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.
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.
Authors: Blanca Elsa Rivera-García; Juan Carlos Esparza-García; Jose Luis Aceves-Chimal; Alfredo Leaños-Miranda; Abraham Majluf-Cruz; Irma Isordia-Salas Journal: Mol Cell Biochem Date: 2013-09-05 Impact factor: 3.396
Authors: Marlene S Williams; Ethan J Weiss; Marc S Sabatine; Daniel I Simon; Wadie F Bahou; Lewis C Becker; Leslie V Parise; Harold L Dauerman; Patricia A French; Susan S Smyth; Richard C Becker Journal: Arterioscler Thromb Vasc Biol Date: 2010-12 Impact factor: 8.311
Authors: Jochen D Muehlschlegel; Tjörvi E Perry; Kuang-Yu Liu; Amanda A Fox; Shane A Smith; Peter Lichtner; Charles D Collard; Stanton K Shernan; John H Hartwig; Simon C Body; Karin M Hoffmeister Journal: Am J Hematol Date: 2012-01-07 Impact factor: 10.047