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Relative risk of cardiovascular disease among people living with HIV : a systematic review and meta‐analysis
Open accessAbstract
Objectives: The aim of this study was to estimate the relative risk of cardiovascular disease ( CVD ) among people living with HIV ( PLHIV ) compared with the HIV ‐uninfected population. Methods: We conducted a systematic review and meta‐analysis of studies from the peer‐reviewed literature. We searched the M edline database for relevant journal articles published before A ugust 2010. Eligible studies were observational and randomized controlled trials, reporting CVD , defined as myocardial infarction ( MI ), ischaemic heart disease, cardiovascular and cerebrovascular events or coronary heart disease among HIV ‐positive adults. Pooled relative risks were calculated for various groupings, including different classes of antiretroviral therapy ( ART ). Results: The relative risk of CVD was 1.61 [95% confidence interval ( CI ) 1.43–1.81] among PLHIV without ART compared with HIV ‐uninfected people. The relative risk of CVD was 2.00 (95% CI 1.70–2.37) among PLHIV on ART compared with HIV ‐uninfected people and 1.52 (95% CI 1.35–1.70) compared with treatment‐naïve PLHIV . We estimate the relative risk of CVD associated with protease inhibitor ( PI )‐, nucleoside reverse transcriptase inhibitor‐ and nonnucleoside reverse transcriptase inhibitor‐based ART to be 1.11 (95% CI 1.05–1.17), 1.05 (95% CI 1.01–1.10) and 1.04 (95% CI 0.99–1.09) per year of exposure, respectively. Not all ART was associated with increased risk; specifically, lopinavir/ritonavir and abacavir were associated with the greater risk and the relative risk of MI for PI ‐based versus non‐ PI ‐based ART was 1.41 (95% CI 1.20–1.65). Conclusion: PLHIV are at increased risk of cardiovascular disease. Although effective in prolonging survival, ART (in particular PI ‐based regimens) is related to further increased risk of CVD events among people at highest initial absolute risk of cardiovascular disease.
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“HIV patients have been found to have a higher risk of cardiovascular events, which was even higher in patients treated with protease inhibitors (Friis‐Moller et al, 2007; Islam et al, 2012; Shah et al, 2018).”
From The struggle of a good friend getting old: cellular senescence in viral responses and therapy (2021) · cites this paper as Islam et al, 2012
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Catapano, A. L., Reiner, Ž., De Backer, G., Graham, I., Taskinen, M.-R., Wiklund, O., Agewall, S., Alegria, E., Chapman, M. J., Durrington, P., et al. (2011) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2011.06.028 · Cited by 706
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“Two recently published systematic reviews collected, analysed, and synthesized the available literature.(2,56) The more recent observational data meta-analysis by”
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“A recent meta-analysis that estimated the relative risk of cardiovascular disease among HIV-infected patients found HIV infection to confer a 61 % increased risk of cardiovascular disease endpoints [8].”
BackgroundNoncalcified Coronary Atherosclerotic Plaque and Immune Activation in HIV-Infected Women
Fitch, K. V., Srinivasa, S., Abbara, S., Burdo, T. H., Williams, K. C., Eneh, P., Lo, J., & Grinspoon, S. K. (2013) · The Journal of Infectious Diseases · doi:10.1093/infdis/jit508 · Cited by 206
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Monocytes as Regulators of Inflammation and HIV-Related Comorbidities during cART
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“(a) Proportion of non-AIDS deaths due to CVD. (b) Proportion of non-AIDS deaths due to malignancies.”
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“Yet, research also suggests that ART can be a risk factor for NCDs like CVD [6,7] and diabetes [8,9], with HIV-infected individuals on ART twice as likely to have CVD as their HIV-negative counterparts [10].”
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BackgroundIntegrating HIV and hypertension management in low-resource settings: Lessons from Malawi
Patel, P., Speight, C., Maida, A., Loustalot, F. V., Giles, D., Phiri, S., GUPTA, S. K., & Raghunathan, P. L. (2018) · PLoS Medicine · doi:10.1371/journal.pmed.1002523 · Cited by 61
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“It has been reported that HIVinfected individuals on ART have a twofold higher risk of CVD compared to matched uninfected individuals [68] and that 41.”
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“This may have major public health implications related to long-term risk of atherosclerotic vascular disease, for which Hiv-infected individuals are already at increased risk because of persistent immune activation.(25) The true proportion with at-risk values may be even higher.”
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“81) among ART-naïve HIVinfected compared with HIV-uninfected people [24, 25].”
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The struggle of a good friend getting old: cellular senescence in viral responses and therapy
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“HIV patients have been found to have a higher risk of cardiovascular events, which was even higher in patients treated with protease inhibitors (Friis-Moller et al , 2007; Islam et al , 2012; Shah et al , 2018).”
Hijmans, J. G., Stockelman, K. A., Garcia, V. P., Levy, M. V., Brewster, L. M., Bammert, T. D., Greiner, J. J., Stauffer, B. L., Connick, E., & DeSouza, C. A. (2019) · Journal of the American Heart Association · doi:10.1161/jaha.118.011134 · Cited by 52
“Traditional risk factors and exposure to ART do not fully account for the increased incidence and severity of vascular disease and events associated with HIV-1.(3) For example, autopsy findings from HIV-1–seropositive children and young adults have reported clinically relevant atherosclerotic lesions and endovascular…”
BackgroundInfluentialChanges in Causes of Death Among Persons with AIDS: San Francisco, California, 1996–2011
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“28,30,31 The elevated risk of death from lung, anal, and liver cancers, coronary heart disease, and liver disease are, at least to some degree, and either directly or indirectly, due to behaviors such as use of tobacco and alcohol, anal sex, and injection drug use that occur in higher frequency…”
Levy, M., Ae, G., Hart, R. A., Happ, L. P., Hadigan, C. M., & Castel, A. D. (2017) · HIV Medicine · doi:10.1111/hiv.12516 · Cited by 53
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“Even though increased CVD risk among HIV-infected patients has been well established [40], one possible explanation for the lack of association between HIV status and cIMT is that specific mechanisms that lead to increased CVD risk among HIV-infected patients may not involve the traditional mechanisms described so far…”
BackgroundShould we expand the concept of coronary heart disease equivalents?
Katsiki, N., Athyros, V. G., Karagiannis, A. I., Wierzbicki, A. S., & Mikhailidis, D. P. (2014) · Current Opinion in Cardiology · doi:10.1097/hco.0000000000000068 · Cited by 49
Gatell, J. M., Assoumou, L., Moyle, G. J., Waters, L. J., Johnson, M. A., Domingo, P., Fox, J., Martínez, E., Stellbrink, H.-J., Guaraldi, G., et al. (2018) · Clinical Infectious Diseases · doi:10.1093/cid/ciy505 · Cited by 49
HIV-related cardiovascular diseases: the search for a unifying hypothesis
Dominick, L., Midgley, N., Swart, L.-M., Sprake, D., Deshpande, G., Laher, I., Joseph, D. E., Teer, E., & Essop, M. F. (2020) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00549.2019 · Cited by 51
“In fact, PLHIV exhibit a 61% increased relative risk for CVD development compared with healthy, noninfected individuals (95).”
BackgroundHIV / HCV coinfection and the risk of cardiovascular disease: A meta‐analysis
Osibogun, O. I., Ogunmoroti, O., Michos, E. D., Spatz, E. S., Olubajo, B., Nasir, K., Madhivanan, P., & Maziak, W. (2017) · Journal of Viral Hepatitis · doi:10.1111/jvh.12725 · Cited by 48
Cardiovascular toxicity of abacavir
Álvarez, Á., Orden, S., Andújar, I., Collado‐Díaz, V., Núñez-Delgado, S., Galindo, M. J., Estrada, V., Apostolova, N., & Esplugues, J. V. (2017) · AIDS · doi:10.1097/qad.0000000000001547 · Cited by 47
“Meta-analysis Due to the difficulty in establishing a consensus, four meta-analyses of the published data have been conducted [30–33]: two, which include clinical trials and cohort studies, support an ABC–MI association [30,31], whereas the remaining two, which only consider clinical trials, do not [32,33].”
BackgroundMethodDimala, C. A., Blencowe, H. K., & Choukem, S. P. (2018) · PLoS ONE · doi:10.1371/journal.pone.0201404 · Cited by 47
Cardiovascular disease risk in an aging HIV population: not just a question of biology
So-Armah, K., & Freiberg, M. S. (2014) · Current Opinion in HIV and AIDS · doi:10.1097/coh.0000000000000065 · Cited by 45
Gut Microbiota in Human Immunodeficiency Virus–Infected Individuals Linked to Coronary Heart Disease
Kehrmann, J., Menzel, J., Saeedghalati, M., Obeid, R., Schulze, C., Holzendorf, V., Farahpour, F., Reinsch, N., Klein‐Hitpaß, L., Streeck, H., et al. (2018) · The Journal of Infectious Diseases · doi:10.1093/infdis/jiy524 · Cited by 49
López-Jiménez, F. A., Simha, V., Thomas, R. J., Allison, T. G., Basu, A., Fernandes, R., Hurst, R. T., Kopecky, S. L., Kullo, I. J., Mulvagh, S. L., et al. (2014) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2014.06.016 · Cited by 45
HIV , highly active antiretroviral therapy and the heart: a cellular to epidemiological review
Lambert, C., Sandesara, P. B., Hirsh, B. J., Shaw, L. J., Lewis, W., Quyyumi, A. A., Schinazi, R., Post, W. S., & Sperling, L. S. (2015) · HIV Medicine · doi:10.1111/hiv.12346 · Cited by 44
Evidence for a vascular microbiome and its role in vessel health and disease
Clifford, A. H., & Hoffman, G. S. (2015) · Current Opinion in Rheumatology · doi:10.1097/bor.0000000000000184 · Cited by 44
“Hepatitis C and HIV have been of particular interest given their known associations with accelerated atherosclerosis [55,56].”
BackgroundHaissman, J. M., Knudsen, A., Hoel, H., Kjær, A., Kristoffersen, U. S., Berge, R. K., Katzenstein, T. L., Svardal, A. M., Ueland, T., Aukrust, P., et al. (2015) · JAIDS Journal of Acquired Immune Deficiency Syndromes · doi:10.1097/qai.0000000000000843 · Cited by 43
Short-term and long-term cardiovascular risk, metabolic syndrome and HIV in Tanzania
Kingery, J. R., Alfred, Y., Smart, L. R., Nash, E., Todd, J., Naguib, M. R., Downs, J. A., Kalluvya, S. E., Kataraihya, J. B., & Peck, R. N. (2016) · Heart · doi:10.1136/heartjnl-2015-309026 · Cited by 43
Recommendations for Managing Drug–Drug Interactions with Statins and HIV Medications
Wiggins, B. S., Lamprecht, D. G., Page, R. L., II, & Saseen, J. J. (2017) · American Journal of Cardiovascular Drugs · doi:10.1007/s40256-017-0222-7 · Cited by 43
Auclair, M., Afonso, P., Capel, E., Caron-Debarle, M., & Capeau, J. (2014) · Antiviral Therapy · doi:10.3851/imp2752 · Cited by 42
Cardiovascular Disease in the Setting of Human Immunodeficiency Virus Infection
Pinto, D. S. M., & Vaz‐da‐Silva, M. (2018) · Current Cardiology Reviews · doi:10.2174/1573403x13666171129170046 · Cited by 42
“pt [8], accounting for high death rates due to AIDS [3, 9], into a chronic disease [4, 10-13].”
BackgroundInfluentialEpidemiology of coronary heart disease in patients with human immunodeficiency virus.
Triant, V. A. (2014) · PubMed · doi:10.3908/ricm15s1s002 · Cited by 41
McGettrick, P., Barco, E. Á., & Mallon, P. W. G. (2018) · Healthcare · doi:10.3390/healthcare6010017 · Cited by 41
“First generation protease inhibitors such as indinavir and saquinavir, although rarely used currently, are also known to affect serum lipid concentrations, with cumulative exposure associated with additional CVD risk [31].”
BackgroundRecent abacavir use and incident cardiovascular disease in contemporary-treated people with HIV
Jaschinski, N., Greenberg, L., Neesgaard, B., Miró, J. M., Grabmeier‐Pfistershammer, K., Wandeler, G., Smith, C. J., Wit, S. D., Wit, F. W. N. M., Pelchen–Matthews, A., et al. (2022) · AIDS · doi:10.1097/qad.0000000000003373 · Cited by 39
“In addition, associations between CVD and certain ARTs are well described [4].”
BackgroundMullis, C. E., & Swartz, T. H. (2020) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2020.00095 · Cited by 41
“In a meta-analysis, PWH when compared to HIV-1 uninfected control patients had an increased relative risk of CVD (40, 41).”
BackgroundLaurence, J. C., Elhadad, S., & Ahamed, J. (2018) · Open Heart · doi:10.1136/openhrt-2018-000823 · Cited by 38
Inflammation Strikes Again: Frailty and HIV
Fukui, S. M., Piggott, D. A., & Erlandson, K. M. (2018) · Current HIV/AIDS Reports · doi:10.1007/s11904-018-0372-5 · Cited by 39
Cardiovascular disease in HIV patients: recent advances in predicting and managing risk
McGettrick, P., Mallon, P. W. G., & Sabin, C. A. (2020) · Expert Review of Anti-infective Therapy · doi:10.1080/14787210.2020.1757430 · Cited by 38
“First-generation PIs such as indinavir and amprenavir, although not currently recommended in treatment guidelines, affect serum lipid concentrations, with cumulative exposure associated with additional CVD risk [20].”
BackgroundMahlangu, K., Modjadji, P., & Madiba, S. (2020) · Healthcare · doi:10.3390/healthcare8030290 · Cited by 35
Environmental carcinogens and mutational pathways in atherosclerosis
Pulliero, A., Godschalk, R., Andreassi, M. G., Curfs, D. M. J., van Schooten, F., & Izzotti, A. (2015) · International Journal of Hygiene and Environmental Health · doi:10.1016/j.ijheh.2015.01.007 · Cited by 37
Editorial: Cardioimmunology: Inflammation and Immunity in Cardiovascular Disease
Lazzerini, P. E., Hamilton, R. M., & Boutjdir, M. (2019) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2019.00181 · Cited by 34
Arnbjerg, C. J., Vestad, B., Hov, J. R., Pedersen, K. K., Jespersen, S., Johannesen, H. H., Holm, K., Halvorsen, B. L., Fallentin, E., Hansen, A. E., et al. (2018) · JAIDS Journal of Acquired Immune Deficiency Syndromes · doi:10.1097/qai.0000000000001693 · Cited by 34
HIV and the growing health burden from noncommunicable diseases in Botswana: modelling study
Haacker, M., Bärnighausen, T., & Atun, R. A. (2019) · Journal of Global Health · doi:10.7189/jogh.09.010428 · Cited by 34
Cardiovascular Disease Burden in Rural Africa: Does HIV and Antiretroviral Treatment Play a Role?
Vos, A. G., Barth, R. E., Klipstein‐Grobusch, K., Tempelman, H. A., Devillé, W. L. J. M., Dodd, C. N., Coutinho, R. A., & Grobbee, D. E. (2020) · Journal of the American Heart Association · doi:10.1161/jaha.119.013466 · Cited by 34
Taylor, K. A., Smyth, E., Rauzi, F., Cerrone, M., Khawaja, A. A., Gazzard, B., Nelson, M. R., Boffito, M., & Emerson, M. (2019) · British Journal of Pharmacology · doi:10.1111/bph.14589 · Cited by 33
Semu, H., Zack, R., Liu, E., Hertzmark, E., Spiegelman, D., Sztam, K. A., Hawkins, C., Chalamila, G., Muya, A., Siril, H., et al. (2014) · Journal of the International Association of Providers of AIDS Care · doi:10.1177/2325957414542574 · Cited by 34
“Excess weight in HIV-infected patients has the potential to exacerbate higher rates of cardiovascular disease seen in HIV-infected patients who receive certain ART medications.(47) Thus, although nutritional status in HIVinfected patients may reflect larger national secular trends in obesity, specific obesity-related…”
BackgroundEffects of HIV-1 gp120 and tat on endothelial cell sensescence and senescence-associated microRNAs
Hijmans, J. G., Stockleman, K., Reiakvam, W., Levy, M. V., Brewster, L. M., Bammert, T. D., Greiner, J. J., Connick, E., & DeSouza, C. A. (2018) · Physiological Reports · doi:10.14814/phy2.13647 · Cited by 31
“Human immunodeficiency virus (HIV)-1 infection is associated with an increased risk and prevalence of atherosclerotic cardiovascular disease (CVD) (Islam et al. 2012; Gibellini et al. 2013; Wang et al. 2015).”
BackgroundControlling the HIV/AIDS epidemic: current status and global challenges
Demberg, T., & Robert-Guroff, M. (2012) · Frontiers in Immunology · doi:10.3389/fimmu.2012.00250 · Cited by 31
“An increased risk for myocardial infarct has been attributed to the protease inhibitors lopinavir/ritonavir and the transcriptase inhibitor abacavir (Fichtenbaum, 2010; Islam et al., 2012a,b; Maggi et al., 2012).”
BackgroundNtusi, N., & Ntsekhe, M. (2016) · ESC Heart Failure · doi:10.1002/ehf2.12087 · Cited by 31
“ported that HIV-associated coronary artery and cerebrovascular disease is common.(37,38) Moreover, compared with HIV uninfected populations, the relative risk (RR) of events was higher both for untreated and ART-treated HIV infected persons (RR = 1.”
BackgroundKnobel, H., Domingo, P., Suárez-Lozano, I., Gutiérrez, F., Estrada, V., Palacios, R., Antela, A., Blanco, J. R., Fulladosa, X., & Refollo, E. (2018) · Enfermedades Infecciosas y Microbiología Clínica · doi:10.1016/j.eimc.2018.09.015 · Cited by 31
Tripathi, A., Liese, A. D., Winniford, M. D., Jerrell, J. M., Albrecht, H., Rizvi, A. A., Zhang, J., & Duffus, W. A. (2014) · Clinical Cardiology · doi:10.1002/clc.22311 · Cited by 31
HIV Disease Activity as a Modulator of Lipoprotein(a) and Allele-Specific Apolipoprotein(a) Levels
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Ambulatory Blood Pressure Monitoring in Individuals with HIV: A Systematic Review and Meta-Analysis
Kent, S. T., Bromfield, S. G., Burkholder, G., Falzon, L., Oparil, S., Overton, E. T., Mugavero, M. J., Schwartz, J. E., Shimbo, D., & Muntner, P. (2016) · PLoS ONE · doi:10.1371/journal.pone.0148920 · Cited by 30
“83) times the risk for CVD outcomes compared with their HIV counterparts [3].”
BackgroundInitiation of antiretroviral therapy at high CD4 cell counts
Longenecker, C. T., & Triant, V. A. (2013) · Current Opinion in HIV and AIDS · doi:10.1097/coh.0000000000000015 · Cited by 30
Continued Interest and Controversy: Vitamin D in HIV
Hsieh, E., & Yin, M. T. (2018) · Current HIV/AIDS Reports · doi:10.1007/s11904-018-0401-4 · Cited by 30
The case for a global focus on multiple chronic conditions
Hajat, C., & Kishore, S. P. (2018) · BMJ Global Health · doi:10.1136/bmjgh-2018-000874 · Cited by 32
Metadata
- Authors
- Islam, F., Wu, J., Jansson, J., & Wilson, D.
- Affiliations
- The Kirby Institute Faculty of Medicine University of New South Wales Sydney NSW Australia
- UNSW Sydney (AU)
- Corresponding author
- Wilson, DP
- ORCID
- Venue
- HIV Medicine
- Publisher
- Wiley
- Published
- 2012-03-14
- Volume
- 13
- Issue
- 8
- Pages
- 453-468
- ISSN
- 1464-2662 (ISSN-L)
- 1468-1293
- OpenAlex
- W1677033108
- Cited by
- 432
- References
- 40
- Citations by year
- 2026: 13 · 2025: 16 · 2024: 28 · 2023: 19 · 2022: 31 · 2021: 39 · 2020: 42 · 2019: 28 · 2018: 44 · 2017: 34 · 2016: 40 · 2015: 29 · 2014: 27 · 2013: 26 · 2012: 15
- FWCI
- 6.87
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- HIV Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Australian Government
- Medical Research Council
- Australian Research Council (DP1093026, FT0991990)
- National Health and Medical Research Council (630495)
- Topics
- Health Sciences › Medicine › Infectious Diseases › HIV-related health complications and treatments
- Health Sciences › Medicine › Infectious Diseases › HIV/AIDS Research and Interventions
- Health Sciences › Medicine › Infectious Diseases › HIV/AIDS drug development and treatment
- Keywords
- cardiovascular disease, people living with HIV, antiretroviral therapy, protease inhibitors, myocardial infarction, ischemic heart disease, coronary artery disease, cerebrovascular events, lopinavir/ritonavir, abacavir, cardiovascular risk
- MeSH terms
- Adult, Cardiovascular Diseases, Humans, Protease Inhibitors, Risk Factors, HIV Infections, Incidence, Reverse Transcriptase Inhibitors, Anti-Retroviral Agents
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