Adrenoceptor Polymorphisms and the Risk of Cardiac Injury and Dysfunction After Subarachnoid Hemorrhage

Abstract

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 μg/L) and the left ventricular ejection fraction (LVEF, abnormal if β1AR Arg389Gly, β1AR Ser49Gly, β2AR Gly16Arg, β2AR Gln27Glu, β2AR Thr164Ile, and α2AR 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 β1AR Arg389Gly (odds ratio [OR] 3.4, P =0.030) and the CC genotype (Gln/Gln) of β2AR Gln27Glu (OR 3.1, P =0.032) were predictive of cTi release. The presence of the α2AR deletion was predictive of reduced LVEF (OR 4.2, P =0.023). The combination of the β1AR 389 CC and the β2AR 27 CC genotypes resulted in a marked increase in the odds of cTi release (OR 15.5, P =0.012). The combination of the β1AR 389 CC and the α2AR 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.