Apolipoproteins mediate Lp-PLA2–CVD link
MedWire News: Associations between circulating levels of lipoprotein-associated phospholipase A2 (Lp-PLA2) and cardiovascular diseases (CVD) are dependent on pro-atherogenic lipid levels, research shows.
The study reveals that moderate associations between Lp-PLA2 activity and occlusive coronary events become nonsignificant after adjustment for apolipoproteins.
Sarah Parish, from the University of Oxford, UK, and colleagues explored the relationship between Lp-PLA2 and CV events by measuring Lp-PLA2 activity and mass and lipid levels in 19,037 patients (aged 40-80 years) at high risk for CVD. The patients were participants in the Heart Protection Study, in which they were randomly assigned to receive daily simvastatin 40 mg or placebo.
During the 5-year follow-up period, the researchers assessed the number of CV events, categorizing them as occlusive coronary events (nonfatal myocardial infarction, coronary revascularizations, or coronary death other than from heart failure or sudden death), major occlusive vascular events (occlusive coronary event, ischemic stroke, or any revascularization), or other cardiac events (hospitalization or death from heart failure, sudden death, or noncoronary cardiac death).
Occlusive coronary events occurred in 2531 patients, and Lp-PLA2 activity and mass were both significantly associated with this outcome. Similar patterns were seen for major occlusive coronary events.
However, when adjustments were made for apolipoprotein (apo)B and apoA-1 levels, these associations became nonsignificant for Lp-PLA2 activity. Attenuation was also seen for Lp-PLA2 mass following adjustments for these apolipoproteins.
In contrast, associations between apoB and occlusive vascular events were highly significant, and changed little after adjustment for other risk factors, including Lp-PLA2.
Writing in the Journal of Internal Medicine, the researchers say that their findings indicate that the association between Lp-PLA2 and CVD depends considerably on pro-atherogenic lipid levels.
Parish's team also reports that 6 weeks of simvastatin treatment significantly reduced patients' Lp-PLA2 activity and mass, by 24% and 39%, respectively, relative to placebo treatment.
"These changes are likely to reflect the potent low-density lipoprotein lowering effects of statins, as most Lp-PLA2 is bound to LDL [low-density lipoprotein]," the researchers explain.
However, the 24% proportional reduction in the risk for major CV events in patients allocated to simvastatin 40 mg did not vary with Lp-PLA2 levels.
The team concludes: "Further clarification of the relevance of Lp-PLA2 to vascular disease requires additional investigations, such as large observational studies of first ever coronary heart disease, genetic studies of loss-of-function mutations, and randomized trials of agents that specifically reduce Lp-PLA2."
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By Nikki Withers