Author + information
- Giovanni Peretto,
- Sara Baggio,
- Marco Magnoni,
- Nicole Cristell,
- Chiara Lanzani,
- Lorena Citterio,
- Paolo Manunta and
- Domenico Cianflone
Background: A complex network of gene-environment interactions may be related to myocardial infarction. To date, several single nucleotide polymorphisms (SNPs) have been investigated as potential determinants in terms of predisposition, prognosis and response to therapy, but with no definite findings.
Methods: We analyzed 491 patients (79,6% males, mean age 61.6 y) with a ST-elevation myocardial infarction (STEMI) occurring as their first clinical manifestation. MACE (death, non-fatal acute coronary syndromes, heart failure, and non-fatal stroke) at 180-day follow-up period were collected. DNA samples of each participant, extracted from whole blood, were analysed using the TaqMan® OpenArray™ Genotyping System for 7 SNPs involved in the renin-angiotensin-aldosterone system (RAAS) and inflammation: rs5051 (AGT), rs4343 (ACE), rs1799998 (CYP11B2), rs1800629 (TNF alpha), rs1800795 (IL-6), rs17222814 (ALOX5AP), rs5065 (NPPA).
Results: A MACE occurred in 46 patients with STEMI. Two SNPs showed a statistically significant independent association with the endpoint: rs5051 (AGT, X2= 20.946, p<0.0001), and rs4343 (ACE, X2=7.338, p=0.026). The rs5051 TT genotype had an up to five-fold increased risk of unfavourable outcome when compared to non-TT genotype cases (TT vs. CC: OR 3.52 (1.61-7.95), p=0.0015; TT vs. CT: OR 4.89 (2.29-7.95), p<0.0001; TT vs. CC&CT: OR 4.24 (2.16-8.21), p<0.0001), whereas rs4343 AA genotype was associated with an up to three-fold increased risk of MACE at 180 days (AA vs. GG: OR 3.04 (1.30-7.53), p=0.0102; AA vs. AG&GG: OR 2.32 (1.18-4.44), p=0.016). Furthermore, pharmacological inhibition of RAAS resulted in a statistically significant reduction of MACE in presence of three genotypes: rs5051 CC (OR=0.16 (0.05-0.59), p=0.0024), rs4343 AA and AG (AA: OR=0.13 (0.04-0.44), p=0.0004; AG: OR=0.37, (0.15-0.93), p=0.0298).
Conclusions: Genetic profiling of rs5051 and rs4343 emerged as a useful tool to predict 6-month prognosis in patients with their first STEMI, suggesting that these polymorphisms may confer an enhanced susceptibility to the benefits of the pharmacological inhibition of RAAS.
Moderated Poster Contributions
Acute and Stable Ischemic Heart Disease Moderated Poster Theater, Poster Hall, Hall C
Friday, March 17, 2017, 11:15 a.m.-11:25 a.m.
Session Title: Post-CAD/MI: Making Tough Predictions About the Future
Abstract Category: 1. Acute and Stable Ischemic Heart Disease: Basic
Presentation Number: 1138M-13
- 2017 American College of Cardiology Foundation