HIV-related comorbidities, including cardiovascular disease (CVD), have assumed a higher profile given the efficacy of antiretroviral therapy (ART). With the increased survival of persons living with HIV, several factors raise the risk for CVD, including the high rate of conventional CVD risk factors,1-8 the presence of HIV-related inflammatory and immunological processes,8,9 and metabolic dysregulations (eg dyslipidemia and insulin resistance) possibly associated with ART.10-12
Accordingly, CVD risk assessment has assumed a more prominent role in the management of HIV-infected persons, particularly those receiving ART. This assessment, however, needs to account for the distinctive factors affecting CVD risk in this population. The standard Framingham model for global CVD risk may not provide the most accurate assessment of the odds of cardiovascular events in HIV-infected persons. As a consequence, a modified predictive model derived from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study, which considers CD4 cell counts and administration of ART in addition to standard risk factors, has been developed (http://www.cphiv.dk/Tools) to alert clinicians to CVD risk in HIV-infected persons requiring more aggressive CVD risk-mitigation interventions.13
Mechanisms of CVD Risk
HIV infection accelerates both atherogenesis and endothelial dysfunction in persons with HIV infection.14-16 These individuals also have a higher occurrence of vulnerability features of coronary plaque.17 In addition, among HIV-infected individuals, markers of inflammation have been shown to be associated with markers of subclinical atherosclerosis,18 as well as CVD events.19,20 The prevalences of traditional CVD risk factors, such as diabetes, dyslipidemia, and hypertension, are also higher in individuals living with HIV.21-24 In a health care system-based cohort study using a large data registry with HIV and non-HIV patients, the HIV cohort had significantly higher proportions of hypertension (21.2% vs 15.9%), diabetes (11.5% vs 6.6%), and dyslipidemia (23.3% vs 17.6%) than the non-HIV cohort (P <.0001 for each comparison).21
Nevertheless, in a large cohort of HIV-positive veterans and a demographically and behaviorally similar cohort of HIV-negative veterans, infection with HIV was associated with a 50% increased risk for acute myocardial infarction beyond that explained by recognized risk factors.14 Together, these findings suggest that CVD-related mechanisms reflect a complex interaction of factors involving established CVD pathways in addition to immunologic and inflammatory sequelae of HIV infection.
Metabolic abnormalities can also occur with antiretroviral drug use, with higher consequent risk for cardiovascular events. Some antiretroviral drugs may promote dyslipidemia and body fat redistribution, in addition to reducing insulin sensitivity, thereby contributing to CVD risk.12,25-27 After initiating ART, increases in total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides may be observed together with low levels of high-density lipoprotein cholesterol.25 Lipohypertrophy and visceral fat deposit may co-occur with dyslipidemia, hypertriglyceridemia, reduced insulin sensitivity, and diabetes.12 The US Department of Health and Human Services guidelines for ART in HIV-1-infected adults concisely summarizes these and other ART-associated cardiovascular-related adverse effects (Table 1).28
Table 1. ART-Associated Common and/or Severe Cardiovascular-Related Adverse Effects