Significant amounts of atherosclerotic plaque have been found in the coronary arteries of people with HIV, even in those considered by traditional measures to be at low-to-moderate risk of future heart disease, according to a study published in JAMA Network Open as reported in a news release from Massachusetts General Hospital.
This finding emerged from the global REPRIEVE (Randomized Trial to Prevent Vascular Events in (HIV) study, in which Massachusetts General Hospital (MGH) is playing a coordinating role. Researchers found that the higher-than-expected levels of plaque could not be attributed simply to traditional cardiovascular disease risk factors like smoking, hypertension, and lipids in the blood, but were independently related to increased arterial inflammation and immune system activation.
“While we know that people living with HIV who are receiving antiretroviral therapy are at increased risk of coronary artery disease, our understanding of the mechanisms behind this phenomenon have been very limited,” says Steven Grinspoon, MD, Chief of the MGH Metabolism Unit and co-principal investigator of REPRIEVE. “The latest findings from REPRIEVE expand our knowledge and provide important insights that set the stage for further studies to identify effective plaque reduction or prevention strategies, such as the possible use of statin medicines.”
REPRIEVE is the largest study of cardiovascular disease among people living with HIV, having enrolled 7,700 participants at more than 100 sites in 12 countries around the world, in collaboration with the AIDS Clinical Trials Group (ACTG).
The newly published results are from a subset of the overall trial, consisting of 755 individuals between the ages of 40 and 75 enrolled in 31 sites across the United States. This is the largest study to assess plaque levels in the arteries of people with HIV who have no known heart disease and are eligible for primary cardiovascular prevention. The study used coronary CT angiography to assess plaque and then correlate results with blood samples that measured inflammation and immune activation.
The MGH-led study found that 49 percent of participants had plaque in their coronary arteries. While significant narrowing of the arteries was rare, nearly a quarter had plaque which the researchers considered “vulnerable,” that is, at risk for potential future cardiovascular problems.
Enabling researchers to assess these nontraditional cardiovascular risk factors were two biomarkers which they hypothesized could reflect premature cardiovascular disease among people with HIV. They are interleukin 6 (IL-6), associated with immune system activation, and LpPLA2, associated with arterial inflammation.
In addition to helping researchers better understand the mechanisms of cardiovascular risk in people with HIV, the two biomarkers will be evaluated in the next phase of REPRIEVE for their ability to predict major events, such as heart attacks and strokes. That ongoing research will also investigate the potential of statin therapy to reduce lipid levels – its primary therapeutic target –as well as plaque and markers of inflammation.
