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

Abstract

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 < or = 0.91 mg/L constituting the lowest quartile (I) and > or = 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 (< or = 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.

Figure 1

Probability value for trend <0.001 for each outcome.

Figure 2

Distribution of estimated GFR (A) and albumin-to-creatinine ratio (B) among the 241 study participants with cystatin C concentrations within the highest quartile of the study sample (≥1.3 mg/L). Light bars represent participants with estimated GFR >60 mL/min per 1.73 m² (A) or without microalbuminuria (B) despite cystatin C concentrations among the highest quartile of the study sample.