Influence of 9p21.3 Genetic Variants on Clinical and Angiographic Outcomes in Early-Onset Myocardial Infarction
Open accessAbstract
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.
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Large-scale GWAS have accounted for less than one-fifth of the cardiovascular risk attributable to genetic determinants.
“Despite extensive investigations in search of causal genetic variants, such as large-scale GWAS, less than one-fifth of attributable cardiovascular risk has been accounted for from genetic determinants (3,4).”
From The contributory role of gut microbiota in cardiovascular disease (2014) · cites this paper as [3]
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Шестерня, П. А., Va, S., & Nikulina, S. Y. (2012) · Сибирский медицинский журнал (Томск)
Genetics of myocardial infarction in clinical practice. Is it ready for prime time?
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- Authors
- Ardissino, D., Berzuini, C., Merlini, P. A., Mannuccio Mannucci, P., Surti, A., Burtt, N., Voight, B., Tubaro, M., Peyvandi, F., Spreafico, M., Celli, P., Lina, D., Notarangelo, M. F., Ferrario, M., Fetiveau, R., Casari, G., Galli, M., Ribichini, F., Rossi, M. L., Bernardi, F., Marziliano, N., Zonzin, P., Mauri, F., Piazza, A., Foco, L., Bernardinelli, L., Altshuler, D., & Kathiresan, S.
- Affiliations
- Ospedale di Parma (IT)
- University of Cambridge (GB)
- Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda (IT)
- Massachusetts General Hospital (US)
- Broad Institute (US)
- University of Milan (IT)
- IRCCS San Camillo Hospital (IT)
- Policlinico San Matteo Fondazione (IT)
- Vita-Salute San Raffaele University (IT)
- Ospedale di Livorno (IT)
- University of Verona (IT)
- University of Ferrara (IT)
- Ospedale Santa Maria della Misericordia di Rovigo (IT)
- University of Turin (IT)
- University of Pavia (IT)
- Corresponding author
- Ardissino, Diego
- ORCID
- Venue
- Journal of the American College of Cardiology
- Publisher
- Elsevier BV
- Published
- 2011-07
- Volume
- 58
- Issue
- 4
- Pages
- 426-434
- ISSN
- 0735-1097 (ISSN-L)
- OpenAlex
- W1990596585
- Cited by
- 80
- References
- 23
- Citations by year
- 2025: 3 · 2024: 2 · 2023: 1 · 2022: 5 · 2021: 3 · 2020: 6 · 2019: 4 · 2018: 4 · 2017: 5 · 2016: 1 · 2015: 6 · 2014: 20 · 2013: 5 · 2012: 12
- FWCI
- 7.78
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of the American College of Cardiology (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
- Institutional Research Information System University of Ferrara (University of Ferrara) (submittedVersion)
- Elsevier eBooks
- Funders
- Pfizer
- Merck
- Almylam
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Acute Myocardial Infarction Research
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Keywords
- early-onset myocardial infarction, coronary artery disease, coronary atherosclerosis progression, coronary revascularization, cardiovascular events, genetic susceptibility, prognosis after myocardial infarction, cardiovascular mortality, myocardial infarction recurrence, coronary angiography
- MeSH terms
- Adult, Chromosomes, Human, Pair 9, Coronary Artery Disease, Female, Humans, Male, Middle Aged, Myocardial Infarction, Case-Control Studies, Coronary Angiography, Age of Onset, Disease Progression, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide
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