Abstract | BACKGROUND: METHODS: Participants in the Women's Health Study prospective cohort were eligible if free of CVD at baseline blood collection (n=27 041). Plasma metabolites were measured via nuclear magnetic resonance spectroscopy. Multivariable Cox regression models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for BCAAs with incident CVD ( myocardial infarction, stroke, and coronary revascularization). RESULTS: We confirmed 2207 CVD events over a mean 18.6 years of follow-up. Adjusting for age, body mass index, and other established CVD risk factors, total BCAAs were positively associated with CVD (per SD: HR, 1.13; 95% CI, 1.08-1.18), comparable to LDL-C ( low-density lipoprotein cholesterol) with CVD (per SD: HR, 1.12; 95% CI, 1.07-1.17). BCAAs were associated with coronary events ( myocardial infarction: HR, 1.16; 95% CI, 1.06-1.26; revascularization: HR, 1.17; 95% CI, 1.11-1.25), and borderline significant association with stroke (HR, 1.07; 95% CI, 0.99-1.15). The BCAA-CVD association was greater (P interaction=0.036) among women who developed T2D before CVD (HR, 1.20; 95% CI, 1.08-1.32) versus women without T2D (HR, 1.08; 95% CI, 1.03-1.14). Adjusting for LDL-C, an established CVD risk factor, did not attenuate these findings; however, adjusting for HbA1c and insulin resistance eliminated the associations of BCAAs with CVD. CONCLUSIONS: Circulating plasma BCAAs were positively associated with incident CVD in women. Impaired BCAA metabolism may capture the long-term risk of the common cause underlying T2D and CVD.
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Authors | Deirdre K Tobias, Patrick R Lawler, Paulo H Harada, Olga V Demler, Paul M Ridker, JoAnn E Manson, Susan Cheng, Samia Mora |
Journal | Circulation. Genomic and precision medicine
(Circ Genom Precis Med)
Vol. 11
Issue 4
Pg. e002157
(04 2018)
ISSN: 2574-8300 [Electronic] United States |
PMID | 29572205
(Publication Type: Journal Article, Observational Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Copyright | © 2018 American Heart Association, Inc. |
Chemical References |
- Amino Acids, Branched-Chain
- Biomarkers
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Topics |
- Amino Acids, Branched-Chain
(blood)
- Biomarkers
(blood)
- Cardiovascular Diseases
(blood, diagnosis, epidemiology)
- Female
- Humans
- Incidence
- Metabolomics
(methods)
- Middle Aged
- Prognosis
- Prospective Studies
- Proton Magnetic Resonance Spectroscopy
- Risk Assessment
- Risk Factors
- Sex Factors
- Time Factors
- United States
(epidemiology)
- Up-Regulation
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