• 作者：Sayanti Bhattacharya ; Christopher B. Granger ; Damian Craig ; Carol Haynes ; James Bain ; Robert D. Stevens ; Elizabeth R. Hauser ; Christopher B. Newgard ; William E. Kraus ; L. Kristin Newby ; Svati H. Shah
• 关键词：Metabolism ; Coronary artery disease ; Branched chain amino acids
• 刊名：Atherosclerosis
• 出版年：January, 2014
• 年：2014
• 卷：232
• 期：1
• 页码：191-196
• 全文大小：277 K

Objective

Methods

We conducted mass-spectrometry-based profiling of 63 metabolites in fasting plasma from 1983 sequential patients undergoing cardiac catheterization. Significant CAD was defined as CADindex聽鈮ヂ?2 (at least one vessel with 鈮?5% stenosis; N聽=聽995) and no CAD as CADindex聽鈮ぢ?3 and no previous cardiac events (N聽=聽610). Individuals (N聽=聽378) with CAD severity between these extremes were excluded. Principal components analysis (PCA) reduced large numbers of correlated metabolites into uncorrelated factors. Association between metabolite factors and significant CAD vs. no CAD was tested using logistic regression; and between metabolite factors and severity of CAD was tested using linear regression.

Results

Of twelve PCA-derived metabolite factors, two were associated with CAD in multivariable models: factor 10, composed of BCAA (adjusted odds ratio, OR, 1.20; 95% CI 1.05-1.35, p聽=聽0.005) and factor 7, composed of short-chain acylcarnitines, which include byproducts of BCAA metabolism (adjusted OR 1.30; 95% CI 1.14-1.48, p聽=聽0.001). After adjustment for glycated albumin (marker of insulin resistance [IR]) both factors 7 (p聽=聽0.0001) and 10 (p聽=聽0.004) remained associated with CAD. Severity of CAD as a continuous variable (including patients with non-obstructive disease) was associated with metabolite factors 2, 3, 6, 7, 8 and 9; only factors 7 and 10 were associated in multivariable models.

Conclusions

We validated the independent association of metabolites involved in BCAA metabolism with CAD extremes. These metabolites may be reporting on novel mechanisms of CAD pathogenesis that are independent of IR and diabetes.