Background
People with HIV (PWH) have an increased risk of cardiovascular disease (CVD), driven by persistent immune activation and metabolic disturbances, despite successful antiretroviral therapy (ART). Alterations in some immune parameters and metabolites have been associated with the CVD onset. However, specific lipidomic, metabolomic, and immunological biomarkers preceding CVD in PWH are still unknown.
Methods
A retrospective case-control study was performed, analyzing 35 PWH on ART 3-18 months before experiencing acute myocardial infarction or acute coronary syndrome and 35 PWH as controls who did not suffer any non-AIDS event, matched by sex, age, active HCV infection, nadir and CD4+ T-cell levels, time since HIV diagnosis, and Framingham Risk Score (FRS), commonly used to predict CVD. 236 lipids and 102 metabolites were detected in plasma by LC-QTOF and GC-qTOF respectively. We performed T cell, monocyte and dendritic cell (DC) deep immunophenotyping by flow cytometry from PBMCs. Mann-Whitney test was used for two group statistic (p>0.05) and ROC curve analysis to determine the predictive potential for CVD of the studied parameters. Enrichment and Pathway analysis was performed by MetaboAnalyst 5.0 software.
Results
Lysophosphatidylcholines (LPC-16:0e, -16:1p, and -O18:1p) were less abundant in PWH before CVD, while 29 lipids, mainly triacylglycerols, were more abundant. Pyruvic acid and d-fructose levels were significantly increased in CVD group. Pyruvic metabolism was the pathway with major impact. We observed increased levels of regulatory and senescent T cells, higher percentages of more differentiated monocyte subsets and lower percentages of myeloid and plasmacytoid DCs in PWH before suffering CVD, comparing with controls. An integrative predictive model combining LPC-O 18:1p, d-fructose, myeloid DCs, and non-classical monocytes achieved high predictive accuracy (AUC 0.831, PPV 0.762, NPV 0.824). The introduction of this combination increased the predictive accuracy of FRS (FRS, AUC 0.742, PPV 1.000, NPV 0.630; FRS + LPC-O 18:1p + d-fructose + myeloid DCs + non-classical monocytes, AUC 0.975, PPV 0.949, NPV 0.919).
Conclusions
Significant alterations in lipidomic, metabolomic and immune profiles precede CVD in PWH. Moreover, the integration of these parameters increase the predictive accuracy of a common risk score for CVD in PWH. These findings underscore the potential for early identification of CVD risk in PWH using a multi-biomarker approach.
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