HIV This Week

Currier JS, Lundgren JD, Carr A, Klein D, Sabin CA, Sax PE, Schouten JT, Smieja M; Working Group 2. Epidemiological evidence for cardiovascular disease in HIV-infected patients and relationship to highly active antiretroviral therapy. Circulation. 2008;118(2):e29-35. 

In the mid-1990s, case reports of myocardial infarction in young patients infected with human immunodeficiency virus (HIV) sparked interest in the relationship between HIV infection and cardiovascular disease. Although the initial focus was primarily on the relationship between dyslipidemia associated with antiretroviral therapy and cardiovascular risk, a broader appreciation of the complex interplay between traditional risk factors for cardiovascular disease and HIV infection has emerged more recently. Several groups of investigators have designed studies to examine various aspects of the relationship between HIV infection, traditional cardiovascular risk factors, antiretroviral therapy, and short- and longer-term cardiovascular risk. Studies have included both clinical end points (myocardial infarction, hospitalization for myocardial infarction or angina, and revascularization) and surrogate markers of atherosclerosis (endothelial function or carotid intima-media thickness). Successive studies have generally improved in quality, with inclusion of data on traditional risk factors, longer follow-up, and more diverse patient populations. HIV and antiretroviral therapy can contribute to an altered risk of cardiovascular disease in 3 principal ways: (1) HIV may serve as a marker to identify a subgroup of the general population with an altered prevalence of traditional cardiovascular risk factors, unrelated to HIV or antiretroviral therapy (e.g., HIV-infected patients may have higher smoking rates); (2) HIV or antiretroviral therapy may affect the risk of developing a traditional cardiovascular risk factor (e.g., HIV or antiretroviral therapy may worsen dyslipidemia); and (3) HIV or antiretroviral therapy may affect the pathogenetic process that leads to cardiovascular disease in ways other than via an effect on traditional risk factors (e.g., through effects on inflammation or endothelial function). Importantly, there is substantial evidence to suggest that all 3 mechanisms are in operation and affect the risk of cardiovascular disease in patients infected with HIV. All 3 factors should be considered in epidemiological studies assessing the relationship between cardiovascular disease and HIV disease.

Editors´note: Many factors can influence cardiovascular risk in people living with HIV. Some increase risks (e.g. lipid problems, insulin resistance, smoking, increasing age) while others decrease risk (antiretroviral treatment reducing inflammation and improving endothelial function). This review provides a helpful framework for understanding cardiovascular risk in relation to HIV infection and determining future research priorities.

Giuliano ID, de Freitas SF, de Souza M, Caramelli B. Subclinic atherosclerosis and cardiovascular risk factors in HIV-infected children: PERI study. Coron Artery Dis. 2008(3):167-172.

Giuliano and colleagues aimed to compare carotid intima-media thickness of children and adolescents with and without HIV infection and determine associations among independent socio-demographic, clinical or cardiovascular variables and carotid intima-media thickness in HIV-infected children and adolescents. This was a matched case-control study comparing 83 HIV-infected and 83 healthy children and adolescents. Clinical and laboratorial parameters, carotid intima-media thickness, and echocardiogram were measured. They found the carotid intima-media thickness was higher in HIV-infected individuals (median 480 mum; interquartile range 463-518 mum) compared with controls (426 mum; range 415-453 mum, P<0.001). In addition, the HIV-infected group showed higher levels of high-sensitive C-reactive protein (medians 1.0 mg/l vs. 0.4 mg/l, P<0.001), glycated hemoglobin (6.1+/-0.9 vs. 5.7+/-0.8%, P=0.028 ) and triglycerides (medians 0.9 vs. 0.8 mmol/l, P=0.031). Finally, this group showed lower levels of total and high-density lipoprotein-cholesterol. After multivariate analysis, increased carotid intima-media thickness was positively associated with stavudine use [odds ratio (OR): 18.9, P=0.005], left atrial/aorta index (OR: 15.6, P=0.019), suprailiac skinfold (OR: 7.9, P=0.019), tachypnea (OR: 5.9, P=0.031), CD8 lymphocyte count (OR: 5.7, P=0.033) and CD4 T-lymphocyte count (OR: 5.5, P=0.025). Carotid intima-media thickness increment was negatively associated with total cholesterol (OR: 0.2, P=0.025) and with CD8 zenith (OR: 0.1, P=0.007). In this sample of children and adolescents, having HIV infection was associated with increased carotid intima-media thickness and elevated prevalence of cardiovascular risk factors. These findings suggest that this group should be included in cardiovascular prevention programs.

Editors´note: In this Brazilian study, cases and controls were matched for age, sex, and economic class. Despite significantly higher intake of calories, lipids, and saturated fatty acids in the control group, the children and adolescents with HIV infection had worse metabolic and vascular parameters. These are likely multi-factorial in origin and the possibility that poor nutrition, physical inactivity, and chronic inflammatory stress are playing roles cannot be excluded.