Abstract
Background In REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV), pitavastatin prevented major adverse cardiovascular events (MACE) and reduced noncalcified coronary plaque (NCP) among people with HIV and low-to-moderate traditional cardiovascular disease (CVD) risk.
Objectives The purpose of this study was to assess the relationship of coronary plaque, inflammation, and subclinical myocardial injury with MACE.
Methods 804 REPRIEVE Mechanistic Substudy participants enrolled from April 2015 to February 2018 at 31 U.S. sites, randomized to pitavastatin 4 mg/day or placebo, and followed for incident MACE (median 6.2 years [Q1-Q3 5.4-7.1]), were assessed for relationships of baseline NCP, markers of inflammation (high-sensitivity C-reactive protein [hs-CRP], interleukin (IL)-6, oxidized low-density lipoprotein, and lipoproprotein-associated phospholipase A2), and subclinical myocardial injury (high-sensitivity cardiac troponin T [hs-cTnT]) with MACE.
Results Among enrolled participants (17% female [139/804], 47% non-White [379/804], median age 51 years, median low-density lipoprotein 105 mg/dL, 10-year atherosclerotic CVD [ASCVD] risk 4.6%, 40% [299/755] with noncalcified plaque), MACE incidence was 7.26/1,000 (95% CI: 4.51-11.7) person-years (17 events) for pitavastatin and 9.15/1,000 person-years (95% CI: 5.97-14.0) (21 events) for placebo. The hazard of MACE was greater in those with (vs without) noncalcified plaque (HR: 2.5; [95% CI: 1.3-4.8]; P = 0.008), with higher levels of hs-CRP (P = 0.049), IL-6 (P = 0.033), and hs-cTnT (P = 0.003) at study entry, persisting after ASCVD risk adjustment. In exploratory prediction modeling, adding hs-CRP, IL-6, and hs-cTnT to ASCVD risk increased the integrated area under the curve to 0.72 and C-statistic to 0.73 (0.62-0.84) vs 0.58 and 0.56 (0.45-0.67) compared to ASCVD risk alone.
Conclusions NCP and higher hs-CRP, IL-6, and hs-cTnT were associated with MACE and improved risk prediction over traditional risk factors in people with HIV without cardiac symptoms and low-to-moderate ASCVD risk. (Evaluating the Use of Pitavastatin to Reduce the Risk of Cardiovascular Disease in HIV-Infected Adults [REPRIEVE]; NCT02344290)