Lipoprotein-Associated Phospholipase A2 Activity Predicts Cardiovascular Events in High Risk Coronary Artery Disease Patients

Abstract

ObjectiveLipoprotein-associated phospholipase A2 (Lp-PLA2) is deemed to play a role in atherosclerosis and plaque destabilization as demonstrated in animal models and in prospective clinical studies. However, most of the literature is either focused on high-risk, apparently healthy patients, or is based on cross sectional studies. Therefore, we tested the hypothesis that serum Lp-PLA2 mass and activity are useful for predicting cardiovascular (CV) events over the coronary atherosclerotic burden and conventional risk factors in high-risk coronary artery disease patients.Methods and ResultsIn a prospective cohort study of 712 Caucasian patients, who underwent coronary angiography and measurement of both Lp-PLA2 mass and activity at baseline, we determined incident CV events at follow-up after splitting the patients into a high and a low Lp-PLA2 mass and activity groups based on ROC analysis and Youden index. Kaplan-Meier and propensity score matching analysis were used to compare CV event-free survival between groups. Follow-up data were obtained in 75% of the cohort after a median of 7.2 years (range 1–12.7 years) during which 129 (25.5%) CV events were observed. The high Lp-PLA2 activity patients showed worse CV event-free survival (66.7% vs. 79.5%, p = 0.023) and acute coronary syndrome-free survival (75.4% vs. 85.6%, p = 0.04) than those in low Lp-PLA2 group.ConclusionsA high Lp-PLA2 activity implies a worse CV prognosis at long term follow up in high-risk Caucasian patients referred for coronary angiography.

Exploring the plasmatic platelet-activating factor acetylhydrolase activity in patients with anti-phospholipid antibodies

“…As expected [11], a significant correlation was found between PAF-AH and total cholesterol ( r  = 0.25; p  = 0.032), a stronger direct correlation with LDL ( r  = 0.46, p  < 0.0001) and a highly significant inverse correlation with HDL ( r  = −0.45, p  < 0.0001). No correlation was found with age and sex (15.5 ± 5 nmol/min/ml in females vs. 15.7 ± 3.3 nmol/min/ml in males).…”

“…Several studies reported a significant association between higher PAF-AH plasmatic activity and the severity of cardiovascular (CV) disease and identified PAF-AH as a marker of vascular inflammation and atherosclerotic plaque instability [9–11]. …”

Lipoprotein‐Associated Phospholipase A 2 Activity Is a Marker of Risk But Not a Useful Target for Treatment in Patients With Stable Coronary Heart Disease

“…Furthermore, in 2 case–control studies, natural deficiency of Lp‐PLA 2 activity due to carriage of the V279F‐null allele in the Lp‐PLA 2 gene was associated with a lower risk of developing CHD 30. In a recent study in European CHD patients, a single‐nucleotide polymorphism of the Lp‐PLA 2 gene was found to be associated with both increased Lp‐PLA 2 activity in plasma and a raised risk of MI 31. Lp‐PLA 2 has also been shown to be highly concentrated in unstable and ruptured atherosclerotic plaques and to be strongly expressed in macrophages in lesions prone to rupture 16.…”

Unraveling the PAF-AH/Lp-PLA2 controversy

“…A study using mice lacking PAF-AH expression suggested that the enzyme may not function in the circulation and that substrate transport to the intracellular compartment may be required before hydrolysis occurs ( 45 ). In addition, the relationship between circulating and tissue PAF-AH and OxPLs has not been critically evaluated, and this issue raises important questions regarding by guest, on April 29, 2019 www.jlr.org Downloaded from Commentary the impact of enzyme, substrate, and products in different biologic compartments. The article by Marathe et al ( 1 ) discusses some of these variables in the intricate biochemistry and biology of PAF-AH, PAF, and related lipids.…”