Lipoprotein-associated phospholipase A2 and risk of incident cardiovascular disease in a multi-ethnic cohort: The multi ethnic study of atherosclerosis

Abstract

Objective Prospective studies reporting a positive association of lipoprotein-associated phospholipase A2 (Lp-PLA2) mass and activity with incident cardiovascular disease (CVD) have included primarily white individuals. We evaluated associations of Lp-PLA2 and first-time cardiovascular events in a healthy multi-ethnic cohort characterized by presence or absence of baseline subclinical atherosclerosis. Methods Lp-PLA2 mass and activity were measured at baseline in 5456 participants in the Multi-Ethnic Study of Atherosclerosis. Individuals were characterized for presence of baseline subclinical disease (coronary artery calcium score>0 or carotid intima-media thickness value>80th percentile) and followed prospectively for development of CVD events (coronary heart disease, ischemic stroke, and cardiovascular death). Results 516 incident CVD events occurred over median follow-up of 10.2 years. In adjusted Cox proportional hazards models, each higher standard deviation of both Lp-PLA2 activity and mass was associated with an increased risk of cardiovascular events; hazard ratios (HR; 95% confidence intervals (CI)) 1.12 (1.01–1.26) for Lp-PLA2 activity and 1.10 (1.01–1.21) for mass. Associations did not differ by subclinical disease status (p-value for interaction 0.99 for Lp-PLA2 activity and 0.32 for Lp-PLA2 mass) and there was no confounding by subclinical atherosclerosis measures. Associations of Lp-PLA2 activity but not mass were weaker in Chinese participants but there were relatively few events among Chinese in race-stratified analysis. Conclusion In this multi-ethnic cohort, Lp-PLA2 was positively associated with CVD risk, regardless of the presence of coronary artery calcium or a thickened carotid-intimal media.

Endothelial Dysfunction in Children With Obstructive Sleep Apnea Is Associated With Elevated Lipoprotein‐Associated Phospholipase A2 Plasma Activity Levels

“…Indeed, Garg and colleagues reported no evidence of such association in a large cohort of adult subjects participating in the Multi‐Ethnic Study of Atherosclerosis . However, the same group reported more recently that Lp‐PLA2 was positively associated with cardiovascular disease risk, irrespective of the presence or absence of coronary artery calcium or of carotid‐intima‐media thickening in the Multi‐Ethnic Study of Atherosclerosis cohort . Notwithstanding such discrepant findings, the remarkably strong association between Lp‐PLA2 and T max in our pediatric cohort as well as the decreases in Lp‐PLA2 following treatment of OSA suggest that the signal to noise regarding the putative link between Lp‐PLA2 and endothelial function is substantially higher, probably due to the absence of coexisting confounders in the pediatric age range.…”

“…50 However, the same group reported more recently that Lp-PLA2 was positively associated with cardiovascular disease risk, irrespective of the presence or absence of coronary artery calcium or of carotid-intima-media thickening in the Multi-Ethnic Study of Atherosclerosis cohort. 51 Notwithstanding such discrepant findings, the remarkably strong association between Lp-PLA2 and T max in our pediatric cohort as well as the decreases in Lp-PLA2 following treatment of OSA suggest that the signal to noise regarding the putative link between Lp-PLA2 and endothelial function is substantially higher, probably due to the absence of coexisting confounders in the pediatric age range. Furthermore, differences in the actual information provided by flow-mediated vasodilation (ie, macrovascular) and T max (microvascular) may also account for some of such discrepancies between children and adults.…”

Biomarkers of Key Biological Pathways in CVD

“…Higher Lp-PLA 2 activity within an atherosclerotic plaque is associated with greater vulnerability of the plaque to rupture. Extending previous research to a multi-ethnic cohort, both Lp-PLA 2 mass and activity were associated with increased risk of incident CVD and CHD in MESA, regardless of the presence of subclinical CVD[10]. …”

Lipoprotein-associated phospholipase A2 and risk of incident peripheral arterial disease in a multi-ethnic cohort: The Multi-Ethnic Study of Atherosclerosis

“…31 For MESA, Lp-PLA 2 activity levels were not associated with incident cardiovascular disease in Chinese participants, but were in the other three ethnic groups. 20 Atherosclerosis is a complex process that can vary across different vascular beds and significant differences in the strength of the association of traditional cardiovascular risk factors such as diabetes or cigarette smoking with PAD versus other forms of atherosclerotic disease have already been established. 32,33 It is possible the relationship of Lp-PLA 2 with PAD may differ from its relationship with other forms of atherosclerotic disease.…”