{"doi":"10.1016/j.jacadv.2025.101781","title":"Coronary Plaque, Inflammation, Subclinical Myocardial Injury, and Major Adverse Cardiovascular Events in the REPRIEVE Substudy","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: A total of 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. 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Ribaudo","orcid":"0000-0002-0394-3990","position":1,"is_corresponding":false},{"id":759908,"name":"Sara McCallum","orcid":"0000-0002-0289-1295","position":2,"is_corresponding":false},{"id":381595,"name":"Markella V. Zanni","orcid":"0000-0002-4711-3956","position":3,"is_corresponding":false},{"id":278980,"name":"Christopher R. deFilippi","orcid":"0000-0002-0660-4943","position":4,"is_corresponding":false},{"id":503214,"name":"Jana Taron","orcid":"0000-0002-1388-7531","position":5,"is_corresponding":false},{"id":322819,"name":"Júlia Karády","orcid":"0000-0002-6640-6260","position":6,"is_corresponding":false},{"id":282486,"name":"Borek Foldyna","orcid":"0000-0002-2466-4827","position":7,"is_corresponding":false},{"id":975377,"name":"Kayla Paradis","orcid":null,"position":8,"is_corresponding":false},{"id":446489,"name":"Sarah M Chu","orcid":null,"position":9,"is_corresponding":false},{"id":1015265,"name":"Marissa R Diggs","orcid":null,"position":10,"is_corresponding":false},{"id":282163,"name":"Tricia H. Burdo","orcid":"0000-0002-4224-7381","position":11,"is_corresponding":false},{"id":396976,"name":"Judith S. Currier","orcid":"0000-0003-4279-4737","position":12,"is_corresponding":false},{"id":329844,"name":"Gerald S. Bloomfield","orcid":"0000-0002-7176-1611","position":13,"is_corresponding":false},{"id":335272,"name":"Carl J. Fichtenbaum","orcid":"0000-0002-6778-7253","position":14,"is_corresponding":false},{"id":380908,"name":"Carlos Malvestutto","orcid":"0000-0003-3156-2965","position":15,"is_corresponding":false},{"id":12096,"name":"Judith A. Aberg","orcid":"0000-0001-8162-0284","position":16,"is_corresponding":false},{"id":282480,"name":"Thomas Mayrhofer","orcid":"0000-0001-6287-5185","position":17,"is_corresponding":false},{"id":282488,"name":"Pamela S. Douglas","orcid":"0000-0001-9876-4049","position":18,"is_corresponding":false},{"id":12007,"name":"Steven Grinspoon","orcid":"0000-0002-6338-000X","position":19,"is_corresponding":false},{"id":282485,"name":"Michael T. Lu","orcid":"0000-0003-4696-9610","position":0,"is_corresponding":true}],"reference_count":28,"raw_metadata":null,"created_at":"2026-07-19T02:48:59.410472Z","pmid":"40373520","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}