Lipoprotein-Associated Phospholipase A2 Activity and Incident Coronary Heart Disease Among Men and Women With Type 2 Diabetes

OBJECTIVE Lipoprotein-associated phospholipase A2 (Lp-PLA2) has been shown to be associated with increased risk of coronary heart disease (CHD) in general adult populations. Because men and women with type 2 diabetes are at particularly high risk for CHD, the aim of this study was to assess the association of Lp-PLA2 with future coronary events among diabetic men and women. RESEARCH DESIGN AND METHODS We measured Lp-PLA2 activity among 740 men and 777 women with confirmed diabetes enrolled in the Health Professionals Follow-Up Study (HPFS) and Nurses' Health Study (NHS). Participants were free of all cardiovascular disease and cancer at baseline. RESULTS During 10 years of follow-up among men and 14 years among women, we documented 178 and 146 cases of CHD, respectively. We defined CHD as coronary artery bypass graft, angioplasty, nonfatal myocardial infarction, and fatal CHD. After adjustment for age, smoking, medical history, and biomarkers including C-reactive protein, HDL, and LDL, the relative risk of total CHD comparing extreme tertiles of Lp-PLA2 was 1.39 (95% CI 1.01–1.90; P trend = 0.03). When we restricted analyses to only nonfatal myocardial infarction and fatal CHD, the relative risk was 1.75 (95% CI 1.05–2.92; P for trend = 0.001). LDL, HDL, C-reactive protein, hormone replacement therapy use, and diabetes duration did not modify these relationships. CONCLUSIONS Levels of Lp-PLA2 activity were significantly associated with incident CHD among men and women with type 2 diabetes, independent of traditional and inflammatory risk factors. This positive association was strongest for more severe clinical end points.