Cystatin C concentration as a risk factor for heart failure in older adults

Ann Intern Med. 2005 Apr 5;142(7):497-505. doi: 10.7326/0003-4819-142-7-200504050-00008.


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

Publication types

  • Comparative Study
  • 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
  • Creatinine / blood
  • Cystatin C
  • Cystatins / blood*
  • Female
  • Follow-Up Studies
  • Glomerular Filtration Rate
  • Heart Failure / blood*
  • Heart Failure / epidemiology*
  • Heart Failure / physiopathology
  • Humans
  • Incidence
  • Kidney / physiopathology
  • Kidney Function Tests / methods*
  • Male
  • Risk Factors
  • United States / epidemiology


  • Biomarkers
  • CST3 protein, human
  • Cystatin C
  • Cystatins
  • Creatinine