Abstract 13479: Association of Plasma Branched Chain Amino Acid With Biomarkers of Inflammation and Lipid Metabolism in Women

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Introduction: We previously observed that circulating branched-chain amino acids (BCAAs) were associated with a higher risk of cardiovascular disease (CVD). However, the relationships of BCAAs with other cardiometabolic pathways other than type 2 diabetes (T2D) are unclear, including inflammation, dyslipidemia, and impaired glucose metabolism. Hypothesis: We hypothesized plasma BCAAs are correlated with cardiometabolic dysfunction in women, independent of shared risk factors. Methods: We conducted a cross-sectional analysis of 19,472 participants (mean age=54.9 years, SD=7.2) in the Women’s Health Study without a history of T2D, CVD, or cancer at baseline blood collection. We used multivariable linear regression models comparing quartiles of BCAAs (sum of fasting isoleucine, leucine and valine concentrations via NMR spectroscopy) with biomarkers of inflammation, lipids, and glucose metabolism, adjusting for age, body mass index, smoking, diet, and other CVD risk factors. Results: Women in the highest vs. lowest quartiles of plasma BCAAs had higher inflammatory markers including high-sensitivity C-reactive protein (hsCRP; adjusted mean: 2.7 vs. 2.0 mg/L), fibrinogen (390 vs. 384 mg/dL), GlycA (420 vs. 384 μmol/L), and soluble intercellular cell adhesion molecule-1 (sICAM-1; 350 vs. 341 ng/mL) (p<0.001 for linear trends across quartiles). Similarly for lipids, women with higher BCAAs had lower HDL-c (48.8 vs. 54.7 mg/dL), and higher LDL-c (142 vs. 135 mg/dL) and triglycerides (142 vs. 114 mg/dL) (p<0.001). BCAAs were positively associated with insulin resistance (lipoprotein insulin resistance [LPIR] score [54.8 vs. 40.0]) and HbA1c (5.2 vs. 5.1%). BCAAs remained associated with GlycA and hsCRP, but not fibrinogen or sICAM-1, when we further adjusted for LPIR and HbA1c, and remained associated with lipids after additional adjustment for HbA1c. Conclusions: Circulating BCAAs are concurrently associated with biomarkers of inflammation, dyslipidemia and impaired glucose metabolism indicative of an overall poorer cardiometabolic health profile. BCAAs remained positively associated with some of these pathways when adjusted for impaired glucose metabolism, suggesting elevated BCAAs may be an independent CVD risk factor in women.