Abstract：
BACKGROUND: Sudden death is the leading cause of mortality in medically refractory epilepsy. Middle-aged persons with epilepsy (PWE) are under investigated regarding their mortality risk and burden of cardiovascular disease (CVD).
METHODS: Using UK Biobank, we identified 7786 (1.6%) participants with diagnoses of epilepsy and 6,171,803 person-years of follow-up (mean 12.30 years, standard deviation 1.74); 566 patients with previous histories of stroke were excluded. The 7220 PWE comprised the study cohort with the remaining 494,676 without epilepsy as the comparator group. Prevalence of CVD was determined using validated diagnostic codes. Cox proportional hazards regression was used to assess all-cause mortality and sudden death risk.
RESULTS: Hypertension, coronary artery disease, heart failure, valvular heart disease, and congenital heart disease were more prevalent in PWE. Arrhythmias including atrial fibrillation/flutter (12.2% vs 6.9%; P < 0.01), bradyarrhythmias (7.7% vs 3.5%; P < 0.01), conduction defects (6.1% vs 2.6%; P < 0.01), and ventricular arrhythmias (2.3% vs 1.0%; P < 0.01), as well as cardiac implantable electric devices (4.6% vs 2.0%; P < 0.01) were more prevalent in PWE. PWE had higher adjusted all-cause mortality (hazard ratio [HR], 3.9; 95% confidence interval [CI], 3.01-3.39), and sudden death-specific mortality (HR, 6.65; 95% CI, 4.53-9.77); and were almost 2 years younger at death (68.1 vs 69.8; P < 0.001).
CONCLUSIONS: Middle-aged PWE have increased all-cause and sudden death-specific mortality and higher burden of CVD including arrhythmias and heart failure. Further work is required to elucidate mechanisms underlying all-cause mortality and sudden death risk in PWE of middle age, to identify prognostic biomarkers and develop preventative therapies in PWE.
METHODS: Using UK Biobank, we identified 7786 (1.6%) participants with diagnoses of epilepsy and 6,171,803 person-years of follow-up (mean 12.30 years, standard deviation 1.74); 566 patients with previous histories of stroke were excluded. The 7220 PWE comprised the study cohort with the remaining 494,676 without epilepsy as the comparator group. Prevalence of CVD was determined using validated diagnostic codes. Cox proportional hazards regression was used to assess all-cause mortality and sudden death risk.
RESULTS: Hypertension, coronary artery disease, heart failure, valvular heart disease, and congenital heart disease were more prevalent in PWE. Arrhythmias including atrial fibrillation/flutter (12.2% vs 6.9%; P < 0.01), bradyarrhythmias (7.7% vs 3.5%; P < 0.01), conduction defects (6.1% vs 2.6%; P < 0.01), and ventricular arrhythmias (2.3% vs 1.0%; P < 0.01), as well as cardiac implantable electric devices (4.6% vs 2.0%; P < 0.01) were more prevalent in PWE. PWE had higher adjusted all-cause mortality (hazard ratio [HR], 3.9; 95% confidence interval [CI], 3.01-3.39), and sudden death-specific mortality (HR, 6.65; 95% CI, 4.53-9.77); and were almost 2 years younger at death (68.1 vs 69.8; P < 0.001).
CONCLUSIONS: Middle-aged PWE have increased all-cause and sudden death-specific mortality and higher burden of CVD including arrhythmias and heart failure. Further work is required to elucidate mechanisms underlying all-cause mortality and sudden death risk in PWE of middle age, to identify prognostic biomarkers and develop preventative therapies in PWE.
摘要：
背景：猝死是药物难治性癫痫死亡的主要原因。正在调查患有癫痫（PWE）的中年人的死亡风险和心血管疾病（CVD）负担。
方法：使用英国生物库，我们确定了7,786名（1.6％）被诊断为癫痫的参与者和6,171,803人年的随访（平均12.30年，SD1.74）；排除了566例有中风史的个体。7,220PWE包括研究队列，其余494,676名无癫痫作为比较组。使用经过验证的诊断代码确定CVD的患病率。Cox比例风险回归用于评估全因死亡率和猝死风险。
结果：高血压，冠状动脉疾病,心力衰竭,心脏瓣膜病,先天性心脏病在PWE中更为普遍。包括心房颤动/扑动在内的心律失常（12.2%vs6.9%；p<0.01），缓慢性心律失常（7.7%vs3.5%；p<0.01），传导缺陷（6.1%vs2.6%；p<0.01），室性心律失常（2.3%vs1.0%；p<0.01），以及心脏可植入电子设备(4.6%vs2.0%;p<0.01)在PWE中更为普遍。PWE有较高的调整后全因死亡率（HR3.9[95%CI，3.01-3.39]），和猝死特异性死亡率(HR6.65[95%CI,4.53-9.77]);并且在死亡时几乎年轻2岁[68.1vs69.8;p<0.001]。
结论：中年PWE增加了全因死亡率和猝死死亡率，和更高的心血管疾病负担，包括心律失常和心力衰竭。需要进一步的工作来阐明中年PWE中全因死亡率和猝死风险的潜在机制，在PWE中确定预后生物标志物并开发预防性治疗。
方法：使用英国生物库，我们确定了7,786名（1.6％）被诊断为癫痫的参与者和6,171,803人年的随访（平均12.30年，SD1.74）；排除了566例有中风史的个体。7,220PWE包括研究队列，其余494,676名无癫痫作为比较组。使用经过验证的诊断代码确定CVD的患病率。Cox比例风险回归用于评估全因死亡率和猝死风险。
结果：高血压，冠状动脉疾病,心力衰竭,心脏瓣膜病,先天性心脏病在PWE中更为普遍。包括心房颤动/扑动在内的心律失常（12.2%vs6.9%；p<0.01），缓慢性心律失常（7.7%vs3.5%；p<0.01），传导缺陷（6.1%vs2.6%；p<0.01），室性心律失常（2.3%vs1.0%；p<0.01），以及心脏可植入电子设备(4.6%vs2.0%;p<0.01)在PWE中更为普遍。PWE有较高的调整后全因死亡率（HR3.9[95%CI，3.01-3.39]），和猝死特异性死亡率(HR6.65[95%CI,4.53-9.77]);并且在死亡时几乎年轻2岁[68.1vs69.8;p<0.001]。
结论：中年PWE增加了全因死亡率和猝死死亡率，和更高的心血管疾病负担，包括心律失常和心力衰竭。需要进一步的工作来阐明中年PWE中全因死亡率和猝死风险的潜在机制，在PWE中确定预后生物标志物并开发预防性治疗。
