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

被引：61

作者：

Ardissino, Diego ^{[1
]}

Berzuini, Carlo ^{[2
]}

Merlini, Piera Angelica ^{[3
]}

Mannucci, Pier Mannuccio ^{[4
]}

Surti, Aarti ^{[5
]}

Burtt, Noel ^{[5
]}

Voight, Benjamin ^{[6
,7
,8
]}

Tubaro, Marco ^{[9
]}

Peyvandi, Flora ^{[4
]}

Spreafico, Marta ^{[4
]}

Celli, Patrizia ^{[10
]}

Lina, Daniela

Notarangelo, Maria Francesca

Ferrario, Maurizio ^{[11
]}

Fetiveau, Raffaela ^{[11
]}

Casari, Giorgio ^{[12
,13
]}

Galli, Michele ^{[14
]}

Ribichini, Flavio ^{[15
]}

Rossi, Marco L. ^{[16
]}

Bernardi, Francesco ^{[17
]}

Marziliano, Nicola ^{[11
]}

Zonzin, Pietro ^{[18
]}

Mauri, Francesco ^{[3
]}

Piazza, Alberto ^{[19
]}

Foco, Luisa ^{[20
]}

Bernardinelli, Luisa ^{[20
,21
]}

Altshuler, David ^{[4
,6
,7
,8
,22
,23
]}

Kathiresan, Sekar ^{[5
,6
,22
]}

机构：

[1] Univ Parma, Azienda Osped, Unita Operat Cardiol, Div Cardiol, I-43100 Parma, Italy

[2] Ctr Math Sci, Stat Lab, Cambridge, England

[3] Azienda Osped Niguarda Ca Granda, Div Cardiol, Milan, Italy

[4] Univ Milan, Osped Maggiore Mangiagalli & Regina Elena, Fdn Ist Ricovero & Cura Carattere Sci, Dept Internal Med & Med Specialties, Milan, Italy

[5] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA

[6] Broad Inst Massachusetts Inst Technol & Harvard U, Program Med & Populat Genet, Cambridge, MA USA

[7] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA

[8] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA

[9] Osped San Filippo Neri, Div Cardiol, Rome, Italy

[10] Osped San Camillo, Div Cardiol, Rome, Italy

[11] Policlin San Matteo, Fdn Ist Ricovero Cura & Carattere Sci, I-27100 Pavia, Italy

[12] Univ Vita Salute San Raffaele, Milan, Italy

[13] Ist Sci San Raffaele, I-20132 Milan, Italy

[14] Osped Livorno, Div Cardiol, Livorno, Italy

[15] Univ Verona, Osped Borgo Trento, Div Cardiol, I-37100 Verona, Italy

[16] Ist Clin Humanitas, Ist Ricovero Cura & Carattere Sci, Div Cardiol, Milan, Italy

[17] Univ Ferrara, Dept Biochem & Mol Biol, I-44100 Ferrara, Italy

[18] Osped Rovigo, Div Cardiol, Rovigo, Italy

[19] Univ Turin, Dept Genet Biol & Biochem, Turin, Italy

[20] Univ Pavia, Dept Appl Hlth Sci, I-27100 Pavia, Italy

[21] MRC, Biostat Unit, Cambridge CB2 2BW, England

[22] Harvard Univ, Sch Med, Dept Med, Boston, MA USA

[23] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA

来源：

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY | 2011年 / 58卷 / 04期

关键词：

early-onset myocardial infarction; outcomes; rs1333040; 9p21.3 genetic variants; CORONARY-ARTERY-DISEASE; CHROMOSOME; 9P21; HEART-DISEASE; 4; SNPS; ASSOCIATION; LOCUS; SUSCEPTIBILITY; REPLICATION; DEATH; RISK;

D O I：

10.1016/j.jacc.2010.11.075

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Objectives The 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. Background 9p21.3 genetic variants are associated with ischemic heart disease, but it is not known whether they influence prognosis after an acute coronary event. Methods Within 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. Results Over 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). Conclusions In 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. (J Am Coll Cardiol 2011;58:426-34) (C) 2011 by the American College of Cardiology Foundation

引用

页码：426 / 434

页数：9

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