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CLINICAL RESEARCH: ACUTE MYOCARDIAL INFARCTION

Platelet glycoprotein IIb/IIIa Pl^A2/Pl^A2 homozygosity associated with risk of ischemic cardiovascular disease and myocardial infarction in young men

The Copenhagen City Heart Study

Stig E. Bojesen, MD, PhD^*, Klaus Juul, MD^*, Peter Schnohr, MD, Anne Tybjærg-Hansen, MD, DMSc and B.ørge G. Nordestgaard, MD, DMSc^*,*

^* Department of Clinical Biochemistry, Herlev University Hospital, Herlev, Denmark
The Copenhagen City Heart Study, Bispebjerg University Hospital, Copenhagen, Denmark
Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark

Manuscript received January 28, 2003; revised manuscript received April 25, 2003, accepted May 9, 2003.

^* Reprint requests and correspondence: Dr. Børge G. Nordestgaard, Department of Clinical Biochemistry, Herlev University Hospital, Herlev Ringvej 75, DK-2730 Herlev, Denmark.
brno{at}herlevhosp.kbhamt.dk

OBJECTIVES: We tested the hypothesis that platelet glycoprotein (GP) IIb/IIIa Pl^A2/Pl^A2 homozygotes or Pl^A1/Pl^A2 heterozygotes versus Pl^A1/Pl^A1 noncarriers have increased risk of ischemic cardiovascular disease and myocardial infarction (MI), stratified for age and gender.

BACKGROUND: The GP IIb/IIIa Pl^A1/Pl^A2 polymorphism influences aggregation of platelets; however, an association between ischemic cardiovascular disease and heterozygosity remains controversial, and association with homozygosity is largely unexplored.

METHODS: We genotyped the participants of the Copenhagen City Heart Study, a prospective cardiovascular investigation of the Danish general population (n = 9,149, 22-year follow-up) and assessed the risk of ischemic cardiovascular disease in heterozygotes or homozygotes versus noncarriers.

RESULTS: Of the participants, 70.0%, 27.3%, and 2.7% were noncarriers, heterozygotes, or homozygotes, respectively. Incidence of ischemic cardiovascular disease was 167 and 103 per 10,000 person-years in homozygous and noncarrier men (log-rank: p = 0.006), whereas this difference was not observed in women (p = 0.33) (genotype·gender interaction: p = 0.03). In homozygous versus noncarrier men <40 years of age, 40 to 50 years, and >50 years at entry, age-adjusted relative risks (RRs) of ischemic cardiovascular disease were 3.6 (1.4 to 9.0), 2.4 (1.3 to 4.6), and 1.0 (0.6 to 1.8), respectively (age·genotype interaction in men: p = 0.04); equivalent multifactorially adjusted RRs were 3.0 (1.1 to 8.0), 2.0 (1.0 to 3.9), and 1.0 (0.6 to 1.8), respectively. The corresponding age-adjusted RR values of MI in men were 5.2 (1.5 to 18), 3.5 (1.6 to 7.5), and 0.5 (0.1 to 1.5), respectively (age·genotype interaction in men: p = 0.002); equivalent multifactorially adjusted RRs were 3.8 (1.0 to 15), 3.1 (1.4 to 6.9), and 0.5 (0.2 to 1.5), respectively.

CONCLUSIONS: Pl^A2/Pl^A2 homozygosity is associated with a three-fold and four-fold risk of ischemic cardiovascular disease and MI in young men.

Abbreviations and Acronyms   CI = confidence interval   GP = glycoprotein   ICD = International Classification of Diseases   MI = myocardial infarction   RR = relative risk

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