Abstract 3605: Lipoprotein-Associated Phospholipase A2 and Myocardial Infarction in Women
Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) is an enzyme that hydrolyzes oxidized phospholipids in low-density lipoprotein, creating pro-inflammatory molecules that are hypothesized to play a role in the development of coronary heart disease. Many of the previous studies that have shown Lp-PLA2 activity to be associated with a moderate increase in risk for CHD have been conducted mostly among men. The one previous study among women was small and reported a modest nonsignificant increase in risk. Thus, the association of Lp-PLA2 with CHD risk in women warrants exploration. We conducted a nested case-control study among participants in the Nurses’ Health Study who provided a blood sample in 1989 –1990. With approximately 15 years of follow-up through 2004 we identified 438 incident cases of fatal and non-fatal MI and used incidence density sampling to match controls to cases (2:1) based on age, smoking status, date of blood draw, and fasting status at the time of blood draw. Lp-PLA2 activity was measured using a colorimetric activity assay. We used conditional logistic regression in multivariate models. Compared to women in the lowest tertile, the relative risk of CHD for women in the second and third tertiles of Lp-PLA2 activity were 1.75 (95% CI 1.26 –2.44) and 2.67 (1.94 – 3.69), respectively (p for trend = 0.002). After further adjustment for LDL cholesterol, c-reactive protein,body mass index, alcohol intake, aspirin use, physical activity, and post-menopausal hormone use, and histories of hypercholesterolemia, diabetes, and hypertension, the relative risks were similar: 1.81 (1.26 – 2.60) comparing the second to the first tertile, and 2.26 (1.54 – 3.30) comparing the third to the first tertile (ptrend < 0.001). Further adjustment for HDL cholesterol modestly attenuated the relative risks to 1.62 (1.13 – 2.35) and 1.81 (1.20 – 2.71) (ptrend= 0.007). The significantly elevated relative risks were not appreciably modified by HDL or LDL. In conclusion, we found that Lp-PLA2 activity was associated with increased risk for MI among women. Adjustment for standard risk factors modestly attenuated this relationship, but Lp-PLA2 remained a strong independent predictor of MI in this population of women healthy at baseline.