Metformin use correlated with lower risk of cardiometabolic diseases and related mortality among US cancer survivors: evidence from a nationally representative cohort study.

BACKGROUND: In the USA, the prolonged effective survival of cancer population has brought significant attention to the rising risk of cardiometabolic morbidity and mortality in this population. This heightened risk underscores the urgent need for research into effective pharmacological interventions for cancer survivors. Notably, metformin, a well-known metabolic regulator with pleiotropic effects, has shown protective effects against cardiometabolic disorders in diabetic individuals. Despite these promising indications, evidence supporting its efficacy in improving cardiometabolic outcomes in cancer survivors remains scarce. METHODS: A prospective cohort was established using a nationally representative sample of cancer survivors enrolled in the US National Health and Nutrition Examination Survey (NHANES), spanning 2003 to 2018. Outcomes were derived from patient interviews, physical examinations, and public-access linked mortality archives up to 2019. The Oxidative Balance Score was utilized to assess participants' levels of oxidative stress. To evaluate the correlations between metformin use and the risk of cardiometabolic diseases and related mortality, survival analysis of cardiometabolic mortality was performed by Cox proportional hazards model, and cross-sectional analysis of cardiometabolic diseases outcomes was performed using logistic regression models. Interaction analyses were conducted to explore the specific pharmacological mechanism of metformin. RESULTS: Among 3995 cancer survivors (weighted population, 21,671,061, weighted mean [SE] age, 62.62 [0.33] years; 2119 [53.04%] females; 2727 [68.26%] Non-Hispanic White individuals), 448 reported metformin usage. During the follow-up period of up to 17 years (median, 6.42 years), there were 1233 recorded deaths, including 481 deaths from cardiometabolic causes. Multivariable models indicated that metformin use was associated with a lower risk of all-cause (hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.47-0.81) and cardiometabolic (HR, 0.65; 95% CI, 0.44-0.97) mortality compared with metformin nonusers. Metformin use was also correlated with a lower risk of total cardiovascular disease (odds ratio [OR], 0.41; 95% CI, 0.28-0.59), stroke (OR, 0.44; 95% CI, 0.26-0.74), hypertension (OR, 0.27; 95% CI, 0.14-0.52), and coronary heart disease (OR, 0.41; 95% CI, 0.21-0.78). The observed inverse associations were consistent across subgroup analyses in four specific cancer populations identified as cardiometabolic high-risk groups. Interaction analyses suggested that metformin use as compared to non-use may counter-balance oxidative stress. CONCLUSIONS: In this cohort study involving a nationally representative population of US cancer survivors, metformin use was significantly correlated with a lower risk of cardiometabolic diseases, all-cause mortality, and cardiometabolic mortality.

Catheter ablation of atrial fibrillation in patients with left bundle branch block.

BACKGROUND: Left bundle branch block (LBBB) and atrial fibrillation (AF) are commonly coexisting conditions. The impact of LBBB on catheter ablation of AF has not been well determined. This study aims to explore the long-term outcomes of patients with AF and LBBB after catheter ablation. METHODS: Forty-two patients with LBBB of 11,752 patients who underwent catheter ablation of AF from 2011 to 2020 were enrolled as LBBB group. After propensity score matching in a 1:4 ratio, 168 AF patients without LBBB were enrolled as non-LBBB group. Late recurrence and a composite endpoint of stroke, all-cause mortality, and cardiovascular hospitalization were compared between the two groups. RESULTS: Late recurrence rate was significantly higher in the LBBB group than that in the non-LBBB group (54.8% vs. 31.5%, p = .034). Multivariate analysis showed that LBBB was an independent risk factor for late recurrence after catheter ablation of AF (hazard ratio [HR] 2.19, 95% confidence interval [CI] 1.09-4.40, p = .031). LBBB group was also associated with a significantly higher incidence of the composite endpoint (21.4% vs. 6.5%, HR 3.98, 95% CI 1.64-9.64, p = .002). CONCLUSIONS: LBBB was associated with a higher risk for late recurrence and a higher incidence of composite endpoint in the patients underwent catheter ablation.

Systolic Blood Pressure Time in Target Range and Incident Atrial Fibrillation in Patients With Hypertension: Insights From the SPRINT Trial.

BACKGROUND: Systolic blood pressure (SBP) time in target range (TTR) indicates the mean value, exposure time, and variability in blood pressure over time. The prognostic value of SBP TTR for incident atrial fibrillation (AF) in patients with hypertension is unclear. METHODS: We performed a post hoc analysis of SPRINT (Systolic Blood Pressure Intervention Trial), a randomized controlled trial comparing intensive (<120 mm Hg) and standard (<140 mm Hg) SBP interventions in participants with hypertension. SBP target ranges for intensive and standard arms were defined as 110 to 130 and 120 to 140 mm Hg, respectively. TTR was calculated by linear interpolation method using SBP from months 0 to 3. We used Cox proportional regression models to assess the association of SBP TTR with incident AF. RESULTS: Among 7939 participants included in this analysis, 187 incident AF cases occurred during follow-up. After multivariable adjustment, a 10% increase in SBP TTR was independently associated with a 7% lower risk of incident AF (hazard ratio, 0.93 [95% CI, 0.88-0.97]; P=0.003). The restricted spline curve depicted a linear and inverse relationship between SBP TTR and incident AF. Sensitivity analyses generated consistent results when calculating TTR over a longer period or setting target range as 110 to 140 mm Hg for the whole population. CONCLUSIONS: Higher SBP TTR independently predicts a lower risk of incident AF. Efforts to attain SBP within 110 to 140 mm Hg over time may be an effective strategy to prevent AF. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01206062.

Antithrombotic strategy and its relationship with outcomes in patients with atrial fibrillation and chronic coronary syndrome.

This study aimed to explore antithrombotic strategy and its relationship with outcomes in patients with atrial fibrillation (AF) at high risk for stroke and chronic coronary syndrome (CCS) in real-world clinical practice. Patients with AF at high risk for stroke complicated with CCS from China Atrial Fibrillation Registry (CAFR) were enrolled. The patients were divided into non-antithrombotic (Non-AT) group, oral anticoagulants (OAC) group, antiplatelet therapy (APT) group (aspirin or clopidogrel), and dual antiplatelet therapy (DAPT) group (aspirin + clopidogrel) according to their antithrombotic strategies at baseline. The patients with OAC + single antiplatelet drug (14 cases) and OAC + dual antiplatelet therapy (7 cases) were excluded for the small sample size. The primary effectiveness outcome was the composite outcome of coronary events, thromboembolism, and all-cause mortality. The primary safety outcome was major bleeding events. From 2011 to 2018, 25,512 patients were included in the CARF study, 769 patients with AF at high risk for stroke and CCS were enrolled in this study. After a follow-up of 47.4 ± 25.3 months, the incidences of primary effectiveness outcome were 44.6%, 25.7%, 43.6%, and 29.1% in the four groups, respectively (P < 0.001). The incidences of primary effectiveness and all-cause mortality were both significantly lower in the OAC group than in the Non-AT group, (25.7% vs. 44.6%, HR 0.53, 95% CI 0.39-0.73, P < 0.001) and (14.6% vs. 38.5%, HR 0.36, 95%CI 0.25-0.52, P < 0.001). In multivariate analysis, age (HR 1.03, 95%CI 1.01-1.05, P = 0.015), heart failure (HR 1.67, 95%CI 1.20-2.33, P = 0.002) and OAC (HR 0.66, 95%CI 0.47-0.91, P = 0.012) were independent factors for the composite outcome. There was no significant difference in major bleeding events between the four groups. OAC monotherapy significantly reduced the primary effectiveness composite outcome and all-cause mortality in the patients with AF at high risk for stroke complicated with CCS. However, there was no significant difference in major bleeding among the different antithrombotic strategies.Trial Registration www.chictr.org.cn (No. ChiCTR-OCH-13003729).