Abstract

CONTEXT: Branched-chain amino acid (BCAAs) levels have been associated with a higher risk of cardiovascular diseases (CVD), but studies of the impact of BCAAs on CVD risk factors have mainly been cross-sectional. OBJECTIVE: We examined the longitudinal association between changes in BCAA levels and CVD risk factors in a lifestyle trial. METHOD: We used data from 708 male and female participants, aged 25 to 78, of the US PREMIER study. Data and biospecimens were from the NHLBI BioLINCC Repository. Participants received lifestyle advice or comprehensive counseling on diet, physical activity, and weight loss. Biomarkers were measured with nuclear magnetic resonance spectroscopy at baseline and the 6-month follow-up. Linear regression models assessed changes in BCAA levels in relation to changes in cardiometabolic risk factors. We adjusted for multiple testing by using false discovery rate-adjusted Q values. RESULTS: Increases in BCAA levels over 6 months (per 1 SD) were associated with increases in insulin resistance (homeostatic model assessment for insulin resistance: β = 0.22, SE = 0.07), inflammation (glycoprotein acetylation: β = 0.03 mmol/L, SE = 0.004), apolipoprotein B (β = 0.02 g/L, SE = 0.006), and very low density lipoprotein cholesterol (β = 0.03 mmol/L, SE = 0.007) over the same period (all Q-values <0.01). Associations with high-density lipoprotein cholesterol and triglycerides differed for valine vs leucine and isoleucine. No significant associations were observed with fasting glucose or blood pressure. CONCLUSION: Increasing levels of BCAAs were associated with insulin resistance, inflammation, and unfavorable lipid profiles, indicating their potential as targets for CVD prevention. Further research is warranted to elucidate how individual BCAAs influence lipid metabolism.