Year: 2012
Type: article
Study design: Observational Study
Abstract: AIMS: We recently identified a metabolic signature of three amino acids (tyrosine, phenylalanine, and isoleucine) that strongly predicts diabetes development. As novel modifiable targets for intervention are needed to meet the expected increase of cardiovascular disease (CVD) caused by the diabetes epidemic, we investigated whether this diabetes-predictive amino acid score (DM-AA score) predicts development of CVD and its functional consequences. METHODS AND RESULTS: We performed a matched case-control study derived from the population-based Malmö Diet and Cancer Cardiovascular Cohort (MDC-CC), all free of CVD. During 12 years of follow-up, 253 individuals developed CVD and were matched for age, sex, and Framingham risk score with 253 controls. Amino acids were profiled in baseline plasma samples, using liquid chromatography-tandem mass spectrometry, and relationship to incident CVD was assessed using conditional logistic regression. We further examined whether the amino acid score also correlated with anatomical [intima-media thickness (IMT) and plaque formation] and functional (exercise-induced myocardial ischaemia) abnormalities. Compared with the lowest quartile of the DM-AA score, the odds ratio (95% confidence interval) for incident CVD in subjects belonging to quartiles 2, 3, and 4 was 1.27 (0.72-2.22), 1.96 (1.07-3.60), and 2.20 (1.12-4.31) (Ptrend = 0.010), respectively, after multivariate adjustment. Increasing quartile of the DM-AA score was cross-sectionally related to carotid IMT (Ptrend = 0.037) and with the presence of at least one plaque larger than 10 mm(2) (Ptrend = 0.001). Compared with the lowest quartile of the DM-AA score, the odds ratio (95% confidence interval) for inducible ischaemia in subjects belonging to quartiles 2, 3, and 4 was 3.31 (1.05-10.4), 4.24 (1.36-13.3), and 4.86 (1.47-16.1) (Ptrend = 0.011), respectively. CONCLUSION: This study identifies branched-chain and aromatic amino acids as novel markers of CVD development and as an early link between diabetes and CVD susceptibility.
Source: European Heart Journal
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: American Heart Association, Fondation Leducq, Crafoordska Stiftelsen, Lunds Universitet, Knut och Alice Wallenbergs Stiftelse, Novo Nordisk Fonden, Region Skåne, Marcus och Amalia Wallenbergs minnesfond, National Institutes of Health, Medical Research Council, National Heart, Lung, and Blood Institute, National Institute of Diabetes and Digestive and Kidney Diseases
Awards: Biomarkers of Prognosis and Response to Therapy in Acute Coronary Syndromes, G1781957139, G250621538, G279324209, Trace Elements and Cardiovascular Disease (CVD) Risks Factors Among Young Adults, Novel Biomarkers to Identify Vulnerable Patients with Coronary Artery Disease, Metabolomic Biomarkers of Early Myocardial Injury, G5384371102, G6144706364, The Framingham Heart Study, Metabolic Profiling of Acute Myocardial Injury in Humans, G8701812459, G9000135092
OpenAlex ID: W1987100478