Cardiac Biomarkers and Risk of Mortality in CKD (the CRIC Study)

Abstract

Introduction: Cardiovascular disease (CVD) is the leading cause of mortality among individuals with chronic kidney disease (CKD). Cardiac biomarkers of myocardial distention, injury, and inflammation may signal unique pathways underlying CVD in CKD. In this analysis, we studied the association of baseline levels and changes in 4 traditional and novel cardiac biomarkers with risk of all-cause, CV, and non-CV mortality in a large cohort of patients with CKD.

Methods: Among 3664 adults with CKD enrolled in the Chronic Renal Insufficiency Cohort Study, we conducted a cohort study to examine the associations of baseline levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP), cardiac high-sensitivity troponin T (hsTnT), growth differentiation factor-15 (GDF-15), and soluble ST-2 (sST-2) with risks of all-cause and cardiovascular (CV) mortality. Among a subcohort of 842 participants, we further examined the associations between change in biomarker levels over 2 years with risk of all-cause mortality. We used Cox proportional hazards regression models and adjusted for demographics, kidney function measures, cardiovascular risk factors, and medication use.

Results: After adjustment, elevated baseline levels of each cardiac biomarker were associated with increased risk of all-cause mortality: NT-proBNP (hazard ratio [HR] = 1.92, 95% confidence interval [CI] = 1.73-2.12); hsTnT (HR = 1.62, 95% CI = 1.48, 1.78]); GDF-15 (HR = 1.61, 95% CI = 1.46-1.78]); and sST-2 (HR = 1.26, CI = 1.16-1.37). Higher baseline levels of all 4 cardiac biomarkers were also associated with increased risk of CV. Declines in NT-proBNP (adjusted HR = 0.55, 95% CI = 0.36-0.86) and sST2 (HR = 0.55, 95% CI = 0.36-0.86]) over 2 years were associated with lower risk of all-cause mortality.

Conclusion: In a large cohort of CKD participants, elevations of NT-proBNP, hsTnT, GDF-15, and sST-2 were independently associated with greater risks of all-cause and CV mortality.

Keywords: cardiac biomarkers; cardiovascular; mortality.

Graphical abstract

Figure 1

(a) Rates of all-cause mortality, by biomarker category. (b) Rates of cardiovascular (CV) mortality, by biomarker category. GDF-15, growth differentiation factor−15; hsTNT, high-sensitivity troponin T; NT-proBNP, N-terminal pro-B-type natriuretic peptide; pys, person-years; sST-2, soluble ST-2.

Figure 1

(a) Rates of all-cause mortality, by biomarker category. (b) Rates of cardiovascular (CV) mortality, by biomarker category. GDF-15, growth differentiation factor−15; hsTNT, high-sensitivity troponin T; NT-proBNP, N-terminal pro-B-type natriuretic peptide; pys, person-years; sST-2, soluble ST-2.