@article {840, title = {Cystatin C and the risk of death and cardiovascular events among elderly persons.}, journal = {N Engl J Med}, volume = {352}, year = {2005}, month = {2005 May 19}, pages = {2049-60}, abstract = {

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.

}, keywords = {Aged, Biomarkers, Cardiovascular Diseases, Cerebrospinal Fluid Proteins, Creatinine, Cystatin C, Cystatins, Female, Follow-Up Studies, Glomerular Filtration Rate, Humans, Kidney, Kidney Diseases, Male, Mortality, Multivariate Analysis, Prognosis, Risk}, issn = {1533-4406}, doi = {10.1056/NEJMoa043161}, author = {Shlipak, Michael G and Sarnak, Mark J and Katz, Ronit and Fried, Linda F and Seliger, Stephen L and Newman, Anne B and Siscovick, David S and Stehman-Breen, Catherine} } @article {827, title = {Cystatin C concentration as a risk factor for heart failure in older adults.}, journal = {Ann Intern Med}, volume = {142}, year = {2005}, month = {2005 Apr 05}, pages = {497-505}, abstract = {

BACKGROUND: 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.

}, keywords = {Aged, Biomarkers, Creatinine, Cystatin C, Cystatins, Female, Follow-Up Studies, Glomerular Filtration Rate, Heart Failure, Humans, Incidence, Kidney, Kidney Function Tests, Male, Risk Factors, United States}, issn = {1539-3704}, doi = {10.7326/0003-4819-142-7-200504050-00008}, author = {Sarnak, Mark J and Katz, Ronit and Stehman-Breen, Catherine O and Fried, Linda F and Jenny, Nancy Swords and Psaty, Bruce M and Newman, Anne B and Siscovick, David and Shlipak, Michael G} } @article {876, title = {Cystatin-C and inflammatory markers in the ambulatory elderly.}, journal = {Am J Med}, volume = {118}, year = {2005}, month = {2005 Dec}, pages = {1416}, abstract = {

PURPOSE: 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.

}, keywords = {Age Factors, Aged, Biomarkers, C-Reactive Protein, Cross-Sectional Studies, Cystatin C, Cystatins, Female, Fibrinogen, Glomerular Filtration Rate, Humans, Kidney Diseases, Male, Predictive Value of Tests, Sensitivity and Specificity}, issn = {1555-7162}, doi = {10.1016/j.amjmed.2005.07.060}, author = {Shlipak, Michael G and Katz, Ronit and Cushman, Mary and Sarnak, Mark J and Stehman-Breen, Catherine and Psaty, Bruce M and Siscovick, David and Tracy, Russell P and Newman, Anne and Fried, Linda} } @article {816, title = {Cystatin-C and mortality in elderly persons with heart failure.}, journal = {J Am Coll Cardiol}, volume = {45}, year = {2005}, month = {2005 Jan 18}, pages = {268-71}, abstract = {

OBJECTIVES: 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.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Creatinine, Cystatin C, Cystatins, Female, Follow-Up Studies, Glomerular Filtration Rate, Heart Failure, Humans, Male, Pilot Projects, Predictive Value of Tests, Risk Assessment, Survival Analysis}, issn = {0735-1097}, doi = {10.1016/j.jacc.2004.09.061}, author = {Shlipak, Michael G and Katz, Ronit and Fried, Linda F and Jenny, Nancy Swords and Stehman-Breen, Catherine O and Newman, Anne B and Siscovick, David and Psaty, Bruce M and Sarnak, Mark J} } @article {865, title = {Kidney function as a predictor of noncardiovascular mortality.}, journal = {J Am Soc Nephrol}, volume = {16}, year = {2005}, month = {2005 Dec}, pages = {3728-35}, abstract = {

Chronic 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.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Cardiovascular Diseases, Cause of Death, Cohort Studies, Confidence Intervals, Creatinine, Cystatin C, Cystatins, Female, Glomerular Filtration Rate, Humans, Kidney Failure, Chronic, Kidney Function Tests, Longitudinal Studies, Male, Probability, Proportional Hazards Models, Risk Assessment, Severity of Illness Index, Survival Analysis, United States}, issn = {1046-6673}, doi = {10.1681/ASN.2005040384}, author = {Fried, Linda F and Katz, Ronit and Sarnak, Mark J and Shlipak, Michael G and Chaves, Paulo H M and Jenny, Nancy Swords and Stehman-Breen, Catherine and Gillen, Dan and Bleyer, Anthony J and Hirsch, Calvin and Siscovick, David and Newman, Anne B} } @article {912, title = {Cystatin C and prognosis for cardiovascular and kidney outcomes in elderly persons without chronic kidney disease.}, journal = {Ann Intern Med}, volume = {145}, year = {2006}, month = {2006 Aug 15}, pages = {237-46}, abstract = {

BACKGROUND: 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.

}, keywords = {Aged, Biomarkers, Cardiovascular Diseases, Creatinine, Cystatin C, Cystatins, Glomerular Filtration Rate, Humans, Kidney, Longitudinal Studies, Prognosis, Proportional Hazards Models, Renal Insufficiency, Chronic, Risk Factors}, issn = {1539-3704}, doi = {10.7326/0003-4819-145-4-200608150-00003}, author = {Shlipak, Michael G and Katz, Ronit and Sarnak, Mark J and Fried, Linda F and Newman, Anne B and Stehman-Breen, Catherine and Seliger, Stephen L and Kestenbaum, Brian and Psaty, Bruce and Tracy, Russell P and Siscovick, David S} } @article {975, title = {Kidney function, electrocardiographic findings, and cardiovascular events among older adults.}, journal = {Clin J Am Soc Nephrol}, volume = {2}, year = {2007}, month = {2007 May}, pages = {501-8}, abstract = {

Chronic 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.

}, keywords = {Aged, Aged, 80 and over, Cardiac Output, Low, Cardiovascular Diseases, Chronic Disease, Coronary Disease, Electrocardiography, Female, Humans, Kidney, Kidney Diseases, Male, Risk Assessment}, issn = {1555-905X}, doi = {10.2215/CJN.04231206}, author = {Kestenbaum, Bryan and Rudser, Kyle D and Shlipak, Michael G and Fried, Linda F and Newman, Anne B and Katz, Ronit and Sarnak, Mark J and Seliger, Stephen and Stehman-Breen, Catherine and Prineas, Ronald and Siscovick, David S} } @article {972, title = {Relationship of uric acid with progression of kidney disease.}, journal = {Am J Kidney Dis}, volume = {50}, year = {2007}, month = {2007 Aug}, pages = {239-47}, abstract = {

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 (6.90 mg/dL [>410 micromol/L]), respectively. In comparison, there was only a modest, but significant, association between quintiles of uric acid levels and progression of kidney function decrease, with adjusted odds ratios of 1.0, 0.88 (95\% confidence interval [CI], 0.64 to 1.21), 1.23 (95\% CI, 0.87 to 1.75), 1.47 (95\% CI, 1.04 to 2.07), and 1.49 (95\% CI, 1.00 to 2.22) for quintiles 1 through 5, respectively. No significant association was found between uric acid level and incident CKD (adjusted odds ratio, 1.00; 95\% CI, 0.89 to 1.14).

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.

}, keywords = {Aged, Aged, 80 and over, Cohort Studies, Cross-Sectional Studies, Disease Progression, Female, Glomerular Filtration Rate, Humans, Kidney Diseases, Male, Prospective Studies, Uric Acid}, issn = {1523-6838}, doi = {10.1053/j.ajkd.2007.05.013}, author = {Chonchol, Michel and Shlipak, Michael G and Katz, Ronit and Sarnak, Mark J and Newman, Anne B and Siscovick, David S and Kestenbaum, Bryan and Carney, Jan Kirk and Fried, Linda F} } @article {1013, title = {Cystatin C and aging success.}, journal = {Arch Intern Med}, volume = {168}, year = {2008}, month = {2008 Jan 28}, pages = {147-53}, abstract = {

BACKGROUND: 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.

}, keywords = {Aged, Aging, Biomarkers, Creatinine, Cystatin C, Cystatins, Female, Follow-Up Studies, Glomerular Filtration Rate, Humans, Kidney, Male}, issn = {0003-9926}, doi = {10.1001/archinternmed.2007.40}, author = {Sarnak, Mark J and Katz, Ronit and Fried, Linda F and Siscovick, David and Kestenbaum, Brian and Seliger, Stephen and Rifkin, Dena and Tracy, Russell and Newman, Anne B and Shlipak, Michael G} } @article {1012, title = {Cystatin C concentration as a predictor of systolic and diastolic heart failure.}, journal = {J Card Fail}, volume = {14}, year = {2008}, month = {2008 Feb}, pages = {19-26}, abstract = {

BACKGROUND: 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.

}, keywords = {Aged, Aged, 80 and over, Biomarkers, Cohort Studies, Confidence Intervals, Cystatin C, Cystatins, Echocardiography, Female, Heart Failure, Diastolic, Heart Failure, Systolic, Humans, Longitudinal Studies, Male, Predictive Value of Tests, Probability, Proportional Hazards Models, Risk Assessment, Sensitivity and Specificity, Stroke Volume, Survival Analysis}, issn = {1532-8414}, doi = {10.1016/j.cardfail.2007.09.002}, author = {Moran, Andrew and Katz, Ronit and Smith, Nicolas L and Fried, Linda F and Sarnak, Mark J and Seliger, Stephen L and Psaty, Bruce and Siscovick, David S and Gottdiener, John S and Shlipak, Michael G} } @article {1062, title = {Rapid kidney function decline and mortality risk in older adults.}, journal = {Arch Intern Med}, volume = {168}, year = {2008}, month = {2008 Nov 10}, pages = {2212-8}, abstract = {

BACKGROUND: 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.

}, keywords = {Aged, Cardiovascular Diseases, Creatinine, Cystatins, Female, Glomerular Filtration Rate, Humans, Kidney, Male, Mortality}, issn = {1538-3679}, doi = {10.1001/archinte.168.20.2212}, author = {Rifkin, Dena E and Shlipak, Michael G and Katz, Ronit and Fried, Linda F and Siscovick, David and Chonchol, Michel and Newman, Anne B and Sarnak, Mark J} } @article {1130, title = {Association of chronic kidney disease with the spectrum of ankle brachial index the CHS (Cardiovascular Health Study).}, journal = {J Am Coll Cardiol}, volume = {54}, year = {2009}, month = {2009 Sep 22}, pages = {1176-84}, abstract = {

OBJECTIVES: 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.

}, keywords = {Aged, Aged, 80 and over, Ankle Brachial Index, C-Reactive Protein, Cardiovascular Diseases, Chronic Disease, Cohort Studies, Cross-Sectional Studies, Female, Glomerular Filtration Rate, Humans, Kidney Diseases, Lipids, Male, Risk Factors}, issn = {1558-3597}, doi = {10.1016/j.jacc.2009.06.017}, author = {Ix, Joachim H and Katz, Ronit and de Boer, Ian H and Kestenbaum, Brian R and Allison, Matthew A and Siscovick, David S and Newman, Anne B and Sarnak, Mark J and Shlipak, Michael G and Criqui, Michael H} } @article {1057, title = {Clinical and subclinical cardiovascular disease and kidney function decline in the elderly.}, journal = {Atherosclerosis}, volume = {204}, year = {2009}, month = {2009 May}, pages = {298-303}, abstract = {

OBJECTIVE: 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.

}, keywords = {Age Factors, Aged, Atherosclerosis, Cardiovascular Diseases, Creatinine, Cystatin C, Female, Glomerular Filtration Rate, Heart Failure, Humans, Kidney, Kidney Diseases, Linear Models, Longitudinal Studies, Male, Odds Ratio, Risk Assessment, Risk Factors, Time Factors, United States}, issn = {1879-1484}, doi = {10.1016/j.atherosclerosis.2008.08.016}, author = {Shlipak, Michael G and Katz, Ronit and Kestenbaum, Bryan and Fried, Linda F and Siscovick, David and Sarnak, Mark J} } @article {1110, title = {Cystatin C, albuminuria, and mortality among older adults with diabetes.}, journal = {Diabetes Care}, volume = {32}, year = {2009}, month = {2009 Oct}, pages = {1833-8}, abstract = {

OBJECTIVE: 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.

}, keywords = {Aged, Aged, 80 and over, Albuminuria, Creatinine, Cystatin C, Diabetes Mellitus, Female, Glomerular Filtration Rate, Humans, Kidney Function Tests, Male, Risk Factors}, issn = {1935-5548}, doi = {10.2337/dc09-0191}, author = {de Boer, Ian H and Katz, Ronit and Cao, Jie J and Fried, Linda F and Kestenbaum, Bryan and Mukamal, Ken and Rifkin, Dena E and Sarnak, Mark J and Shlipak, Michael G and Siscovick, David S} } @article {1131, title = {Obesity and change in estimated GFR among older adults.}, journal = {Am J Kidney Dis}, volume = {54}, year = {2009}, month = {2009 Dec}, pages = {1043-51}, abstract = {

BACKGROUND: 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.

}, keywords = {Aged, Aging, Body Composition, Body Mass Index, Chronic Disease, Cohort Studies, Creatinine, Cystatin C, Female, Glomerular Filtration Rate, Humans, Kidney, Kidney Diseases, Longitudinal Studies, Male, Obesity, Risk Factors}, issn = {1523-6838}, doi = {10.1053/j.ajkd.2009.07.018}, author = {de Boer, Ian H and Katz, Ronit and Fried, Linda F and Ix, Joachim H and Luchsinger, Jose and Sarnak, Mark J and Shlipak, Michael G and Siscovick, David S and Kestenbaum, Bryan} } @article {1144, title = {Rapid decline of kidney function increases cardiovascular risk in the elderly.}, journal = {J Am Soc Nephrol}, volume = {20}, year = {2009}, month = {2009 Dec}, pages = {2625-30}, abstract = {

Chronic 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.

}, keywords = {Aged, Aged, 80 and over, Cardiovascular Diseases, Creatinine, Cystatin C, Female, Glomerular Filtration Rate, Heart Failure, Humans, Longitudinal Studies, Male, Myocardial Infarction, Peripheral Vascular Diseases, Renal Insufficiency, Chronic, Risk Factors, Stroke, Time Factors, United States}, issn = {1533-3450}, doi = {10.1681/ASN.2009050546}, author = {Shlipak, Michael G and Katz, Ronit and Kestenbaum, Bryan and Siscovick, David and Fried, Linda and Newman, Anne and Rifkin, Dena and Sarnak, Mark J} } @article {1089, title = {Rate of kidney function decline in older adults: a comparison using creatinine and cystatin C.}, journal = {Am J Nephrol}, volume = {30}, year = {2009}, month = {2009}, pages = {171-8}, abstract = {

BACKGROUND/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.

}, keywords = {Age Factors, Aged, Creatinine, Cystatin C, Disease Progression, Female, Glomerular Filtration Rate, Humans, Kidney, Kidney Diseases, Male, Risk Factors}, issn = {1421-9670}, doi = {10.1159/000212381}, author = {Shlipak, Michael G and Katz, Ronit and Kestenbaum, Bryan and Fried, Linda F and Newman, Anne B and Siscovick, David S and Stevens, Lesley and Sarnak, Mark J} } @article {1128, title = {Age and cystatin C in healthy adults: a collaborative study.}, journal = {Nephrol Dial Transplant}, volume = {25}, year = {2010}, month = {2010 Feb}, pages = {463-9}, abstract = {

BACKGROUND: 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.

}, keywords = {Adult, Aged, Aged, 80 and over, Cross-Sectional Studies, Cystatin C, Humans, Kidney, Middle Aged, Reference Values}, issn = {1460-2385}, doi = {10.1093/ndt/gfp474}, author = {Odden, Michelle C and Tager, Ira B and Gansevoort, Ron T and Bakker, Stephan J L and Katz, Ronit and Fried, Linda F and Newman, Anne B and Canada, Robert B and Harris, Tamara and Sarnak, Mark J and Siscovick, David and Shlipak, Michael G} } @article {1149, title = {Albuminuria, impaired kidney function and cardiovascular outcomes or mortality in the elderly.}, journal = {Nephrol Dial Transplant}, volume = {25}, year = {2010}, month = {2010 May}, pages = {1560-7}, abstract = {

BACKGROUND: 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.

}, keywords = {Aged, Albuminuria, Cardiovascular Diseases, Creatinine, Cystatin C, Female, Glomerular Filtration Rate, Heart Failure, Humans, Male, Myocardial Infarction, Risk Factors}, issn = {1460-2385}, doi = {10.1093/ndt/gfp646}, author = {Rifkin, Dena E and Katz, Ronit and Chonchol, Michel and Fried, Linda F and Cao, Jie and de Boer, Ian H and Siscovick, David S and Shlipak, Michael G and Sarnak, Mark J} } @article {1186, title = {Alcohol consumption and kidney function decline in the elderly: alcohol and kidney disease.}, journal = {Nephrol Dial Transplant}, volume = {25}, year = {2010}, month = {2010 Oct}, pages = {3301-7}, abstract = {

BACKGROUND: 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.

}, keywords = {Aged, Aging, Alcohol Drinking, Cohort Studies, Cystatin C, Female, Glomerular Filtration Rate, Humans, Kidney, Kidney Diseases, Male, Prospective Studies}, issn = {1460-2385}, doi = {10.1093/ndt/gfq188}, author = {Menon, Vandana and Katz, Ronit and Mukamal, Kenneth and Kestenbaum, Bryan and de Boer, Ian H and Siscovick, David S and Sarnak, Mark J and Shlipak, Michael G} } @article {1190, title = {Association between baseline kidney function and change in CRP: an analysis of the cardiovascular health study.}, journal = {Nephron Clin Pract}, volume = {115}, year = {2010}, month = {2010}, pages = {c114-21}, abstract = {

BACKGROUND: 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.

}, keywords = {Aged, Biomarkers, C-Reactive Protein, Cardiovascular Diseases, Cohort Studies, Cross-Sectional Studies, Female, Follow-Up Studies, Glomerular Filtration Rate, Humans, Kidney Function Tests, Longitudinal Studies, Male, Residence Characteristics}, issn = {1660-2110}, doi = {10.1159/000312874}, author = {Rifkin, Dena E and Katz, Ronit and Fried, Linda F and Kestenbaum, Bryan and Jenny, Nancy Swords and Newman, Anne B and Siscovick, David S and Shlipak, Michael G and Sarnak, Mark J} } @article {1177, title = {Cystatin C and sudden cardiac death risk in the elderly.}, journal = {Circ Cardiovasc Qual Outcomes}, volume = {3}, year = {2010}, month = {2010 Mar}, pages = {159-64}, abstract = {

BACKGROUND: 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.

}, keywords = {Age Factors, Aged, Biomarkers, Chi-Square Distribution, Creatinine, Cystatin C, Death, Sudden, Cardiac, Female, Glomerular Filtration Rate, Humans, Incidence, Kidney Diseases, Longitudinal Studies, Male, Proportional Hazards Models, Risk Assessment, Risk Factors, Time Factors, United States, Up-Regulation}, issn = {1941-7705}, doi = {10.1161/CIRCOUTCOMES.109.875369}, author = {Deo, Rajat and Sotoodehnia, Nona and Katz, Ronit and Sarnak, Mark J and Fried, Linda F and Chonchol, Michel and Kestenbaum, Bryan and Psaty, Bruce M and Siscovick, David S and Shlipak, Michael G} } @article {1223, title = {Genome-wide association studies of serum magnesium, potassium, and sodium concentrations identify six Loci influencing serum magnesium levels.}, journal = {PLoS Genet}, volume = {6}, year = {2010}, month = {2010 Aug 05}, abstract = {

Magnesium, 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.

}, keywords = {Adult, Aged, European Continental Ancestry Group, Female, Genome-Wide Association Study, Humans, Magnesium, Male, Middle Aged, Polymorphism, Single Nucleotide, Potassium, Sodium}, issn = {1553-7404}, doi = {10.1371/journal.pgen.1001045}, author = {Meyer, Tamra E and Verwoert, Germaine C and Hwang, Shih-Jen and Glazer, Nicole L and Smith, Albert V and van Rooij, Frank J A and Ehret, Georg B and Boerwinkle, Eric and Felix, Janine F and Leak, Tennille S and Harris, Tamara B and Yang, Qiong and Dehghan, Abbas and Aspelund, Thor and Katz, Ronit and Homuth, Georg and Kocher, Thomas and Rettig, Rainer and Ried, Janina S and Gieger, Christian and Prucha, Hanna and Pfeufer, Arne and Meitinger, Thomas and Coresh, Josef and Hofman, Albert and Sarnak, Mark J and Chen, Yii-Der Ida and Uitterlinden, Andr{\'e} G and Chakravarti, Aravinda and Psaty, Bruce M and van Duijn, Cornelia M and Kao, W H Linda and Witteman, Jacqueline C M and Gudnason, Vilmundur and Siscovick, David S and Fox, Caroline S and K{\"o}ttgen, Anna} } @article {1166, title = {Impaired kidney function and atrial fibrillation in elderly subjects.}, journal = {J Card Fail}, volume = {16}, year = {2010}, month = {2010 Jan}, pages = {55-60}, abstract = {

BACKGROUND: 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.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Atrial Fibrillation, Cohort Studies, Cross-Sectional Studies, Female, Follow-Up Studies, Glomerular Filtration Rate, Humans, Kidney Diseases, Kidney Function Tests, Male}, issn = {1532-8414}, doi = {10.1016/j.cardfail.2009.07.002}, author = {Deo, Rajat and Katz, Ronit and Kestenbaum, Bryan and Fried, Linda and Sarnak, Mark J and Psaty, Bruce M and Siscovick, David S and Shlipak, Michael G} } @article {1127, title = {Inflammatory biomarkers and decline in kidney function in the elderly: the Cardiovascular Health Study.}, journal = {Nephrol Dial Transplant}, volume = {25}, year = {2010}, month = {2010 Jan}, pages = {119-24}, abstract = {

BACKGROUND: 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.

}, keywords = {Aged, Biomarkers, C-Reactive Protein, Cohort Studies, Cystatin C, Female, Glomerular Filtration Rate, Humans, Inflammation, Intercellular Adhesion Molecule-1, Interleukin-6, Kidney, Logistic Models, Longitudinal Studies, Male, Prospective Studies, Serum Albumin}, issn = {1460-2385}, doi = {10.1093/ndt/gfp429}, author = {Keller, Christopher and Katz, Ronit and Sarnak, Mark J and Fried, Linda F and Kestenbaum, Bryan and Cushman, Mary and Shlipak, Michael G} } @article {1348, title = {Antihypertensive medication use and change in kidney function in elderly adults: a marginal structural model analysis.}, journal = {Int J Biostat}, volume = {7}, year = {2011}, month = {2011}, pages = {Article 34}, abstract = {

BACKGROUND: 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 {\textpm} 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.

}, keywords = {Aged, Antihypertensive Agents, Cystatin C, Data Interpretation, Statistical, Female, Glomerular Filtration Rate, Humans, Hypertension, Kidney, Longitudinal Studies, Male, Models, Statistical}, issn = {1557-4679}, doi = {10.2202/1557-4679.1320}, author = {Odden, Michelle C and Tager, Ira B and van der Laan, Mark J and Delaney, Joseph A C and Peralta, Carmen A and Katz, Ronit and Sarnak, Mark J and Psaty, Bruce M and Shlipak, Michael G} } @article {1230, title = {Chronic kidney disease and the risk of end-stage renal disease versus death.}, journal = {J Gen Intern Med}, volume = {26}, year = {2011}, month = {2011 Apr}, pages = {379-85}, abstract = {

BACKGROUND: 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.

}, keywords = {Aged, Aged, 80 and over, Cause of Death, Cohort Studies, Female, Follow-Up Studies, Humans, Kidney Failure, Chronic, Longitudinal Studies, Male, Prospective Studies, Renal Insufficiency, Chronic, Risk Factors, Treatment Outcome}, issn = {1525-1497}, doi = {10.1007/s11606-010-1511-x}, author = {Dalrymple, Lorien S and Katz, Ronit and Kestenbaum, Bryan and Shlipak, Michael G and Sarnak, Mark J and Stehman-Breen, Catherine and Seliger, Stephen and Siscovick, David and Newman, Anne B and Fried, Linda} } @article {1286, title = {Chronic kidney disease in octogenarians.}, journal = {Clin J Am Soc Nephrol}, volume = {6}, year = {2011}, month = {2011 Jun}, pages = {1410-7}, abstract = {

BACKGROUND 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.

}, keywords = {Age Factors, Aged, 80 and over, Analysis of Variance, Biomarkers, Cardiovascular Diseases, Chi-Square Distribution, Chronic Disease, Creatinine, Cross-Sectional Studies, Cystatin C, Diabetes Mellitus, Female, Glomerular Filtration Rate, Humans, Kidney, Kidney Diseases, Logistic Models, Male, Models, Biological, Prevalence, Risk Assessment, Risk Factors, United States}, issn = {1555-905X}, doi = {10.2215/CJN.08801010}, author = {Shastri, Shani and Tighiouart, Hocine and Katz, Ronit and Rifkin, Dena E and Fried, Linda F and Shlipak, Michael G and Newman, Anne B and Sarnak, Mark J} } @article {1256, title = {Cystatin C identifies chronic kidney disease patients at higher risk for complications.}, journal = {J Am Soc Nephrol}, volume = {22}, year = {2011}, month = {2011 Jan}, pages = {147-55}, abstract = {

Although 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.

}, keywords = {Aged, Aged, 80 and over, Biomarkers, Cardiovascular Diseases, Chronic Disease, Creatinine, Cystatin C, Disease Progression, Female, Glomerular Filtration Rate, Heart Failure, Humans, Kidney Diseases, Kidney Failure, Chronic, Male, Middle Aged, Predictive Value of Tests, Retrospective Studies, Risk Factors}, issn = {1533-3450}, doi = {10.1681/ASN.2010050483}, author = {Peralta, Carmen A and Katz, Ronit and Sarnak, Mark J and Ix, Joachim and Fried, Linda F and de Boer, Ian and Palmas, Walter and Siscovick, David and Levey, Andrew S and Shlipak, Michael G} } @article {1277, title = {Longitudinal association of depressive symptoms with rapid kidney function decline and adverse clinical renal disease outcomes.}, journal = {Clin J Am Soc Nephrol}, volume = {6}, year = {2011}, month = {2011 Apr}, pages = {834-44}, abstract = {

BACKGROUND 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.

}, keywords = {Acute Kidney Injury, Aged, Chronic Disease, Cohort Studies, Comorbidity, Depression, Female, Follow-Up Studies, Glomerular Filtration Rate, Humans, Kidney Diseases, Longitudinal Studies, Male}, issn = {1555-905X}, doi = {10.2215/CJN.03840510}, author = {Kop, Willem J and Seliger, Stephen L and Fink, Jeffrey C and Katz, Ronit and Odden, Michelle C and Fried, Linda F and Rifkin, Dena E and Sarnak, Mark J and Gottdiener, John S} } @article {1283, title = {Retinal microvascular signs and functional loss in older persons: the cardiovascular health study.}, journal = {Stroke}, volume = {42}, year = {2011}, month = {2011 Jun}, pages = {1589-95}, abstract = {

BACKGROUND 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.

}, keywords = {Aged, Cardiovascular Diseases, Depressive Disorder, Frontal Lobe, Humans, Microcirculation, Neuropsychological Tests, Retinal Diseases, Retinal Vessels, Risk Factors}, issn = {1524-4628}, doi = {10.1161/STROKEAHA.110.605261}, author = {Kim, Dae Hyun and Newman, Anne B and Hajjar, Ihab and Strotmeyer, Elsa S and Klein, Ronald and Newton, Elizabeth and Sarnak, Mark J and Burke, Gregory L and Lipsitz, Lewis A} } @article {1312, title = {Serum 25-hydroxyvitamin D and change in estimated glomerular filtration rate.}, journal = {Clin J Am Soc Nephrol}, volume = {6}, year = {2011}, month = {2011 Sep}, pages = {2141-9}, abstract = {

BACKGROUND 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.

}, keywords = {Aged, Female, Glomerular Filtration Rate, Humans, Kidney Diseases, Male, Prospective Studies, Vitamin D}, issn = {1555-905X}, doi = {10.2215/CJN.02640311}, author = {de Boer, Ian H and Katz, Ronit and Chonchol, Michel and Ix, Joachim H and Sarnak, Mark J and Shlipak, Michael G and Siscovick, David S and Kestenbaum, Bryan} } @article {1329, title = {Vitamin D, parathyroid hormone, and cardiovascular events among older adults.}, journal = {J Am Coll Cardiol}, volume = {58}, year = {2011}, month = {2011 Sep 27}, pages = {1433-41}, abstract = {

OBJECTIVES: 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.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Biomarkers, Cardiovascular Diseases, Cohort Studies, Female, Follow-Up Studies, Humans, Male, Parathyroid Hormone, Prospective Studies, Vitamin D}, issn = {1558-3597}, doi = {10.1016/j.jacc.2011.03.069}, author = {Kestenbaum, Bryan and Katz, Ronit and de Boer, Ian and Hoofnagle, Andy and Sarnak, Mark J and Shlipak, Michael G and Jenny, Nancy S and Siscovick, David S} } @article {1350, title = {Vitamin D, parathyroid hormone, and sudden cardiac death: results from the Cardiovascular Health Study.}, journal = {Hypertension}, volume = {58}, year = {2011}, month = {2011 Dec}, pages = {1021-8}, abstract = {

Recent 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.

}, keywords = {Aged, Cardiovascular Diseases, Comorbidity, Death, Sudden, Cardiac, Diabetes Mellitus, Female, Follow-Up Studies, Humans, Hypertension, Incidence, Kidney, Male, Middle Aged, Minerals, Parathyroid Hormone, Proportional Hazards Models, Risk Factors, Socioeconomic Factors, United States, Vitamin D}, issn = {1524-4563}, doi = {10.1161/HYPERTENSIONAHA.111.179135}, author = {Deo, Rajat and Katz, Ronit and Shlipak, Michael G and Sotoodehnia, Nona and Psaty, Bruce M and Sarnak, Mark J and Fried, Linda F and Chonchol, Michel and de Boer, Ian H and Enquobahrie, Daniel and Siscovick, David and Kestenbaum, Bryan} } @article {5862, title = {Apolipoprotein E and kidney function in older adults.}, journal = {Clin Nephrol}, volume = {78}, year = {2012}, month = {2012 Sep}, pages = {174-80}, abstract = {

BACKGROUND: 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.

}, keywords = {Aged, Aged, 80 and over, Alleles, Apolipoproteins E, Confidence Intervals, Creatinine, Cross-Sectional Studies, Cystatin C, Disease Progression, European Continental Ancestry Group, Female, Gene Frequency, Genotype, Glomerular Filtration Rate, Humans, Kidney, Male, Odds Ratio, Renal Insufficiency, Chronic, Risk Factors}, issn = {0301-0430}, author = {Seshasai, Rebecca Kurnik and Katz, Ronit and de Boer, Ian H and Siscovick, David and Shlipak, Michael G and Rifkin, Dena E and Sarnak, Mark J} } @article {1392, title = {Fibroblast growth factor-23 and death, heart failure, and cardiovascular events in community-living individuals: CHS (Cardiovascular Health Study).}, journal = {J Am Coll Cardiol}, volume = {60}, year = {2012}, month = {2012 Jul 17}, pages = {200-7}, abstract = {

OBJECTIVES: 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.

}, keywords = {Aged, Aged, 80 and over, Biomarkers, Female, Fibroblast Growth Factors, Heart Failure, Humans, Kidney Function Tests, Male, Mortality, Renal Insufficiency, Chronic, United States}, issn = {1558-3597}, doi = {10.1016/j.jacc.2012.03.040}, author = {Ix, Joachim H and Katz, Ronit and Kestenbaum, Bryan R and de Boer, Ian H and Chonchol, Michel and Mukamal, Kenneth J and Rifkin, Dena and Siscovick, David S and Sarnak, Mark J and Shlipak, Michael G} } @article {1395, title = {Kidney function and mortality in octogenarians: Cardiovascular Health Study All Stars.}, journal = {J Am Geriatr Soc}, volume = {60}, year = {2012}, month = {2012 Jul}, pages = {1201-7}, abstract = {

OBJECTIVES: 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) .

}, keywords = {Aged, 80 and over, Analysis of Variance, Cardiovascular Diseases, Chi-Square Distribution, Creatinine, Cystatin C, Diabetes Mellitus, Female, Glomerular Filtration Rate, Humans, Hypertension, Kidney Diseases, Male, Prevalence, Proportional Hazards Models, Retrospective Studies, Risk Factors, United States}, issn = {1532-5415}, doi = {10.1111/j.1532-5415.2012.04046.x}, author = {Shastri, Shani and Katz, Ronit and Rifkin, Dena E and Fried, Linda F and Odden, Michelle C and Peralta, Carmen A and Chonchol, Michel and Siscovick, David and Shlipak, Michael G and Newman, Anne B and Sarnak, Mark J} } @article {1366, title = {Long-term assessment of inflammation and healthy aging in late life: the Cardiovascular Health Study All Stars.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {67}, year = {2012}, month = {2012 Sep}, pages = {970-6}, abstract = {

BACKGROUND: 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.

}, keywords = {Aged, Aged, 80 and over, Aging, C-Reactive Protein, Cardiovascular Diseases, Cognition, Cohort Studies, Cross-Sectional Studies, Female, Humans, Inflammation, Inflammation Mediators, Interleukin-6, Longitudinal Studies, Male, Risk Factors, Vermont}, issn = {1758-535X}, doi = {10.1093/gerona/glr261}, author = {Jenny, Nancy S and French, Benjamin and Arnold, Alice M and Strotmeyer, Elsa S and Cushman, Mary and Chaves, Paulo H M and Ding, Jingzhong and Fried, Linda P and Kritchevsky, Stephen B and Rifkin, Dena E and Sarnak, Mark J and Newman, Anne B} } @article {1351, title = {Retinal microvascular signs and disability in the Cardiovascular Health Study.}, journal = {Arch Ophthalmol}, volume = {130}, year = {2012}, month = {2012 Mar}, pages = {350-6}, abstract = {

OBJECTIVE: 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.

}, keywords = {Activities of Daily Living, Aged, Carotid Artery Diseases, Cognition Disorders, Diagnostic Techniques, Ophthalmological, Disability Evaluation, Follow-Up Studies, Humans, Hypertension, Incidence, Kaplan-Meier Estimate, Microcirculation, Predictive Value of Tests, Prevalence, Prognosis, Prospective Studies, Retinal Diseases, Risk Factors, Smoking}, issn = {1538-3601}, doi = {10.1001/archophthalmol.2011.360}, author = {Kim, Dae Hyun and Chaves, Paulo H M and Newman, Anne B and Klein, Ronald and Sarnak, Mark J and Newton, Elizabeth and Strotmeyer, Elsa S and Burke, Gregory L and Lipsitz, Lewis A} } @article {1322, title = {The risk of infection-related hospitalization with decreased kidney function.}, journal = {Am J Kidney Dis}, volume = {59}, year = {2012}, month = {2012 Mar}, pages = {356-63}, abstract = {

BACKGROUND: 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.

}, keywords = {Aged, Cohort Studies, Female, Glomerular Filtration Rate, Hospitalization, Humans, Infection, Kidney, Male, Risk Factors}, issn = {1523-6838}, doi = {10.1053/j.ajkd.2011.07.012}, author = {Dalrymple, Lorien S and Katz, Ronit and Kestenbaum, Bryan and de Boer, Ian H and Fried, Linda and Sarnak, Mark J and Shlipak, Michael G} } @article {5999, title = {Blood pressure components and decline in kidney function in community-living older adults: the Cardiovascular Health Study.}, journal = {Am J Hypertens}, volume = {26}, year = {2013}, month = {2013 Aug}, pages = {1037-44}, abstract = {

BACKGROUND: 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.

}, keywords = {Aged, Blood Pressure, Cohort Studies, Cystatin C, Diastole, Disease Progression, Female, Glomerular Filtration Rate, Humans, Hypertension, Logistic Models, Longitudinal Studies, Male, Pulse, Renal Insufficiency, Chronic, Systole}, issn = {1941-7225}, doi = {10.1093/ajh/hpt067}, author = {Rifkin, Dena E and Katz, Ronit and Chonchol, Michel and Shlipak, Michael G and Sarnak, Mark J and Fried, Linda F and Newman, Anne B and Siscovick, David S and Peralta, Carmen A} } @article {7377, title = {Cystatin C versus creatinine in determining risk based on kidney function.}, journal = {N Engl J Med}, volume = {369}, year = {2013}, month = {2013 Sep 05}, pages = {932-43}, abstract = {

BACKGROUND: 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.).

}, keywords = {Creatinine, Cystatin C, Glomerular Filtration Rate, Humans, Kidney Failure, Chronic, Kidney Function Tests, Reference Standards, Renal Insufficiency, Chronic, Risk, Risk Assessment}, issn = {1533-4406}, doi = {10.1056/NEJMoa1214234}, author = {Shlipak, Michael G and Matsushita, Kunihiro and Arnl{\"o}v, Johan and Inker, Lesley A and Katz, Ronit and Polkinghorne, Kevan R and Rothenbacher, Dietrich and Sarnak, Mark J and Astor, Brad C and Coresh, Josef and Levey, Andrew S and Gansevoort, Ron T} } @article {5854, title = {Hypertension and low HDL cholesterol were associated with reduced kidney function across the age spectrum: a collaborative study.}, journal = {Ann Epidemiol}, volume = {23}, year = {2013}, month = {2013 Mar}, pages = {106-11}, abstract = {

PURPOSE: 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.

}, keywords = {Adult, Age Factors, Aged, Aged, 80 and over, Aging, Causality, Cholesterol, LDL, Cohort Studies, Comorbidity, Cross-Sectional Studies, Cystatin C, Female, Humans, Hypertension, Kidney Function Tests, Male, Netherlands, Obesity, Prevalence, Renal Insufficiency, Chronic, Risk Factors, Smoking, United States}, issn = {1873-2585}, doi = {10.1016/j.annepidem.2012.12.004}, author = {Odden, Michelle C and Tager, Ira B and Gansevoort, Ron T and Bakker, Stephan J L and Fried, Linda F and Newman, Anne B and Katz, Ronit and Satterfield, Suzanne and Harris, Tamara B and Sarnak, Mark J and Siscovick, David and Shlipak, Michael G} } @article {6136, title = {Kidney function and prevalent and incident frailty.}, journal = {Clin J Am Soc Nephrol}, volume = {8}, year = {2013}, month = {2013 Dec}, pages = {2091-9}, abstract = {

BACKGROUND 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.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Aging, Biomarkers, Creatinine, Cross-Sectional Studies, Cystatin C, Fatigue, Female, Frail Elderly, Geriatric Assessment, Glomerular Filtration Rate, Humans, Incidence, Independent Living, Kidney, Kidney Diseases, Logistic Models, Male, Motor Activity, Multivariate Analysis, Muscle Weakness, Odds Ratio, Phenotype, Prevalence, Prospective Studies, Risk Factors, Time Factors, United States, Weight Loss}, issn = {1555-905X}, doi = {10.2215/CJN.02870313}, author = {Dalrymple, Lorien S and Katz, Ronit and Rifkin, Dena E and Siscovick, David and Newman, Anne B and Fried, Linda F and Sarnak, Mark J and Odden, Michelle C and Shlipak, Michael G} } @article {6239, title = {Fibroblast growth factor 23, the ankle-brachial index, and incident peripheral artery disease in the Cardiovascular Health Study.}, journal = {Atherosclerosis}, volume = {233}, year = {2014}, month = {2014 Mar}, pages = {91-6}, abstract = {

BACKGROUND: 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.

}, keywords = {Aged, Ankle Brachial Index, Cardiovascular Diseases, Cross-Sectional Studies, Fibroblast Growth Factors, Humans, Incidence, Peripheral Arterial Disease, Risk Factors}, issn = {1879-1484}, doi = {10.1016/j.atherosclerosis.2013.12.015}, author = {Garimella, Pranav S and Ix, Joachim H and Katz, Ronit and Chonchol, Michel B and Kestenbaum, Bryan R and de Boer, Ian H and Siscovick, David S and Shastri, Shani and Hiramoto, Jade S and Shlipak, Michael G and Sarnak, Mark J} } @article {6308, title = {Fibroblast growth factor-23 and the long-term risk of hospital-associated AKI among community-dwelling older individuals.}, journal = {Clin J Am Soc Nephrol}, volume = {9}, year = {2014}, month = {2014 Feb}, pages = {239-46}, abstract = {

BACKGROUND 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.

}, keywords = {Acute Kidney Injury, Age Factors, Aged, Aged, 80 and over, Albuminuria, Biomarkers, Creatinine, Cystatin C, Female, Fibroblast Growth Factors, Glomerular Filtration Rate, Hospitalization, Humans, Independent Living, Kidney, Longitudinal Studies, Male, Prognosis, Proportional Hazards Models, Prospective Studies, Risk Factors, Time Factors}, issn = {1555-905X}, doi = {10.2215/CJN.05830513}, author = {Brown, Jeremiah R and Katz, Ronit and Ix, Joachim H and de Boer, Ian H and Siscovick, David S and Grams, Morgan E and Shlipak, Michael and Sarnak, Mark J} } @article {6364, title = {Kidney function and cognitive health in older adults: the Cardiovascular Health Study.}, journal = {Am J Epidemiol}, volume = {180}, year = {2014}, month = {2014 Jul 01}, pages = {68-75}, abstract = {

Recent 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.

}, keywords = {Aged, Cardiovascular Diseases, Cognition, Cognition Disorders, Cystatin C, Female, Glomerular Filtration Rate, Health Status, Humans, Kidney, Kidney Diseases, Male, Neuropsychological Tests}, issn = {1476-6256}, doi = {10.1093/aje/kwu102}, author = {Darsie, Brendan and Shlipak, Michael G and Sarnak, Mark J and Katz, Ronit and Fitzpatrick, Annette L and Odden, Michelle C} } @article {6363, title = {Prognostic implications of microvascular and macrovascular abnormalities in older adults: cardiovascular health study.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {69}, year = {2014}, month = {2014 Dec}, pages = {1495-502}, abstract = {

BACKGROUND: 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.

}, keywords = {Aged, Aged, 80 and over, Aging, Ankle Brachial Index, Disability Evaluation, Electrocardiography, Female, Follow-Up Studies, Forecasting, Humans, Life Expectancy, Magnetic Resonance Imaging, Male, Microcirculation, Prognosis, Prospective Studies, Risk Factors, Vascular Malformations}, issn = {1758-535X}, doi = {10.1093/gerona/glu074}, author = {Kim, Dae Hyun and Grodstein, Francine and Newman, Anne B and Chaves, Paulo H M and Odden, Michelle C and Klein, Ronald and Sarnak, Mark J and Patel, Kushang V and Lipsitz, Lewis A} } @article {6588, title = {Risk factors for cardiovascular disease across the spectrum of older age: the Cardiovascular Health Study.}, journal = {Atherosclerosis}, volume = {237}, year = {2014}, month = {2014 Nov}, pages = {336-42}, abstract = {

OBJECTIVE: 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.

}, keywords = {Aged, Aged, 80 and over, Blood Pressure, C-Reactive Protein, Cardiovascular Diseases, Cholesterol, HDL, Cholesterol, LDL, Diabetes Complications, Diabetes Mellitus, Female, Humans, Inflammation, Kidney, Kidney Diseases, Lipids, Male, Natriuretic Peptide, Brain, Obesity, Peptide Fragments, Risk Factors}, issn = {1879-1484}, doi = {10.1016/j.atherosclerosis.2014.09.012}, author = {Odden, Michelle C and Shlipak, Michael G and Whitson, Heather E and Katz, Ronit and Kearney, Patricia M and deFilippi, Chris and Shastri, Shani and Sarnak, Mark J and Siscovick, David S and Cushman, Mary and Psaty, Bruce M and Newman, Anne B} } @article {6659, title = {Development and validation of a model to predict 5-year risk of death without ESRD among older adults with CKD.}, journal = {Clin J Am Soc Nephrol}, volume = {10}, year = {2015}, month = {2015 Mar 6}, pages = {363-71}, abstract = {

BACKGROUND 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 ({\textpm}5.6) years and an eGFR of 47 ({\textpm}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 ({\textpm}2.8) years and an eGFR of 50 ({\textpm}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.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Albuminuria, Continental Population Groups, Creatinine, Diabetes Mellitus, Female, Glomerular Filtration Rate, Heart Failure, Humans, Male, Proportional Hazards Models, Regression Analysis, Renal Insufficiency, Chronic, Risk Factors, Sex Factors, Smoking, Stroke}, issn = {1555-905X}, doi = {10.2215/CJN.04650514}, author = {Bansal, Nisha and Katz, Ronit and de Boer, Ian H and Peralta, Carmen A and Fried, Linda F and Siscovick, David S and Rifkin, Dena E and Hirsch, Calvin and Cummings, Steven R and Harris, Tamara B and Kritchevsky, Stephen B and Sarnak, Mark J and Shlipak, Michael G and Ix, Joachim H} } @article {6662, title = {Fibroblast growth factor 23 and sudden versus non-sudden cardiac death: the Cardiovascular Health Study.}, journal = {Am J Kidney Dis}, volume = {66}, year = {2015}, month = {2015 Jul}, pages = {40-6}, abstract = {

BACKGROUND: 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.

}, keywords = {Aged, Aged, 80 and over, Biomarkers, Comorbidity, Death, Sudden, Cardiac, Electrocardiography, Female, Fibroblast Growth Factors, Follow-Up Studies, Heart Arrest, Heart Diseases, Humans, Kaplan-Meier Estimate, Male, Prospective Studies, Renal Insufficiency, Chronic, Risk Factors, Sympathetic Nervous System, United States}, issn = {1523-6838}, doi = {10.1053/j.ajkd.2014.10.025}, author = {Deo, Rajat and Katz, Ronit and de Boer, Ian H and Sotoodehnia, Nona and Kestenbaum, Bryan and Mukamal, Kenneth J and Chonchol, Michel and Sarnak, Mark J and Siscovick, David and Shlipak, Michael G and Ix, Joachim H} } @article {6797, title = {A Meta-analysis of the Association of Estimated GFR, Albuminuria, Age, Race, and Sex With Acute Kidney Injury.}, journal = {Am J Kidney Dis}, volume = {66}, year = {2015}, month = {2015 Oct}, pages = {591-601}, abstract = {

BACKGROUND: 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.

}, keywords = {Acute Kidney Injury, Adolescent, Adult, African Americans, Age Distribution, Aged, Albuminuria, Continental Population Groups, European Continental Ancestry Group, Female, Glomerular Filtration Rate, Humans, Incidence, Male, Middle Aged, Predictive Value of Tests, Prognosis, Severity of Illness Index, Sex Distribution, Young Adult}, issn = {1523-6838}, doi = {10.1053/j.ajkd.2015.02.337}, author = {Grams, Morgan E and Sang, Yingying and Ballew, Shoshana H and Gansevoort, Ron T and Kimm, Heejin and Kovesdy, Csaba P and Naimark, David and Oien, Cecilia and Smith, David H and Coresh, Josef and Sarnak, Mark J and Stengel, B{\'e}n{\'e}dicte and Tonelli, Marcello} } @article {6796, title = {A Meta-analysis of the Association of Estimated GFR, Albuminuria, Diabetes Mellitus, and Hypertension With Acute Kidney Injury.}, journal = {Am J Kidney Dis}, volume = {66}, year = {2015}, month = {2015 Oct}, pages = {602-12}, abstract = {

BACKGROUND: 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.

}, keywords = {Acute Kidney Injury, Adult, Aged, Comorbidity, Diabetes Mellitus, Disease Progression, Female, Glomerular Filtration Rate, Humans, Hypertension, Incidence, Kidney Failure, Chronic, Male, Middle Aged, Prognosis, Renal Insufficiency, Chronic}, issn = {1523-6838}, doi = {10.1053/j.ajkd.2015.02.338}, author = {James, Matthew T and Grams, Morgan E and Woodward, Mark and Elley, C Raina and Green, Jamie A and Wheeler, David C and de Jong, Paul and Gansevoort, Ron T and Levey, Andrew S and Warnock, David G and Sarnak, Mark J} } @article {6852, title = {Microvascular and Macrovascular Abnormalities and Cognitive and Physical Function in Older Adults: Cardiovascular Health Study.}, journal = {J Am Geriatr Soc}, volume = {63}, year = {2015}, month = {2015 Sep}, pages = {1886-93}, abstract = {

OBJECTIVES: 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.

}, keywords = {Aged, Aged, 80 and over, Cognition, Cross-Sectional Studies, Female, Humans, Male, Neuropsychological Tests, Vascular Malformations}, issn = {1532-5415}, doi = {10.1111/jgs.13594}, author = {Kim, Dae Hyun and Grodstein, Francine and Newman, Anne B and Chaves, Paulo H M and Odden, Michelle C and Klein, Ronald and Sarnak, Mark J and Lipsitz, Lewis A} } @article {6624, title = {Serum urate levels and the risk of hip fractures: data from the Cardiovascular Health Study.}, journal = {Metabolism}, volume = {64}, year = {2015}, month = {2015 Mar}, pages = {438-46}, abstract = {

PURPOSE: 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.

}, keywords = {Aged, Aged, 80 and over, Body Mass Index, Cohort Studies, Estrogen Replacement Therapy, Female, Health Surveys, Hip Fractures, Humans, Kaplan-Meier Estimate, Male, Prospective Studies, Risk, Sex Factors, United States, Uric Acid}, issn = {1532-8600}, doi = {10.1016/j.metabol.2014.11.006}, author = {Mehta, Tapan and B{\r u}zkov{\'a}, Petra and Sarnak, Mark J and Chonchol, Michel and Cauley, Jane A and Wallace, Erin and Fink, Howard A and Robbins, John and Jalal, Diana} } @article {6770, title = {Urinary uromodulin, kidney function, and cardiovascular disease in elderly adults.}, journal = {Kidney Int}, volume = {88}, year = {2015}, month = {2015 Nov}, pages = {1126-34}, abstract = {

Urinary 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.

}, keywords = {Aged, Aged, 80 and over, Albuminuria, Biomarkers, Cardiovascular Diseases, Case-Control Studies, Creatinine, Disease Progression, Female, Glomerular Filtration Rate, Heart Failure, Humans, Incidence, Kidney Failure, Chronic, Male, Proportional Hazards Models, Uromodulin}, issn = {1523-1755}, doi = {10.1038/ki.2015.192}, author = {Garimella, Pranav S and Biggs, Mary L and Katz, Ronit and Ix, Joachim H and Bennett, Michael R and Devarajan, Prasad and Kestenbaum, Bryan R and Siscovick, David S and Jensen, Majken K and Shlipak, Michael G and Chaves, Paulo H M and Sarnak, Mark J} } @article {6660, title = {Urine Collagen Fragments and CKD Progression-The Cardiovascular Health Study.}, journal = {J Am Soc Nephrol}, volume = {26}, year = {2015}, month = {2015 Oct}, pages = {2494-503}, abstract = {

Tubulointerstitial 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 ({\textpm}SD) was 78{\textpm}5 years, mean eGFR was 63{\textpm}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.

}, keywords = {Aged, Cardiovascular Diseases, Case-Control Studies, Disease Progression, Female, Heart Failure, Humans, Kidney Failure, Chronic, Male, Peptide Fragments, Procollagen, Prospective Studies, Renal Insufficiency, Chronic}, issn = {1533-3450}, doi = {10.1681/ASN.2014070696}, author = {Ix, Joachim H and Biggs, Mary L and Mukamal, Kenneth and Djouss{\'e}, Luc and Siscovick, David and Tracy, Russell and Katz, Ronit and Delaney, Joseph A and Chaves, Paulo and Rifkin, Dena E and Hughes-Austin, Jan M and Garimella, Pranav S and Sarnak, Mark J and Shlipak, Michael G and Kizer, Jorge R} } @article {6990, title = {Fibroblast Growth Factor-23 and Frailty in Elderly Community-Dwelling Individuals: The Cardiovascular Health Study.}, journal = {J Am Geriatr Soc}, volume = {64}, year = {2016}, month = {2016 Feb}, pages = {270-6}, abstract = {

OBJECTIVES: 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 {\textpm} 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 {\textpm} 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.

}, keywords = {Aged, Anthropometry, Biomarkers, Cardiovascular Diseases, Cross-Sectional Studies, Enzyme-Linked Immunosorbent Assay, Female, Fibroblast Growth Factors, Frail Elderly, Glomerular Filtration Rate, Humans, Independent Living, Longitudinal Studies, Male, Phenotype, Risk Factors, Surveys and Questionnaires}, issn = {1532-5415}, doi = {10.1111/jgs.13951}, author = {Beben, Tomasz and Ix, Joachim H and Shlipak, Michael G and Sarnak, Mark J and Fried, Linda F and Hoofnagle, Andrew N and Chonchol, Michel and Kestenbaum, Bryan R and de Boer, Ian H and Rifkin, Dena E} } @article {8095, title = {Galectin-3 and Soluble ST2 and Kidney Function Decline in Older Adults: The Cardiovascular Health Study (CHS).}, journal = {Am J Kidney Dis}, volume = {67}, year = {2016}, month = {2016 06}, pages = {994-6}, keywords = {Aged, Cohort Studies, Creatinine, Cystatin C, Female, Galectin 3, Glomerular Filtration Rate, Humans, Interleukin-1 Receptor-Like 1 Protein, Logistic Models, Longitudinal Studies, Male, Prognosis, Renal Insufficiency, Chronic}, issn = {1523-6838}, doi = {10.1053/j.ajkd.2015.12.022}, author = {Bansal, Nisha and Katz, Ronit and Seliger, Stephen and DeFilippi, Christopher and Sarnak, Mark J and Delaney, Joseph A and Christenson, Robert and de Boer, Ian H and Kestenbaum, Bryan and Robinson-Cohen, Cassianne and Ix, Joachim H and Shlipak, Michael G} }