Cardiac and kidney markers for cardiovascular prediction in individuals with chronic kidney disease: the Atherosclerosis Risk in Communities study

Abstract

Objective: Traditional predictors suboptimally predict cardiovascular disease (CVD) in individuals with chronic kidney disease (CKD). This study compared 5 nontraditional cardiac and kidney markers on the improvement of cardiovascular prediction among those with CKD.

Approach and results: Among 8622 participants aged 52 to 75 years in the Atherosclerosis Risk in Communities (ARIC) Study, cardiac troponin T, N-terminal pro-B-type natriuretic peptide, cystatin C, β2-microglobulin, and β-trace protein were compared for improvement in predicting incident CVD after stratifying by CKD status (940 participants with CKD [kidney dysfunction or albuminuria]). During a median follow-up of 11.9 years, there were 1672 CVD events including coronary disease, stroke, and heart failure (336 cases in CKD). Every marker was independently associated with incident CVD in participants with and without CKD. The adjusted hazard ratios (per 1 SD) were larger for cardiac markers than for kidney markers, particularly in CKD (1.61 [95% confidence interval, 1.43-1.81] for cardiac troponin T, 1.50 [1.34-1.68] for N-terminal pro-B-type natriuretic peptide, and <1.26 for kidney markers). Particularly in CKD group, cardiac markers compared with kidney markers contributed to greater c-statistic increment (0.032-0.036 versus 0.012-0.015 from 0.679 with only conventional predictors in CKD and 0.008-0.011 versus 0.002-0.010 from 0.697 in non-CKD) and categorical net reclassification improvement (0.086-0.127 versus 0.020-0.066 in CKD and 0.057-0.077 versus 0.014-0.048 in non-CKD). The superiority of cardiac markers was largely consistent in individual CVD outcomes.

Conclusions: A greater improvement in cardiovascular prediction was observed for cardiac markers than for kidney markers in people with CKD. These results suggest that cardiac troponin T and N-terminal pro-B-type natriuretic peptide are useful for better CVD risk classification in this population.

Keywords: biological markers; cardiovascular diseases; risk assessment.

Figure

Adjusted incidence rate of CVD in those with and without CKD according to novel cardiac and kidney markers and their distributions. Adjusted incidence rate of CVD in those with and without CKD according to cardiac and kidney markers and their distributions. The solid lines (red for CKD and blue for non-CKD) show estimated incidence rates of CVD (per 1,000 person-years) and 95% CIs (whiskers and shaded area) with spline (knots at thresholds defining quartiles) for (A) cTnT, (B) NT-proBNP, (C) cystatin C, (D) B2M, (E) BTP, and (F) hsCRP. The incidence rate was adjusted to mean age, men, and whites, and the plot was truncated at 0.5th and 99.5th percentile of each marker. The dash lines (red for CKD and blue for non-CKD) show the kernel density estimate for each marker.