CVD increasing in patients with HIV

Extended survival and ART may put patients with HIV at risk for cardiovascular events.

Issue: August 2008

Cardiovascular disease has become a major cause of mortality among patients with HIV, according to researchers from the American Heart Association.

Patients with HIV are living longer due to antiretroviral therapy; but these patients are increasingly at risk for CVD. Both HIV and ART may affect a patient’s cardiovascular system. However, the reasons for the increased mortality risk have yet to be determined. Patients with HIV have exhibited such contributors to CVD as dyslipidemia, insulin resistance, inflammation, kidney abnormalities and changes in body composition.

A new report

A new report regarding CVD in patients with HIV was recently published in Circulation. The report includes data on the potential association between lipid levels and ART.

Though there are limited findings on direct cellular infection, the myocardium and vascular endothelium may be affected by HIV. Patients with HIV who have not yet been treated with ART have exhibited endothelial dysfunction. Initiation of ART treatment only moderately improved this function, according to the researchers.

Researchers who worked on the report wrote that “macrophages and other reservoir cells infected with HIV may affect vascular and myocardial function.” The researchers also suggested that plaque formation may be influenced by alterations in lipid metabolism. The high prevalence of smoking among patients with HIV may also put them at risk for CVD.

The effects of ART on the heart and vasculature appear to vary depending on the agent. However, the effects may not be dependent on the class of drug. “Toxicities may vary among drugs in a similar class and with respect both to cause and to whether exposure occurs in utero, in childhood or during adult life,” the researchers wrote.

Findings

Patients with HIV may be 70% to 80% more likely to have a myocardial infarction than people who do not. This may increase for older patients, but the risk is lower for younger patients with HIV, according to the researchers.

Patients with HIV also have been shown to exhibit low levels of HDL cholesterol and elevated levels of triglycerides. Other metabolic abnormalities which have been seen in patients with HIV include subcutaneous fat loss and relative visceral fat gain. However, the researchers have yet to determine whether these conditions are the result of HIV, ART or environmental factors which include lifestyle, dietary intake and weight changes associated with improved health.

Increased coronary artery calcium scores have been reported in patients with HIV. The researchers cited findings from preliminary studies in which hypertension was moderately associated with patients with HIV.

Various effects of ART on the cardiovascular system have been observed. Ritonavir (Norvir, Abbott) has been shown to increase triglycerides. Indinavir (Crixivan, Merck), stavudine (Zerit, Bristol-Myers Squibb) and other protease inhibitors have contributed to insulin resistance. Stavudine and zidovudine (Retrovir, GlaxoSmithKline) may adversely affect myocardial function and depletion of mitochondrial DNA, according to the researchers.

Some results have shown that increased carotid intimal-medial thickness associated with traditional risk factors and protease inhibitor use has been observed in patients with HIV.

Though ART generally improves endothelial function, older protease inhibitor regimens, including those which contain indinavir, may adversely affect endothelial function.

Clinicians should be encouraged to use the Framingham risk score to measure the risk for CVD in their patients with HIV. However, the researchers stressed that the Framingham risk score does not include factors associated with HIV and that an HIV-specific risk-assessment model needs to be developed. The model should include components for screening, prediction and treatment methods.

Though a greater number of studies of HIV and ART effects on the cardiovascular system are being conducted, questions remain. “These included the need to establish the specific effects of individual ART agents and identify the direct effects of HIV, as well as related indirect effects, establish biomarkers for vascular and myocardial dysfunction and develop effective treatment strategies for these cardiovascular complications,” the researchers wrote. – by Rob Volansky

For more information:

Grinspoon S, Grunfeld C, Kotler D, et al. State of the Science Conference: initiative to decrease cardiovascular risk and increase quality of care for patients living with HIV/AIDS: executive summary. Circulation. 2008;118:198-210.