Glycoprotein IIIa P1(A1/A2) polymorphism and sudden cardiac death

OBJECTIVES We studied the association of the Pl(A1/A2) polymorphism with co ronary thrombosis, myocardial infarction (MI) and sudden cardiac death (SCD ) in autopsied victims of sudden death. BACKGROUND Sudden cardiac death is one of the leading symptoms of coronary heart disease in early middle age. Platelet glycoprotein (GP)IIb/IIIa fibri nogen receptors play a key role in coronary thrombosis and MI. Pl(A1/A2) po lymorphism of the gene for GPIIIa has been previously studied in hospital M I patients. Significance of the Pl(A1/A2) polymorphism in victims of SCD is nor known. METHODS The Pl(A1/A2) polymorphism was studied in the Helsinki Sudden Death Study comprising 700 autopsied middle-aged white Finnish men (33 to 70 yea rs, mean 53 years) who suffered sudden or violent out-of-hospital death. RESULTS Prevalence of the A2 allele decreased with age in the series. This decrease was observed among victims of SCD (n = 281) but not in men who die d violently (n = 258) or of other diseases (n = 127). Of SCD victims below 50 years, 39.7% were carriers of the A2 allele compared with 28.3% among me n under 50 who died of other causes (odds ratio [OR] 2.5, p = 0.01). Men wi th acute fatal coronary thrombosis (n = 39) were more often (OR 3.4, p < 0. 01) carriers of the A2 allele than were men (n = 242) with SCD in the absen ce of acute corollary thrombosis (48.7% vs. 24.4%, respectively). In additi on, men with MI and recent or old thrombosis (n = 67) were more often (OR 3 .6, p = 0.005) carriers of the A2 allele than were men (n = 123) with MI in the absence of thrombosis (44.8% vs. 20.3%, respectively). These associati ons were especially strong in men under 60. CONCLUSIONS Our results suggest that the A2 allele of the Pl(A1/A2) Polymor phism of GPIIIa is a major risk factor of coronary thrombosis and may be on e important predictor of SCD in early middle age. (J Am Coll Cardiol 2000;3 6:1317-23) (C) 2000 by the American College of Cardiology.