The catechol-O-methyltransferase (COMT) variant rs4818 may be associated with a reduced risk for cardiovascular disease (CVD) and lower fibrinogen levels, but not subclinical atherosclerosis, according to a study published in the Journal of the American Heart Association.

An enzyme in the estrogen and catecholamine pathway, COMT — and in particular, 2 of its variants, rs4680 and rs4818 — has been associated with the rate of CVD in women in previous studies.

In this prospective study, the Multi-Ethnic Study of Atherosclerosis (MESA), 6814 participants (38% white, 28% black, 22% Hispanic, 12% Asian) who were asymptomatic and did not have CVD were enrolled between 2000 and 2012. Study participants underwent an initial examination and 4 follow-up visits and were asked about CVD risk factors and medication intake, including aspirin.

The study’s primary outcome was a composite of myocardial infarction, resuscitated cardiac arrest, stroke, and death from coronary heart disease or stroke. In addition, subclinical atherosclerosis was evaluated by assessing carotid artery intima-media thickness (IMT) and coronary artery calcium (CAC) using ultrasonography and computed tomography, respectively.

In this cohort, there were 498 cardiovascular events that occurred during 65,957 person-years of follow-up. During this time, the COMT variant rs4818, but not rs4680, was found to be associated with a reduced CVD risk (adjusted hazard ratio [aHR], 0.85; 95% CI, 0.74-0.98; P =.02) as well as lower fibrinogen levels (P =.007). No other CVD risk factors were found to be associated with rs4818.

The aHR for the association between the rs4818 variant and CVD risk was 0.79 (95% CI, 0.65-0.95; P =02) and 0.89 (95% CI, 0.71-1.13; P =.34; Pinteraction =.39) in participants who took aspirin <3 and ≥3 days per week, respectively. There was no relationship detected between rs4680 and CVD risk according to aspirin use. Neither CAC nor carotid IMT was found to be associated with COMT allelic variants.

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“These results build upon our previous work…demonstrating that common genetic variation in COMT is associated with risk of CVD in a multiracial population of men and women,” noted the authors. “These results suggest a plausible role of COMT in the latter stages of CVD.”

Conflicts of Interest Disclosures

Psaty serves on the steering committee of the Yale University Open Data Access Project funded by Johnson & Johnson. The remaining authors have no disclosures to report.

Reference

Hall KT, Battinelli E, Chasman DI, et al. Catechol‐O‐methyltransferase and cardiovascular disease: MESA. J Am Heart Assoc. 2019;8(24):1-9. doi:10.1161/jaha.119.014986