Distribution and Correlates of Lipoprotein-Associated Phospholipase A 2 in an Elderly Cohort: The Cardiovascular Health Study Curt D. Furberg, MD, PhD, à Jeanenne J. Nelson, PhD, w Cam Solomon, PhD, z Mary Cushman, MD, MSc, §k Nancy Swords Jenny, PhD, § and Bruce M. Psaty, MD, PhD z OBJECTIVES: To determine whether high levels of lipo- protein-associated phospholipase A 2 (Lp-PLA 2 ) are associ- ated with prevalent cardiovascular disease (CVD) and to evaluate factors most influencing Lp-PLA 2 levels in a com- munity-based cohort of older adults. DESIGN: Cross-sectional. SETTING: The Cardiovascular Health Study (CHS), a population-based cohort study of men and women aged 65 and older. PARTICIPANTS: Five thousand five hundred thirty-one CHS participants. MEASUREMENTS: Levels of Lp-PLA 2 activity were de- termined using stored blood samples from the baseline examination. RESULTS: Mean Lp-PLA 2 was higher in participants with electrocardiographically determined ventricular conduc- tion defect and major Q-wave abnormality and was pos- itively correlated with left ventricular (LV) mass. It was high in those with echocardiographically determined abnormal LV ejection fraction, which persisted after adjustment. Mean Lp-PLA 2 was also higher in participants with mild renal insufficiency and kidney disease. After multivariable adjustment, there was a modest but significant 27% greater risk of prevalent CHF per standard deviation increment of Lp-PLA 2 and a modest but significant 12% greater risk of prevalent myocardial infarction. Lp-PLA 2 was weakly but mainly most strongly correlated with cholesterol and lipo- proteins, but those correlations were not especially strong. Lp-PLA 2 was weakly positively correlated with soluble intercellular adhesion molecule-1 but not interleukin-6. In total, all factors considered could explain only 29% of Lp-PLA 2 activity. CONCLUSION: Novel findings in the study are the asso- ciations, in those aged 65 and older, between Lp-PLA 2 activity and LV dysfunction, CHF, and renal disease. CVD risk factors only minimally explain levels of Lp-PLA 2 . J Am Geriatr Soc 56:792–799, 2008. Key words: Lp-PLA 2 ; cardiovascular disease; older adults T he role of inflammation in atherosclerotic processes, from initial plaque formation to destabilization and subsequent rupture of atherosclerotic plaques, is well ac- cepted. 1,2 Lipoprotein-associated phospholipase A 2 (Lp- PLA 2 ) is a plasma marker produced by the same blood- borne inflammatory cells that contribute to atherosclerosis pathologyFmonocytes, macrophages, and T-lympho- cytes. 3,4 Lp-PLA 2 expression is greater in people with ad- vanced human coronary lesions, and it co-localizes with cells undergoing apoptosis. 5 Lp-PLA 2 acts rapidly after low-density lipoprotein (LDL) oxidation to hydrolyze one of the fatty acid moieties (sn-2) of the phospholipids to produce two inflammatory moleculesFoxidized nonesteri- fied fatty acids and lysophosphatidylcholine. Epidemiolog- ical studies have reported associations between high levels of Lp-PLA 2 and major risk factors for cardiovascular dis- ease (CVD), subclinical CVD, and prevalent and incident CVD. 6–20 The strongest direct relationships observed in most studies have been reported for total cholesterol and LDL-C, male sex, and age. The association with high-den- sity lipoprotein cholesterol (HDL-C) is inverse. High levels of Lp-PLA 2 were independently associated with angio- graphically documented coronary artery disease, 7,17 calci- fied coronary artery plaques, 14 and greater carotid intimal medial thickness. 16 Cross-sectional studies have reported relationships between Lp-PLA 2 and prevalent CVD 9,16 and Address correspondence to Curt Furberg, MD, PhD, Division of Public Health Sciences, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1063. E-mail: cfurberg@wfubmc.edu DOI: 10.1111/j.1532-5415.2008.01667.x From the à Division of Public Health Sciences, School of Medicine, Wake Forest University, Winston-Salem, North Carolina; w Worldwide Epidemio- logy, GlaxoSmithKline, Research Triangle Park, North Carolina; z Department of Biostatistics, University of Washington, Seattle, Washington; § Departments of Pathology; and k Medicine, College of Medicine, University of Vermont, Burlington, Vermont. JAGS 56:792–799, 2008 r 2008, Copyright the Authors Journal compilation r 2008, The American Geriatrics Society 0002-8614/08/$15.00