02989nas 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 a
BACKGROUND: 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/97202916nas 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/106202881nas 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/114903253nas 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/117703867nas a2200745 4500008004100000022001400041245012900055210006900184260001300253300001100266490000600277520177500283653002802058653002102086653001102107653001702118653003402135653000902169653001102178653000902189653001702198653001402215100001602229700001902245700001902264700002102283700002202304700002002326700002302346700001902369700002402388700002202412700001902434700001902453700002002472700001902492700002102511700002002532700001202552700002002564700002102584700002302605700001202628700001902640700002002659700002102679700002002700700002202720700003002742700002102772700002302793700001902816700002602835700002002861700002802881700002102909700002002930700002002950700002402970700002402994700002803018700002103046700001803067856003603085 2010 eng d a1942-326800aMultiple genetic loci influence serum urate levels and their relationship with gout and cardiovascular disease risk factors.0 aMultiple genetic loci influence serum urate levels and their rel c2010 Dec a523-300 v33 aBACKGROUND: Elevated serum urate levels can lead to gout and are associated with cardiovascular risk factors. We performed a genome-wide association study to search for genetic susceptibility loci for serum urate and gout and investigated the causal nature of the associations of serum urate with gout and selected cardiovascular risk factors and coronary heart disease (CHD).
METHODS AND RESULTS: Meta-analyses of genome-wide association studies (GWAS) were performed in 5 population-based cohorts of the Cohorts for Heart and Aging Research in Genome Epidemiology consortium for serum urate and gout in 28 283 white participants. The effect of the most significant single-nucleotide polymorphism at all genome-wide significant loci on serum urate was added to create a genetic urate score. Findings were replicated in the Women's Genome Health Study (n=22 054). Single-nucleotide polymorphisms at 8 genetic loci achieved genome-wide significance with serum urate levels (P=4×10(-8) to 2×10(-242) in SLC22A11, GCKR, R3HDM2-INHBC region, RREB1, PDZK1, SLC2A9, ABCG2, and SLC17A1). Only 2 loci (SLC2A9, ABCG2) showed genome-wide significant association with gout. The genetic urate score was strongly associated with serum urate and gout (odds ratio, 12.4 per 100 μmol/L; P=3×10(-39)) but not with blood pressure, glucose, estimated glomerular filtration rate, chronic kidney disease, or CHD. The lack of association between the genetic score and the latter phenotypes also was observed in the Women's Genome Health Study.
CONCLUSIONS: The genetic urate score analysis suggested a causal relationship between serum urate and gout but did not provide evidence for one between serum urate and cardiovascular risk factors and CHD.
10aCardiovascular Diseases10aCoronary Disease10aFemale10aGenetic Loci10aGenome-Wide Association Study10aGout10aHumans10aMale10aRisk Factors10aUric Acid1 aYang, Qiong1 aKöttgen, Anna1 aDehghan, Abbas1 aSmith, Albert, V1 aGlazer, Nicole, L1 aChen, Ming-Huei1 aChasman, Daniel, I1 aAspelund, Thor1 aEiriksdottir, Gudny1 aHarris, Tamara, B1 aLauner, Lenore1 aNalls, Michael1 aHernandez, Dena1 aArking, Dan, E1 aBoerwinkle, Eric1 aGrove, Megan, L1 aLi, Man1 aKao, W, H Linda1 aChonchol, Michel1 aHaritunians, Talin1 aLi, Guo1 aLumley, Thomas1 aPsaty, Bruce, M1 aShlipak, Michael1 aHwang, Shih-Jen1 aLarson, Martin, G1 aO'Donnell, Christopher, J1 aUpadhyay, Ashish1 aDuijn, Cornelia, M1 aHofman, Albert1 aRivadeneira, Fernando1 aStricker, Bruno1 aUitterlinden, André, G1 aParé, Guillaume1 aParker, Alex, N1 aRidker, Paul, M1 aSiscovick, David, S1 aGudnason, Vilmundur1 aWitteman, Jacqueline, C1 aFox, Caroline, S1 aCoresh, Josef uhttps://chs-nhlbi.org/node/123502601nas 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/131203030nas 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/135003302nas 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/139203370nas a2200553 4500008004100000022001400041245007500055210006900130260000900199300001100208490000600219520184200225653001002067653003902077653000902116653002502125653001302150653001802163653001902181653002002200653002802220653001202248653001102260653003202271653002602303653003702329653002102366653001102387653000902398653001602407653002002423653002302443100002102466700002002487700001902507700002102526700001802547700002002565700001902585700002002604700002102624700002402645700002202669700002002691700002102711700002402732700002402756856003602780 2012 eng d a1932-620300aHemoglobin A1c and arterial and ventricular stiffness in older adults.0 aHemoglobin A1c and arterial and ventricular stiffness in older a c2012 ae479410 v73 aOBJECTIVE: Arterial and ventricular stiffening are characteristics of diabetes and aging which confer significant morbidity and mortality; advanced glycation endproducts (AGE) are implicated in this stiffening pathophysiology. We examined the association between HbA(1c), an AGE, with arterial and ventricular stiffness measures in older individuals without diabetes.
RESEARCH DESIGN & METHODS: Baseline HbA(1c) was measured in 830 participants free of diabetes defined by fasting glucose or medication use in the Cardiovascular Health Study, a population-based cohort study of adults aged ≥ 65 years. We performed cross-sectional analyses using baseline exam data including echocardiography, ankle and brachial blood pressure measurement, and carotid ultrasonography. We examined the adjusted associations between HbA(1c) and multiple arterial and ventricular stiffness measures by linear regression models and compared these results to the association of fasting glucose (FG) with like measures.
RESULTS: HbA(1c) was correlated with fasting and 2-hour postload glucose levels (r = 0.21; p<0.001 for both) and positively associated with greater body-mass index and black race. In adjusted models, HbA(1c) was not associated with any measure of arterial or ventricular stiffness, including pulse pressure (PP), carotid intima-media thickness, ankle-brachial index, end-arterial elastance, or left ventricular mass (LVM). FG levels were positively associated with systolic, diastolic and PP and LVM.
CONCLUSIONS: In this sample of older adults without diabetes, HbA(1c) was not associated with arterial or ventricular stiffness measures, whereas FG levels were. The role of AGE in arterial and ventricular stiffness in older adults may be better assessed using alternate AGE markers.
10aAdult10aAfrican Continental Ancestry Group10aAged10aAnkle Brachial Index10aArteries10aBlood Glucose10aBlood Pressure10aBody Mass Index10aCross-Sectional Studies10aFasting10aFemale10aGenetic Association Studies10aGlycated Hemoglobin A10aGlycation End Products, Advanced10aHeart Ventricles10aHumans10aMale10aMiddle Aged10aUltrasonography10aVascular Stiffness1 aZieman, Susan, J1 aKamineni, Aruna1 aIx, Joachim, H1 aBarzilay, Joshua1 aDjoussé, Luc1 aKizer, Jorge, R1 aBiggs, Mary, L1 ade Boer, Ian, H1 aChonchol, Michel1 aGottdiener, John, S1 aSelvin, Elizabeth1 aNewman, Anne, B1 aKuller, Lewis, H1 aSiscovick, David, S1 aMukamal, Kenneth, J uhttps://chs-nhlbi.org/node/586003458nas 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/139502921nas 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/599903280nas a2200469 4500008004100000022001400041245013300055210006900188260001300257300001200270490000700282520195800289653000902247653002202256653001702278653001102295653003002306653001802336653001102354653002502365653000902390653001602399653002402415653000902439653002102448100002102469700002102490700002102511700001802532700002002550700002002570700002202590700001602612700001902628700001802647700002202665700002402687700002002711700002402731700001902755856003602774 2013 eng d a1945-719700aFibroblast growth factor 23, bone mineral density, and risk of hip fracture among older adults: the cardiovascular health study.0 aFibroblast growth factor 23 bone mineral density and risk of hip c2013 Aug a3323-310 v983 aCONTEXT: Fibroblast growth factor 23 (FGF23) is a phosphaturic hormone that also inhibits calcitriol synthesis.
OBJECTIVE: Our objective was to evaluate the relationships of plasma FGF23 concentrations with bone mineral density (BMD) and hip fracture in community-dwelling older adults.
DESIGN AND SETTING: Linear regression and Cox proportional hazard models were used to examine the associations of plasma FGF23 concentrations with BMD and incident hip fracture, respectively. Analyses were also stratified by chronic kidney disease.
PARTICIPANTS: Participants included 2008 women and 1329 men ≥65 years from the 1996 to 1997 Cardiovascular Health Study visit.
MAIN OUTCOME MEASURES: Dual x-ray absorptiometry measured total hip (TH) and lumbar spine (LS) BMD in 1291 participants. Hip fracture incidence was assessed prospectively through June 30, 2008 by hospitalization records in all participants.
RESULTS: Women had higher plasma FGF23 concentrations than men (75 [56-107] vs 66 [interquartile range = 52-92] relative units/mL; P < .001). After adjustment, higher FGF23 concentrations were associated with greater total hip and lumbar spine BMD in men only (β per doubling of FGF23 = 0.02, with 95% confidence interval [CI] = 0.001-0.04 g/cm(2), and 0.03 with 95% CI = 0.01-0.06 g/cm(2)). During 9.6 ± 5.1-11.0 years of follow-up, 328 hip fractures occurred. Higher FGF23 concentrations were not associated with hip fracture risk in women or men (adjusted hazard ratio = 0.95, with 95% CI = 0.78-1.15, and 1.09 with 95% CI = 0.82-1.46 per doubling of FGF23). Results did not differ by chronic kidney disease status (P > .4 for interactions).
CONCLUSIONS: In this large prospective cohort of community-dwelling older adults, higher FGF23 concentrations were weakly associated with greater lumbar spine and total hip BMD but not with hip fracture risk.
10aAged10aAged, 80 and over10aBone Density10aFemale10aFibroblast Growth Factors10aHip Fractures10aHumans10aLongitudinal Studies10aMale10aMiddle Aged10aProspective Studies10aRisk10aSpinal Fractures1 aJovanovich, Anna1 aBůzková, Petra1 aChonchol, Michel1 aRobbins, John1 aFink, Howard, A1 ade Boer, Ian, H1 aKestenbaum, Bryan1 aKatz, Ronit1 aCarbone, Laura1 aLee, Jennifer1 aLaughlin, Gail, A1 aMukamal, Kenneth, J1 aFried, Linda, F1 aShlipak, Michael, G1 aIx, Joachim, H uhttps://chs-nhlbi.org/node/599602980nas a2200409 4500008004100000022001400041245012500055210006900180260001300249300001000262490000800272520179200280653000902072653001102081653003002092653002102122653001102143653003402154653002502188653000902213653003302222653001702255653002002272100002102292700001902313700002102332700001602353700001602369700002202385700002002407700001702427700002402444700002402468700002102492700002102513856003602534 2013 eng d a1879-148400aFibroblast growth factor 23, left ventricular mass, and left ventricular hypertrophy in community-dwelling older adults.0 aFibroblast growth factor 23 left ventricular mass and left ventr c2013 Nov a114-90 v2313 aOBJECTIVES: In chronic kidney disease (CKD), high FGF23 concentrations are associated with left ventricular hypertrophy (LVH), cardiovascular events, and death. The associations of FGF23 with left ventricular mass (LVM) and LVH in the general population and the influence of CKD remains uncertain.
METHODS: C-terminal plasma FGF23 concentrations were measured, and LVM and LVH evaluated by echocardiogram among 2255 individuals ≥65 years in the Cardiovascular Health Study. Linear regression analysis adjusting for demographics, cardiovascular, and kidney related risk factors examined the associations of FGF23 concentrations with LVM. Analyses were stratified by CKD status and adjusted linear and logistic regression analysis explored the associations of FGF23 with LVM and LVH.
RESULTS: Among the entire cohort, higher FGF23 concentrations were associated with greater LVM in adjusted analyses (β = 6.71 [95% CI 4.35-9.01] g per doubling of FGF23). 32% (n = 624) had CKD (eGFR <60 mL/min/1.73 m(2) and/or urine albumin-to-creatinine ratio >30 mg/g). Associations were stronger among participants with CKD (p interaction = 0.006): LVM β = 9.71 [95% CI 5.86-13.56] g per doubling of FGF23 compared to those without CKD (β = 3.44 [95% CI 0.77, 6.11] g per doubling of FGF23). While there was no significant interaction between FGF23 and CKD for LVH (p interaction = 0.25), the OR (1.46 95% CI [1.20-1.77]) in the CKD group was statistically significant and of larger magnitude than the OR for in the no CKD group (1.12 [95% CI 0.97-1.48]).
CONCLUSION: In a large cohort of older community-dwelling adults, higher FGF23 concentrations were associated with greater LVM and LVH with stronger relationships in participants with CKD.
10aAged10aFemale10aFibroblast Growth Factors10aHeart Ventricles10aHumans10aHypertrophy, Left Ventricular10aLongitudinal Studies10aMale10aRenal Insufficiency, Chronic10aRisk Factors10aUltrasonography1 aJovanovich, Anna1 aIx, Joachim, H1 aGottdiener, John1 aMcFann, Kim1 aKatz, Ronit1 aKestenbaum, Bryan1 ade Boer, Ian, H1 aSarnak, Mark1 aShlipak, Michael, G1 aMukamal, Kenneth, J1 aSiscovick, David1 aChonchol, Michel uhttps://chs-nhlbi.org/node/737904205nas a2200529 4500008004100000022001400041245014500055210006900200260001300269300001100282490000700293520262400300653003102924653001002955653000902965653002202974653001502996653001903011653002803030653002203058653001103080653003103091653001103122653002803133653000903161653001603170653003503186653004203221653001603263100002003279700002203299700002103321700002503342700002503367700001903392700002403411700001903435700002203454700003003476700002403506700002403530700002403554700002203578700001703600700002203617856003603639 2014 eng d a1523-683800aEstimated GFR and circulating 24,25-dihydroxyvitamin D3 concentration: a participant-level analysis of 5 cohort studies and clinical trials.0 aEstimated GFR and circulating 2425dihydroxyvitamin D3 concentrat c2014 Aug a187-970 v643 aBACKGROUND: Decreased glomerular filtration rate (GFR) leads to reduced production of 1,25-dihydroxyvitamin D3 from 25-hydroxyvitamin D3 (25[OH]D3). Effects of low GFR on vitamin D catabolism are less well understood. We tested associations of estimated GFR (eGFR) with the circulating concentration of 24,25-dihydroxyvitamin D3 (24,25[OH]2D3), the most abundant product of 25(OH)D3 catabolism, across populations with a wide range of GFRs.
STUDY DESIGN: Cross-sectional study.
SETTING & PARTICIPANTS: 9,596 participants in 5 cohort studies and clinical trials: the Diabetes Control and Complications Trial (N=1,193), Multi-Ethnic Study of Atherosclerosis (N=6,470), Cardiovascular Health Study (N=932), Seattle Kidney Study (N=289), and Hemodialysis Study (N=712).
PREDICTOR: eGFR.
OUTCOME: Circulating 24,25(OH)2D3 concentration.
MEASUREMENTS: GFR was estimated from serum creatinine using the Chronic Kidney Disease Epidemiology Collaboration equation. Vitamin D metabolites were measured by mass spectrometry.
RESULTS: Circulating 24,25(OH)2D3 concentration was correlated with circulating 25(OH)D3 concentration (Pearson r range, 0.64-0.88). This correlation was weaker with lower eGFRs. Moreover, the increment in 24,25(OH)2D3 concentration associated with higher 25(OH)D3 concentration (slope) was lower with lower eGFRs: 2.06 (95% CI, 2.01-2.10), 1.77 (95% CI, 1.74-1.81), 1.55 (95% CI, 1.48-1.62), 1.17 (95% CI, 1.05-1.29), 0.92 (95% CI, 0.74-1.10), 0.61 (95% CI, 0.22-1.00), and 0.37 (95% CI, 0.35-0.39) ng/mL of 24,25(OH)2D3 per 10 ng/mL of 25(OH)D3 for eGFRs≥90, 60-89, 45-59, 30-44, 15-29, and <15 mL/min/1.73 m2 and end-stage renal disease treated with hemodialysis, respectively. As a result, at a 25(OH)D3 concentration of 20 ng/mL, mean 24,25(OH)2D3 concentrations were 2.92 (95% CI, 2.87-2.96), 2.68 (95% CI, 2.64-2.72), 2.35 (95% CI, 2.26-2.45), 1.92 (95% CI, 1.74-2.10), 1.69 (95% CI, 1.43-1.95), 1.14 (95% CI, 0.62-1.66), and 1.04 (95% CI,1.02-1.07) ng/mL for each category, respectively. This interaction was independent of other relevant clinical characteristics. Race, diabetes, urine albumin excretion, and circulating parathyroid hormone and fibroblast growth factor 23 concentrations more modestly modified the association of 24,25(OH)2D3 with 25(OH)D3.
LIMITATIONS: Lack of direct pharmacokinetic measurements of vitamin D catabolism.
CONCLUSIONS: Lower eGFR is associated strongly with reduced vitamin D catabolism, as measured by circulating 24,25(OH)2D3 concentration.
10a24,25-Dihydroxyvitamin D 310aAdult10aAged10aAged, 80 and over10aBiomarkers10aCohort Studies10aCross-Sectional Studies10aDiabetes Mellitus10aFemale10aGlomerular Filtration Rate10aHumans10aKidney Failure, Chronic10aMale10aMiddle Aged10aObservational Studies as Topic10aRandomized Controlled Trials as Topic10aYoung Adult1 ade Boer, Ian, H1 aSachs, Michael, C1 aChonchol, Michel1 aHimmelfarb, Jonathan1 aHoofnagle, Andrew, N1 aIx, Joachim, H1 aKremsdorf, Robin, A1 aLin, Yvonne, S1 aMehrotra, Rajnish1 aRobinson-Cohen, Cassianne1 aSiscovick, David, S1 aSteffes, Michael, W1 aThummel, Kenneth, E1 aTracy, Russell, P1 aWang, Zhican1 aKestenbaum, Bryan uhttps://chs-nhlbi.org/node/634003407nas a2200553 4500008004100000022001400041245015800055210006900213260001600282300001200298490000800310520176800318653000902086653002202095653002402117653001602141653001802157653001102175653003102186653002202217653003102239653001802270653001102288653003402299653000902333653001602342653001502358653003202373653003302405653001702438653001802455653003402473653002702507653001402534100002002548700002202568700001602590700002302606700002302629700002502652700001902677700002102696700001502717700001902732700002402751700002202775700002002797856003602817 2014 eng d a1524-453900aFibroblast growth factor-23 and incident atrial fibrillation: the Multi-Ethnic Study of Atherosclerosis (MESA) and the Cardiovascular Health Study (CHS).0 aFibroblast growth factor23 and incident atrial fibrillation the c2014 Jul 22 a298-3070 v1303 aBACKGROUND: Fibroblast growth factor-23 (FGF-23) is a hormone that promotes urinary phosphate excretion and regulates vitamin D metabolism. Circulating FGF-23 concentrations increase markedly in chronic kidney disease and are associated with increased risk of clinical cardiovascular events. FGF-23 may promote atrial fibrillation (AF) by inducing left ventricular hypertrophy and diastolic and left atrial dysfunction.
METHODS AND RESULTS: We tested the associations of circulating FGF-23 concentration with incident AF among 6398 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) and 1350 participants in the Cardiovascular Health Study (CHS), all free of clinical cardiovascular disease at baseline. Over a median of 7.7 and 8.0 years of follow-up, we observed 291 and 229 incident AF events in MESA and CHS, respectively. In multivariable Cox proportional hazards models, each 2-fold-higher FGF-23 concentration was associated with a 41% higher risk of incident AF in MESA (hazard ratio, 1.41; 95% confidence interval, 1.13-1.76; P=0.003) and a 30% higher risk of incident AF in CHS (hazard ratio, 1.30; 95% confidence interval, 1.05-1.61; P=0.016) after adjustment for potential confounding characteristics, including kidney disease. Serum phosphate concentration was significantly associated with incident AF in MESA (hazard ratio, 1.15 per 0.5 mg/dL; 95% confidence interval, 1.02-1.31; P=0.023) but not CHS. In MESA, an association of low estimated glomerular filtration rate with incident AF was partially attenuated by adjustment for FGF-23.
CONCLUSION: Higher circulating FGF-23 concentration is associated with incident AF and may, in part, explain the link between chronic kidney disease and AF.
10aAged10aAged, 80 and over10aAtrial Fibrillation10aComorbidity10aEthnic Groups10aFemale10aFibroblast Growth Factor 310aFollow-Up Studies10aGlomerular Filtration Rate10aHeart Failure10aHumans10aHypertrophy, Left Ventricular10aMale10aMiddle Aged10aPhosphates10aProportional Hazards Models10aRenal Insufficiency, Chronic10aRisk Factors10aUnited States10aVentricular Dysfunction, Left10aVentricular Remodeling10aVitamin D1 aMathew, Jehu, S1 aSachs, Michael, C1 aKatz, Ronit1 aPatton, Kristen, K1 aHeckbert, Susan, R1 aHoofnagle, Andrew, N1 aAlonso, Alvaro1 aChonchol, Michel1 aDeo, Rajat1 aIx, Joachim, H1 aSiscovick, David, S1 aKestenbaum, Bryan1 ade Boer, Ian, H uhttps://chs-nhlbi.org/node/639903793nas 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/666202646nas 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/662402728nas a2200241 4500008004100000022001400041245010300055210006900158260001600227520198200243100002202225700002002247700001902267700002102286700002202307700001802329700001702347700001802364700002402382700002402406700002002430856003602450 2016 ENG d a1468-201X00aAssociation of inflammatory, lipid and mineral markers with cardiac calcification in older adults.0 aAssociation of inflammatory lipid and mineral markers with cardi c2016 Jul 133 aOBJECTIVE: Calcification of the aortic valve and adjacent structures involves inflammatory, lipid and mineral metabolism pathways. We hypothesised that circulating biomarkers reflecting these pathways are associated with cardiac calcification in older adults.
METHODS: We investigated the associations of various biomarkers with valvular and annular calcification in the Cardiovascular Health Study. Of the 5888 participants, up to 3585 were eligible after exclusions for missing biomarker, covariate or echocardiographic data. We evaluated analytes reflecting lipid (lipoprotein (Lp) (a), Lp-associated phospholipase A2 (LpPLA2) mass and activity), inflammatory (interleukin-6, soluble (s) CD14) and mineral metabolism (fetuin-A, fibroblast growth factor (FGF)-23) pathways that were measured within 5 years of echocardiography. The relationships of plasma biomarkers with aortic valve calcification (AVC), aortic annular calcification (AAC) and mitral annular calcification (MAC) were assessed with relative risk (RR) regression.
RESULTS: Calcification was prevalent: AVC 59%, AAC 45% and MAC 41%. After adjustment, Lp(a), LpPLA2 mass and activity and sCD14 were positively associated with AVC. RRs for AVC per SD (95% CI) were as follows: Lp(a), 1.051 (1.022 to 1.081); LpPLA2 mass, 1.036 (1.006 to 1.066) and LpPLA2 activity, 1.037 (1.004 to 1.071); sCD14, 1.039 (1.005 to 1.073). FGF-23 was positively associated with MAC, 1.040 (1.004 to 1.078) and fetuin-A was negatively associated, 0.949 (0.911 to 0.989). No biomarkers were significantly associated with AAC.
CONCLUSION: This study shows novel associations of circulating FGF-23 and fetuin-A with MAC, and LpPLA2 and sCD14 with AVC, confirming that previously reported for Lp(a). Further investigation of Lp and inflammatory pathways may provide added insight into the aetiology of AVC, while study of phosphate regulation may illuminate the pathogenesis of MAC.
1 aBortnick, Anna, E1 aBartz, Traci, M1 aIx, Joachim, H1 aChonchol, Michel1 aReiner, Alexander1 aCushman, Mary1 aOwens, David1 aBarasch, Eddy1 aSiscovick, David, S1 aGottdiener, John, S1 aKizer, Jorge, R uhttps://chs-nhlbi.org/node/712003388nas 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/699002938nas 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/736902608nas a2200241 4500008004100000022001400041245009900055210006900154260001300223300001400236490000700250520187800257100002202135700002002157700002202177700002002199700002202219700002402241700002502265700001902290700002102309856003602330 2017 eng d a1533-345000aFibroblast Growth Factor 23 and the Risk of Infection-Related Hospitalization in Older Adults.0 aFibroblast Growth Factor 23 and the Risk of InfectionRelated Hos c2017 Apr a1239-12460 v283 aWithin monocytes, 1,25-dihydroxyvitamin D [1,25(OH)2D] is important for production of cathelicidins, which in turn, are critical for antibacterial action. Fibroblast growth factor 23 (FGF23) decreases 1,25(OH)2D production and thus, could increase infection risk. We examined this possibility in 3141 community-dwelling adults ages ≥65 years old at baseline in the Cardiovascular Health Study using Cox proportional hazards models to examine the association between FGF23 concentrations and first infection-related hospitalizations and determine whether associations differed by the presence of CKD (eGFR<60 ml/min per 1.73 m(2) [n=832] or urine albumin-to-creatinine ratio >30 mg/g [n=577]). Mean±SD age of participants was 78±5 years old, 60% of participants were women, and the median plasma FGF23 concentration was 70 (interquartile range, 53-99) relative units per milliliter. In fully adjusted models, higher FGF23 concentrations associated with higher risk of first infection-related hospitalization (hazard ratio [HR], 1.11; 95% confidence interval [95% CI], 1.03 to 1.20 per doubling of FGF23) during a median follow-up of 8.6 years. In participants with or without CKD (defined by eGFR), FGF23 concentration associated with first infection-related hospitalization with HRs of 1.24 (95% CI, 1.08 to 1.42) and 1.06 (95% CI, 0.97 to 1.17) per doubling of FGF23, respectively (P=0.13 for interaction). Associations did not differ between groups when stratified by urine albumin-to-creatinine ratio. In sensitivity analyses, the addition of serum calcium, phosphorus, 25-hydroxyvitamin D, intact parathyroid hormone, and 24,25-dihydroxyvitamin D did not meaningfully change the estimates. In conclusion, in community-dwelling older adults, higher plasma FGF23 concentrations independently associated with the risk of first infection-related hospitalization.
1 aNowak, Kristen, L1 aBartz, Traci, M1 aDalrymple, Lorien1 ade Boer, Ian, H1 aKestenbaum, Bryan1 aShlipak, Michael, G1 aGarimella, Pranav, S1 aIx, Joachim, H1 aChonchol, Michel uhttps://chs-nhlbi.org/node/735402478nas a2200241 4500008004100000022001400041245012400055210007000179260001600249300000700265490000700272520174300279100001702022700002102039700002002060700001802080700002102098700002402119700002102143700001902164700001702183856003602200 2017 eng d a1471-236900aHigher plasma transforming growth factor (TGF)-β is associated with kidney disease in older community dwelling adults.0 aHigher plasma transforming growth factor TGFβ is associated with c2017 Mar 21 a980 v183 aBACKGROUND: TGF-β is induced in the vasculature with aging suggesting that high plasma TGF-β levels may be a risk factor for chronic kidney disease (CKD) in older adults.
METHODS: We conducted a cross-sectional analysis of the association between plasma TGF-β levels and CKD including data for 1722 older adults who had participated in the 1996/97 visit of the Cardiovascular Health Study (CHS). Prevalent CKD was defined as eGFR < 60 mL/min/1.73 m(2) or urinary albumin/creatinine ratio (ACR) ≥30 mg/g. We also evaluated whether baseline TGF-β levels predicted change in eGFR, cardiovascular (CV) events, or mortality in longitudinal analysis.
RESULTS: Plasma TGF-β levels were significantly and independently associated with lower eGFR in cross-sectional analysis. Doubling of TGF-β was significantly associated with lower eGFR (β estimate after adjusting for CV risk factors = -1.18, 95% CI -2.03, -0.32). We observed no association with albuminuria. There was no association between baseline TGF-β and change in eGFR, but each doubling of TGF-β at baseline was associated with increased risk of a composite outcome of CV events and mortality, adjusted HR 1.10 (95% C.I. 1.02- 1.20, p = 0.006).
CONCLUSION: In this large cohort of community-dwelling older individuals, high plasma TGF-β levels are modestly, but independently associated with lower eGFR but not with albuminuria in cross-sectional analysis. In addition, TGF-β levels are associated with increased risk of CV events and mortality. Further research is needed to determine the direction of association between plasma TGF-β and the risk of CKD and CKD-associated morbidities in older adults.
1 aMehta, Tapan1 aBůzková, Petra1 aKizer, Jorge, R1 aDjoussé, Luc1 aChonchol, Michel1 aMukamal, Kenneth, J1 aShlipak, Michael1 aIx, Joachim, H1 aJalal, Diana uhttps://chs-nhlbi.org/node/735103140nas a2200289 4500008004100000022001400041245015000055210006900205260001300274300000700287490000700294520224800301100002102549700001302570700002002583700002202603700001902625700002102644700002002665700001802685700002202703700002402725700002102749700002402770700002002794856003602814 2017 eng d a1862-351400aRelationship of bone mineral density with valvular and annular calcification in community-dwelling older people: The Cardiovascular Health Study.0 aRelationship of bone mineral density with valvular and annular c c2017 Dec a520 v123 aAssociations between bone mineral density and aortic valvular, aortic annular, and mitral annular calcification were investigated in a cross-sectional analysis of a population-based cohort of 1497 older adults. Although there was no association between continuous bone mineral density and outcomes, a significant association between osteoporosis and aortic valvular calcification in men was found.
INTRODUCTION: The process of cardiac calcification bears a resemblance to skeletal bone metabolism and its regulation. Experimental studies suggest that bone mineral density (BMD) and valvular calcification may be reciprocally related, but epidemiologic data are sparse.
METHODS: We tested the hypothesis that BMD of the total hip and femoral neck measured by dual-energy X-ray absorptiometry (DXA) is inversely associated with prevalence of three echocardiographic measures of cardiac calcification in a cross-sectional analysis of 1497 older adults from the Cardiovascular Health Study. The adjusted association of BMD with aortic valve calcification (AVC), aortic annular calcification (AAC), and mitral annular calcification (MAC) was assessed with relative risk (RR) regression.
RESULTS: Mean (SD) age was 76.2 (4.8) years; 58% were women. Cardiac calcification was highly prevalent in women and men: AVC, 59.5 and 71.0%; AAC 45.1 and 46.7%; MAC 42.8 and 39.5%, respectively. After limited and full adjustment for potential confounders, no statistically significant associations were detected between continuous BMD at either site and the three measures of calcification. Assessment of WHO BMD categories revealed a significant association between osteoporosis at the total hip and AVC in men (adjusted RR compared with normal BMD = 1.24 (1.01-1.53)). In graded sensitivity analyses, there were apparent inverse associations between femoral neck BMD and AVC with stenosis in men, and femoral neck BMD and moderate/severe MAC in women, but these were not significant.
CONCLUSION: These findings support further investigation of the sex-specific relationships between low BMD and cardiac calcification, and whether processes linking the two could be targeted for therapeutic ends.
1 aMassera, Daniele1 aXu, Shuo1 aBartz, Traci, M1 aBortnick, Anna, E1 aIx, Joachim, H1 aChonchol, Michel1 aOwens, David, S1 aBarasch, Eddy1 aGardin, Julius, M1 aGottdiener, John, S1 aRobbins, John, R1 aSiscovick, David, S1 aKizer, Jorge, R uhttps://chs-nhlbi.org/node/748802495nas 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/7561