Electrocardiographic left ventricular hypertrophy, β₃ adrenergic receptor polymorphism and endpoint of ACEI treatment of hypertension

Objectives: Current treatment strategies for essential hypertension are effective only in a portion of patients. Many factors influence the therapeutic effect, including the status of left ventricular hypertrophy (LVH) and genetic variations. LVH influences the intensity of left ventricular depolarization and is a risk factor for many cardiovascular events independent of conventional predictors. The β₃-adrenergic receptor (ADRB3) gene polymorphism is also associated with elevated blood pressure (BP) and cardiovascular disorders. In this study, we examined the impact of LVH (diagnosed by an electrocardiograph) and ADRB3 polymorphism on response to anti-hypertensive therapy. Methods: We treated a hypertensive cohort with benazepril for a period of 15 days, and evaluated the drug effect by BP drop (ΔBP). We performed standard ECG measurement on each subject and determined ADRB3 genotypes experimentally. Smoothing plots were first used to visualize the relationship, and additive models were fitted to investigate the role of LVH and ADRB3 polymorphism as well as their interactions with the treatment effect. Results: Electrocardiographic LVH was positively associated baseline BP, and negatively associated with ΔBP. The relationship was in a linear pattern. The association is greatly modified by ADRB3 genotype. In ADRB3 wildtype patients, the effect size increased, however, among ADRB3 mutant subjects, the association was attenuated and remained statistically non-significant. Conclusion: Our results suggested the predictive value of electrocardiographically diagnosed LVH to the anti-hypertensive treatment effectiveness, and pointed out the importance of gene-environment interaction. Our finding could have significant clinical implications to optimize the therapeutic dose range based on the ECG indexes.