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Influence of 9p21.3 Genetic Variants on Clinical and Angiographic Outcomes in Early-Onset Myocardial Infarction

By Diego Ardissino, Carlo Berzuini, Piera Angelica Merlini, Pier Mannuccio Mannucci, Aarti Surti, Noel Burtt, Benjamin Voight, Marco Tubaro, Flora Peyvandi, Marta Spreafico, Patrizia Celli, Daniela Lina, Maria Francesca Notarangelo, Maurizio Ferrario, Raffaela Fetiveau, Giorgio Casari, Michele Galli, Flavio Ribichini, Marco L. Rossi, Francesco Bernardi, Nicola Marziliano, Pietro Zonzin, Francesco Mauri, Alberto Piazza, Luisa Foco, Luisa Bernardinelli, David Altshuler and Sekar Kathiresan

Abstract

ObjectivesThe purpose of this study was to test whether the 9p21.3 variant rs1333040 influences the occurrence of new cardiovascular events and coronary atherosclerosis progression after early-onset myocardial infarction.Background9p21.3 genetic variants are associated with ischemic heart disease, but it is not known whether they influence prognosis after an acute coronary event.MethodsWithin the Italian Genetic Study of Early-onset Myocardial Infarction, we genotyped rs1333040 in 1,508 patients hospitalized for a first myocardial infarction before the age of 45 years who underwent coronary angiography without index event coronary revascularization. They were followed up for major cardiovascular events and angiographic coronary atherosclerosis progression.ResultsOver 16,599 person-years, there were 683 cardiovascular events and 492 primary endpoints: 77 cardiovascular deaths, 223 reoccurrences of myocardial infarction, and 383 coronary artery revascularizations. The rs1333040 genotype had a significant influence (p = 0.01) on the primary endpoint, with an adjusted hazard ratio of 1.19 (95% confidence interval [CI]: 1.08 to 1.37) for heterozygous carriers and 1.41 (95% CI: 1.06 to 1.87) for homozygous carriers. Analysis of the individual components of the primary endpoints provided no significant evidence that the rs1333040 genotype influenced the hazard of cardiovascular death (p = 0.24) or the reoccurrence of myocardial infarction (p = 0.57), but did provide significant evidence that it influenced on the hazard of coronary revascularization, with adjusted heterozygous and homozygous ratios of 1.38 (95% CI: 1.17 to 1.63) and 1.90 (95% CI: 1.36 to 2.65) (p = 0.00015), respectively. It also significantly influenced the angiographic endpoint of coronary atherosclerosis progression (p = 0.002).ConclusionsIn early-onset myocardial infarction, the 9p21.3 variant rs1333040 affects the progression of coronary atherosclerosis and the probability of coronary artery revascularization during long-term follow-up

Publisher: American College of Cardiology Foundation. Published by Elsevier Inc.
Year: 2011
DOI identifier: 10.1016/j.jacc.2010.11.075
OAI identifier:

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