Inflammatory, Cardiac, and Lipid-Related Biomarkers in Relation to Residual MACE Risk in the REPRIEVE Trial

Residual major adverse cardiovascular event (MACE) risk persists despite successful prevention of cardiovascular disease (CVD) with statin therapy among people with HIV (PWH). Identifying key biomarkers related to residual cardiovascular risk is critical for PWH.

The objective of the current analysis was to assess the association of immune, inflammatory, cardiac, and lipid-related biomarkers among contemporary antiretroviral therapy-treated PWH in the REPRIEVE global primary cardiovascular prevention trial in residual risk analyses.

We assessed relationships of baseline inflammatory, cardiac, and lipid-related biomarkers to incident MACE using Cox models adjusted for randomized statin treatment and atherosclerotic CVD risk. Population attributable fractions (PAFs) were assessed for biomarkers.

Of the 7769 REPRIEVE participants, 7,005 (90%) had biomarker data available at baseline, with the median follow-up of 5.6 years. Relatively high percentages of participants had elevated inflammatory (high-sensitivity C-reactive protein >3 mg/L [49%], interleukin [IL]-6 ≥3.3 pg/mL [33%]) and cardiac markers (high-sensitivity troponin ≥6 ng/L [35%], N-terminal pro-B-type natriuretic peptide ≥50 pg/mL [33%]). Inflammatory biomarkers showed minimal correlation with cardiac or lipid biomarkers (apolipoprotein B-100, oxidized low-density lipoprotein, and lipoprotein(a)). Individual biomarkers were related to MACE in analyses adjusted for PCE and statin randomization, with the largest HRs for IL-6 (HR: 2.2; 95% CI: 1.3-3.9) and high-sensitivity troponin (HR: 2.2; 95% CI: 1.2-4.1) comparing those with highest vs lowest biomarker levels. PAFs were highest for IL-6, 18.6% (95% CI: 7.4%-30.5%) and high-sensitivity C-reactive protein 17.2% (95% CI: 1.6%-32.9%).

Among PWH with low-moderate predicted CVD risk and well-controlled HIV, persistent inflammation, innate immune activation, and subclinical cardiac dysfunction are common, and strongly relate to residual MACE risk, accounting for a large PAF. (Evaluating the Use of Pitavastatin to Reduce the Risk of Cardiovascular Disease in HIV-Infected Adults [REPRIEVE]; NCT02344290.