Kidney Dysfunction and Fatal Cardiovascular Disease
Background: Impaired kidney function has been associated with increased risk for death, myocardial infarction, stroke, and heart failure in high-risk populations. We evaluated whether impaired kidney function predicted risk of fatal cardiovascular disease independent of prevalent and incident cardiovascular events.
Methods: The Health, Aging, and Body Composition study is a cohort of well-functioning, elderly participants aged 70 to 79 years at entry. We measured serum cystatin C and creatinine from baseline plasma samples of 3044 participants and followed them over 6 years, examining the associations among kidney function, cardiovascular death, and incident cardiovascular events. Cystatin C was categorized as low (<0.84 mg/L), medium (0.84-1.18 mg/L), or high (≥1.19 mg/L); serum creatinine (cutoff value of ≥1.3 in women and ≥1.5 in men) and estimated glomerular filtration rate (eGFR; greater and less than 60 mL/min per 1.73 m) were dichotomized.
Results: During follow-up, 242 cardiovascular deaths occurred, of which 69 were in participants without prior cardiovascular events; 294 incident cardiovascular events occurred including 135 myocardial infarctions and 163 strokes. Higher cystatin C concentrations were significantly associated with cardiovascular death (adjusted hazard ratio [HR] 1.70, 95% confidence interval [CI] 1.05-2.76 for the medium cystatin C group; and HR 2.24, 95% CI 1.30-3.86 for the high cystatin C group, relative to the low cystatin C group). The point estimate was of greater magnitude in the analysis that excluded prevalent cardiovascular disease (adjusted HR 2.68, 95% CI 0.94-7.70 for the medium cystatin C group; and HR 4.91, 95% CI, 1.55-15.54 for the high cystatin C group). Elevated creatinine levels (adjusted HR 1.54, 95% CI 1.02-2.33, and HR 2.28, 95% CI 1.10-4.73 among participants without a history of cardiovascular disease) were also associated with cardiovascular death. No significant association was found between low eGFR and cardiovascular death. In addition, cystatin C, low eGFR, or elevated creatinine levels were not associated with other cardiovascular events.
Conclusion: Impaired kidney function is a strong predictor of cardiovascular death, particularly among participants without prior history of cardiovascular disease.

Chronic kidney disease (CKD) has been associated with an increased risk of death and adverse cardiovascular events. The primary measure for CKD in clinical settings, estimated glomerular filtration rate (eGFR) <60 mL/min per 1.73 m calculated from the serum creatinine concentration, is relatively insensitive for detecting mild to moderate reductions in kidney function. Cystatin C is an alternative measure of kidney function that appears to approximate glomerular filtration rate better than creatinine or estimated glomerular filtration rate (eGFR). We determined the association between each of these measures of kidney function with incident cardiovascular events, including death, myocardial infarction (MI), stroke, and coronary heart disease (CHD). In addition, we specifically evaluated whether kidney dysfunction predicted risk of fatal cardiovascular disease in persons without any previous prevalent or incident cardiovascular events.