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(Circulation. 2007;115:173-179.)
© 2007 American Heart Association, Inc.

Coronary Heart Disease

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; 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.).

Correspondence to Joachim H. Ix, MD, Division of Nephrology, Department of Medicine, Box 0532, HSE 672, University of California at San Francisco, San Francisco, CA 94143-0532. E-mail jix{at}medicine.ucsf.edu

Received June 6, 2006; accepted November 1, 2006.

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.

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