Lu Michael T, Ribaudo Heather J, McCallum Sara, Zanni Markella V, deFilippi Christopher, Taron Jana, Karady Julia, Foldyna Borek, Paradis Kayla, Chu Sarah M, Diggs Marissa R, Burdo Tricia H, Currier Judith S, Bloomfield Gerald S, Fichtenbaum Carl J, Malvestutto Carlos D, Aberg Judith A, Mayrhofer Thomas, Douglas Pamela S, Grinspoon Steven K
Cardiovascular Imaging Research Center, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
JACC Adv. 2025 May 14;4(6 Pt 1):101781. doi: 10.1016/j.jacadv.2025.101781.
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.
The purpose of this study was to assess the relationship of coronary plaque, inflammation, and subclinical myocardial injury with MACE.
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.
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.
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).
在“REPRIEVE（预防HIV患者血管事件随机试验）”中，匹伐他汀可预防主要不良心血管事件（MACE），并减少HIV患者及中低传统心血管疾病（CVD）风险人群的非钙化冠状动脉斑块（NCP）。
本研究旨在评估冠状动脉斑块、炎症和亚临床心肌损伤与MACE之间的关系。
2015年4月至2018年2月期间，在美国31个地点招募了804名“REPRIEVE机制亚研究”参与者，随机分为匹伐他汀4mg/天组或安慰剂组，并随访MACE事件（中位时间6.2年[第一四分位数-第三四分位数5.4-7.1]），评估基线NCP、炎症标志物（高敏C反应蛋白[hs-CRP]、白细胞介素（IL）-6、氧化低密度脂蛋白和脂蛋白相关磷脂酶A2）以及亚临床心肌损伤（高敏心肌肌钙蛋白T[hs-cTnT]）与MACE之间的关系。
在入组参与者中（17%为女性[139/804]，47%为非白人[379/804]，中位年龄51岁，中位低密度脂蛋白105mg/dL，10年动脉粥样硬化性CVD[ASCVD]风险4.6%，40%[299/755]有非钙化斑块），匹伐他汀组MACE发病率为7.26/1000人年（95%CI：4.51-11.7）（17例事件），安慰剂组为9.15/1000人年（95%CI：5.97-14.0）（21例事件）。有（对比无）非钙化斑块者发生MACE的风险更高（HR：2.5；[95%CI：1.3-4.8]；P=0.008），研究入组时hs-CRP（P=0.049）、IL-6（P=0.033）和hs-cTnT水平较高者也是如此（P=0.003），在ASCVD风险调整后仍然如此。在探索性预测模型中，在ASCVD风险基础上加入hs-CRP、IL-6和hs-cTnT后，曲线下综合面积增加到0.72，C统计量增加到0.73（0.62-0.84），而单独的ASCVD风险曲线下综合面积为0.58，C统计量为0.56（0.45-0.67）。
在无心脏症状且ASCVD风险中低的HIV患者中，NCP以及较高的hs-CRP、IL-6和hs-cTnT与MACE相关，且相较于传统风险因素可改善风险预测。（评估匹伐他汀降低HIV感染成人心血管疾病风险[REPRIEVE]；NCT02344290）
