β1Adrenergic Receptor Polymorphisms And Heart Failure:Susceptibility,Response To β-Blocker Therapy And Prognosis

Background:The overall prevalence of HF is increasing because of the ageing of the population and the success in prolonging survival in patients suffering coronary events. The β-blockers are mainstay of current treatment of heart failure (HF) in guideline, for their administration has beneficial effects on left ventricular (LV) function and prognosis. However, in clinical practice, the response to β-blocker therapy and prognosis of HF are variable among patients. It is therefore important to identify the risk factors for HF so that preventive measurements can be undertaken early; and anticipation the response to β-blockers would help the physicians to make therapeutic decision. Thus there are needs for risk stratification tools of HF predictors of response to β-blockers treatment, which are still challenges in the real world.Given the crucial role of adrenergic pathway in myocardial function and marked alternations in β1-adrenoceptor (β1-AR) mediated signal transduction in heart failure, previous studies have examined the β1-AR genetic polymorphisms: Arg389Gly and Ser49Gly would whether affect the susceptibility, response to β-blocker therapy and prognosis of heart failure, with inconsistent results.Aims We performed a meta-analysis of studies evaluating the impact of (31-AR polymorphisms on susceptibility to HF, the response to β-blocker therapy and the prognosis of HF, and aimed to provide a reference for individualized heart failure prevention and therapy.Data Sources:Electronic databases were systematically searched before August2011. We extracted data sets and performed meta-analysis with standardized methods.Data Extraction:Two reviewers independently extracted information regarding study characteristics, the distribution of the Arg389Gly and Ser49Gly genotype for cases and controls, the changes of LVEF, LVEDd and LVESd with β-blockers treatment, and occurrences of all-cause mortality and combined endpoints.Methods and ResultsA total of27studies met our inclusion criteria. It was found that only in East Asians, the Gly389allele significantly increased the HF risk, and Gly389homozygotes had higher risk of HF than Arg389carriers. However, the Gly389allele and Gly389homozygotes trended to decrease the risk of HF in whites. With the similar reduction of heart rate, the Arg389homozygotes performed a better response to β-blocker therapy:the improvments of LVEF, LVEDd and LVESd with β-blockers treatment were significantly better in Arg389homozygotes than that in the Gly389homozygotes; but the prognoses were similar in the two groups. The Ser49Gly polymorphism did not impact the risk or prognosis of HF.ConclusionBased on our meta-analysis, the Gly389allele and Gly389homozygotes were risk factors in East Asians while trend to protect whites against HF. Furthermore, Arg389homozygote is significantly associated with a favorable response to β-blocker treatment in HF patients. However, neither of the two polymorphisms is an independent predictor of the prognosis of HF.