Metabolomic Profiling of Left Ventricular Diastolic Dysfunction in Women With or at Risk for HIV Infection: The Women's Interagency HIV Study

Background: People living with HIV have an increased risk of left ventricular diastolic dysfunction (LVDD) and heart failure. HIV-associated LVDD may reflect both cardiomyocyte and systemic metabolic derangements, but the underlying pathways remain unclear. Methods and Results: To explore such pathways, we conducted a pilot study in the Bronx and Brooklyn sites of the WIHS (Women's Interagency HIV Study) who participated in concurrent, but separate, metabolomics and echocardiographic ancillary studies. Liquid chromatography tandem mass spectrometry–based metabolomic profiling was performed on plasma samples from 125 HIV-infected (43 with LVDD) and 35 HIV-uninfected women (9 with LVDD). Partial least squares discriminant analysis identified polar metabolites and lipids in the glycerophospholipid-metabolism and fatty-acid-oxidation pathways associated with LVDD. After multivariable adjustment, LVDD was significantly associated with higher concentrations of diacylglycerol 30:0 (odds ratio [OR], 1.60, 95% CI [1.01–2.55]); triacylglycerols 46:0 (OR 1.60 [1.04–2.48]), 48:0 (OR 1.63 [1.04–2.54]), 48:1 (OR 1.62 [1.01–2.60]), and 50:0 (OR 1.61 [1.02–2.53]); acylcarnitine C7 (OR 1.88 [1.21–2.92]), C9 (OR 1.99 [1.27–3.13]), and C16 (OR 1.80 [1.13–2.87]); as well as lower concentrations of phosphocholine (OR 0.59 [0.38–0.91]). There was no evidence of effect modification of these relationships by HIV status. Conclusions: In this pilot study, women with or at risk of HIV with LVDD showed alterations in plasma metabolites in the glycerophospholipid-metabolism and fatty-acid-oxidation pathways. Although these findings require replication, they suggest that improved understanding of metabolic perturbations and their potential modification could offer new approaches to prevent cardiac dysfunction in this high-risk group.