Relation between the A1166C angiotensin II type 1 receptor gene polymorphism and cardiovascular outcomes after...

The A1166C polymorphism of the angiotensin II type 1 receptor (AT1R) gene, which appears to be the main receptor mediating the pleitropic vascular effects of angiotensin II in human beings, has been associated with the risk of myocardial infarction (MI), the severity of coronary vasoconstriction and the occurrence of sudden death. The question therefore arises whether the A1166C polymorphism constitutes a hereditary risk factor of survival after an acute myocardial infarction.

In a large prospective study of 970 consecutive patients with a recent myocardial infarction the A1166C polymorphism was detected using a PCR based protocol. During the follow-up period (median, 2.5 years), 75 patients died and 62 from cardiovascular causes. The prespecified primary and secondary end points considered were total mortality and cardiovascular mortality. No differences between AA, AC, and CC groups were observed with respect to baseline clinical characteristics. Beyond conventional risk factors like age (RR=2.8 [1.6-5.0] 95% CI; p<0.001), hypercholesterolemia (RR=2.1 [1.2-3.7] 95% CI; p<0.014) or low left ventricular ejection fraction (RR=2.7 [1.5-4.8] 95% CI; p<0.002), the AT1R CC genotype was also identified as a strong independent predictor of death after myocardial infarction (RR=3.2 [1.5-7.0] 95% CI ; p<0.004). After adjustment for mortality causes, the AT1R CC genotype was confirmed to be an independent predictor of cardiovascular death after myocardial infarction (RR=2.8 [1.2-6.5] 95% CI; p<0.021).

The AT1R CC genotype after adjustment is a strong predictor of death in post MI patients. This new finding may help to identify high risk post MI patients who may benefit from new therapeutic strategies.