Men With HIV Have Higher Risk, Greater Extent of CAD

Laurie Barclay, MD

March 31, 2014

Coronary artery plaque is more prevalent and extensive in HIV-infected men compared with uninfected men, according to findings of a cross-sectional study published March 31 in Annals of Internal Medicine. The increased disease is independent of risk factors for coronary artery disease (CAD).

"Advances in the treatment of HIV infection have led to dramatic decreases in AIDS-related mortality," write Wendy S. Post, MD, from the Johns Hopkins University School of Medicine, Ciccarone Center for the Prevention of Heart Disease, Baltimore, Maryland, and colleagues. "This extension in expected survival has led to the emergence of chronic noninfectious age-related diseases, such as [CAD]. Increased risk for CAD has been associated with HIV infection and antiretroviral therapy."

The goal of this study was to compare prevalence and severity of coronary atherosclerosis among HIV-infected men and uninfected men on the basis of the presence and extent of coronary artery calcium (CAC) on noncontrast cardiac computed tomography (CT) and of any plaque; noncalcified, mixed, or calcified plaque; or stenosis on coronary CT angiography.

Participants in the Multicenter AIDS Cohort Study included 618 HIV-infected and 383 uninfected men who have sex with men. Inclusion criteria were age 40 to 70 years, weight less than 136 kg (200 pounds), and no history of coronary revascularization.

"The major strengths of this study include the large sample size of a well-defined cohort of HIV-infected and uninfected participants," Matthew S. Freiberg, MD, section chief of chronic disease translational research and associate professor of medicine and epidemiology at the University of Pittsburgh, Pennsylvania, told Medscape Medical News when asked for independent comment.

All of the participants underwent noncontrast CT, and 759 also underwent coronary CT angiography. After adjustment for age, race, CT center, and cohort, HIV-infected men had greater prevalence of coronary atherosclerosis than did uninfected men. For CAC, prevalence ratio (PR) was 1.21 (95% confidence interval [CI], 1.08 - 1.35; P = .001). PR was 1.14 for any plaque (95% CI, 1.05 - 1.24; P = .001), 1.28 for noncalcified plaque (95% CI, 1.13 - 1.45; P < .001), and 1.35 for mixed plaque (95% CI, 1.10 - 1.65; P = .004).

After further adjustment for CAD risk factors, associations remained significant between HIV infection and any plaque or noncalcified plaque (P < .005). After CAD risk factor adjustment, HIV-infected men had a greater extent of noncalcified plaque (P = .026). HIV-infected men also had a greater prevalence of more than 50% coronary artery stenosis (PR, 1.48; 95% CI, 1.06 - 2.07; P = .020), but adjustment for CAD risk factors abolished this association.

Other factors associated with greater than 50% coronary stenosis were longer duration of highly active antiretroviral therapy (PR, 1.09; 95% CI, 1.02 - 1.17; P = .007) and lower nadir CD4+ T-cell count (PR, 0.80; 95% CI, 0.69 - 0.94; P = .005).

Cardiovascular Risk Factor Modification Needed for HIV-Infected Men

Study limitations noted by the authors were the cross-sectional observational study design and inclusion of only men.

"The cross-sectional study design, however, is the important and necessary first step to document that prevalence of noncalcified plaque, which is not seen on noncontrast CT that is classically used for coronary artery calcium studies, is more common among HIV-infected people compared to uninfected people after adjusting for traditional CVD [cardiovascular disease] risk factors," Dr. Freiberg said.

To improve long-term outcomes among HIV-infected men, the investigators recommend an effort to address and reduce traditional cardiovascular risk factors.

"While numerous studies suggest that HIV-infected people are at an increased risk of CVD as compared to uninfected people, the exact mechanisms driving this excess risk in this population is not clear," Dr. Freiberg explained. "The fact that noncalcified plaque was associated with increased aging in the HIV[-infected] but not uninfected population provides potential insights into the underlying mechanisms."

In terms of additional research, Dr. Freiberg recommends a longitudinal study to determine whether the prevalence of noncalcified plaque is associated with future incident CVD events.

"As noted by Dr. Post and colleagues, noncalcified plaque may be prone to rupture," Dr. Freiberg concluded. "If this plaque is more common and ultimately associated with incident CHD in this population, these findings may help explain some of the excess risk of CHD in this population."

An accompanying editorial by Judith S. Currier, MD, from David Geffen School of Medicine, University of California, Los Angeles, and James H. Stein, MD, from the University of Wisconsin School of Medicine and Public Health in Madison, points out the need for prevention of long-term comorbid conditions as the population of HIV-infected men ages.

"While we wait for results of longitudinal studies aimed at clarifying the mechanisms of disease and identifying effective strategies for prevention, it is critical that we not lose sight of the importance of addressing well-established risk factors for cardiovascular disease in the HIV-infected population," they write. "Efforts to address smoking cessation, blood pressure control, and screening and treatment of lipid and glucose disorders need to remain at the forefront of our endeavors to ensure that the gains in the treatment of HIV infection translate into the most favorable long-term outcomes possible."

The National Heart, Lung, and Blood Institute funded this study, with additional support from the National Center for Advancing Translational Sciences, a component of the National Institutes of Health and National Institutes of Health Roadmap for Medical Research. The National Institute of Allergy and Infectious Diseases funded the Multicenter AIDS Cohort Study, with additional supplemental funding from the National Cancer Institute. The study authors have reported various financial disclosures involving the National Institutes of Health; Toshiba; GE; ICON Medical Imaging; Gilead Sciences; Janssen Pharmaceuticals; Merck; Bristol-Myers Squibb; the National Institute of Allergy and Infectious Diseases; the National Heart, Lung, and Blood Institute; Abbvie; EMD-Serono; ViiV Healthcare; and/or GSK. Full conflict-of-interest information is available on the journal's Web site. Dr. Stein reports receiving grants from Gilead; a patent, "Ultrasonic Apparatus and Method for Providing Quantitative Indication of Risk of Coronary Heart Disease," with royalties paid to Wisconsin Alumni Research Foundation; and acting as chair of a data and safety monitoring board for Lilly for lipid medication. Dr. Currier has reported receiving grants from Merck and Company and personal fees from ViiV, as well as collaboration with 2 of the study authors. Dr. Freiberg has disclosed no relevant financial relationships.

Ann Intern Med. 2014;160:458-467, 509-510.


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