Abstract 10769: Circulating Branched-Chain Amino Acids, Incident Cardiovascular Disease, and Mortality in the African American Study of Kidney Disease and Hypertension

Abstract

Introduction: Branched-chain amino acids (BCAAs), i.e., leucine, isoleucine, and valine, are involved in glucose regulation, immunity, and cell signaling. Higher circulating BCAAs were associated with incident cardiovascular disease (CVD) in the general population which may be mediated by insulin resistance. BCAA’s role in CVD in the absence of diabetes is unclear. Hypothesis: BCAAs are associated with cardiovascular outcomes in non-diabetic chronic kidney disease (CKD), a highly prevalent condition that substantially alters circulating metabolites and elevates CVD risk. Methods: In the African American Study of Kidney Disease and Hypertension (AASK), we conducted serum metabolomic profiling and assessed associations between BCAAs and risks for incident CVD (hospitalization for nonfatal myocardial infarction, cardiac revascularization, heart failure, stroke, or cardiovascular death), cardiovascular death, and all-cause mortality using multivariable Cox regression. Results: In 962 participants (mean age 56 years, 39% women, mean glomerular filtration rate [GFR] 48 ml/min/1.73m 2 , mean fasting blood glucose 94 mg/dl, mean low density lipoprotein cholesterol [LDLc] 137 mg/dl), BCAAs were minimally correlated with GFR, proteinuria, C-reactive protein, LDLc, or blood glucose. During follow-up (median 7.4 years), there were 192 CVD events (myocardial infarction or revascularization, n=57; stroke, n=74; heart failure, n=74) and 220 deaths of which 54 were cardiovascular deaths. Adjusted for covariates, no association was found between BCAAs and incident CVD, but higher BCAAs were associated with lower cardiovascular death (per doubling BCAA, HR=0.52, 95%CI 0.31-0.87; p=0.013 for isoleucine; HR=0.30, 95%CI 0.13-0.68, p=0.004 for leucine, HR=0.39, 95%CI 0.16-0.94, p=0.04 for valine). Associations were unchanged accounting for all-cause death as competing risk using Fine-Gray modeling. Leucine and isoleucine were associated with lower all-cause mortality (HR=0.57, 95%CI 0.36-0.96, p=0.035 for leucine; HR=0.70, 95%CI 0.49-1.00, p=0.049 for isoleucine). Conclusions: In African Americans with non-diabetic CKD, higher circulating BCAAs were associated with lower cardiovascular death, lower mortality, but not incident CVD.