Circulation. 2005;111:570-575
doi: 10.1161/01.CIR.0000154553.12214.CD
doi: 10.1161/01.CIR.0000154553.12214.CD
(Circulation. 2005;111:570-575.)
© 2005 American Heart Association, Inc.
Coronary Heart Disease |
Lipoprotein-Associated Phospholipase A2 Activity Is Associated With Risk of Coronary Heart Disease and Ischemic Stroke
The Rotterdam Study
From the Departments of Epidemiology and Biostatistics (H.-H.S.O., I.M.v.d.M., A.H., T.S., M.M.B.B., J.C.M.W.) and Neurology (P.J.K.), Erasmus Medical Center, Rotterdam, the Netherlands.
Reprint requests to Dr J.C.M. Witteman, Department of Epidemiology and Biostatistics, Erasmus Medical Center, PO Box 1738, 3000 DR Rotterdam, The Netherlands. E-mail j.witteman{at}erasmusmc.nl
Received June 11, 2004; revision received October 30, 2004; accepted November 15, 2004.
Background— Lipoprotein-associated phospholipase A2 (Lp-PLA2) has been proposed as an inflammatory marker of cardiovascular disease. In the present study, we investigated whether Lp-PLA2 is an independent predictor of coronary heart disease and ischemic stroke.
Methods and Results— The Rotterdam Study is a population-based follow-up study in 7983 subjects 
55 years of age. We performed a case-cohort study, including 308 coronary heart disease cases, 110 ischemic stroke cases, and a random sample of 1820 subjects. We used Cox proportional-hazard models with modification of the standard errors based on robust variance estimates to compute hazard ratios adjusted for age, sex, body mass index, systolic blood pressure, non-HDL cholesterol, HDL cholesterol, diabetes, smoking, alcohol consumption, cholesterol-lowering medication, white blood cell count, and C-reactive protein. Compared with the first quartile of Lp-PLA2 activity, multivariate-adjusted hazard ratios for coronary heart disease for the second, third, and fourth quartiles were 1.39 (95% CI, 0.92 to 2.10), 1.99 (95% CI, 1.32 to 3.00), and 1.97 (95% CI, 1.28 to 3.02), respectively (P for trend=0.01). Corresponding multivariate-adjusted hazard ratios for ischemic stroke were 1.08 (95% CI, 0.55 to 2.11), 1.58 (95% CI, 0.82 to 3.04), and 1.97 (95% CI, 1.03 to 3.79) (P for trend=0.03). The relation between Lp-PLA2 and coronary heart disease was present in both subjects with non-HDL cholesterol levels below the median and those with non-HDL cholesterol levels above the median.
Conclusions— This study shows that Lp-PLA2 activity is an independent predictor of coronary heart disease and ischemic stroke in the general population.
Key Words: coronary disease • epidemiology • inflammation • stroke
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|
|
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|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
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|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
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|
|
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|
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