Urinary creatinine excretion rate and mortality in persons with coronary artery disease: the Heart and Soul Study

Abstract

Background: In persons with coronary artery disease, low body mass index is associated with greater mortality; however, it is uncertain whether low muscle mass is a risk factor for mortality in this setting.

Methods and results: In this study, 903 individuals with coronary artery disease provided 24-hour urine collections. We measured urine creatinine and volume and calculated creatinine excretion rate, a marker of muscle mass. Cox proportional-hazards models evaluated the association of creatinine excretion rate with mortality risk. Over a median follow-up of 6.0 years, 232 participants (26%) died. Compared with the highest sex-specific creatinine excretion rate tertile, the lowest tertile (<1068 mg/d in men, <766 mg/d in women) was associated with >2-fold risk of mortality (hazard ratio, 2.30; 95% confidence interval, 1.51 to 3.51) in models adjusted for age, sex, race, cystatin C-based estimated glomerular filtration rate, body mass index, traditional cardiovascular disease risk factors, and C-reactive protein levels. The association was essentially unaltered with further adjustment for physical fitness, left ventricular mass, left ventricular ejection fraction, or fasting insulin and glucose levels.

Conclusions: Lower creatinine excretion rate is strongly associated with mortality in outpatients with coronary artery disease, independently of conventional measures of body composition, kidney function, and traditional coronary artery disease risk factors. Future studies should determine whether low creatinine excretion rate may be a modifiable risk factor for mortality among persons with coronary artery disease, potentially through resistive exercise training or nutrition interventions.

Figure 1. The Association of Body Mass Index (A) and Waist Hip Ratio (B) with Creatinine Excretion Rate are Fairly Linear in Persons with Coronary Artery Disease

Age and sex adjusted spline functions demonstrating the cross-sectional association of body mass index (A) and waist hip ratio (B) with creatinine excretion rate in persons with coronary artery disease. Solid line represents the hazard ratio, and dotted lines represent the 95% confidence intervals. The extreme 5% of the data distribution was excluded to avoid implausible extrapolation from the extremes of the data.

Figure 2. Survival by Creatinine Excretion Tertiles in Persons with Coronary Artery Disease

Kaplan Meier survival curve demonstrating the unadjusted association of creatinine excretion tertiles with mortality in persons with coronary artery disease.

Figure 3. Age and Sex Adjusted Association of Body Mass Index Quint iles with Mortality in Persons with Coronary Artery Disease

Models adjusted for age and sex. Second BMI quintile (24.1–26.5 kg/m²) served as the reference category. Error bars reflect 95% confidence intervals.

Figure 4. Adjusted* Association of Creatinine Excretion Rate with Mortality in Persons with Coronary Artery Disease

Natural piecewise cubic spline function demonstrating that the adjusted association of creatinine excretion rate with mortality was fairly linear in persons with coronary artery disease. Solid line represents the hazard ratio, and dotted lines represent the 95% confidence intervals. The extreme 5% of the data distribution was excluded to avoid implausible extrapolation from the extremes of the data. *The spline function was adjusted for age, sex, race, BMI (lowest quintile vs. greater), diabetes, hypertension, current smoking, systolic blood pressure, diastolic blood pressure, total cholesterol, HDL cholesterol, eGFR, and Ln(CRP).