Microbiota-dependent marker TMAO is elevated in silent ischemia but is not associated with first-time myocardial infarction in HIV infection

OBJECTIVES: HIV-infection is associated with increased risk of coronary heart disease (CHD) beyond that explained by traditional risk factors, and altered gut microbiota has been proposed as a potential trigger. Trimethylamine-N-oxide (TMAO) is a pro-atherogenic substance formed in the liver from trimethylamine, exclusively generated by gut microbiota from dietary phosphatidylcholine. We aimed to investigate if TMAO is associated with subclinical and clinical CHD in HIV-infection.

METHODS: Two previously described cohorts were examined: 1. Cross-sectional cohort of HIV-infected persons and uninfected controls with known atherosclerotic plaque burden as assessed by myocardial perfusion scintigraphy, coronary artery calcium score (CACS), and intima media thickness (IMT), and 2. Nested case-control study of HIV-infected persons with first-time myocardial infarction (MI) compared to HIV-infected persons without MI, assessed at four time points from before initiation of antiretroviral treatment (ART) to last sample before the case's MI (median 51, range 0-239 days).

RESULTS: There was no difference in plasma TMAO when comparing HIV-infected persons and uninfected controls. TMAO was elevated in HIV-infected persons with myocardial perfusion defects, but was not associated with CACS score, IMT, or Framingham risk score. In the nested case control study, plasma TMAO was not associated with first-time MI. However, TMAO increased after ART introduction and was associated with use of protease inhibitors in both cohorts.

CONCLUSIONS: TMAO was elevated in HIV-infected persons with myocardial perfusion defects, but was not associated with first-time MI. Our data question TMAO as a useful biomarker of cardiovascular risk in HIV-infection, at least in ART-treated individuals.