Abstract
Objective-The nonproteinogenic amino acid homoarginine has been postulated to have antiatherosclerotic effects as a weak substrate of nitric oxide synthase. This investigation in the population-based Dallas Heart Study (DHS) aimed to evaluate the association of homoarginine with clinical and subclinical cardiovascular outcomes.
Approach and Results-Plasma homoarginine was measured in 3514 participants of the DHS using liquid chromatographytandem mass spectrometry. Associations between homoarginine and major adverse cardiovascular events and all-cause mortality were analyzed using Cox proportional hazard models adjusting for cardiovascular risk factors. Linear regression was used to assess cross-sectional associations between homoarginine and subclinical cardiovascular disease, including coronary artery calcium measured by electron beam-computed tomography, and aortic plaque burden and aortic wall thickness by MRI. Median age was 43 (interquartile range, 36-52) years, with 56% women and 52% black participants. Median follow-up was 9.4 (9.0-9.8) years. Median plasma homoarginine was 2.80 (2.14-3.54) ìmol/L. In multivariable models, higher homoarginine was associated with lower rate of major adverse cardiovascular events (hazard ratio, 0.86; 95% confidence interval, 0.75-0.98) and lower all-cause mortality (hazard ratio, 0.82; 0.73-0.92; per 1 log SD increase in homoarginine). Homoarginine was inversely and independently associated with aortic wall thickness (β-estimate, .0.04; P<0.01) but not with aortic plaque burden and coronary artery calcium.
Conclusions-Homoarginine is inversely associated with subclinical vascular disease and with risk for cardiovascular disease events. Additional studies are needed to evaluate whether the regulation of plasma homoarginine could emerge as a novel therapeutic option to improve outcomes in cardiovascular disease.
Original language | English (US) |
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Pages (from-to) | 2501-2507 |
Number of pages | 7 |
Journal | Arteriosclerosis, thrombosis, and vascular biology |
Volume | 34 |
Issue number | 11 |
DOIs | |
State | Published - Nov 1 2014 |
Keywords
- Atherosclerosis
- Epidemiology
- Nitric oxide
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine