Progression of Coronary Atherosclerosis in MACS

The Multicenter AIDS Cohort Study (MACS) is a long-standing and ongoing multi-center observational longitudinal cohort study of men who have sex with men. CT coronary artery calcium (CAC) and ultrasound carotid intima media thickness (IMT) and plaque have been measured in over 900 MACS participants. A second examination has been performed as well as the more sensitive and specific imaging modality of CT angiography to examine potential associations between HIV infection and/or HAART and CVD and to identify factors associated with subclinical and ultimately clinical CVD. CT angiography of the coronary arteries has allowed visualization of both calcified (advanced) atherosclerotic plaque as well as non-calcified plaque including estimates of vascular luminal obstruction (stenosis). We have obtainedCT angiographic imaging (CTA), as well as measures of inflammatory, metabolic, and anthropomorphic parameters in HIV-infected and HIV-seronegative (control) men, in addition to repeat measurement of CAC and carotid IMT/plaque Specifically, we measured subclinical coronary atherosclerosis using cardiac computer tomography (CT) scans in over 960 men, including coronary CT angiography in over 740 eligible men. We found a greater prevalence and extent of non-calcified coronary plaque in HIV-infected men compared with HIV-uninfected men, even after adjusting for traditional cardiovascular disease risk factors. Among HIV-infected men, coronary artery stenosis greater than 50% was associated with longer duration of HAART therapy, the presence of plasma HIV viremia, and lower nadir CD4+ cell count. We also found that advancing age was associated with a greater prevalence of non-calcified plaque in HIV-infected men, but not in uninfected individuals. While calcified plaque is thought to represent plaque that is more advanced and stable, non-calcified plaque may be more prone to rupture, potentially leading to thrombus formation and greater risk for acute coronary syndromes. Our hypothesis is that HIV-infected persons have a unique atherosclerotic phenotype as a potential mechanism for increased cardiovascular risk. However, since our study was cross-sectional, questions remain regarding the dynamics of plaque formation and maturation in HIV, which can only be addressed with a longitudinal study. There are also potential biases inherent to cross-sectional studies, which may not be seen in longitudinal studies. In addition, recent reports suggest an increased incidence of sudden cardiac death (SCD) among HIV-infected persons. The potential substrates for SCD are not well defined in the HIV population.