74).
CONCLUSIONS: A simple prediction tool using nine readily available clinical variables can assist in predicting 5-year mortality risk in elderly patients with CKD, which may be useful in counseling patients and guiding clinical decision making.
10aAge Factors10aAged10aAged, 80 and over10aAlbuminuria10aContinental Population Groups10aCreatinine10aDiabetes Mellitus10aFemale10aGlomerular Filtration Rate10aHeart Failure10aHumans10aMale10aProportional Hazards Models10aRegression Analysis10aRenal Insufficiency, Chronic10aRisk Factors10aSex Factors10aSmoking10aStroke1 aBansal, Nisha1 aKatz, Ronit1 ade Boer, Ian, H1 aPeralta, Carmen, A1 aFried, Linda, F1 aSiscovick, David, S1 aRifkin, Dena, E1 aHirsch, Calvin1 aCummings, Steven, R1 aHarris, Tamara, B1 aKritchevsky, Stephen, B1 aSarnak, Mark, J1 aShlipak, Michael, G1 aIx, Joachim, H uhttps://chs-nhlbi.org/node/665903793nas a2200493 4500008004100000022001400041245010900055210006900164260001300233300000900246490000700255520239600262653000902658653002202667653001502689653001602704653002702720653002402747653001102771653003002782653002202812653001702834653001902851653001102870653002602881653000902907653002402916653003302940653001702973653003102990653001803021100001503039700001603054700002003070700002203090700002203112700002403134700002103158700002003179700002103199700002403220700001903244856003603263 2015 eng d a1523-683800aFibroblast growth factor 23 and sudden versus non-sudden cardiac death: the Cardiovascular Health Study.0 aFibroblast growth factor 23 and sudden versus nonsudden cardiac c2015 Jul a40-60 v663 aBACKGROUND: Elevated fibroblast growth factor 23 (FGF-23) concentrations are associated with greater risk of cardiovascular events and mortality, especially among people with chronic kidney disease (CKD). Because individuals with CKD are at an increased risk of sudden cardiac death (SCD), we sought to understand whether FGF-23 level is a stronger risk factor for SCD versus non-SCD.
STUDY DESIGN: Cohort study.
SETTING & PARTICIPANTS: 3,244 participants 65 years or older in the community-based Cardiovascular Health Study.
PREDICTOR: Plasma FGF-23 concentrations.
OUTCOMES: We assessed SCD and non-SCD in these analyses. SCD was adjudicated rigorously and was defined as a sudden pulseless condition of cardiac origin in a previously stable person occurring out of hospital or in the emergency department.
MEASUREMENTS: We estimated associations of baseline FGF-23 concentrations with SCD and non-SCD using Cox proportional hazards models after adjustment for demographics, cardiovascular risk factors, comorbid conditions, and kidney function. We also tested whether associations differed by CKD status.
RESULTS: During a median follow-up of 8.1 years, there were 118 adjudicated SCD and 570 non-SCD events. After multivariable adjustment for demographics, cardiovascular risk factors, comorbid conditions, and parameters of kidney function, higher FGF-23 concentrations were an independent risk factor for non-SCD (HR [per doubling], 1.17; 95% CI, 1.06-1.30). However, elevated FGF-23 concentrations were not associated independently with SCD (HR [per doubling], 1.07; 95% CI, 0.85-1.35). In stratified analysis by CKD status (36.5% of cohort), doubling of FGF-23 concentrations was associated independently with non-SCD (adjusted HR, 1.26; 95% CI, 1.10-1.45). A similar magnitude of association was observed between FGF-23 level and SCD in the CKD subgroup; however, it was not significant (HR, 1.20; 95% CI, 0.89-1.62).
LIMITATIONS: Limited power to detect moderate-sized effects between FGF-23 level and SCD in both the primary and stratified analyses.
CONCLUSIONS: In this population-based study, FGF-23 level elevations were associated independently with non-SCD. Among individuals with CKD, the associations between FGF-23 level and SCD and non-SCD were similar.
10aAged10aAged, 80 and over10aBiomarkers10aComorbidity10aDeath, Sudden, Cardiac10aElectrocardiography10aFemale10aFibroblast Growth Factors10aFollow-Up Studies10aHeart Arrest10aHeart Diseases10aHumans10aKaplan-Meier Estimate10aMale10aProspective Studies10aRenal Insufficiency, Chronic10aRisk Factors10aSympathetic Nervous System10aUnited States1 aDeo, Rajat1 aKatz, Ronit1 ade Boer, Ian, H1 aSotoodehnia, Nona1 aKestenbaum, Bryan1 aMukamal, Kenneth, J1 aChonchol, Michel1 aSarnak, Mark, J1 aSiscovick, David1 aShlipak, Michael, G1 aIx, Joachim, H uhttps://chs-nhlbi.org/node/666203482nas a2200541 4500008004100000022001400041245011500055210006900170260001300239300001200252490000700264520194200271653002402213653001502237653001002252653002202262653002102284653000902305653001602314653003402330653004002364653001102404653003102415653001102446653001402457653000902471653001602480653003002496653001402526653003002540653002102570653001602591100002102607700001902628700002402647700002302671700001702694700002202711700001902733700001802752700002002770700001802790700002002808700002502828700002202853710002902875856003602904 2015 eng d a1523-683800aA Meta-analysis of the Association of Estimated GFR, Albuminuria, Age, Race, and Sex With Acute Kidney Injury.0 aMetaanalysis of the Association of Estimated GFR Albuminuria Age c2015 Oct a591-6010 v663 aBACKGROUND: Acute kidney injury (AKI) is a serious global public health problem. We aimed to quantify the risk of AKI associated with estimated glomerular filtration rate (eGFR), albuminuria (albumin-creatinine ratio [ACR]), age, sex, and race (African American and white).
STUDY DESIGN: Collaborative meta-analysis.
SETTING & POPULATION: 8 general-population cohorts (1,285,049 participants) and 5 chronic kidney disease (CKD) cohorts (79,519 participants).
SELECTION CRITERIA FOR STUDIES: Available eGFR, ACR, and 50 or more AKI events.
PREDICTORS: Age, sex, race, eGFR, urine ACR, and interactions.
OUTCOME: Hospitalized with or for AKI, using Cox proportional hazards models to estimate HRs of AKI and random-effects meta-analysis to pool results.
RESULTS: 16,480 (1.3%) general-population cohort participants had AKI over a mean follow-up of 4 years; 2,087 (2.6%) CKD participants had AKI over a mean follow-up of 1 year. Lower eGFR and higher ACR were strongly associated with AKI. Compared with eGFR of 80mL/min/1.73m(2), the adjusted HR of AKI at eGFR of 45mL/min/1.73m(2) was 3.35 (95% CI, 2.75-4.07). Compared with ACR of 5mg/g, the risk of AKI at ACR of 300mg/g was 2.73 (95% CI, 2.18-3.43). Older age was associated with higher risk of AKI, but this effect was attenuated with lower eGFR or higher ACR. Male sex was associated with higher risk of AKI, with a slight attenuation in lower eGFR but not in higher ACR. African Americans had higher AKI risk at higher levels of eGFR and most levels of ACR.
LIMITATIONS: Only 2 general-population cohorts could contribute to analyses by race; AKI identified by diagnostic code.
CONCLUSIONS: Reduced eGFR and increased ACR are consistent strong risk factors for AKI, whereas associations of AKI with age, sex, and race may be weaker in more advanced stages of CKD.
10aAcute Kidney Injury10aAdolescent10aAdult10aAfrican Americans10aAge Distribution10aAged10aAlbuminuria10aContinental Population Groups10aEuropean Continental Ancestry Group10aFemale10aGlomerular Filtration Rate10aHumans10aIncidence10aMale10aMiddle Aged10aPredictive Value of Tests10aPrognosis10aSeverity of Illness Index10aSex Distribution10aYoung Adult1 aGrams, Morgan, E1 aSang, Yingying1 aBallew, Shoshana, H1 aGansevoort, Ron, T1 aKimm, Heejin1 aKovesdy, Csaba, P1 aNaimark, David1 aOien, Cecilia1 aSmith, David, H1 aCoresh, Josef1 aSarnak, Mark, J1 aStengel, Bénédicte1 aTonelli, Marcello1 aCKD Prognosis Consortium uhttps://chs-nhlbi.org/node/679703439nas a2200469 4500008004100000022001400041245013200055210006900187260001300256300001100269490000700280520210300287653002402390653001002414653000902424653001602433653002202449653002402471653001102495653003102506653001102537653001702548653001402565653002802579653000902607653001602616653001402632653003302646100002202679700002102701700001902722700001702741700002002758700002202778700001802800700002302818700002102841700002202862700002002884710002902904856003602933 2015 eng d a1523-683800aA Meta-analysis of the Association of Estimated GFR, Albuminuria, Diabetes Mellitus, and Hypertension With Acute Kidney Injury.0 aMetaanalysis of the Association of Estimated GFR Albuminuria Dia c2015 Oct a602-120 v663 aBACKGROUND: Diabetes mellitus and hypertension are risk factors for acute kidney injury (AKI). Whether estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (ACR) remain risk factors for AKI in the presence and absence of these conditions is uncertain.
STUDY DESIGN: Meta-analysis of cohort studies.
SETTING & POPULATION: 8 general-population (1,285,045 participants) and 5 chronic kidney disease (CKD; 79,519 participants) cohorts.
SELECTION CRITERIA FOR STUDIES: Cohorts participating in the CKD Prognosis Consortium.
PREDICTORS: Diabetes and hypertension status, eGFR by the 2009 CKD Epidemiology Collaboration creatinine equation, urine ACR, and interactions.
OUTCOME: Hospitalization with AKI, using Cox proportional hazards models to estimate HRs of AKI and random-effects meta-analysis to pool results.
RESULTS: During a mean follow-up of 4 years, there were 16,480 episodes of AKI in the general-population and 2,087 episodes in the CKD cohorts. Low eGFRs and high ACRs were associated with higher risks of AKI in individuals with or without diabetes and with or without hypertension. When compared to a common reference of eGFR of 80mL/min/1.73m(2) in nondiabetic patients, HRs for AKI were generally higher in diabetic patients at any level of eGFR. The same was true for diabetic patients at all levels of ACR compared with nondiabetic patients. The risk gradient for AKI with lower eGFRs was greater in those without diabetes than with diabetes, but similar with higher ACRs in those without versus with diabetes. Those with hypertension had a higher risk of AKI at eGFRs>60mL/min/1.73m(2) than those without hypertension. However, risk gradients for AKI with both lower eGFRs and higher ACRs were greater for those without than with hypertension.
LIMITATIONS: AKI identified by diagnostic code.
CONCLUSIONS: Lower eGFRs and higher ACRs are associated with higher risks of AKI among individuals with or without either diabetes or hypertension.
10aAcute Kidney Injury10aAdult10aAged10aComorbidity10aDiabetes Mellitus10aDisease Progression10aFemale10aGlomerular Filtration Rate10aHumans10aHypertension10aIncidence10aKidney Failure, Chronic10aMale10aMiddle Aged10aPrognosis10aRenal Insufficiency, Chronic1 aJames, Matthew, T1 aGrams, Morgan, E1 aWoodward, Mark1 aElley, Raina1 aGreen, Jamie, A1 aWheeler, David, C1 ade Jong, Paul1 aGansevoort, Ron, T1 aLevey, Andrew, S1 aWarnock, David, G1 aSarnak, Mark, J1 aCKD Prognosis Consortium uhttps://chs-nhlbi.org/node/679603103nas a2200337 4500008004100000022001400041245013200055210006900187260001300256300001200269490000700281520211200288653000902400653002202409653001402431653002802445653001102473653001102484653000902495653002902504653002702533100001902560700002402579700002002603700002302623700002302646700001802669700002002687700002202707856003602729 2015 eng d a1532-541500aMicrovascular and Macrovascular Abnormalities and Cognitive and Physical Function in Older Adults: Cardiovascular Health Study.0 aMicrovascular and Macrovascular Abnormalities and Cognitive and c2015 Sep a1886-930 v633 aOBJECTIVES: To evaluate and compare the associations between microvascular and macrovascular abnormalities and cognitive and physical function
DESIGN: Cross-sectional analysis of the Cardiovascular Health Study (1998-1999).
SETTING: Community.
PARTICIPANTS: Individuals with available data on three or more of five microvascular abnormalities (brain, retina, kidney) and three or more of six macrovascular abnormalities (brain, carotid artery, heart, peripheral artery) (N = 2,452; mean age 79.5).
MEASUREMENTS: Standardized composite scores derived from three cognitive tests (Modified Mini-Mental State Examination, Digit-Symbol Substitution Test, Trail-Making Test (TMT)) and three physical tests (gait speed, grip strength, 5-time sit to stand)
RESULTS: Participants with high microvascular and macrovascular burden had worse cognitive (mean score difference = -0.30, 95% confidence interval (CI) = -0.37 to -0.24) and physical (mean score difference = -0.32, 95% CI = -0.38 to -0.26) function than those with low microvascular and macrovascular burden. Individuals with high microvascular burden alone had similarly lower scores than those with high macrovascular burden alone (cognitive function: -0.16, 95% CI = -0.24 to -0.08 vs -0.13, 95% CI = -0.20 to -0.06; physical function: -0.15, 95% CI = -0.22 to -0.08 vs -0.12, 95% CI = -0.18 to -0.06). Psychomotor speed and working memory, assessed using the TMT, were only impaired in the presence of high microvascular burden. Of the 11 vascular abnormalities considered, white matter hyperintensity, cystatin C-based glomerular filtration rate, large brain infarct, and ankle-arm index were independently associated with cognitive and physical function.
CONCLUSION: Microvascular and macrovascular abnormalities assessed using noninvasive tests of the brain, kidney, and peripheral artery were independently associated with poor cognitive and physical function in older adults. Future research should evaluate the usefulness of these tests in prognostication.
10aAged10aAged, 80 and over10aCognition10aCross-Sectional Studies10aFemale10aHumans10aMale10aNeuropsychological Tests10aVascular Malformations1 aKim, Dae, Hyun1 aGrodstein, Francine1 aNewman, Anne, B1 aChaves, Paulo, H M1 aOdden, Michelle, C1 aKlein, Ronald1 aSarnak, Mark, J1 aLipsitz, Lewis, A uhttps://chs-nhlbi.org/node/685202646nas a2200433 4500008004100000022001400041245009700055210006900152260001300221300001100234490000700245520147400252653000901726653002201735653002001757653001901777653003301796653001101829653001901840653001801859653001101877653002601888653000901914653002401923653000901947653001601956653001801972653001401990100001702004700002102021700002002042700002102062700002002083700001802103700002002121700001802141700001702159856003602176 2015 eng d a1532-860000aSerum urate levels and the risk of hip fractures: data from the Cardiovascular Health Study.0 aSerum urate levels and the risk of hip fractures data from the C c2015 Mar a438-460 v643 aPURPOSE: Uric acid inhibits vitamin D activation experimentally and higher serum urate levels are associated with higher parathyroid hormone levels in humans suggesting a link between uric acid and bone health. We hypothesized that hyperuricemia may increase the risk of fractures in older adults.
METHODS: 1963 men and 2729 women ≥65 years of age who participated in the Cardiovascular Health Study and had baseline serum urate levels were included in the study. The primary outcome was incident hip fracture, assessed prospectively through June, 2008 by inpatient and outpatient records. The analysis was stratified by sex a priori.
RESULTS: There was a U-shaped relationship between serum urate levels and hip fractures in men. Men in the lowest and the highest urate quartiles (<4.88 and ≥6.88 mg/dL respectively) had a significantly higher rate of fractures in unadjusted analysis. However, upon multivariate adjustment, only the HR for hip fracture in highest quartile versus the reference remained significant (HR 1.9; 95% C.I. 1.1, 3.1; p value 0.02). High serum urate levels were not associated with hip fractures in women.
CONCLUSION: In this large prospective cohort of community-dwelling older adults, increased serum urate levels were associated with an increased risk of hip fractures in men. Further studies are needed to confirm these findings and to understand the mechanisms that underlie them.
10aAged10aAged, 80 and over10aBody Mass Index10aCohort Studies10aEstrogen Replacement Therapy10aFemale10aHealth Surveys10aHip Fractures10aHumans10aKaplan-Meier Estimate10aMale10aProspective Studies10aRisk10aSex Factors10aUnited States10aUric Acid1 aMehta, Tapan1 aBůzková, Petra1 aSarnak, Mark, J1 aChonchol, Michel1 aCauley, Jane, A1 aWallace, Erin1 aFink, Howard, A1 aRobbins, John1 aJalal, Diana uhttps://chs-nhlbi.org/node/662402888nas a2200481 4500008004100000022001400041245008700055210006900142260001300211300001200224490000700236520154100243653000901784653002201793653001601815653001501831653002801846653002501874653001501899653002401914653001101938653003101949653001801980653001101998653001402009653002802023653000902051653003202060653001502092100002502107700001902132700001602151700001902167700002402186700002202210700002502232700002402257700002202281700002402303700002302327700002002350856003602370 2015 eng d a1523-175500aUrinary uromodulin, kidney function, and cardiovascular disease in elderly adults.0 aUrinary uromodulin kidney function and cardiovascular disease in c2015 Nov a1126-340 v883 aUrinary uromodulin (uUMOD) is the most common secreted tubular protein in healthy adults. However, the relationship between uUMOD and clinical outcomes is still unclear. Here we measured uUMOD in 192 participants of the Cardiovascular Health Study with over a 30% decline in estimated glomerular filtration rate (eGFR) over 9 years, 54 with incident end-stage renal disease (ESRD), and in a random subcohort of 958 participants. The association of uUMOD with eGFR decline was evaluated using logistic regression and with incident ESRD, cardiovascular disease, heart failure, and mortality using Cox proportional regression. Mean age was 78 years and median uUMOD was 25.8 μg/ml. In a case-control study evaluating eGFR decline (192 cases and 231 controls), each 1-s.d. higher uUMOD was associated with a 23% lower odds of eGFR decline (odds ratio 0.77 (95% CI 0.62-0.96)) and a 10% lower risk of mortality (hazard ratio 0.90 (95% CI 0.83-0.98)) after adjusting for demographics, eGFR, albumin/creatinine ratio, and other risk factors. There was no risk association of uUMOD with ESRD, cardiovascular disease, or heart failure after multivariable adjustment. Thus, low uUMOD levels may identify persons at risk of progressive kidney disease and mortality above and beyond established markers of kidney disease, namely eGFR and the albumin/creatinine ratio. Future studies need to confirm these results and evaluate whether uUMOD is a marker of tubular health and/or whether it plays a causal role in preserving kidney function.
10aAged10aAged, 80 and over10aAlbuminuria10aBiomarkers10aCardiovascular Diseases10aCase-Control Studies10aCreatinine10aDisease Progression10aFemale10aGlomerular Filtration Rate10aHeart Failure10aHumans10aIncidence10aKidney Failure, Chronic10aMale10aProportional Hazards Models10aUromodulin1 aGarimella, Pranav, S1 aBiggs, Mary, L1 aKatz, Ronit1 aIx, Joachim, H1 aBennett, Michael, R1 aDevarajan, Prasad1 aKestenbaum, Bryan, R1 aSiscovick, David, S1 aJensen, Majken, K1 aShlipak, Michael, G1 aChaves, Paulo, H M1 aSarnak, Mark, J uhttps://chs-nhlbi.org/node/677003025nas a2200469 4500008004100000022001400041245008200055210006900137260001300206300001300219490000700232520171300239653000901952653002801961653002501989653002402014653001102038653001802049653001102067653002802078653000902106653002202115653001602137653002402153653003302177100001902210700001902229700002102248700001802269700002102287700001902308700001602327700002302343700001802366700002002384700002602404700002502430700002002455700002402475700002002499856003602519 2015 eng d a1533-345000aUrine Collagen Fragments and CKD Progression-The Cardiovascular Health Study.0 aUrine Collagen Fragments and CKD ProgressionThe Cardiovascular H c2015 Oct a2494-5030 v263 aTubulointerstitial fibrosis is common with ageing and strongly prognostic for ESRD but is poorly captured by eGFR or urine albumin to creatinine ratio (ACR). Higher urine levels of procollagen type III N-terminal propeptide (PIIINP) mark the severity of tubulointerstitial fibrosis in biopsy studies, but the association of urine PIIINP with CKD progression is unknown. Among community-living persons aged ≥65 years, we measured PIIINP in spot urine specimens from the 1996 to 1997 Cardiovascular Health Study visit among individuals with CKD progression (30% decline in eGFR over 9 years, n=192) or incident ESRD (n=54) during follow-up, and in 958 randomly selected participants. We evaluated associations of urine PIIINP with CKD progression and incident ESRD. Associations of urine PIIINP with cardiovascular disease, heart failure, and death were evaluated as secondary end points. At baseline, mean age (±SD) was 78±5 years, mean eGFR was 63±18 ml/min per 1.73 m(2), and median urine PIIINP was 2.6 (interquartile range, 1.4-4.2) μg/L. In a case-control study (192 participants, 231 controls), each doubling of urine PIIINP associated with 22% higher odds of CKD progression (adjusted odds ratio, 1.22; 95% confidence interval, 1.00 to 1.49). Higher urine PIIINP level was also associated with incident ESRD, but results were not significant in fully adjusted models. In a prospective study among the 958 randomly selected participants, higher urine PIIINP was significantly associated with death, but not with incident cardiovascular disease or heart failure. These data suggest higher urine PIIINP levels associate with CKD progression independently of eGFR and ACR in older individuals.
10aAged10aCardiovascular Diseases10aCase-Control Studies10aDisease Progression10aFemale10aHeart Failure10aHumans10aKidney Failure, Chronic10aMale10aPeptide Fragments10aProcollagen10aProspective Studies10aRenal Insufficiency, Chronic1 aIx, Joachim, H1 aBiggs, Mary, L1 aMukamal, Kenneth1 aDjoussé, Luc1 aSiscovick, David1 aTracy, Russell1 aKatz, Ronit1 aDelaney, Joseph, A1 aChaves, Paulo1 aRifkin, Dena, E1 aHughes-Austin, Jan, M1 aGarimella, Pranav, S1 aSarnak, Mark, J1 aShlipak, Michael, G1 aKizer, Jorge, R uhttps://chs-nhlbi.org/node/666003388nas a2200457 4500008004100000022001400041245012000055210006900175260001300244300001000257490000700267520205200274653000902326653001802335653001502353653002802368653002802396653003802424653001102462653003002473653001802503653003102521653001102552653002302563653002502586653000902611653001402620653001702634653003102651100001802682700001902700700002402719700002002743700002002763700002502783700002102808700002502829700002002854700002002874856003602894 2016 eng d a1532-541500aFibroblast Growth Factor-23 and Frailty in Elderly Community-Dwelling Individuals: The Cardiovascular Health Study.0 aFibroblast Growth Factor23 and Frailty in Elderly CommunityDwell c2016 Feb a270-60 v643 aOBJECTIVES: To evaluate whether fibroblast growth factor 23 (FGF-23) is related to frailty and to characterize the nature of their joint association with mortality.
DESIGN: Cross-sectional analysis for frailty and longitudinal cohort analysis for mortality.
SETTING: Cardiovascular Health Study.
PARTICIPANTS: Community-dwelling individuals (N = 2,977; mean age 77.9 ± 4.7, 40% male, 83% white).
MEASUREMENTS: The predictor was serum FGF-23 concentration (C-terminal enzyme-linked immunosorbent assay), and the outcomes were frailty status (determined according to frailty phenotype criteria of weight loss, weakness, exhaustion, slowness, and low physical activity) and mortality. Multinomial logistic regression was used to assess the cross-sectional association between FGF-23 and frailty and prefrailty, adjusting for demographic characteristics, cardiovascular disease and risk factors, and kidney markers. Proportional hazards Cox proportional hazards regression was used to assess the association between FGF-23, frailty, and all-cause mortality.
RESULTS: Mean estimated glomerular filtration rate (eGFR) was 64 ± 17 mL/min per 1.73 m(2) . Median FGF-23 was 70.3 RU/mL (interquartile range 53.4-99.2); 52% were prefrail, and 13% were frail. After multivariate adjustment, each doubling in FGF-23 concentration was associated with 38% (95% confidence interval (CI) = 17-62%) higher odds of frailty than of nonfrailty and 16% (95% CI = 3-30%) higher odds of prefrailty. FGF-23 (hazard ratio (HR) = 1.16, 95% CI = 1.10-1.23) and frailty (HR = 1.82, 95% CI = 1.57-2.12) were independently associated with mortality, but neither association was meaningfully attenuated when adjusted for the other.
CONCLUSION: In a large cohort of older adults, higher FGF-23 was independently associated with prevalent frailty and prefrailty. FGF-23 and frailty were independent and additive risk factors for mortality. FGF-23 may be a marker for functional outcomes.
10aAged10aAnthropometry10aBiomarkers10aCardiovascular Diseases10aCross-Sectional Studies10aEnzyme-Linked Immunosorbent Assay10aFemale10aFibroblast Growth Factors10aFrail Elderly10aGlomerular Filtration Rate10aHumans10aIndependent Living10aLongitudinal Studies10aMale10aPhenotype10aRisk Factors10aSurveys and Questionnaires1 aBeben, Tomasz1 aIx, Joachim, H1 aShlipak, Michael, G1 aSarnak, Mark, J1 aFried, Linda, F1 aHoofnagle, Andrew, N1 aChonchol, Michel1 aKestenbaum, Bryan, R1 ade Boer, Ian, H1 aRifkin, Dena, E uhttps://chs-nhlbi.org/node/699001271nas a2200433 4500008004100000022001400041245011500055210006900170260001200239300001000251490000700261653000900268653001900277653001500296653001500311653001100326653001500337653003100352653001100383653004200394653002000436653002500456653000900481653001400490653003300504100001800537700001600555700002100571700002700592700002000619700002300639700002400662700002000686700002200706700003000728700001900758700002400777856003600801 2016 eng d a1523-683800aGalectin-3 and Soluble ST2 and Kidney Function Decline in Older Adults: The Cardiovascular Health Study (CHS).0 aGalectin3 and Soluble ST2 and Kidney Function Decline in Older A c2016 06 a994-60 v6710aAged10aCohort Studies10aCreatinine10aCystatin C10aFemale10aGalectin 310aGlomerular Filtration Rate10aHumans10aInterleukin-1 Receptor-Like 1 Protein10aLogistic Models10aLongitudinal Studies10aMale10aPrognosis10aRenal Insufficiency, Chronic1 aBansal, Nisha1 aKatz, Ronit1 aSeliger, Stephen1 aDeFilippi, Christopher1 aSarnak, Mark, J1 aDelaney, Joseph, A1 aChristenson, Robert1 ade Boer, Ian, H1 aKestenbaum, Bryan1 aRobinson-Cohen, Cassianne1 aIx, Joachim, H1 aShlipak, Michael, G uhttps://chs-nhlbi.org/node/809502938nas a2200205 4500008004100000022001400041245009500055210006900150260001600219520228600235100002502521700002002546700001902566700002102585700002402606700002202630700002402652700002002676856003602696 2016 eng d a1523-683800aUrinary Uromodulin and Risk of Urinary Tract Infections: The Cardiovascular Health Study.0 aUrinary Uromodulin and Risk of Urinary Tract Infections The Card c2016 Oct 283 aBACKGROUND: Laboratory studies suggest that urinary uromodulin, the most common protein in the urine of healthy adults, may protect against urinary tract infection (UTI). Epidemiologic studies evaluating this relationship in humans are lacking.
STUDY DESIGN: Prospective longitudinal cohort study.
SETTING & PARTICIPANTS: 953 participants enrolled in the Cardiovascular Health Study.
PREDICTOR: Uromodulin assayed using enzyme-linked immunosorbent assay in spot urine samples.
OUTCOMES: Composite of outpatient UTI events or UTI-related hospitalizations and each of them individually identified using International Classification of Diseases, Ninth Revision (ICD-9) codes using negative binomial regression with robust standard errors adjusted for age, race, sex, body mass index, diabetes, estimated glomerular filtration rate, and urinary albumin and urinary creatinine excretion.
RESULTS: Median uromodulin level was 25.9 (IQR, 17.3-38.9) μg/mL, mean age of participants was 78 years, 61% were women, and 15% were black. There were 331 outpatient UTI events and 87 UTI-related hospitalizations among 186 participants during a median 9.9 years of follow-up. Persons in the highest quartile (>38.93μg/mL) of uromodulin concentration had a significantly lower risk for the composite outcome (incidence rate ratio [IRR], 0.47; 95% CI, 0.29-0.79) compared with those in the lowest quartile (≤17.26μg/mL). This association remained significant for outpatient UTI events (highest vs lowest quartile even after excluding those with prior UTI: IRR, 0.42; 95% CI, 0.23-0.77). The direction of association with UTI hospitalization was similar, but not statistically significant (IRR, 0.78; 95% CI, 0.39-1.58).
LIMITATIONS: Use of ICD-9 codes to identify outcomes and lack of generalizability to younger populations.
CONCLUSIONS: High urinary uromodulin levels are associated with lower risk for UTI in older community-dwelling adults independent of traditional UTI risk factors. This finding supports prior laboratory data indicating a protective role of uromodulin against UTI. Further research is needed to understand if this may lead to new treatments to prevent or treat UTI.
1 aGarimella, Pranav, S1 aBartz, Traci, M1 aIx, Joachim, H1 aChonchol, Michel1 aShlipak, Michael, G1 aDevarajan, Prasad1 aBennett, Michael, R1 aSarnak, Mark, J uhttps://chs-nhlbi.org/node/736903877nas a2200313 4500008004100000022001400041245014800055210006900203260001600272300001200288490000600300520290500306100001803211700001603229700003003245700002303275700002203298700002403320700002003344700002403364700001903388700002003407700002203427700001903449700002103468700001803489700002003507856003603527 2017 eng d a2380-659100aAbsolute Rates of Heart Failure, Coronary Heart Disease, and Stroke in Chronic Kidney Disease: An Analysis of 3 Community-Based Cohort Studies.0 aAbsolute Rates of Heart Failure Coronary Heart Disease and Strok c2017 Mar 01 a314-3180 v23 aImportance: Cardiovascular disease is the leading cause of morbidity and mortality in patients with chronic kidney disease (CKD). Understanding the relative contributions of cardiovascular disease event types to the excess burden of cardiovascular disease is important for developing effective strategies to improve outcomes.
Objective: To determine absolute rates and risk differences of incident heart failure (HF), coronary heart disease (CHD), and stroke in participants with vs without CKD.
Design, Setting and Participants: We pooled participants without prevalent cardiovascular disease from 3 community-based cohort studies: the Jackson Heart Study, Cardiovascular Health Study, and Multi-Ethnic Study of Atherosclerosis. The Jackson Heart Study was conducted between 2000 and 2010, the Cardiovascular Health Study was conducted between 1989 and 2003, and the Multi-Ethnic Study of Atherosclerosis was conducted between 2000 and 2012.
Exposures: Chronic kidney disease was defined as estimated glomerular filtration rate less than 60 mL/min/1.73 m2, calculated using the combined creatinine-cystatin C CKD-Epidemiology Collaboration Equation.
Main Outcomes and Measures: Poisson regression was used to calculate incidence rates (IRs) and risk differences of adjudicated incident HF, CHD, and stroke, comparing participants with vs without CKD.
Results: Among 14 462 participants, the mean (SD) age was 63 (12) years, 59% (n = 8533) were women, and 44% (n = 6363) were African American. Overall, 1461 (10%) had CKD (mean [SD] estimated glomerular filtration rate, 49 [10] mL/min/1.73 m2). Unadjusted IRs for participants with and without CKD, respectively, were 22.0 (95% CI, 19.3-24.8) and 6.2 (95% CI, 5.8-6.7) per 1000 person-years for HF; 24.5 (95% CI, 21.6-27.5) and 8.4 (95% CI, 7.9-9.0) per 1000 person-years for CHD; and 13.4 (95% CI, 11.3-15.5) and 4.8 (95% CI, 4.4-5.3) for stroke. Adjusting for demographics, cohort, hypertension, diabetes, hyperlipidemia, and tobacco use, risk differences comparing participants with vs without CKD (per 1000 person-years) were 2.3 (95% CI, 1.2-3.3) for HF, 2.3 (95% CI, 1.2-3.4) for CHD, and 0.8 (95% CI, 0.09-1.5) for stroke. Among African American and Hispanic participants, adjusted risk differences comparing participants with vs without CKD for HF were 3.5 (95% CI, 1.5-5.5) and 7.8 (95% CI, 2.2-13.3) per 1000 person-years, respectively.
Conclusions and Relevance: Among 3 diverse community-based cohorts, CKD was associated with an increased risk of HF that was similar in magnitude to CHD and greater than stroke. The excess risk of HF associated with CKD was particularly large among African American and Hispanic individuals. Efforts to improve health outcomes for patients with CKD should prioritize HF in addition to CHD prevention.
1 aBansal, Nisha1 aKatz, Ronit1 aRobinson-Cohen, Cassianne1 aOdden, Michelle, C1 aDalrymple, Lorien1 aShlipak, Michael, G1 aSarnak, Mark, J1 aSiscovick, David, S1 aZelnick, Leila1 aPsaty, Bruce, M1 aKestenbaum, Bryan1 aCorrea, Adolfo1 aAfkarian, Maryam1 aYoung, Bessie1 ade Boer, Ian, H uhttps://chs-nhlbi.org/node/733702583nas a2200205 4500008004100000022001400041245014800055210006900203260001600272520187300288100002802161700002202189700002402211700002002235700002002255700002002275700002302295700002302318856003602341 2017 eng d a1941-722500aAssociation of Blood Pressure Trajectory With Mortality, Incident Cardiovascular Disease, and Heart Failure in the Cardiovascular Health Study.0 aAssociation of Blood Pressure Trajectory With Mortality Incident c2017 Mar 103 aBACKGROUND: Common blood pressure (BP) trajectories are not well established in elderly persons, and their association with clinical outcomes is uncertain.
METHODS: We used hierarchical cluster analysis to identify discrete BP trajectories among 4,067 participants in the Cardiovascular Health Study using repeated BP measures from years 0 to 7. We then evaluated associations of each BP trajectory cluster with all-cause mortality, incident cardiovascular disease (CVD, defined as stroke or myocardial infarction) (N = 2,837), and incident congestive heart failure (HF) (N = 3,633) using Cox proportional hazard models.
RESULTS: Median age was 77 years at year 7. Over a median 9.3 years of follow-up, there were 2,475 deaths, 659 CVD events, and 1,049 HF events. The cluster analysis identified 3 distinct trajectory groups. Participants in cluster 1 (N = 1,838) had increases in both systolic (SBP) and diastolic (DBP) BPs, whereas persons in cluster 2 (N = 1,109) had little change in SBP but declines in DBP. Persons in cluster 3 (N = 1,120) experienced declines in both SBP and DBP. After multivariable adjustment, clusters 2 and 3 were associated with increased mortality risk relative to cluster 1 (hazard ratio = 1.21, 95% confidence interval: 1.06-1.37 and hazard ratio = 1.20, 95% confidence interval: 1.05-1.36, respectively). Compared to cluster 1, cluster 3 had higher rates of incident CVD but associations were not statistically significant in demographic-adjusted models (hazard ratio = 1.16, 95% confidence interval: 0.96-1.39). Findings were similar when stratified by use of antihypertensive therapy.
CONCLUSIONS: Among community-dwelling elders, distinct BP trajectories were identified by integrating both SBP and DBP. These clusters were found to have differential associations with outcomes.
1 aSmitson, Christopher, C1 aScherzer, Rebecca1 aShlipak, Michael, G1 aPsaty, Bruce, M1 aNewman, Anne, B1 aSarnak, Mark, J1 aOdden, Michelle, C1 aPeralta, Carmen, A uhttps://chs-nhlbi.org/node/736203262nas a2200313 4500008004100000022001400041245020200055210006900257260001600326300001400342490000700356520223900363100001802602700002202620700001902642700002402661700002002685700001502705700001602720700002202736700001702758700003002775700002002805700002402825700002202849700001802871700002302889856003602912 2017 eng d a1555-905X00aeGFR and Albuminuria in Relation to Risk of Incident Atrial Fibrillation: A Meta-Analysis of the Jackson Heart Study, the Multi-Ethnic Study of Atherosclerosis, and the Cardiovascular Health Study.0 aeGFR and Albuminuria in Relation to Risk of Incident Atrial Fibr c2017 Sep 07 a1386-13980 v123 aBACKGROUND AND OBJECTIVES: The incidence of atrial fibrillation is high in ESRD, but limited data are available on the incidence of atrial fibrillation across a broad range of kidney function. Thus, we examined the association of eGFR and urine albumin-to-creatinine ratio with risk of incident atrial fibrillation.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We meta-analyzed three prospective cohorts: the Jackson Heart Study, the Multi-Ethnic Study of Atherosclerosis, and the Cardiovascular Health Study. Cox regression models were performed examining the association of eGFR and urine albumin-to-creatinine ratio with incident atrial fibrillation adjusting for demographics and comorbidity. In additional analyses, we adjusted for measures of subclinical cardiovascular disease (by electrocardiogram and cardiac imaging) and interim heart failure and myocardial infarction events.
RESULTS: In the meta-analyzed study population of 16,769 participants without prevalent atrial fibrillation, across categories of decreasing eGFR (eGFR>90 [reference], 60-89, 45-59, 30-44, and <30 ml/min per 1.73 m(2)), there was a stepwise increase in the adjusted risk of incident atrial fibrillation: hazard ratios (95% confidence intervals) were 1.00, 1.09 (0.97 to 1.24), 1.17 (1.00 to 1.38), 1.59 (1.28 to 1.98), and 2.03 (1.40 to 2.96), respectively. There was a stepwise increase in the adjusted risk of incident atrial fibrillation across categories of increasing urine albumin-to-creatinine ratio (urine albumin-to-creatinine ratio <15 [reference], 15-29, 30-299, and ≥300 mg/g): hazard ratios (95% confidence intervals) were 1.00, 1.04 (0.83 to 1.30), 1.47 (1.20 to 1.79), and 1.76 (1.18 to 2.62), respectively. The associations were consistent after adjustment for subclinical cardiovascular disease measures and interim heart failure and myocardial infarction events.
CONCLUSIONS: In this meta-analysis of three cohorts, reduced eGFR and elevated urine albumin-to-creatinine ratio were significantly associated with greater risk of incident atrial fibrillation, highlighting the need for further studies to understand mechanisms linking kidney disease with atrial fibrillation.
1 aBansal, Nisha1 aZelnick, Leila, R1 aAlonso, Alvaro1 aBenjamin, Emelia, J1 ade Boer, Ian, H1 aDeo, Rajat1 aKatz, Ronit1 aKestenbaum, Bryan1 aMathew, Jehu1 aRobinson-Cohen, Cassianne1 aSarnak, Mark, J1 aShlipak, Michael, G1 aSotoodehnia, Nona1 aYoung, Bessie1 aHeckbert, Susan, R uhttps://chs-nhlbi.org/node/746403136nas a2200313 4500008004100000022001400041245012400055210006900179260001600248300001200264490000700276520219200283100002602475700002002501700001802521700001602539700002002555700001502575700002502590700002002615700002402635700002202659700002002681700002002701700002202721700002402743700001902767856003602786 2017 eng d a1555-905X00aThe Relation of Serum Potassium Concentration with Cardiovascular Events and Mortality in Community-Living Individuals.0 aRelation of Serum Potassium Concentration with Cardiovascular Ev c2017 Feb 07 a245-2520 v123 aBACKGROUND AND OBJECTIVES: Hyperkalemia is associated with adverse outcomes in patients with CKD and in hospitalized patients with acute medical conditions. Little is known regarding hyperkalemia, cardiovascular disease (CVD), and mortality in community-living populations. In a pooled analysis of two large observational cohorts, we investigated associations between serum potassium concentrations and CVD events and mortality, and whether potassium-altering medications and eGFR<60 ml/min per 1.73 m(2) modified these associations.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Among 9651 individuals from the Multi-Ethnic Study of Atherosclerosis (MESA) and the Cardiovascular Health Study (CHS), who were free of CVD at baseline (2000-2002 in the MESA and 1989-1993 in the CHS), we investigated associations between serum potassium categories (<3.5, 3.5-3.9, 4.0-4.4, 4.5-4.9, and ≥5.0 mEq/L) and CVD events, mortality, and mortality subtypes (CVD versus non-CVD) using Cox proportional hazards models, adjusting for demographics, time-varying eGFR, traditional CVD risk factors, and use of potassium-altering medications.
RESULTS: Compared with serum potassium concentrations between 4.0 and 4.4 mEq/L, those with concentrations ≥5.0 mEq/L were at higher risk for all-cause mortality (hazard ratio, 1.41; 95% confidence interval, 1.12 to 1.76), CVD death (hazard ratio, 1.50; 95% confidence interval, 1.00 to 2.26), and non-CVD death (hazard ratio, 1.40; 95% confidence interval, 1.07 to 1.83) in fully adjusted models. Associations of serum potassium with these end points differed among diuretic users (Pinteraction<0.02 for all), such that participants who had serum potassium ≥5.0 mEq/L and were concurrently using diuretics were at higher risk of each end point compared with those not using diuretics.
CONCLUSIONS: Serum potassium concentration ≥5.0 mEq/L was associated with all-cause mortality, CVD death, and non-CVD death in community-living individuals; associations were stronger in diuretic users. Whether maintenance of potassium within the normal range may improve clinical outcomes requires future study.
1 aHughes-Austin, Jan, M1 aRifkin, Dena, E1 aBeben, Tomasz1 aKatz, Ronit1 aSarnak, Mark, J1 aDeo, Rajat1 aHoofnagle, Andrew, N1 aHomma, Shunichi1 aSiscovick, David, S1 aSotoodehnia, Nona1 aPsaty, Bruce, M1 ade Boer, Ian, H1 aKestenbaum, Bryan1 aShlipak, Michael, G1 aIx, Joachim, H uhttps://chs-nhlbi.org/node/734702495nas a2200265 4500008004100000022001400041245011100055210006900166260001300235300001200248490000800260520168800268100002201956700001601978700002001994700002502014700002102039700002402060700002002084700002502104700002002129700002502149700001902174856003602193 2018 eng d a1873-276300aThe 24,25 to 25-hydroxyvitamin D ratio and fracture risk in older adults: The cardiovascular health study.0 a2425 to 25hydroxyvitamin D ratio and fracture risk in older adul c2018 Feb a124-1300 v1073 a25-hydroxyvitamin D [25(OH)D] may not optimally indicate vitamin D receptor activity. Higher concentrations of its catabolic product 24,25-dihydroxyvitmin D [24,25(OH)2D] and a higher ratio of 24,25(OH)2D to 25(OH)D (the vitamin D metabolite ratio [VMR]) may provide additional information on receptor activity. We compared the strength of associations of these markers with serum PTH concentrations, hip bone mineral density (BMD), and risk of incident hip fracture in community-living older participants in the Cardiovascular Health Study. Among 890 participants, the mean age was 78years, 60% were women, and the mean 25(OH)D was 28±11ng/ml. In cross-sectional analysis, the strength of association of each vitamin D measure with PTH was similar; a 1% higher 25(OH)D, 24,25(OH)2D, and VMR were associated with 0.32%, 0.25%, and 0.26% lower PTH, respectively (p<0.05 for all). Among 358 participants with available BMD data, we found no associations of 25(OH)D or VMR with BMD, whereas higher 24,25(OH)2D was modestly associated with greater hip BMD (1% higher 24,25(OH)2D associated with 0.04% [95% CI 0.01-0.08%] higher BMD). Risk of incident hip fracture risk was evaluated using a case-cohort design. There were 289 hip fractures during a mean follow up time of 8.4years. Both higher 24,25(OH)2D and VMR were associated with lower risk of hip fracture (HR per SD higher, 0.73 [0.61, 0.87] and 0.74 [0.61, 0.88], respectively) whereas 25(OH)D was not associated with hip fracture (HR 0.93 [0.79, 1.10]). We conclude that evaluating vitamin D status by incorporating assessment of 24,25(OH)D and the VMR provides information on bone health above and beyond 25(OH)D alone.
1 aGinsberg, Charles1 aKatz, Ronit1 ade Boer, Ian, H1 aKestenbaum, Bryan, R1 aChonchol, Michel1 aShlipak, Michael, G1 aSarnak, Mark, J1 aHoofnagle, Andrew, N1 aRifkin, Dena, E1 aGarimella, Pranav, S1 aIx, Joachim, H uhttps://chs-nhlbi.org/node/756103623nas a2200589 4500008004100000022001400041245009600055210006900151260001600220520189500236100002702131700002202158700002102180700002002201700002402221700002202245700002002267700002402287700001502311700001802326700001802344700002102362700002202383700001802405700002002423700002502443700002002468700002102488700002202509700002302531700002002554700002502574700002502599700001902624700002502643700002002668700002202688700002102710700001902731700001902750700002302769700002102792700002102813700001902834700001702853700002202870700002102892700002402913700002602937710003402963856003602997 2018 eng d a1460-238500aLow thyroid function is not associated with an accelerated deterioration in renal function.0 aLow thyroid function is not associated with an accelerated deter c2018 Apr 183 aBackground: Chronic kidney disease (CKD) is frequently accompanied by thyroid hormone dysfunction. It is currently unclear whether these alterations are the cause or consequence of CKD. This study aimed at studying the effect of thyroid hormone alterations on renal function in cross-sectional and longitudinal analyses in individuals from all adult age groups.
Methods: Individual participant data (IPD) from 16 independent cohorts having measured thyroid stimulating hormone, free thyroxine levels and creatinine levels were included. Thyroid hormone status was defined using clinical cut-off values. Estimated glomerular filtration rates (eGFR) were calculated by means of the four-variable Modification of Diet in Renal Disease (MDRD) formula. For this IPD meta-analysis, eGFR at baseline and eGFR change during follow-up were computed by fitting linear regression models and linear mixed models in each cohort separately. Effect estimates were pooled using random effects models.
Results: A total of 72 856 individuals from 16 different cohorts were included. At baseline, individuals with overt hypothyroidism (n = 704) and subclinical hypothyroidism (n = 3356) had a average (95% confidence interval) -4.07 (-6.37 to -1.78) and -2.40 (-3.78 to -1.02) mL/min/1.73 m2 lower eGFR as compared with euthyroid subjects (n = 66 542). In (subclinical) hyperthyroid subjects (n = 2254), average eGFR was 3.01 (1.50-4.52) mL/min/1.73 m2 higher. During 329 713 patient years of follow-up, eGFR did not decline more rapidly in individuals with low thyroid function compared with individuals with normal thyroid function.
Conclusions: Low thyroid function is not associated with a deterioration of renal function. The cross-sectional association may be explained by renal dysfunction causing thyroid hormone alterations.
1 aMeuwese, Christiaan, L1 avan Diepen, Merel1 aCappola, Anne, R1 aSarnak, Mark, J1 aShlipak, Michael, G1 aBauer, Douglas, C1 aFried, Linda, P1 aIacoviello, Massimo1 aVaes, Bert1 aDegryse, Jean1 aKhaw, Kay-Tee1 aLuben, Robert, N1 aAsvold, Bjørn, O1 aBjøro, Trine1 aVatten, Lars, J1 ade Craen, Anton, J M1 aTrompet, Stella1 aIervasi, Giorgio1 aMolinaro, Sabrina1 aCeresini, Graziano1 aFerrucci, Luigi1 aDullaart, Robin, P F1 aBakker, Stephan, J L1 aJukema, Wouter1 aKearney, Patricia, M1 aStott, David, J1 aPeeters, Robin, P1 aFranco, Oscar, H1 aVölzke, Henry1 aWalsh, John, P1 aBremner, Alexandra1 aSgarbi, José, A1 aMaciel, Rui, M B1 aImaizumi, Misa1 aOhishi, Waka1 aDekker, Friedo, W1 aRodondi, Nicolas1 aGussekloo, Jacobijn1 aElzen, Wendy, P J den1 aThyroid Studies Collaboration uhttps://chs-nhlbi.org/node/780502544nas a2200229 4500008004100000022001400041245011800055210006900173260001600242520180400258100002002062700002102082700001902103700002202122700002402144700002302168700002402191700001802215700002002233700002502253856003602278 2019 eng d a1440-179700aAssociation of serum and urinary uromodulin and their correlates in older adults-The Cardiovascular Health Study.0 aAssociation of serum and urinary uromodulin and their correlates c2019 Dec 173 aUromodulin is released into serum (sUMOD) and urine (uUMOD) exclusively by renal tubular cells. Both sUMOD and uUMOD are correlated with estimated glomerular filtration rate (eGFR), and associated with mortality and cardiovascular disease (CVD). However, no study to our knowledge has measured both sUMOD and uUMOD in the same population, thus the relationship of sUMOD with uUMOD with one another, and their respective correlates have not been evaluated simultaneously. We evaluated the correlations of sUMOD, uUMOD with eGFR in a random sub-cohort (n = 933) of the Cardiovascular Health Study and their associations with demographic and laboratory parameters and CVD risk factors using multi-variable linear regression analysis. The mean age of the cohort was 78 years, 40% were male and 15% were Black. The mean sUMOD level was 127 ng/mL, uUMOD was 30 500 ng/mL and eGFR was 63 mL/min/1.73 m . Correlation between sUMOD and uUMOD, adjusted for eGFR was moderate (r = 0.27 [95% confidence interval = 0.21-0.33]). The correlation of eGFR with sUMOD (r = 0.44 [0.39-0.49]) was stronger than with uUMOD (r = 0.21 [0.15-0.27]). In multi-variable analysis adjusting sUMOD for uUMOD and vice versa, sUMOD was independently associated with eGFR (β = 1.3 [1.1-1.6]), log2 C-reactive protein (β = -4.2 [-6.8 to -1.6]) and male sex (β = -13.6 [-22.7 to -4.5]). In contrast, male sex was associated with higher uUMOD (β = 3700 [400-7000]), while diabetes (β = -6400 [-10 600 to -2100]) and hypertension (-4300 [-7500 to -1100]) were associated with lower uUMOD levels. We conclude that sUMOD is more strongly associated with eGFR compared with uUMOD. Correlates of sUMOD and uUMOD differ substantially, suggesting that apical and basolateral secretion may be differentially regulated.
1 aSteubl, Dominik1 aBůzková, Petra1 aIx, Joachim, H1 aDevarajan, Prasad1 aBennett, Michael, R1 aChaves, Paolo, H M1 aShlipak, Michael, G1 aBansal, Nisha1 aSarnak, Mark, J1 aGarimella, Pranav, S uhttps://chs-nhlbi.org/node/827902803nas a2200229 4500008004100000022001400041245012600055210006900181260001600250520205500266100002002321700002102341700002502362700001902387700002202406700002402428700002302452700002402475700001802499700002002517856003602537 2019 eng d a1460-238500aAssociation of serum uromodulin with mortality and cardiovascular disease in the elderly-the Cardiovascular Health Study.0 aAssociation of serum uromodulin with mortality and cardiovascula c2019 Mar 213 aBACKGROUND: Uromodulin (UMOD) is released by renal tubular cells into the serum (sUMOD) and urine. Lower urine UMOD has been linked to mortality and cardiovascular disease but much less is known about sUMOD. We evaluated the association of sUMOD with these outcomes in community-dwelling older adults.
METHODS: We measured sUMOD in a random subcohort of 933 participants enrolled in the Cardiovascular Health Study. The associations of sUMOD with all-cause mortality, incident heart failure (HF) and incident cardiovascular disease (CVD; myocardial infarction, stroke and mortality due to coronary disease or stroke) were evaluated using multivariable Cox regression, adjusting for study participants' demographics, estimated glomerular filtration rate (eGFR), albuminuria and CVD risk factors. Generalized additive models with splines were used to address the functional form of sUMOD with outcomes. Due to nonlinear associations of sUMOD with all outcomes, 2.5% of the values on either end of the sUMOD distribution were excluded from the analyses, limiting the range of sUMOD to 34.3-267.1 ng/mL.
RESULTS: The mean age was 78 ± 5 years, 40% were male, sUMOD level was 127 ± 64 ng/mL, eGFR was 63 mL/min/1.73 m2 and 42% had CKD defined as eGFR <60 mL/min/1.73 m2. Patients in the lower sUMOD quartiles had lower eGFR and higher albuminuria (P < 0.01, respectively). During a median follow-up of 9.9 years, 805 patients died, 283 developed HF and 274 developed CVD. In multivariable analysis, higher sUMOD was significantly associated with a lower hazard for mortality {hazard ratio [HR] 0.89 [95% confidence interval (CI) 0.80-0.99] per 1 standard deviation (SD) higher sUMOD}, CVD [HR 0.80 (95% CI 0.67-0.96)] and the composite endpoint [HR 0.88 (95% CI 0.78-0.99)]; the association with HF was not statistically significant [HR 0.84 (95% CI 0.70-1.01)].
CONCLUSION: Higher sUMOD is independently associated with a lower risk for mortality and CVD in older adults.
1 aSteubl, Dominik1 aBůzková, Petra1 aGarimella, Pranav, S1 aIx, Joachim, H1 aDevarajan, Prasad1 aBennett, Michael, R1 aChaves, Paulo, H M1 aShlipak, Michael, G1 aBansal, Nisha1 aSarnak, Mark, J uhttps://chs-nhlbi.org/node/8007