Objective: To investigate the associations between b 1 -adrenergic receptor (ADRB1) and cytochrome P450 2D6 (CYP2D6) gene polymorphisms and b-blocker treatment outcomes in patients with hypertension. Methods: Chinese patients with essential hypertension were treated with the b-blocker metoprolol and followed up for 12 weeks. xTAG Õ liquid-chip technology was used for CYP2D6 100 C > T and ADRB1 1165G > C genotyping. Associations between gene polymorphisms and antihypertensive therapy outcomes were assessed by generalized linear model fitting. A decrease of ! 10 mmHg in systolic blood pressure indicated an effective treatment outcome. Results: A total of 93 patients were included in the study. Mutant allele frequencies of 61.29% and 58.60% were obtained for ADRB1 and CYP2D6, respectively. There was no significant interaction between the effects of ADRB1 and CYP2D6 gene polymorphisms on treatment outcome. Patients homozygous for the mutant ADRB1 genotype (CC) had better treatment outcomes than those heterozygous for the mutation (GC). Interestingly, b-blocker treatment duration was an independent factor associated with treatment outcome. Conclusions: The ADRB1 1165G > C gene polymorphism and b-blocker treatment duration are independent factors associated with b-blocker treatment outcome. These findings suggest that the selection of antihypertensive therapy should take into consideration the patient's genotype.

The effects of berberine on cardiac function of heart failure after myocardial infarction and its possible mechanism were investigated. The anterior descending branches of 50 female Wistar rats were ligatured to establish the model of heart failure after myocardial infarction. At 4 weeks after successful modeling, the rats were randomly divided into two groups receiving 4-week gavage with saline (Sal group) and berberine (Ber group), while the sham-operation group (Sham group) was set up. After 4 weeks, the hemodynamics and serum BNP in rats were measured. The hearts of rats were taken to detect the degree of myocardial fibrosis. The myocardial cell apoptosis was detected. The expressions and changes in myocardial apoptosis-related proteins, including Bcl-2, Bax and caspase-3, were detected. The expression and changes in GRP78, CHOP and caspase-12 in myocardial tissue were detected. The results showed that Berberine improved the cardiac function of rats after myocardial infarction. After myocardial infarction, myocardial fibrosis and apoptosis were observed around the infarction area, berberine improved the myocardial fibrosis and reduced cell apoptosis. Furthermore, berberine alleviated endoplasmic reticulum stress (ERS) after myocardial infarction. In conclusion, Berberine can inhibit the myocardium cell apoptosis of heart failure after myocardial infarction, and its mechanism may be realized by affecting the ERS in myocardial tissue of heart failure after myocardial infarction and CHOP and caspase-12 apoptotic signaling pathway, upregulating Bcl-2/Bax expression and downregulating caspase-3 expression, thus inhibiting the cardiac remodeling and protecting the cardiac function.

We assessed the association of CYP2B6, CYP3A5, and CYP2C19 polymorphisms with sibutramine pharmacokinetics. Forty six healthy male subjects were enrolled, and their CYP2B6 (*4 and *6), CYP3A5 (*3), and CYP2C19 (*2, and *3) genotypes were analyzed. After a single 15-mg dose of sibutramine was administered, plasma concentrations of sibutramine and its metabolites, M1 and M2, were measured. CYP2B6 and CYP3A5 polymorphisms did not affect the pharmacokinetics of sibutramine and its metabolites. However, the CYP2C19 genotype substantially influenced plasma levels of sibutramine and its metabolites. The mean area under the curve (AUC) of sibutramine in CYP2C19 intermediate metabolizers (IMs; *1/*2 or *1/*3) and poor metabolizers (PMs; *2/*2, *2/*3)) was 18.5 and 252.2% higher, respectively, than the AUC in extensive metabolizers (EMs, *1/*1) (P < 0.001). The AUC of M1 metabolite in IMs and PMs was 22.5 and 148.0% higher, respectively, than that of EMs (P < 0.001). Our findings indicate that the CYP2C19 genotype substantially affects the pharmacokinetics of sibutramine.

Many trials have shown improvements in left ventricular function, exercise capacity, and quality of life after catheter ablation (CA) of atrial fibrillation (AF) in patients with heart failure (HF). We sought to evaluate the impact of CA on hard outcomes in a retrospective cohort study. AF patients with symptomatic HF from 3 hospitals were included. Our primary endpoint was major adverse cardiac events (MACEs), a composite of all-cause mortality, stroke, and unplanned hospitalization. In total, 90 patients underwent CA and 304 ones received rate control (RaC) were included. After a mean follow-up of 13.5 ± 5.3 months, 82.2% of patients in CA group got freedom from AF; all patients in RaC group remained in AF. CA group had a significant decreased risk of MACEs compared with RaC group (13.3% vs 29.3%, hazard ratio [HR] 0.51, 95% confidence interval [CI]: 0.32–0.82, P = .005). After propensity score matched for confounding factors, difference in MACEs remained significant between groups (13.3% vs 25.6%, HR 0.50, 95% CI: 0.26–0.98, P = .044). Multivariate regression analysis also indicated that CA was significantly associated with a lower risk of MACEs in overall cohort (HR 0.486, 95% CI: 0.253–0.933, P = .030) and in propensity-matched cohort (HR 0.482, 95% CI: 0.235–0.985, P = .045). Besides, age and NYHA class were associated with an increased risk of MACEs. In conclusion, the present study demonstrated that CA for AF in HF patients could reduce the risk of MACEs in a mid-term follow-up. Thus, CA may be a reasonable option for this population.