Elevated Lp-PLA2 Levels Linked to CV Events in Stable CHD

From the American Heart Association

CHICAGO—In patients with stable coronary heart disease (CHD), lipoprotein-associated phospholipase A2 (Lp-PLA₂) is a significant predictor of adverse cardiovascular (CV) outcomes, said Marc Sabatine, MD, MPH, at the recent American Heart Association annual meeting.

Lp-PLA₂ is an enzyme that hydrolyzes oxidized phospholipids, thereby activating an inflammatory response and proatherogenic molecules. As a result, Lp-PLA₂ serves as a specific indicator of vascular inflammation.

Previous studies have not shown uniformity in Lp-PLA₂’s ability to predict CHD event risk. In the West of Scotland Coronary Prevention Study (WOSCOPS), Lp-PLA₂ was associated with increased risk for CV events in men. But women in the Women’s Health Initiative did not show an increased CHD risk with higher levels of Lp-PLA₂. In WOSCOPS, there was a trend toward an increased association between Lp-PLA₂ and CHD risk among persons using statins, except in those on intensive statin therapy, said Dr Sabatine.

He and colleagues used 3778 participants enrolled in the PEACE (Prevention of Events with Angiotensin Converting Enzyme Inhibition) trial as their study sample. PEACE was a randomized controlled trial of trandolapril (Mavik) in patients with stable CHD and an ejection fraction ≥40%.

The patients were divided into quartiles based on their baseline Lp-PLA₂ levels and followed for a mean of 4.8 years.

In an unadjusted analysis, the composite end point of CV death, myocardial infarction, revascularization, unstable angina, and stroke was 16% more likely to occur in those with Lp-PLA₂ levels in the second quartile compared with the first (lowest) quartile. Risk increased by 28% and 51% with Lp-PLA₂ levels in the third and fourth quartiles, respectively, compared with the first quartile (P <.001 for trend across the quartiles).

The majority of the association was driven by an increased risk for coronary revascularization procedures and unstable angina, said Dr Sabatine of Harvard Medical School.

In an adjusted analysis, there was only modest attenuation in the association between Lp-PLA₂ and the risk of the composite end point (P <.001 for trend across the quartiles), such that risk was increased by 41% with levels in the highest quartile compared with the lowest quartile. The increased risk &#8220;was independent of traditional risk factors and high-sensitivity C-reactive protein,&#8221; said Dr Sabatine.

Statins and other lipid-lowering therapies are known to lower levels of Lp-PLA₂. The finding probably will not influence current practice, as these patients will most likely be taking a statin anyway, he said. &#8220;There are a couple of compounds in the works that lower Lp-PLA₂,&#8221; he said. &#8220;It will be interesting to see if this becomes a target of treatment.&#8221;