251 Renin-angiotensin-aldosterone system polymorphisms: a role or a hole in occurrence and long-term prognosis of acute myocardial infarction at Tunisian older people

Abstract

Myocardial infarction (MI) is one of the major causes of death all over the world. Because MI frequently occurs suddenly without any preceding clinical symptoms, the prediction of MI is clinically of great importance. Angiotensin II is produced primarily by angiotensin I-converting enzyme (ACE) within atherosclerotic lesions and ACE level correlates with the severity of vessel wall damage. We analyzed the evolution with age of the frequencies of the I/D polymorphism of the ACE, A1166C of the angiotensin II AT1 receptor (AT1R), and M235T of the angiotensinogen (AGT) gene in a healthy population and he subsequent comparison to age- and sex-matched groups of MI patients. To investigate the influence of increasing age on the incidence and remaining lifetime risk of myocardial infarction in a cohort of older men. Polymorphisms of the AGT, ACE (I/D) and AGTR1 (A1166C) genes in patients and controls were analyzed using allele-specific PCR, and PCR-rflp. A total of 140 healthy subjects and 119 individuals with MI were divided into two groups < 65 and > 65 years old. The evolution with age showed that the AGT M allele (P < 0.001) and the ACE I allele (P < 0.05) frequency decreased with age. The TT genotype frequency increased in patients with MI > 65 years (OR = 3.52; 95% CI; 3.12–5.54). The AA genotype showed a similar behaviour (OR = 2.9; 95% CI; 1.11–5.6). The DD genotype increased in the MI > 65 group (OR = 6.66; 95% CI; 2.02–21.9). Serum ACE activity was positively associated to age (r = 0.38, p = 0.000). Patients with DD genotype > 65 years was significantly higher (119.7 ± 50.8 U/L) than in patients with DD genotype < 65 years (96.9 ± 31.4 U/L, p = 0.039). The incidence of new cardiovascular disease continued to increase after age 65 but was most often diagnosed at death. These findings suggest that people aged 60 and older have a substantial amount of undiagnosed disease. We propose that the study of the allele frequency evolution in an healthy population at different ages is essential to determine risk factors for MI in case-control studies.