Statin treatment may reduce cardiovascular risk in people with HIV not only by lowering cholesterol but also by reducing coronary plaque and inflammation, Professor Steven Grinspoon told the Conference on Retroviruses and Opportunistic Infections (CROI 2025) in San Francisco last week.
He was reporting results from a substudy of the REPRIEVE trial, the international study which showed that daily use of pitavastatin by people with HIV reduced the risk of a major cardiovascular event such as stroke or heart attack by 36% in people judged to have a low-to-moderate risk of heart disease.
The substudy looked at how underlying coronary artery disease and inflammation affected the risk of cardiovascular disease and the response to statin treatment in 804 participants from the United States. It found some evidence that trial participants with pre-existing coronary plaque derived greater benefit from taking pitavastatin as preventive treatment than those without signs of coronary artery disease.
Non-calcified plaque accumulates in the arteries long before any symptoms of heart disease such as angina or heart failure develop and is associated with higher levels of total cholesterol and LDL cholesterol. Non-calcified plaque is unstable, which means that the plaques, which are accumulations of cholesterol, white blood cells and tiny fibres, can rupture, leading to blood clots and heart attacks. Statin treatment can stabilise and eventually shrink non-calcified plaque by removing the cholesterol.
The REPRIEVE Mechanistic study evaluated non-calcified coronary plaque by CT angiography and measured subclinical myocardial injury (damage to the heart muscle) using high-sensitivity troponin (hs-cTnT) in 755 participants. A high-sensitivity troponin test is used in routine clinical practice to detect whether acute chest pain is caused by injury to the heart. If troponin is present, it is a sign that the heart muscle has been damaged. A previous analysis of these participants showed that even a low level of hs-cTnT (>9.6ng/l) was associated with the presence of subclinical coronary plaque.
Non-calcified plaque was found in 40% of participants at baseline. Participants with non-calcified plaque were two-and-a half times more likely to experience a major cardiovascular event during the five-year study (hazard ratio (HR) 2.5, confidence interval (CI) 1.3, 4.8, p=0.008). Adjusting for ASCVD (atherosclerotic cardiovascular disease) risk score moderated the relationship slightly (HR 2.1, CI 1.1, 4.0, p=0.028) but the increased risk remained statistically significant.
The study also evaluated the impact of pitavastatin on cardiovascular events in people with or without non-calcified plaque. The study showed a non-significant trend towards a greater impact of pitavastatin on major cardiovascular events in those with non-calcified plaque at baseline (HR 0.56, CI 0.24, 1.31) than in those without (HR 1.28, CI 0.44, 3.26), p=0.008.
Pitavastatin also had a greater impact on the risk of cardiovascular events in people with higher levels of hs-cTnT (>7.5ng/l), although again, this trend was not statistically significant (HR 0.68, CI 0.30, 1.53 vs. HR 1.66, CI 0.40, 6.93).
The study also measured three markers of inflammation (hs-CRP, IL-6, and LpPLA-2) in 790 participants to evaluate whether higher baseline levels of inflammation were associated with a higher risk of cardiovascular events. Elevated levels of hs-CRP (P=0.049) and higher IL-6 (P=0.033) at study entry were associated with major cardiovascular events.
The study findings suggest that pitavastatin may reduce cardiovascular risk in people with HIV not only by lowering cholesterol but also by reducing coronary plaque and inflammation, Professor Grinspoon concluded. He said further work is needed to investigate if the biomarkers identified in the study – hs-CRP, IL-6 and hs-cTnT – can be used in combination to identify which people with HIV with lower cardiovascular disease risk scores might benefit most from preventive treatment with statins.
Lu MT et al (presenter Grinspoon S). Plaque, inflammation, subclinical myocardial injury, and MACE in the REPRIEVE Mechanistic Substudy. Conference on Retroviruses and Opportunistic Infections, San Francisco, abstract 178, 2025.