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CLINICAL RESEARCH: CORONARY HEART DISEASE

Lipoprotein-Associated Phospholipase A2 Is an Independent Predictor of Incident Coronary Heart Disease in an Apparently Healthy Older Population

The Rancho Bernardo Study

Lori B. Daniels, MD^_*,_*, Gail A. Laughlin, PhD, Mark J. Sarno, BA, Ricki Bettencourt, MS, Robert L. Wolfert, PhD and Elizabeth Barrett-Connor, MD

^_* Division of Cardiology, Department of Medicine, University of California at San Diego, San Diego, California
Department of Family and Preventive Medicine, University of California at San Diego, La Jolla, California
diaDexus, Inc., South San Francisco, California.

Manuscript received June 27, 2007; revised manuscript received October 10, 2007, accepted October 11, 2007.

^_* Reprint requests and correspondence: Dr. Lori B. Daniels, Mail Code 0986, 9350 Campus Point Drive, Suite 1D, La Jolla, California 92037. (Email: lbdaniels{at}ucsd.edu).

Objectives: Lipoprotein-associated phospholipase A2 (Lp-PLA2) levels predict incident coronary heart disease (CHD) in adults without known CHD, independent of heart disease risk factors. We examined whether the independent association was apparent in older adults.

Background: Serum levels of Lp-PLA2, an enzyme that hydrolyzes oxidized phospholipids to yield potentially proatherogenic particles, have been associated with CHD and may help predict cardiovascular risk.

Methods: Participants were 1,077 community-dwelling men and women, median age 72 years, who had no known CHD at baseline (1984 to 1987) when blood samples and risk factor data were collected. Participants were followed for CHD events for a mean of 16 years, through 2002. Cox proportional hazards regression models were used to examine the association of serum Lp-PLA2 with incident CHD (myocardial infarction, angina, or coronary revascularization).

Results: The Lp-PLA2 levels positively correlated with age (r = 0.09), body mass index (r = 0.11), low-density lipoprotein (r = 0.37), triglycerides (r = 0.25), and C-reactive protein (r = 0.10), and negatively correlated with high-density lipoprotein (r = –0.27) (all p < 0.05). During follow-up, 228 participants had incident CHD events. Lipoprotein-associated phospholipase A2 levels in the second, third, and fourth quartiles predicted an increased risk of CHD compared with the lowest quartile (hazard ratios 1.66, 1.80, and 1.89, respectively; p < 0.05 for each). This association persisted after adjusting for C-reactive protein and other CHD risk factors.

Conclusions: Elevated Lp-PLA2 levels predict CHD events in apparently healthy older adults, independent of CHD risk factors.

Abbreviations and Acronyms   BMI = body mass index   CHD = coronary heart disease   CI = confidence interval   CRP = C-reactive protein   HDL = high-density lipoprotein   HR = hazard ratio   LDL = low-density lipoprotein   Lp-PLA2 = lipoprotein-associated phospholipase A2

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