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WOSCOPS Lipoprotein-Associated Phospholipase A2 Substudy - WOSCOPS Lipoprotein-Associated Phospholipase A2 Substudy
Description:
The goal of the case-control study was to evaluate the association of several inflammatory markers with the risk of subsequent coronary events in men with hypercholesterolemia.
Study Design
Study Design:
Patients Screened: 6,595
Patients Enrolled: 1,740
Mean Patient Age: mean age in substudy 56.8 years
Female: 0
Patient Populations:
Trial inclusion criteria: 45 to 64-year-old men and LDL cholesterol level >4.5 mmol/l (174 mg/dl)
Primary Endpoints:
Cases were defined as patients with either nonfatal MI, death from CHD, or revascularization.
Drug/Procedures Used:
Patients were drawn from the West of Scotland Coronary Prevention Study (WOSCOPS), a trial that evaluated pravastatin for the prevention of coronary events. For this substudy, cases were defined as patients with either nonfatal myocardial infarction (MI), death from coronary heart disease (CHD), or revascularization (n=580).
For each case, two controls were selected and matched on the basis of age and smoking status (n=1160). Plasma total cholesterol, triglycerides, very-low-density lipoprotein, low-density lipoprotein (LDL), high-density lipoprotein (HDL), white-cell count, fibrinogen, C-reactive protein (CRP), and lipoprotein-associated phospholipase A2 were measured at baseline.
Concomitant Medications:
At randomization, 6.2% of cases and 2.9% of controls were taking aspirin.
Principal Findings:
On univariate analysis, several markers were associated with risk of coronary event (per increase of 1 standard deviation): CRP (relative risk [RR] for death/MI 1.28, 95% confidence interval [CI] 1.14-1.43; RR for revascularization 1.21, 95% CI 0.94-1.55; RR for death/MI or revascularization 1.27, 95% CI 1.14-1.42, p<0.001); white blood cell count (RR for death/MI 1.22, 95% CI 1.09-1.37; RR for revascularization 1.23, 95% CI 0.96-1.57; RR for death/MI or revascularization 1.22, 95% CI 1.10-1.36, p<0.001); fibrinogen levels (RR for death/MI 1.17, 95% CI 1.06-1.36; RR for revascularization 1.28, 95% CI 1.01-1.61; RR for death/MI or revascularization 1.19, 95% CI 1.07-1.31, p=0.001); and lipoprotein-associated phospholipase A2 (RR for death/MI 1.20, 95% CI 1.08-1.35; RR for revascularization 1.17, 95% CI 0.92-1.50; RR for death/MI or revascularization 1.20, 95% CI 1.08-1.34, p<0.001).
However, after adjusting for age, systolic blood pressure, and lipoprotein levels in a multivariate model including all of the markers, only lipoprotein-associated phospholipase A2 remained significantly associated with the composite event (RR 1.18, 95% CI 1.05-1.33, p=0.005), while CRP (RR 1.13, 95% CI 0.98-1.29, p=0.09) and white-cell count (RR 1.10, 95% CI 0.97-1.25, p=0.14) were of borderline significance and fibrinogen was not significant (RR 1.02, 95% CI 0.90-1.15, p=0.79).
Interpretation:
Among men with hypercholesterolemia enrolled in the WOSCOPS trial, levels of lipoprotein-associated phospholipase A2, an enzyme that is regulated by mediators of inflammation, was associated with the risk of CHD, independent of other markers of inflammation and risk factors. Other markers of inflammation including CRP, white-cell count, and fibrinogen levels were also associated with the risk of CHD, as has been shown in other recent studies.
According to the authors, lipoprotein-associated phospholipase A2 acts as a key agent in the release of products of LDL oxidation into the artery wall, potentially leading to atherogenesis. Lipoprotein-associated phospholipase A2 may be a useful tool in a multimarker risk stratification approach.
References:
Packard CJ, O'Reilly DS, Caslake MJ, et al. Lipoprotein-associated phospholipase A2 as an independent predictor of coronary heart disease. West of Scotland Coronary Prevention Study Group. N Engl J Med 2000;343:1148-55.
Keywords: Coronary Artery Disease, Myocardial Infarction, Atherosclerosis, Cholesterol, LDL, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Leukocyte Count, Lipoproteins, VLDL, Blood Pressure, Risk Factors, Hypercholesterolemia, Smoking, Inflammation Mediators, C-Reactive Protein, Case-Control Studies, Pravastatin, Confidence Intervals, Fibrinogen, Lipoproteins, HDL, Triglycerides, 1-Alkyl-2-acetylglycerophosphocholine Esterase
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