Does Lipoprotein associated Phospholipase A2 Improve Mortality Prediction among Coronary
Heart Disease Patients in Israel?

Batya Sapir 2 Michal Benderly 1,2 Reuven Zimlichman 3
1Cardiovascular Epidemiology unit, The Gertner Institute for Epidemiology and Health Policy Research, Sheba Medical Center, Tel-Hashomer, Ramat Gan
2Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv
3The Brunner Institute for Cardiovascular Research, Sackler Faculty of Medicine, Tel Aviv University; Edith Wolfson Medical Center, Holon
Background: Lipoprotein associated Phospholipase A2 (Lp-PLA2) is a specific biomarker of vascular inflammation and  atherosclerosis. Lp-PLA2 levels were reported to be associated with coronary heart disease (CHD) and mortality. In contrary, data on the association between Lp-PLA2 activity and prognosis among CHD patients are scarce.

Method: Among 3122 CHD patients included in the Bezafibrate Infraction Prevention (BIP) study, 2538 survived to the 5th follow-up year and had available frozen blood samples. Lp-PLA2 activity was measured with calorimetric activity method. 

Results: patients in the 3rd activity tertile (≥ 247.21 nmol/ml/min) were on average, a year younger, two centimeters taller, had lower systolic blood pressure, with higher prevalence of: men, metabolic syndrome, coronary artery bypass graft and smoking compared to 1st tertile (≤ 202.00) patients (p trend≤0.01 for all). Patients in the 3rd tertile had also higher total and low density lipoprotein cholesterol (LDL-C), non-high density lipoprotein cholesterol (nonHDL-C), triglyceride and fibrinogen and lower HDL-C levels. Lp-PLA2 correlated with age (R=-0.065), HDL-C (-0.435), LDL-C (0.344), nonHDL-C (0.373), fibrinogen (0.142) or hemoglobin (0.239)
but not with C-reactive protein. 

Over 8.3 follow-up years (209,158 person-months), 554 patients died. Patients in the 3rd activity tertile had higher cumulative mortality probability compared to the 1st or 2nd (202.01-247.20) tertiles (Figure). The age and sex adjusted mortality hazard ratio (HR) associated with the 3rd tertile was 1.35 compared to the 1st tertile (95% confidence interval: 1.10-1.66). HR did not significantly change upon further adjustment for: diabetes mellitus, hypertension, body mass index, CHD family history, smoking, education and ethnicity. However, inclusion of Lp-PLA2 activity in the model did not improve its discrimination ability beyond other risk factors (C index=0.685 vs 0.683 with and without activity, respectively).  

Conclusion: Lp-PLA2 activity is a marker of mortality among chronic CHD patients but does not improve prediction beyond other risk factors.
 




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