Parveen K Garg1, Robyn L McClelland2, Nancy S Jenny3, Michael H Criqui4, Philip Greenland5, Robert S Rosenson6, David S Siscovick7, Neal Jorgensen2, Mary Cushman8. 1. Division of Cardiovascular Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. 2. Department of Biostatistics, University of Washington, Seattle, WA, USA. 3. Department of Pathology and Laboratory Medicine, University of Vermont College of Medicine, Burlington, VT, USA. 4. Department of Family & Preventive Medicine, University of California in San Diego, La Jolla, CA, USA. 5. Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA; Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. 6. Mount Sinai Heart, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 7. New York Academy of Medicine, New York, NY, USA. 8. Department of Pathology and Laboratory Medicine, University of Vermont College of Medicine, Burlington, VT, USA; Department of Medicine, University of Vermont College of Medicine, Burlington, VT, USA. Electronic address: mary.cushman@uvm.edu.
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.
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 arterycalcium 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 arterycalcium or a thickened carotid-intimal media.
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