TY - JOUR
T1 - Transmethylamine-n-oxide is associated with diffuse cardiac fibrosis in people living with hiv
AU - Colaco, Nalini A.
AU - Wang, Teresa S.
AU - Ma, Yifei
AU - Scherzer, Rebecca
AU - Ilkayeva, Olga R.
AU - Desvigne-Nickens, Patrice
AU - Braunwald, Eugene
AU - Hernandez, Adrian F.
AU - Butler, Javed
AU - Shah, Svati H.
AU - Shah, Sanjiv J.
AU - Hsue, Priscilla Y.
N1 - Funding Information:
This study was funded by the National Institute of Health (NHLBI PO515992 to J.B., National Institute of Allergy and Infectious Diseases K24AI112393-06 to P.Y.H.) and the Center for AIDS Research University of California, San Francisco (to N.A.C.).
Publisher Copyright:
© 2021 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.
PY - 2021/8/17
Y1 - 2021/8/17
N2 - 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 myocar-dial 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 myocar-dial 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.
AB - 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 myocar-dial 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 myocar-dial 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.
KW - Diastolic dysfunction
KW - HIV
KW - Myocardial fibrosis
KW - Transmethylamine-N-oxide
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U2 - 10.1161/JAHA.120.020499
DO - 10.1161/JAHA.120.020499
M3 - Article
C2 - 34365799
AN - SCOPUS:85113228163
SN - 2047-9980
VL - 10
JO - Journal of the American Heart Association
JF - Journal of the American Heart Association
IS - 16
M1 - e020499
ER -
