Baltimore, MD—Levels of PCSK9, a protein involved in cholesterol metabolism, are higher in HIV patients and those with high cholesterol. Now, a small new pilot study finds that a 6-week course of a cholesterol-lowering medication improved the function of the coronary arteries that provide oxygen to the heart in a group of those patients.

The report in the Journal of the American Heart Association looked at the effect of the PCSK9 inhibitor evolocumab and found a significant improvement in coronary health among participants in the pilot study.

“PCSK9 (proprotein convertase subtilisin/kexin type 9) is well recognized for its important role in cholesterol metabolism,” according to Johns Hopkins Medicine–led researchers. “Elevated levels are associated with increased cardiovascular risk and inhibition with PCSK9 antibodies (PCSK9i) lowers cardiovascular events in patients with coronary artery disease. PCSK9 levels are also elevated in people living with HIV (PLWH) and those with dyslipidemia. Because increased PCSK9 in PLWH is associated with impaired coronary endothelial function, a barometer of coronary vascular health, we tested the hypothesis that PCSK9i improves impaired coronary endothelial function in dyslipidemia without coronary artery disease and in PLWH with nearly optimal/above goal low‐density lipoprotein cholesterol levels.”

The small single‐center study involved 19 people living with HIV and 11 with dyslipidemia to evaluate the effects of the PCSK9i evolocumab on coronary endothelial function using cine 3T MRI to noninvasively measure coronary endothelial function. The changes were assessed in coronary cross‐sectional area and coronary blood flow from rest to that during isometric handgrip exercise, a known endothelial‐dependent vasodilator.

“Before evolocumab, there was a decrease or no coronary vasodilation and no increase in coronary blood flow (the normal responses) to isometric handgrip exercise in either group. Following 6 weeks of evolocumab, 480 mg q4 weeks, the % cross‐sectional area changes from rest to isometric handgrip exercise were +5.6±5.5% and +4.5±3.1% in the PLWH and dyslipidemia groups, respectively, both P <.01 versus baseline. Improved cross‐sectional area was paralleled by a significant coronary blood flow improvement in both groups,” researchers advise.

The authors write that their data represent the first evidence that PCSK9 inhibition improves coronary artery health in PLWH and people with dyslipidemia.

The study suggests a possible method to limit cardiovascular disease risk in those living with HIV and other cardiovascular risk factors, such as high cholesterol, by improving the function of blood vessels.

“We hypothesized that PCSK9 mediates an inflammatory response that impairs vascular function in addition to its effects on cholesterol metabolism, and we tested this idea with the protein’s inhibitor to learn whether it could help people who have impaired blood vessel function,” explained lead author Thorsten M. Leucker, MD, PhD, assistant professor of medicine at the Johns Hopkins University School of Medicine. “We were surprised that this worked so well, but also heartened that there may be a way we can improve blood vessel function in those with increased inflammation.”

Changes appeared to be swift and significant. Researchers report that, after the 6-week treatment with the PCSK9 inhibitor, the participants living with HIV had an average 7.9% increase in coronary artery area and a 10.1% increase in blood flow during the handgrip exercise when compared with the resting value. They point out that the changes were significantly greater than the changes from rest to handgrip exercise during the baseline pretreatment visit.

Participants with high blood lipids also had improvements in coronary artery area and an increase in blood flow after 6 weeks of treatment, according to the report.

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