Plasma branched-chain amino acid and cardiovascular disease risk factors: a longitudinal analysis of a lifestyle trial

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 25-78, of the U.S. 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 NMR 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 (HOMA-IR: Beta = 0.22, SE = 0.07), inflammation (GlycA: Beta = 0.03 mmol/l, SE = 0.004), ApoB (Beta = 0.02 g/l, SE = 0.006), and VLDL-cholesterol (Beta = 0.03 mmol/l, SE = 0.007) over the same period (all Q-values <0.01). Associations with HDL-cholesterol and triglycerides differed for valine versus 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.