Cystatin C and the risk of death and cardiovascular events among elderly persons.
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.
Shlipak
Michael G
MG
General Internal Medicine Section, Veterans Affairs Medical Center, University of California, San Francisco, USA. shlip@itsa.ucsf.edu
Sarnak
Mark J
MJ
Katz
Ronit
R
Fried
Linda F
LF
Seliger
Stephen L
SL
Newman
Anne B
AB
Siscovick
David S
DS
Stehman-Breen
Catherine
C
D000368:Aged; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000453:epidemiology* / Q000209:etiology; D002556:Cerebrospinal Fluid Proteins / Q000097:blood; D003404:Creatinine / Q000097:blood*; D055316:Cystatin C; D015891:Cystatins / Q000097:blood*; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006801:Humans; D007668:Kidney / Q000502:physiology; D007674:Kidney Diseases / Q000097:blood* / Q000150:complications / Q000175:diagnosis; D008297:Male; D009026:Mortality; D015999:Multivariate Analysis; D011379:Prognosis; D012306:Risk
D015415:Biomarkers; C525030:CST3 protein, human; D002556:Cerebrospinal Fluid Proteins; D055316:Cystatin C; D015891:Cystatins; D003404:Creatinine