Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2025 Dec 16;14(24):e043757.
doi: 10.1161/JAHA.125.043757. Epub 2025 Dec 11.

Baseline ECG and Cardiovascular Outcomes in People With HIV: Insights From REPRIEVE

Aya Awwad  1 , Christopher de Filippi  2 , Heather Ribaudo  3 , Markella V Zanni  1 , Carl J Fichtenbaum  4 , Carlos D Malvestutto  5 , Judith A Aberg  6 , Marissa R Diggs  1 , Sarah M Chu  1 , Alex B Lu  1 , Craig A Sponseller  7 , Shashwatee Bagchi  8 , Celestine Wanjalla  9 , Graham Smith  10 , Kara W Chew  11 , Judith S Currier  11 , Sophia Zhao  1 , Michael T Lu  12 , Pamela S Douglas  13 , Steven K Grinspoon  1 , Gerald S Bloomfield  13   14
Affiliations
Randomized Controlled Trial

Baseline ECG and Cardiovascular Outcomes in People With HIV: Insights From REPRIEVE

Aya Awwad et al. J Am Heart Assoc. .

Abstract

Background: With antiretroviral therapy, people with HIV (PWH) have an increased burden of cardiovascular disease. The REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV) trial demonstrated that pitavastatin reduces major adverse cardiovascular events (MACEs) among PWH at low to moderate traditional atherosclerotic risk. Electrocardiographic abnormalities are common in PWH, but little is known about their association with MACEs. We sought to examine whether baseline electrocardiographic abnormalities are associated with increased MACE risk among a global primary cardiovascular disease prevention cohort of PWH in REPRIEVE.

Methods: In this observational analysis, entry electrocardiographic abnormalities were adjudicated and classified as major or minor abnormalities. Multivariable cause-specific Cox proportional hazards models assessed the association of electrocardiographic abnormalities with MACEs while stratifying for treatment effect. The model improvement with the addition of the ECG to a model with the pooled cohort equations risk score was examined.

Results: Among 7719 participants (median age, 50 years; 69% men), 49% had ≥1 electrocardiographic abnormality, with 3% classified as major. Over a median of 5.6 years, a major electrocardiographic abnormality was associated with a 2.42-fold (95% CI, 1.49-3.91) higher hazard of incident MACEs, whereas minor abnormalities were not. Specific abnormalities associated with MACEs were chamber enlargement and infarct/ischemia pattern. No significant subgroup- or treatment-related interaction was observed. Adding electrocardiographic findings to traditional risk factors increased the C-statistic modestly (+0.01).

Conclusions: Among PWH in REPRIEVE, electrocardiographic abnormalities were common, but major electrocardiographic abnormalities were rare. Though major abnormalities were associated with increased hazard of MACEs, routine electrocardiographic screening is unlikely to improve the prediction of future cardiovascular events in this primary prevention population with low to moderate cardiovascular risk.

Keywords: ECG; HIV; risk stratification; screening.

PubMed Disclaimer

Conflict of interest statement

C.D. reports funding from the National Institutes of Health, Abbott Diagnostics, FujiRebio, Quidel‐Ortho, Randox, Roche Diagnostics, and Siemens Healthineers outside the scope of this submitted work. He also reported REPRIEVE substudy funding as a subcontract from the National Institutes of Health through the Massachusetts General Hospital outside the scope of this work. He also reports consulting for Abbott Diagnostics, Quidel‐Ortho, Roche Diagnostics, Siemens Healthineers, and TOSOH outside the scope of this submitted work. He receives royalty payments from UpToDate. He is a coinvestor for patent 10509044, outside the scope of this submitted work. H.J.R. reports grants from Kowa Pharmaceuticals during the conduct of the study, as well as grants from the National Institutes of Health/National Institute of Allergy and Infectious Diseases, National Institutes of Health/National Heart, Lung, and Blood Institute, National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases, and National Institutes of Health/National Institute on Aging, outside of the submitted work. Markella V. Zanni reports grant support through her institution from the National Institutes of Health/National Institute of Allergy and Infectious Diseases and Gilead Sciences, Inc., relevant to the conduct of the study, as well as grants from National Institutes of Health/National Institute of Allergy and Infectious Diseases and National Institutes of Health/National Heart, Lung, and Blood Institute; support for attending the Conference on Retroviruses and Opportunistic Infections and International Workshop for HIV and Women from the conference organizing committee when abstract reviewer or speaker; and participation in DSMB for National Institutes of Health–funded studies, outside the submitted work. C.J.F. reports research grant support through his institution from Gilead Sciences and ViiV Healthcare. C.D.M. reports institutional research support by Lilly and honoraria from ViiV Healthcare, Gilead Sciences, and Pfizer for advisory board membership, all outside the submitted work. J.A.A. reports grants from Massachusetts General Hospital during the conduct of the study; institutional research support for clinical trials from Gilead Sciences, GlaxoSmithKline, Janssen, Macrogenics, Merck, Pfizer, Regeneron, and ViiV Healthcare; and personal fees for advisory boards from GlaxoSmithKline/ViiV, Invivyd, Merck, and Regeneron; and participation on the Data Safety and Monitoring Board for Kintor Pharmaceuticals, all outside the submitted work. C.A.S. reports as full‐time equivalent with Kowa Pharmaceuticals America, Inc. J.S.C. reports consulting fees from Merck and Company outside the submitted work. M.T.L. reports grant support through his institution from the National Institutes of Health/National Heart, Lung, and Blood Institute and Kowa Pharmaceuticals America for the conduct of the study. He also reports research support to his institution from the American Heart Association, AstraZeneca, Ionis, Johnson & Johnson Innovation, MedImmune, the National Academy of Medicine, the National Institutes of Health/National Heart, Lung, and Blood Institute, and the Risk Management Foundation of the Harvard Medical Institutions Inc. outside of the submitted work. S.K.G. reports grant support through his institution from National Institutes of Health, Kowa Pharmaceuticals America, Inc., Gilead Sciences, Inc., and ViiV Healthcare for the conduct of the study; personal fees from Theratechnologies and ViiV; and service on the Scientific Advisory Board of Marathon Asset Management, all outside the submitted work. The remaining authors have no disclosures to report.

Figures

Figure 1
Figure 1. Cause‐specific Cox proportional hazards regression models for the association of electrocardiographic abnormalities and first primary MACE.
Both the unadjusted and adjusted models were stratified by treatment allocation. Adjusted models included the exposure (electrocardiographic abnormality) and were adjusted for age, sex, race, Global Burden of Disease region, cigarette smoking, substance use, total cholesterol, low‐density lipoprotein cholesterol, high‐density lipoprotein cholesterol, systolic and diastolic blood pressure, fasting glucose, body mass index group, family history of premature cardiovascular disease, ART duration at entry, ART regimen class, and HIV‐1 RNA viral load. Missing values in fasting glucose and HIV‐1 RNA were handled using a missing indicator approach. The adjusted models included 7698 participants and 256 events. ART indicates antiretroviral therapy; HR, hazard ratio; IVCD, intraventricular conduction delay; and MACE, major adverse cardiovascular event.
See this image and copyright information in PMC

References

    1. Freiberg MS, Duncan MS, Alcorn C, Chang CH, Kundu S, Mumpuni A, Smith EK, Loch S, Bedigian A, Vittinghoff E, et al. HIV infection and the risk of World Health Organization‐defined sudden cardiac death. J Am Heart Assoc. 2021;10:e021268. doi: 10.1161/JAHA.121.021268 - DOI - PMC - PubMed
    1. Boulle A, Schomaker M, May MT, Hogg RS, Shepherd BE, Monge S, Keiser O, Lampe FC, Giddy J, Ndirangu J, et al. Mortality in patients with HIV‐1 infection starting antiretroviral therapy in South Africa, Europe, or North America: a collaborative analysis of prospective studies. PLoS Med. 2014;11:e1001718. doi: 10.1371/journal.pmed.1001718 - DOI - PMC - PubMed
    1. Shah ASV, Stelzle D, Lee KK, Beck EJ, Alam S, Clifford S, Longenecker CT, Strachan F, Bagchi S, Whiteley W, et al. Global burden of atherosclerotic cardiovascular disease in people living with HIV: systematic review and meta‐analysis. Circulation. 2018;138:1100–1112. doi: 10.1161/CIRCULATIONAHA.117.033369 - DOI - PMC - PubMed
    1. Triant VA, Perez J, Regan S, Massaro JM, Meigs JB, Grinspoon SK, D’Agostino RB Sr. Cardiovascular risk prediction functions underestimate risk in HIV infection. Circulation. 2018;137:2203–2214. doi: 10.1161/CIRCULATIONAHA.117.028975 - DOI - PMC - PubMed
    1. Grinspoon SK, Fitch KV, Zanni MV, Fichtenbaum CJ, Umbleja T, Aberg JA, Overton ET, Malvestutto CD, Bloomfield GS, Currier JS, et al. Pitavastatin to prevent cardiovascular disease in HIV infection. N Engl J Med. 2023;389:687–699. doi: 10.1056/NEJMoa2304146 - DOI - PMC - PubMed

Publication types

Substances

LinkOut - more resources