Characteristics, Prevention, and Management of Cardiovascular Disease in People Living With HIV: A Scientific Statement From the American Heart Association

Abstract

As early and effective antiretroviral therapy has become more widespread, HIV has transitioned from a progressive, fatal disease to a chronic, manageable disease marked by elevated risk of chronic comorbid diseases, including cardiovascular diseases (CVDs). Rates of myocardial infarction, heart failure, stroke, and other CVD manifestations, including pulmonary hypertension and sudden cardiac death, are significantly higher for people living with HIV than for uninfected control subjects, even in the setting of HIV viral suppression with effective antiretroviral therapy. These elevated risks generally persist after demographic and clinical risk factors are accounted for and may be partly attributed to chronic inflammation and immune dysregulation. Data on long-term CVD outcomes in HIV are limited by the relatively recent epidemiological transition of HIV to a chronic disease. Therefore, our understanding of CVD pathogenesis, prevention, and treatment in HIV relies on large observational studies, randomized controlled trials of HIV therapies that are underpowered to detect CVD end points, and small interventional studies examining surrogate CVD end points. The purpose of this document is to provide a thorough review of the existing evidence on HIV-associated CVD, in particular atherosclerotic CVD (including myocardial infarction and stroke) and heart failure, as well as pragmatic recommendations on how to approach CVD prevention and treatment in HIV in the absence of large-scale randomized controlled trial data. This statement is intended for clinicians caring for people with HIV, individuals living with HIV, and clinical and translational researchers interested in HIV-associated CVD.

Keywords: AHA Scientific Statements; HIV; cardiovascular diseases; preventive medicine.

Figure 1.. Conceptual model of the changing epidemiology of myocardial infarction (MI) and heart failure (HF) risk in HIV.

ART indicates antiretroviral therapy; and CVD, cardiovascular disease.

Figure 2.. Global burden of atherosclerotic cardiovascular disease in people living with HIV.

A, Population-attributable fraction by country and (B) disability-adjusted life-years per 100000 people by country. Reprinted from Shah et al. Copyright © 2018, American Heart Association, Inc.

Figure 3.. Proposed mechanisms of myocardial dysfunction and heart failure in HIV.

ART indicates antiretroviral therapy.

Figure 4.. Pragmatic approach to atherosclerotic cardiovascular disease (ASCVD) risk assessment and prevention in treated HIV infection.

This figure applies to people with treated HIV. For people with uncontrolled HIV, the first priority is appropriate HIV therapy to achieve viral suppression per the HIV provider. Thresholds based on findings of elevated CVD risk at current or nadir CD4 count <200, <350, and <500 cells/mm³ in Silverberg et al, Lichtenstein et al, and Triant et al. Hazard ratios and incidence rate ratios of 1.4 to 2.1 for myocardial infarction (MI) for people living with HIV (PLWH) vs uninfected people demonstrated in Freiberg et al, Triant et al, and Silverberg et al. Hazard ratio of stroke for PLWH vs uninfected people was 1.40 in Chow et al. ABI indicates ankle-brachial index; ACC/AHA, American College of Cardiology/American Heart Association; apoB, apolipoprotein B; ART, antiretroviral therapy; CAC, coronary artery calcium; CAD, coronary artery disease; CK, creatine kinase; CVD, cardiovascular disease; D:A:D, Data Collection on Adverse Events of Anti-HIV Drugs; hsCRP, high sensitivity C-reactive protein; LFT, liver function test; LDL-C, low-density lipoprotein cholesterol; Lp(a), lipoprotein A; and PCSK9, proprotein convertase subtilisin-kexin type 9.

Figure 5.. Cardiovascular risk of HIV compared with traditional risk factors.

OR indicates odds ratio; PAR, population-attributable risk; and RR, relative risk. Reprinted from Hsue and Waters.