Michael T. Lu MD, MPH , Heather J. Ribaudo PhD , Sara McCallum MPH , Markella V. Zanni MD , Christopher deFilippi MD , Jana Taron MD , Julia Karady MD, PhD, MPH , Borek Foldyna MD, PhD , Kayla Paradis MBA , Sarah M. Chu MSN , Marissa R. Diggs BA , Tricia H. Burdo PhD , Judith S. Currier MD , Gerald S. Bloomfield MD, MPH , Carl J. Fichtenbaum MD , Carlos D. Malvestutto MD, MPH , Judith A. Aberg MD , Thomas Mayrhofer PhD , Pamela S. Douglas MD , Steven K. Grinspoon MD
{"title":"冠状动脉斑块、炎症、亚临床心肌损伤和主要不良心血管事件的研究","authors":"Michael T. Lu MD, MPH , Heather J. Ribaudo PhD , Sara McCallum MPH , Markella V. Zanni MD , Christopher deFilippi MD , Jana Taron MD , Julia Karady MD, PhD, MPH , Borek Foldyna MD, PhD , Kayla Paradis MBA , Sarah M. Chu MSN , Marissa R. Diggs BA , Tricia H. Burdo PhD , Judith S. Currier MD , Gerald S. Bloomfield MD, MPH , Carl J. Fichtenbaum MD , Carlos D. Malvestutto MD, MPH , Judith A. Aberg MD , Thomas Mayrhofer PhD , Pamela S. Douglas MD , Steven K. Grinspoon MD","doi":"10.1016/j.jacadv.2025.101781","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Objectives</h3><div>The purpose of this study was to assess the relationship of coronary plaque, inflammation, and subclinical myocardial injury with MACE.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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]; <em>P</em> = 0.008), with higher levels of hs-CRP (<em>P</em> = 0.049), IL-6 (<em>P</em> = 0.033), and hs-cTnT (<em>P</em> = 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.</div></div><div><h3>Conclusions</h3><div>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]; <span><span>NCT02344290</span><svg><path></path></svg></span>)</div></div>","PeriodicalId":73527,"journal":{"name":"JACC advances","volume":"4 6","pages":"Article 101781"},"PeriodicalIF":0.0000,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Coronary Plaque, Inflammation, Subclinical Myocardial Injury, and Major Adverse Cardiovascular Events in the REPRIEVE Substudy\",\"authors\":\"Michael T. Lu MD, MPH , Heather J. Ribaudo PhD , Sara McCallum MPH , Markella V. Zanni MD , Christopher deFilippi MD , Jana Taron MD , Julia Karady MD, PhD, MPH , Borek Foldyna MD, PhD , Kayla Paradis MBA , Sarah M. Chu MSN , Marissa R. Diggs BA , Tricia H. Burdo PhD , Judith S. Currier MD , Gerald S. Bloomfield MD, MPH , Carl J. Fichtenbaum MD , Carlos D. Malvestutto MD, MPH , Judith A. Aberg MD , Thomas Mayrhofer PhD , Pamela S. Douglas MD , Steven K. Grinspoon MD\",\"doi\":\"10.1016/j.jacadv.2025.101781\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><div>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.</div></div><div><h3>Objectives</h3><div>The purpose of this study was to assess the relationship of coronary plaque, inflammation, and subclinical myocardial injury with MACE.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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]; <em>P</em> = 0.008), with higher levels of hs-CRP (<em>P</em> = 0.049), IL-6 (<em>P</em> = 0.033), and hs-cTnT (<em>P</em> = 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.</div></div><div><h3>Conclusions</h3><div>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. 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Coronary Plaque, Inflammation, Subclinical Myocardial Injury, and Major Adverse Cardiovascular Events in the REPRIEVE Substudy
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)
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