Time to Recognize HIV Infection as a Major Cardiovascular Risk Factor
2018; Lippincott Williams & Wilkins; Volume: 138; Issue: 11 Linguagem: Inglês
10.1161/circulationaha.118.036211
ISSN1524-4539
AutoresPriscilla Y. Hsue, David D. Waters,
Tópico(s)Diabetes, Cardiovascular Risks, and Lipoproteins
ResumoHomeCirculationVol. 138, No. 11Time to Recognize HIV Infection as a Major Cardiovascular Risk Factor Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessEditorialPDF/EPUBTime to Recognize HIV Infection as a Major Cardiovascular Risk Factor Priscilla Y. Hsue, MD and David D. Waters, MD Priscilla Y. HsuePriscilla Y. Hsue Priscilla Hsue, MD, Room 5G1 Cardiology, Zuckerberg San Francisco General Hospital, 1001 Potrero Avenue, San Francisco, CA 94110. Email E-mail Address: [email protected] University of California San Francisco, Zuckerberg San Francisco General Hospital. and David D. WatersDavid D. Waters University of California San Francisco, Zuckerberg San Francisco General Hospital. Originally published10 Sep 2018https://doi.org/10.1161/CIRCULATIONAHA.118.036211Circulation. 2018;138:1113–1115This article is commented on by the following:Time to Recognize HIV Infection as a Major Cardiovascular Risk FactorArticle, see p 1100According to statistics from the World Health Organization, ≈36.7 million people are currently living with HIV, and 1.8 million become infected every year. Antiretroviral therapy has largely transformed HIV infection into a chronic disease. As a consequence, it is estimated that by the year 2030, 73% of HIV-infected individuals will be ≥50 years of age, and 78% of individuals living with HIV will have cardiovascular disease (CVD).1 Individuals infected with HIV have a significantly increased risk for a variety of cardiovascular complications, including acute myocardial infarction,2 heart failure with both reduced and preserved ejection fraction,3 sudden cardiac death,4 peripheral arterial disease,5 and stroke.6 In the United States, CVD has become a key contributor to mortality among individuals living with HIV.7The systematic review of longitudinal studies of CVD in HIV by Shah and colleagues8 in this issue of Circulation includes 80 studies with 793 635 individuals living with HIV and a follow-up of 3.5 million person-years. A random-effects meta-analysis was performed to derive a pooled rate and risk of CVD among people living with HIV and to estimate the burden of CVD and HIV at the national, regional, and global levels. The authors report that the relative risk of CVD in persons living with HIV is 2.16 (95% CI, 1.68–2.77) as compared with uninfected individuals. Over the past 26 years, the global population attributable fraction from CVD in the setting of HIV increased from 0.36% (95% CI, 0.21–0.56) to 0.92% (95% CI, 0.55–1.41), and disability-adjusted life-years increased from 0.74 (95% CI, 0.44–1.16) to 2.57 (95% CI, 1.53–3.92) million. Most of these increases took place in sub-Saharan Africa and the Asia Pacific regions.The authors deserve high praise for the vast scope of their study and the large volume of work involved. Some of their findings confirm previous studies but on a broader scale (eg, the risk of incident CVD being 2-fold higher in HIV and similar to other high-risk groups such as patients with diabetes mellitus).2 Most of the limitations of the study are inherent in this type of research and are unavoidable. First, myocardial infarction and stroke are defined differently across the aggregated studies, and the majority of cases were not clinically adjudicated but were categorized using coding. This lack of standardization of myocardial infarction definition may be particularly problematic in HIV, where approximately half are type 29 (ie, demand related, such as in the setting of sepsis or illicit drug use).Second, in a meta-analysis such as this without patient-level data, the contributions of traditional risk factors (eg, high levels of smoking and the metabolic syndrome) and HIV-specific risk factors (eg, HIV medication, degree of HIV control, level of inflammation) cannot be adjusted for or even ascertained. In addition, the cardiovascular risk of patients infected with HIV is likely distinctly different before and after the introduction of antiretroviral therapy. Although the authors report that the impact of HIV and CVD was highest among individuals in sub-Saharan Africa, this finding is based on only a small number of studies from this region; most of the data come from the United States and Europe. All of these issues likely contributed to the substantial heterogeneity for pooled risk ratios, as noted by the authors.However, despite these limitations, the study by Shah et al8 demands our attention because of its global scope and sobering conclusions: a doubling of cardiovascular risk in people living with HIV, coupled with a tripling of the global burden of CVD in HIV. What are the implications of these findings?Among the general population, the relative impact of traditional risk factors has been shifting over the past 2 to 3 decades. Hypercholesterolemia can now be well controlled with drug therapy in most patients, and control of hypertension has improved, at least in wealthier countries. The incidence and prevalence of type 2 diabetes mellitus has increased dramatically across most of the globe because of a higher prevalence of overweight and obesity, but outcomes in well-treated patients with established diabetes mellitus has improved.10 The impact of smoking on cardiovascular risk has diminished because smoking rates have decreased in many countries and many at-risk groups, whereas in other places, little progress has been made.Although HIV accounts for a relatively small proportion of CVD compared with these major risk factors, the relative risk of a cardiovascular event in a person living with HIV is in the range of traditional risk factors. The Figure compares the relative risk and population attributable risk of HIV from the study of Shah et al8 and odds ratios and traditional risk factors from the INTERHEART study.11 Because odds ratios can give inflated estimates of risk when the outcome is common,12 it is likely that the relative risks of traditional risk factors in INTERHEART are smaller and thus closer to that of HIV. Although the relative risk is unlikely to change much, the impact of HIV on CVD can only worsen as the HIV population ages. Has the time come to recognize HIV infection as a major cardiovascular risk factor, alongside diabetes mellitus, hypertension, hyperlipidemia, and smoking?Download figureDownload PowerPointFigure. Cardiovascular risk of HIV compared to traditional risk factors. Because ORs can give inflated estimates of risk when the outcome is common,12 it is likely that the RRs of traditional risk factors in the INTERHEART study are smaller and thus closer to that of HIV. aRisk of acute MI, adjusted for age, sex, and smoking. Adjustment for confounders was limited to those available in the primary studies. bRisk of ASCVD (CVD, stroke, or MI). cHigh ApoB/ApoA1 ratio. dOR (99% CI) for current smoking; PAR for any smoking. ePAR for 2015 using prevalence data for HIV for the 15- to 49-year-old group. Apo indicates apolipoprotein; ASCVD, atherosclerotic cardiovascular disease; CVD, cardiovascular disease; HIV, human immunodeficiency virus; MI, myocardial infarction; OR, odds ratio; PAR, population attributable risk; and RR, risk ratio.Such recognition might have salutary consequences. First, elevating HIV infection to the status of a major cardiovascular risk factor might stimulate research in this area. Treatment of CVD among individuals living with HIV relies on clinical trial data from non-HIV populations, although HIV-associated atherosclerosis has distinct features (such as more noncalcified plaques) and mechanisms, including chronic inflammation/immune activation and the impact of antiretroviral therapy. Clinical trial data specific to HIV would be helpful; however, it is not feasible in an era of limited resources to do outcome-driven clinical trials for all types of interventions and patient populations. As such, smaller proof-of-concept mechanistic studies that target HIV-specific factors will be critical to move the field forward. Precision medicine approaches, including omics methodologies, studies of healthcare disparities, digital monitoring, and implementation science aimed at cardiovascular risk in HIV, will also be invaluable.It is important to note that elevating HIV to the level of the other major risk factors could improve awareness, and thus the prevention, detection, and treatment of CVD among individuals living with HIV, along with better control of their traditional risk factors. All of these things could theoretically reduce CVD and CVD mortality in HIV. Often neither the HIV specialist nor the cardiologist has the requisite knowledge to treat these individuals optimally, and awareness among all caregivers of the excess cardiovascular risk remains crucial. Traditional risk calculators underestimate cardiovascular risk in HIV,13 but recognition of HIV as a major risk factor would reduce the need for risk calculation. The European Society of Cardiology guidelines recommend lipid-lowering therapy to reduce low-density lipoprotein cholesterol to <70 mg/dL in individuals infected with HIV.14In 2004, our group reported rapid carotid artery intima-media progression in HIV and concluded that this finding would presage a high rate of cardiovascular events.15 Fourteen years later, the study by Shah et al8 confirms this high rate of cardiovascular events on a global scale. The rate continues to increase even in the setting of treated and suppressed HIV disease. The key challenges for cardiologists and HIV clinicians continue to be unraveling the mechanisms underlying HIV-associated atherosclerosis, accurately predicting individuals at risk, and providing interventions to reduce this risk. The time to consider HIV as a cardiovascular risk factor is now.AcknowledgmentsThe authors would like to thank Shirley Smith, Envision Pharma Group, West Sussex, UK, for creating the figure.Sources of FundingThis work was funded in part by the National Institute of Allergy and Infectious Diseases (K24AI112393 to P.Y.H.).DisclosuresDr Hsue has received honoraria from Gilead and Merck outside of the submitted work. Dr Waters reports no conflicts of interest.FootnotesThe opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.https://www.ahajournals.org/journal/circPriscilla Hsue, MD, Room 5G1 Cardiology, Zuckerberg San Francisco General Hospital, 1001 Potrero Avenue, San Francisco, CA 94110. Email priscilla.[email protected]eduReferences1. Smit M, Brinkman K, Geerlings S, Smit C, Thyagarajan K, Sighem Av, de Wolf F, Hallett TB; ATHENA Observational Cohort. 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Waters D and Hsue P (2019) Introduction to Cardiovascular Issues in HIV, Canadian Journal of Cardiology, 10.1016/j.cjca.2018.12.009, 35:3, (233-234), Online publication date: 1-Mar-2019. Waters D and Hsue P (2019) Lipid Abnormalities in Persons Living With HIV Infection, Canadian Journal of Cardiology, 10.1016/j.cjca.2018.11.005, 35:3, (249-259), Online publication date: 1-Mar-2019. Related articlesTime to Recognize HIV Infection as a Major Cardiovascular Risk FactorPriscilla Y. Hsue, et al. Circulation. 2018;138:1113-1115 September 11, 2018Vol 138, Issue 11 Advertisement Article InformationMetrics © 2018 American Heart Association, Inc.https://doi.org/10.1161/CIRCULATIONAHA.118.036211PMID: 30354392 Originally publishedSeptember 10, 2018 KeywordsEditorialscardiovascular diseaseHIVPDF download Advertisement SubjectsAtherosclerosisInflammatory Heart Disease
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