Cystatin C and the risk of death and cardiovascular events among elderly persons

N Engl J Med. 2005 May 19;352(20):2049-60. doi: 10.1056/NEJMoa043161.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Biomarkers / blood
  • Cardiovascular Diseases / epidemiology*
  • Cardiovascular Diseases / etiology
  • Cerebrospinal Fluid Proteins / blood
  • Creatinine / blood*
  • Cystatin C
  • Cystatins / blood*
  • Female
  • Follow-Up Studies
  • Glomerular Filtration Rate
  • Humans
  • Kidney / physiology
  • Kidney Diseases / blood*
  • Kidney Diseases / complications
  • Kidney Diseases / diagnosis
  • Male
  • Mortality*
  • Multivariate Analysis
  • Prognosis
  • Risk


  • Biomarkers
  • CST3 protein, human
  • Cerebrospinal Fluid Proteins
  • Cystatin C
  • Cystatins
  • Creatinine