Trimethylamine Oxidation into the Proatherogenic Trimethylamine N-Oxide Is Higher in Coronary Heart Disease Men: From the CORDIOPREV Study

Purpose: Cardiovascular disease (CVD) is more prevalent in men than women, but the mechanisms responsible for this are not fully understood. We aimed to evaluate differences in trimethylamine (TMA), a microbial metabolite and its oxidized form, trimethylamine N-oxide (TMAO), which is thought to promote atherosclerosis, between men and women with coronary heart disease (CHD), using as a reference a non-CVD population. Materials and Methods: This study was carried out within the framework of the CORDIOPREV study (NCT00924937; June 19, 2009), a clinical trial which included 827 men and 175 women with CHD, with a non-CVD population of 375 individuals (270 men and 105 women) as a reference group. Plasma TMA and TMAO were measured by HPLC-MS/MS. The carotid study was ultrasonically assessed bilaterally by the quantification of intima-media thickness of both common carotid arteries (IMT-CC). Results: We found higher TMAO levels and TMAO/TMA ratio in CHD men than CHD women (p=0.034 and p=0.026, respectively). No TMA sex differences were found in CHD patients. The TMA and TMAO levels and TMAO/TMA ratio were lower, and no differences between sexes were found in the non-CVD population. TMAO levels in CHD patients were consistent with higher IMT-CC and more carotid plaques (p=0.032 and p=0.037, respectively) and lower cholesterol efflux in CHD men than CHD women (p<0.001). Conclusions: Our results suggest that CHD men have augmented TMAO levels compared with CHD women, presumably as a consequence of higher rate of TMA to TMAO oxidation, which could be associated with CVD, as these sex differences are not observed in a non-CVD population.