The latest consensus has changed CYP2D6 genotyping among Chinese population, while its impact on metoprolol tolerance and adverse events in elderly Chinese patients with cardiovascular diseases remains unclear. In this study, we prospectively included elderly patients who started metoprolol treatment for cardiovascular indications. According to the latest consensus on CYP2D6 genotype-to-phenotype translation, the patients were categorized as normal, intermediate, or poor metabolizers (NMs, IMs, or PMs, respectively) by detecting the presence of the CYP2D6*1, *2, *5, *10, and *14. Logistic regression model was used to analyze the correlation between the CYP2D6 phenotype and incidence of adverse events, which were assessed over a 12-week period. In this study, there were 651 (62.7%) NMs, 385 (37.1%) IMs, and 3 (0.3%) PMs. After 12 weeks of follow-up, compared with NMs, IMs had the lower maintenance dose [50.0 (25.0–50.0) mg/day vs. 25.0 (25.0–50.0) mg/day, p < 0.001] and lower weight-adjusted maintenance doses (0.52 ± 0.25 mg/day/kg vs. 0.42 ± 0.22 mg/day/kg, p < 0.001), and had higher incidence of postural hypotension (6.0% vs. 10.9%, p = 0.006), bradycardia (21.5% vs. 28.6%, p = 0.011), asystole (0.8% vs. 3.1%, p = 0.009) and syncope (2.0% vs. 6.2%, p = 0.001). In logistic regression model, the overall incidence of adverse events was 1.37-fold larger in IMs than in NMs (odds ratio = 1.37, 95% confidence interval = 1.05–1.79, p = 0.021). We conclude that IMs have lower tolerance and higher incidence of metoprolol-related adverse events than NMs in elderly Chinese patients with cardiovascular diseases. CYP2D6 genotyping is justifiable in elderly patients to minimize the risk of adverse events and ensure the benefits of metoprolol.

Background The allostatic load (AL) refers to the cumulative weakening of multiple physiological systems caused by repeated adaptation of the body to stressors There are still no studies have focused on the association between AL and the prognosis of patients with heart failure with preserved ejection fraction (HFpEF). The present study aimed to investigate the association between AL and adverse outcomes, including mortality and HF admission, among elderly male patients with HFpEF. Methods We conducted a prospective cohort study of 1111 elderly male patients with HFpEF, diagnosed between 2015 and 2019 and followed up through 2021. We constructed an AL measure using a combination of 12 biomarkers. The diagnosis of HFpEF was made according to the 2021 European Society of Cardiology guidelines. A Cox proportional hazards model was used to determine the associations between AL and adverse outcomes. Results In multivariate analysis, AL was significantly associated with increased risk of all-cause mortality (medium AL: adjusted hazard ratio [HR] = 2.53; 95% confidence interval [CI] 1.37–4.68; high AL: HR = 4.21; 95% CI 2.27–7.83; per-score increase: HR = 1.31; 95% CI 1.18–1.46), cardiovascular mortality (medium AL: HR = 2.67; 95% CI 1.07–6.68; high AL: HR = 3.13; 95% CI 1.23–7.97; per-score increase: HR = 1.20; 95% CI 1.03–1.40), non-cardiovascular mortality (medium AL: HR = 2.45; 95% CI 1.06–5.63; high AL: HR = 5.81; 95% CI 2.55–10.28; per-score increase: HR = 1.46; 95% CI 1.26–1.69), and HF admission (medium AL: HR = 2.68; 95% CI 1.43–5.01; high AL: HR = 3.24; 95% CI 1.69–6.23; per-score increase: HR = 1.24; 95% CI 1.11–1.39). Consistent results were found in multiple subgroup analyses. Conclusions A higher AL was associated with poor prognosis in elderly men with HFpEF. AL relies on information that is easily obtained in physical examinations and laboratory parameters and can be assessed in various care and clinical settings to help risk stratification of HFpEF patients.

Background The present study aimed to investigate the association between allostatic load (AL) and adverse outcomes, including mortality and heart failure (HF) admission, among elderly male patients who had heart failure with preserved ejection fraction (HFpEF). Methods A prospective cohort study of 1111 elderly male patients with HFpEF, diagnosed between 2015 and 2019 and followed up through 2021. We constructed an AL measure using a combination of 10 biomarkers, including fasting glucose, hemoglobin, systolic blood pressure, diastolic blood pressure, heart rate, total cholesterol, triglycerides, highdensity lipoprotein cholesterol, neutrophil-to-lymphocyte ratio, and creatinine. The diagnosis of HFpEF was made according to the 2016 European Society of Cardiology guidelines. A Cox proportional hazards model was used to determine the associations between AL and adverse outcomes. Results In multivariate analysis, AL was significantly associated with increased risk of all-cause mortality (medium AL: adjusted hazard ratio [HR] = 2.75; 95% confidence interval [CI] 1.31–5.75; high AL: HR = 3.22; 95% CI 1.44–7.19; per-score increase: HR = 1.27; 95% CI 1.13–1.43), cardiovascular mortality (medium AL: HR = 3.42; 95% CI 1.16–10.13; high AL: HR = 4.14; 95% CI 1.27–13.43; per-score increase: HR = 1.28; 95% CI 1.07–1.53), non-cardiovascular mortality (medium AL: HR = 2.96; 95% CI 1.05–8.32; high AL: HR = 3.53; 95% CI 1.12–11.14; per-score increase: HR = 1.33; 95% CI 1.13–1.57), and HF admission (medium AL: HR = 2.32; 95% CI 1.10–4.87; high AL: HR = 3.03; 95% CI 1.33–6.92; per-score increase: HR = 1.24; 95% CI 1.10–1.40). Consistent results were found in multiple subgroup analyses. Conclusions A higher AL burden was associated with increased risk for poor prognosis in elderly men with HFpEF. AL relies on information that is easily obtained in regular physical examinations and can be assessed in various care and clinical settings to determine risk and help improve prognosis in patients with HFpEF.