Changes in Lipoprotein-Associated Phospholipase A2 Activity Predict Coronary Events and Partly Account for the Treatment Effect of Pravastatin: Results From the Long-term Intervention with Pravastatin in Ischemic Disease Study

Autor: Malcolm J. West, Elizabeth H Barnes, Harvey D. White, David M. Hunt, Tanja Zeller, Stefan Blankenberg, Andrew Tonkin, Anthony C Keech, Paul J. Nestel, David R. Sullivan, Ian C. Marschner, Ralph A.H. Stewart, John Simes, Peter L. Thompson, David Colquhoun
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Zdroj: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
Popis: Background Lipoprotein‐associated phospholipase A2 (Lp‐ PLA 2 ) levels are associated with coronary heart disease ( CHD ) in healthy individuals and in patients who have had ischemic events. Methods and Results The Long‐term Intervention with Pravastatin in Ischemic Disease ( LIPID ) study randomized 9014 patients with cholesterol levels of 4.0 to 7.0 mmol/L to placebo or pravastatin 3 to 36 months after myocardial infarction or unstable angina and showed a reduction in CHD and total mortality. We assessed the value of baseline and change in Lp‐ PLA 2 activity to predict outcomes over a 6‐year follow‐up, the effect of pravastatin on Lp‐ PLA 2 levels, and whether pravastatin treatment effect was related to Lp‐ PLA 2 activity change. Lp‐ PLA 2 was measured at randomization and 1 year, and levels were grouped as quartiles. The prespecified end point was CHD death or nonfatal myocardial infarction. Baseline Lp‐ PLA 2 activity was positively associated with CHD events ( P P =0.66). In 6518 patients who were event free at 1 year, change in Lp‐ PLA 2 was a significant independent predictor of subsequent CHD events after adjustment for these risk factors, including LDL cholesterol and LDL cholesterol changes ( P PLA 2 by 16% compared with placebo ( P PLA 2 change, the pravastatin treatment effect was reduced from 23% to 10% ( P =0.26), with 59% of the treatment effect accounted for by changes in Lp‐ PLA 2 . Similar reductions in treatment effect were seen after adjustment for LDL cholesterol change. Conclusion Reduction in Lp‐ PLA 2 activity during the first year was a highly significant predictor of CHD events, independent of change in LDL cholesterol, and may account for over half of the benefits of pravastatin in the LIPID study.
Databáze: OpenAIRE