HIV Positive Men Have More Atherosclerosis and Higher Vascular Age than Uninfected Men

		SUMMARY: HIV positive men without clinical coronary artery disease were more likely than uninfected men to have atherosclerosis and subclinical signs coronary artery disease, including 6.5% with significant blockage, according to a recent computed tomography study. In this analysis, risk increased with longer duration of HIV infection. A related analysis found that people with HIV had a "vascular age" 15 years greater than their chronological age. This study produced the surprising finding that people with higher CD4 counts were more likely to develop coronary artery disease.

By Liz Highleyman

Research indicates that people with HIV have a higher risk of cardiovascular disease, but the relative contributions of HIV infection itself, antiretroviral therapy (ART), and traditional risk factors (such as increasing age and smoking) are not fully understood.

In the first study, published in the January 16, 2010 issue of AIDS, Janet Lo from Harvard Medical School and colleagues investigated the degree of subclinical atherosclerosis and its relationship to traditional and non-traditional risk factors.

Atherosclerosis, or "hardening of the arteries," refers to the build-up of plaque composed of cholesterol, calcium, and other substances in the arteries, leading to inflammatory changes and impaired blood flow. People with coronary artery disease -- atherosclerosis of the coronary arteries that supply blood to the heart -- may experience symptoms such as angina and are at increased risk for myocardial infarction (MI), or heart attack.

This study included 78 HIV positive men, with an average age of 46.5 years and an average duration of HIV infection of 13.5 years. The average CD4 count was high at 523 cells/mm3, and 81% had an undetectable viral load.

A control group included 32 HIV negative men of similar age and demographic and cardiovascular risk factors. HIV positive and negative participants had similar Framingham 10-year MI risk scores, family history of coronary artery disease, and smoking status. In both groups, participants did not have a history or symptoms of existing coronary artery disease.

The researchers used computed tomography coronary angiography (CT scans of blood vessels) to determine prevalence of coronary atherosclerosis, coronary stenosis (narrowing of arteries), and amount of plaque.

Results

	Overall, 6.5% of the HIV positive participants had angiographic evidence of obstructive coronary artery disease (defined as > 70% narrowing), compared with none of the HIV negative control subjects.
	HIV positive men had significantly higher measures for multiple indicators of coronary heart disease compared with HIV negative men:
	Coronary atherosclerosis: 59% vs 34%, respectively (P = 0.02); Coronary plaque volume: 55.9 vs 0 microl (P = 0.02); Number of coronary segments with plaque: 1 vs 0 (P = 0.03); Prevalence of Agatston calcium score > 0: 46% vs 25% (P = 0.04).
	Among HIV positive participants, the following factors were significantly associated with plaque burden:
	Framingham risk score; Total cholesterol level; Low-density lipoprotein (LDL or "bad" cholesterol) level; CD4/CD8 ratio; Monocyte chemoattractant protein 1 (MCP-1) level.
	Duration of HIV infection was significantly associated with plaque volume and number of segments with plaque.
	This association remained significant after adjusting for age, traditional risk factors, and duration of antiretroviral therapy.

"Young, asymptomatic, HIV-infected men with long-standing HIV disease demonstrate an increased prevalence and degree of coronary atherosclerosis compared with non-HIV-infected patients," the study authors concluded. "Both traditional and nontraditional risk factors contribute to atherosclerotic disease in HIV-infected patients."

"Our data highlight the need to address cardiac risk reduction early in the course of HIV disease, before significant subclinical disease accrues and before cardiac events occur," they recommended.

Coronary Aging

In the second study, published in the December 1, 2009 issue of Clinical Infectious Diseases, Giovanni Guaraldi from the University of Modena and Reggio Emilia in Italy and colleagues investigated whether HIV positive people on stable ART showed evidence of greater vascular (blood vessel) aging.

This cross-sectional analysis included 400 HIV positive patients attending a cardio-metabolic clinic. Most were men and the mean age was 48 years. Participants underwent computed tomography imaging to identify coronary artery calcium -- an indicator of atherosclerosis. Vascular age was estimated based on the extent of calcium using published equations.

Results

	162 patients (40.5%) showed evidence of increased vascular age.
	On average, vascular age was 15 years higher than chronological age (range 1-43 years higher).
	In a univariate analysis, increased vascular age was associated with the following factors:
	Older chronological age; Male sex; Hypertension (high blood pressure); Systolic blood pressure; Duration of ART; Fasting glucose level; Fasting serum triglyceride level; Total cholesterol level; LDL level; High-density lipoprotein (HDL or "good" cholesterol) level; Presence of metabolic syndrome.
	In a multivariate analysis controlling for potentially confounding factors, higher current CD4 cell count was the only significant predictor of increased vascular age (P = .005).

"Increased vascular age is frequent among HIV-infected patients and appears to be associated with CD4+ cell count," the investigators concluded. "If these findings were to be confirmed in prospective trials, a positive response to ART with an increase in CD4+ cell count may become a marker of increased risk of atherosclerosis development."

The researchers were unable to explain theunexpected CD4 count findings, but suggested that greater inflammation might play a role.

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References

J Lo, S Abbara, L Shturman, and others. Increased prevalence of subclinical coronary atherosclerosis detected by coronary computed tomography angiography in HIV-infected men. AIDS 24(2): 243-253 (Abstract). January 16, 2009.

G Guaraldi, S Zona, N Alexopoulos, and others. Coronary Aging in HIV-Infected Patients. Clinical Infectious Diseases 49(11): 1756-1762 (Abstract). December 1, 2009.