European Heart Journal Advance Access published online on August 17, 2009
European Heart Journal, doi:10.1093/eurheartj/ehp309
Expression of lipoprotein-associated phospholipase A2 in carotid artery plaques predicts long-term cardiac outcome
1 Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA
2 Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, MN, USA
3 Department of Neurosurgery, Mayo Clinic College of Medicine, Rochester, MN, USA
4 Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, MN, USA
Received 20 January 2009; revised 9 June 2009; accepted 16 July 2009 * Corresponding author. Tel: +1 507 255 4152, Fax: +1 507 255 2550, Email: lerman.amir{at}mayo.edu
Aims: The aim was to test the hypothesis that carotid artery plaque expression of lipoprotein-associated phospholipase A2 (Lp-PLA2) predicts cardiac events.
Methods and results: Prospective cohort study of 162 consecutive patients undergoing elective carotid endarterectomy. Lipoprotein-associated phospholipase A2 content was quantified by immunoblotting and lysophosphatidylcholine (lysoPC) by liquid chromatography tandem mass spectrometry. Additional biomolecular profiling by immunoblotting included C-reactive protein, p67phox, and matrix metalloproteinase-2 and -9. Macrophage plaque content was determined by quantitative immunostaining, plaque collagen content by quantitative Sirius red staining. Follow-up for cardiac death and non-fatal acute myocardial infarction was accomplished over a period of 48 ± 14 months. Expression of Lp-PLA2 and lysoPC was higher in carotid plaques of patients with than without cardiac events [median 1.6 (25th, 75th percentile 0.9, 2.5) vs. 0.8 (0.5, 2.0), P = 0.01 and 413 (281, 443) vs. 226 (96, 351) mmol/L, P = 0.03]. Smoking and point increase in carotid Lp-PLA2 expression but no other traditional cardiovascular risk factor, histological or molecular marker remained predictive of cardiac events in the multivariate Cox proportional hazard analyses [HR 3.65 (1.36–9.83), P = 0.01 and HR 1.34 (1.01–1.77), P = 0.039]. Carotid plaque Lp-PLA2 expression above the median constituted a more than three times higher risk for cardiac events [HR 3.39 (1.13–10.17), P = 0.03].
Conclusion: Lipoprotein-associated phospholipase A2 expression in carotid artery plaques is a predictor of long-term cardiac outcome. The current study supports the concept of atherosclerosis as a systemic disease with multi-focal complications and personalized medicine.
Key Words: Arteriosclerosis • Cardiovascular diseases • Plaque • Prognosis