Renin-angiotensin-aldosterone system polymorphisms: a role or a hole in occurrence and long-term prognosis of acute myocardial infarction at young age

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Abstract
Background The renin-angiotensin-aldosterone system (RAAS) is involved in the cardiovascular homeostasis as shown by previous studies reporting a positive association between specific RAAS genotypes and an increased risk of myocardial infarction. Anyhow the prognostic role in a long-term follow-up has not been yet investigated. Aim of the study was to evaluate the influence of the most studied RAAS genetic Single Nucleotide Polymorphisms (SNPs) on the occurrence and the long-term prognosis of acute myocardial infarction (AMI) at young age in an Italian population. Methods The study population consisted of 201 patients and 201 controls, matched for age and sex (mean age 40 ± 4 years; 90.5% males). The most frequent conventional risk factors were smoke (p < 0.001), family history for coronary artery diseases (p < 0.001), hypercholesterolemia (p = 0.001) and hypertension (p = 0.002). The tested genetic polymorphisms were angiotensin converting enzyme insertion/deletion (ACE I/D), angiotensin II type 1 receptor (AGTR1) A1166C and aldosterone synthase (CYP11B2) C-344T. Considering a long-term follow-up (9 ± 4 years) we compared genetic polymorphisms of patients with and without events (cardiac death, myocardial infarction, revascularization procedures). Results We found a borderline significant association of occurrence of AMI with the ACE D/I polymorphism (DD genotype, 42% in cases vs 31% in controls; p = 0.056). DD genotype remained statistically involved in the incidence of AMI also after adjustment for clinical confounders. On the other hand, during the 9-year follow-up (65 events, including 13 deaths) we found a role concerning the AGTR1: the AC heterozygous resulted more represented in the event group (p = 0.016) even if not independent from clinical confounders. Anyhow the Kaplan-Meier event free curves seem to confirm the unfavourable role of this polymorphism. Conclusion Polymorphisms in RAAS genes can be important in the onset of a first AMI in young patients (ACE, CYP11B2 polymorphisms), but not in the disease progression after a long follow-up period. Larger collaborative studies are needed to confirm these results.

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