Association of Branched-Chain Amino Acids with Carotid Intima-Media Thickness and Coronary Artery Disease Risk Factors

Abstract

BackgroundRecent studies have determined that branched-chain (BCAAs) and aromatic (AAAs) amino acids are strongly correlated with obesity and atherogenic dyslipidemia and are strong predictors of diabetes. However, it is not clear if these amino acids are capable of identifying subjects with coronary artery disease (CAD), particularly with subclinical atherosclerosis who are at risk of developing CAD.MethodsFour hundred and seventy two Chinese subjects (272 males and 200 females, 42–97 y of age) undergoing physical exams were recruited at random for participation in the cross-sectional study. Serum BCAAs and AAAs were measured using our previously reported isotope dilution liquid chromatography tandem mass spectrometry method. Bilateral B-mode carotid artery images for carotid intima-media thickness (cIMT) were acquired at end diastole and cIMT values more than 0.9 mm were categorized as increased. Correlations of BCAAs with cIMT and other CAD risk factors were analyzed.ResultsBCAAs and AAAs were significantly and positively associated with risk factors of CAD, e.g., cIMT, BMI, waist circumference, blood pressure, fasting blood glucose, TG, apoB, apoB/apoAI ratio, apoCII, apoCIII and hsCRP, and were significantly and negatively associated with HDL-C and apoAI. Stepwise multiple linear regression analysis revealed that age (β = 0.175, P<0.001), log BCAA (β = 0.147, P<0.001) and systolic blood pressure (β = 0.141, P = 0.012) were positively and independently associated with cIMT. In the logistic regression model, the most and only powerful laboratory factor correlated with increased cIMT was BCAA (the odds ratio of the fourth quartile compared to the first quartile was 2.679; P = 0.009).ConclusionBCAAs are independently correlated with increased cIMT. This correlation would open a new field of research in the mechanistic understanding and risk assessment of CAD.

Plasma Branched-Chain Amino Acids and Incident Cardiovascular Disease in the PREDIMED Trial

“…On the one hand, BCAA-rich diets or diets supplemented with BCAAs could improve metabolic health (14) and they could have benefits in patients with heart failure (15). On the other hand, several studies have shown detrimental associations between high plasma values of BCAAs and cardiometabolic diseases (16), especially obesity (17), insulin resistance (18), diabetes (7), and carotid intima-media thickness (19). Potential mechanisms underlying the effects of BCAAs are yet to be elucidated.…”

Branched-Chain Amino Acid Levels Are Related with Surrogates of Disturbed Lipid Metabolism among Older Men

“…High serum branched-chain amino acid (BCAA; isoleucine, leucine, and valine) concentrations have been shown to be predictors or markers of insulin resistance (1), obesity (2, 3), diabetes (4, 5), and atherogenetic dyslipidemia (6, 7) and response to a test meal (8). A 12-year prospective follow-up study of initially normoglycemic individuals showed an association between high serum BCAA levels and incidence of type 2 diabetes (4).…”

Diabetes and branched‐chain amino acids: What is the link?

“…Given these associations with IR, it is not surprising that a number of studies have shown higher BCAA levels in people with and prior to development of type 2 diabetes (T2D), although this has particularly been shown in Caucasian and Asian ethnic groups while not appearing to occur in African Americans . Similarly, higher BCAA levels track with cardiovascular disease …”