Adrenoceptor polymorphisms and the risk of cardiac injury and dysfunction after subarachnoid hemorrhage

Background and Purpose-Cardiac abnormalities occur commonly after subarachnoid hemorrhage (SAH) and may be caused by excessive release of catecholamines from the myocardial sympathetic nerves. We hypothesized that adrenoceptor polymorphisms resulting in greater catecholamine sensitivity would be associated with an increased risk of cardiac injury. Methods-This was a prospective cohort study. The primary outcome variables were the serum level of cardiac troponin I (cTi, abnormal if > 1.0 mu g/L) and the left ventricular ejection fraction (LVEF, abnormal if < 50%). Six adrenoceptor polymorphisms were genotyped: beta 1AR Arg389Gly, beta 1AR Ser49Gly, beta 2AR Gly16Arg, beta 2AR Gln27Glu, beta 2AR Thr164Ile, and alpha 2AR del322-325. The effect of each polymorphism on the risk of developing cardiac abnormalities was quantified using multivariable logistic regression. Results-The study included 182 patients. The CC genotype (Arg/Arg) of beta 1AR Arg389Gly (odds ratio [OR] 3.4, P = 0.030) and the CC genotype (Gln/Gln) of beta 2AR Gln27Glu (OR 3.1, P = 0.032) were predictive of cTi release. The presence of the a2AR deletion was predictive of reduced LVEF (OR 4.2, P = 0.023). The combination of the beta 1AR 389 CC and the beta 2AR 27 CC genotypes resulted in a marked increase in the odds of cTi release (OR 15.5, P = 0.012). The combination of the beta 1AR 389 CC and the alpha 2AR deletion genotypes resulted in a marked increase in the odds of developing a reduced LVEF (OR 10.3, P = 0.033). Conclusions-Genetic polymorphisms of the adrenoceptors are associated with an increased risk of cardiac abnormalities after SAH. These data support the hypothesis that cardiac dysfunction after SAH is a form of neurocardiogenic injury.