Sedighi Jamschid, Luedde Mark, Boettger Priyanka, Bengel Philipp, Bauer Pascal, Sossalla Samuel, Rozo Sánchez Samuel Eduardo, Kostev Karel
Medical Clinic I, Cardiology and Angiology, Justus-Liebig-University, Giessen, Germany.
Christian-Albrechts-University of Kiel, Kiel, Germany.
Diabetes Obes Metab. 2025 Oct;27(10):5822-5830. doi: 10.1111/dom.16637. Epub 2025 Jul 22.
Obesity is a well-established risk factor for atrial fibrillation (AF). However, the extent to which this association is driven by obesity-related comorbidities such as hypertension, diabetes and heart failure versus a potential direct effect of obesity itself remains unclear. Differentiating between these pathways is important for developing effective and targeted prevention strategies. To investigate the association between body mass index (BMI) and incident AF using both multivariable Cox regression and causal mediation analysis (CMA), quantifying the extent to which this risk is mediated by obesity-related comorbidities.
This retrospective cohort study used the Disease Analyzer database (IQVIA) to identify patients aged ≥40 years with documented BMI in German general practices between 2005 and 2023. Patients were categorised as normal weight (18.5-24.9 kg/m), overweight (25.0-29.9 kg/m) or obese (≥30 kg/m). The primary outcome was a new diagnosis of AF within 10 years. Multivariable Cox regression models were used and adjusted for age, sex and cardiometabolic comorbidities. CMA was used to estimate the proportion of AF risk mediated through diabetes, hypertension, dyslipidaemia, coronary artery disease and heart failure.
Of the 392 146 patients included in the study, AF incidence was 7.2% in normal weight, 10.1% in overweight and 13.2% in obese individuals over 10 years. Obesity was associated with a significant increase in AF risk (HR 1.43; 95% CI 1.38-1.48), with a higher risk observed in men. CMA showed that 27% of the obesity-related AF risk (106% excess total risk) was mediated through comorbidities, while 79% represented a direct effect. In women, the proportion of mediated effects was higher (up to 30.1%), suggesting sex-specific differences in disease pathways.
Obesity significantly increases the risk of AF through both comorbidity-related and potentially independent pathways. While nearly one-third of the excess risk may be preventable through the management of cardiometabolic conditions, a notable proportion of the association remains unexplained by these mediators. These findings highlight the need for comprehensive strategies that address both obesity itself and its associated diseases to reduce the burden of AF.
肥胖是心房颤动（AF）公认的危险因素。然而，这种关联在多大程度上是由肥胖相关的合并症（如高血压、糖尿病和心力衰竭）驱动的，还是肥胖本身存在潜在的直接影响，目前尚不清楚。区分这些途径对于制定有效且有针对性的预防策略很重要。本研究旨在通过多变量Cox回归和因果中介分析（CMA）来探究体重指数（BMI）与新发AF之间的关联，并量化肥胖相关合并症介导这种风险的程度。
这项回顾性队列研究使用疾病分析器数据库（IQVIA），以识别2005年至2023年期间在德国普通诊所中记录有BMI的≥40岁患者。患者被分为正常体重（18.5 - 24.9kg/m²）、超重（25.0 - 29.9kg/m²）或肥胖（≥30kg/m²）。主要结局是10年内新发AF诊断。使用多变量Cox回归模型，并对年龄、性别和心血管代谢合并症进行调整。CMA用于估计通过糖尿病、高血压、血脂异常、冠状动脉疾病和心力衰竭介导的AF风险比例。
在纳入研究的392146例患者中，正常体重者10年内心房颤动发生率为7.2%，超重者为10.1%，肥胖者为13.2%。肥胖与AF风险显著增加相关（风险比1.43；95%置信区间1.38 - 1.48），男性的风险更高。CMA显示，27%的肥胖相关AF风险（总风险超额106%）是由合并症介导的，而79%代表直接效应。在女性中，介导效应的比例更高（高达30.1%），表明疾病途径存在性别差异。
肥胖通过合并症相关途径和潜在的独立途径显著增加AF风险。虽然通过管理心血管代谢疾病可预防近三分之一的超额风险，但这些中介因素仍无法解释相当一部分关联。这些发现凸显了需要采取综合策略来应对肥胖本身及其相关疾病，以减轻心房颤动的负担。
