Background People living with HIV are at increased risk of developing diastolic dysfunction,
heart failure, and
sudden cardiac death, all of which have been characterized by higher levels of myocardial
fibrosis. Transmethylamine-N-
oxide (
TMAO), a dietary gut metabolite, is linked to the development of myocardial
fibrosis in animal models. However, it is unclear whether
TMAO plays a role in the development of myocardial
fibrosis in people living with HIV. Methods and Results The study population consisted of participants enrolled in the multisite cross-sectional study called CHART-HIV (Characterizing Heart Function on Anti-Retroviral
Therapy). Participants underwent echocardiography, cardiac magnetic resonance imaging,
biomarker analysis, and targeted assessment of gut-related circulating metabolites; diastolic dysfunction was determined by study-specific criteria. Multivariable linear regression models were performed to examine the relationship of gut-related metabolites with serum and imaging measures of myocardial
fibrosis. Models were adjusted for traditional cardiovascular, inflammatory, and HIV-related risk factors. Diastolic dysfunction was present in 94 of 195 individuals (48%) in CHART-HIV; this cohort demonstrated higher prevalence of
hypertension,
hyperlipidemia, and
chronic kidney disease as well as higher plasma levels of both
TMAO and
choline.
TMAO levels were associated with parameters reflecting increased left ventricular filling pressures and with a marker of the innate immune system.
TMAO levels correlated with diffuse myocardial
fibrosis (R=0.35; P<0.05) as characterized by myocardial extracellular volume fraction as well as
biomarkers reflective of myocardial
fibrosis. Conclusions In this study of people living with HIV, the gut metabolite
TMAO was associated with underlying diffuse myocardial
fibrosis and found to be a potential marker of early structural
heart disease. The mechanistic role of the gut microbiome in HIV-associated
cardiovascular disease warrants further investigation. Registration URL: https://clinicaltrials.gov; Unique identifier: NCT02860156.