@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 {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 {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} }