TY - JOUR
T1 - Platelet glycoprotein IIb/IIIa Pl(A2)/Pl(A2) homozygosity associated with risk of ischemic cardiovascular disease and myocardial infarction in young men
T2 - the Copenhagen City Heart Study
AU - Bojesen, Stig E
AU - Juul, Klaus
AU - Schnohr, Peter
AU - Tybjaerg-Hansen, Anne
AU - Nordestgaard, Børge G
AU - Copenhagen City Heart Study
PY - 2003/8/20
Y1 - 2003/8/20
N2 - 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.
AB - 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.
KW - Adult
KW - Antigens, Human Platelet/genetics
KW - Demography
KW - Denmark/epidemiology
KW - Female
KW - Homozygote
KW - Humans
KW - Incidence
KW - Male
KW - Middle Aged
KW - Myocardial Infarction/epidemiology
KW - Myocardial Ischemia/epidemiology
KW - Platelet Glycoprotein GPIIb-IIIa Complex/genetics
KW - Polymorphism, Genetic
KW - Prospective Studies
KW - Risk
U2 - 10.1016/s0735-1097(03)00781-2
DO - 10.1016/s0735-1097(03)00781-2
M3 - Journal article
C2 - 12932598
SN - 0735-1097
VL - 42
SP - 661
EP - 667
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
IS - 4
ER -