Published Online
on December 26, 2006

A more recent version of this article appeared on January 16, 2007

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Submitted on June 6, 2006
Accepted on November 1, 2006

Association of Cystatin C With Mortality, Cardiovascular Events, and Incident Heart Failure Among Persons With Coronary Heart Disease. Data From the Heart and Soul Study

Joachim H. Ix MD^*, Michael G. Shlipak MD, MPH, Glenn M. Chertow MD, MPH, and Mary A. Whooley MD

From the Division of Nephrology (J.H.I., G.M.C.), Department of Medicine (J.H.I., M.G.S., G.M.C., M.A.W.), and Department of Epidemiology and Biostatistics (M.G.S., G.M.C., M.A.W.), University of California at San Francisco; and Section of General Internal Medicine, Veterans Affairs Medical Center, San Francisco, Calif (M.G.S., M.A.W.).

^* To whom correspondence should be addressed. E-mail: jix{at}medicine.ucsf.edu.

Background--Serum creatinine and related estimating equations predict cardiovascular events and mortality among persons with coronary heart disease (CHD). Cystatin C is a novel and sensitive endogenous marker of kidney function. Whether cystatin C concentrations are associated with adverse events among ambulatory persons with CHD is unknown.

Methods and Results--Nine hundred ninety ambulatory persons with CHD were categorized into quartiles of serum cystatin C at inception, with 0.91 mg/L constituting the lowest quartile (I) and 1.30 mg/L constituting the highest (IV). Cox proportional hazards models evaluated time to all-cause mortality, cardiovascular events (composite of CHD death, myocardial infarction, and stroke), and incident heart failure. After a median follow-up of 37 months, 132 participants (13%) died, 101 (10%) had cardiovascular events, and 57 (7%) had incident heart failure. Compared with participants in the lowest cystatin C quartile, those in the highest quartile were at increased risk of all-cause mortality (hazard ratio, 3.6; 95% CI, 1.8 to 7.0), cardiovascular events (hazard ratio, 2.0; 95% CI, 1.0 to 3.8), and incident heart failure (hazard ratio, 2.6; 95% CI, 1.0 to 6.9) in analyses adjusted for traditional cardiovascular risk factors. Cystatin C in the highest quartile predicted similar risk for these outcomes among participants with lower (60 mL/min per 1.73 m²) or higher estimated glomerular filtration rate and among participants with or without microalbuminuria.

Conclusions--High cystatin C concentrations predict substantial increased risks of all-cause mortality, cardiovascular events, and incident heart failure among ambulatory persons with CHD. This risk is not completely captured by measures of kidney function routinely used in clinical practice.

Key words: coronary disease • cystatin C • heart failure • kidney • mortality • myocardial infarction • stroke

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