TY - JOUR
T1 - Expression of lipoprotein-associated phospholipase A2 in carotid artery plaques predicts long-term cardiac outcome
AU - Herrmann, Joerg
AU - Mannheim, Dallit
AU - Wohlert, Christine
AU - Versari, Daniele
AU - Meyer, Fredric B.
AU - McConnell, Joseph P.
AU - Gössl, Mario
AU - Lerman, Lilach O.
AU - Lerman, Amir
N1 - Funding Information:
This study was supported by NIH grants: K24, HL-69840, R01 HL-63911, DK73608, HL77131, HL085307, and HL092954, the Mayo Stiftung, and by an award from the Mayo Clinic Clinical Immunology and Immunotherapeutic program.
PY - 2009/12
Y1 - 2009/12
N2 - 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 resultsProspective 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].ConclusionLipoprotein-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.
AB - 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 resultsProspective 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].ConclusionLipoprotein-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.
KW - Arteriosclerosis
KW - Cardiovascular diseases
KW - Plaque
KW - Prognosis
UR - http://www.scopus.com/inward/record.url?scp=71549159171&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=71549159171&partnerID=8YFLogxK
U2 - 10.1093/eurheartj/ehp309
DO - 10.1093/eurheartj/ehp309
M3 - Article
C2 - 19689974
AN - SCOPUS:71549159171
SN - 0195-668X
VL - 30
SP - 2930
EP - 2938
JO - European heart journal
JF - European heart journal
IS - 23
ER -