Department of Medical Epidemiology and Biostatistics (F.E., J. Sun, D.B., A.F., J.F.L.), Karolinska Institutet, Stockholm, Sweden.
Department of Gastroenterology and Hepatology, Clarunis University Center for Gastrointestinal and Liver Diseases, Basel, Switzerland (F.E.).
Circ Cardiovasc Qual Outcomes. 2024 Nov;17(11):e010912. doi: 10.1161/CIRCOUTCOMES.124.010912. Epub 2024 Nov 6.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a risk factor for cardiovascular disease. However, whether family members of individuals with MASLD also share an increased cardiovascular risk is unknown.
We created a nationwide multigenerational cohort study identifying all family members of Swedish adults diagnosed with biopsy-proven MASLD (1969-2017) and of matched general population comparators (by age, sex, calendar year, and county of residence). We calculated incidence rates and used Cox models to calculate adjusted hazard ratios (aHRs) and 95% CIs for incident major adverse cardiovascular events (MACE), including acute myocardial infarction, stroke, hospitalization for heart failure, or cardiovascular death. Cox models were adjusted for education, country of birth, diabetes, hypertension, obesity, dyslipidemia, chronic kidney disease, chronic obstructive pulmonary disease, and the Charlson comorbidity index.
We identified 22 267 MASLD first-degree relatives (FDRs; parents, siblings, and offspring) and 5687 MASLD spouses, as well as 118 056 comparator FDRs and 29 389 comparator spouses without earlier cardiovascular disease. Overall, the mean age was 41.8 years (SD, 18.0), and 51.5% were females. Over a median of 24.6 years, the incidence rate for MACE was higher in MASLD FDRs than in comparator FDRs (65.0 versus 62.5/10 000 person-years; aHR, 1.06 [95% CI, 1.01-1.11]). MASLD FDRs had higher rates of acute myocardial infarction (23.0 versus 20.9/10 000 person-years; aHR, 1.09 [95% CI, 1.01-1.18]) and cardiovascular death (aHR, 1.09 [95% CI, 1.01-1.18]). Across generations of FDRs, the risk of MACE was uniformly increased with no differences by relationship (ie, parents, siblings, and offspring; >0.05). MASLD spouses were also at an increased risk of MACE (117.6 versus 103.5/10 000 person-years; aHR, 1.09 [95% CI, 1.01-1.18]).
First-degree relatives of individuals with biopsy-proven MASLD are at slightly higher risk of incident MACE, but absolute risks do not support early screening for cardiovascular disease. Shared lifestyle factors may be the main contributors, as spouses of MASLD patients also had higher risks of MACE.
代谢功能障碍相关脂肪性肝病（MASLD）是心血管疾病的一个危险因素。然而，MASLD 患者的家庭成员是否也存在心血管风险增加尚不清楚。
我们创建了一个全国性的多代队列研究，确定了所有瑞典成年人的家族成员（1969-2017 年），这些成年人被诊断为经活检证实的 MASLD，以及年龄、性别、日历年份和居住地相匹配的一般人群对照者。我们计算了发病率，并使用 Cox 模型计算了主要不良心血管事件（MACE）的校正危险比（aHR）和 95%置信区间（CI），包括急性心肌梗死、中风、心力衰竭住院或心血管死亡。Cox 模型调整了教育、出生国、糖尿病、高血压、肥胖、血脂异常、慢性肾脏病、慢性阻塞性肺疾病和 Charlson 合并症指数。
我们确定了 2267 名 MASLD 一级亲属（父母、兄弟姐妹和子女）和 5687 名 MASLD 配偶，以及 118056 名对照 FDR 和 29389 名对照配偶，这些人以前没有心血管疾病。总体而言，平均年龄为 41.8 岁（标准差为 18.0），51.5%为女性。在中位数为 24.6 年的随访期间，与对照 FDR 相比，MASLD FDR 的 MACE 发生率更高（65.0 与 62.5/10000 人年；aHR，1.06[95%CI，1.01-1.11]）。MASLD FDR 发生急性心肌梗死的比例更高（23.0 与 20.9/10000 人年；aHR，1.09[95%CI，1.01-1.18]）和心血管死亡（aHR，1.09[95%CI，1.01-1.18]）。在各代 FDR 中，MACE 的风险均呈均匀增加趋势，且无差异（即父母、兄弟姐妹和子女；>0.05）。MASLD 配偶发生 MACE 的风险也增加（117.6 与 103.5/10000 人年；aHR，1.09[95%CI，1.01-1.18]）。
经活检证实的 MASLD 患者的一级亲属发生 MACE 的风险略高，但绝对风险不支持早期筛查心血管疾病。共同的生活方式因素可能是主要的促成因素，因为 MASLD 患者的配偶发生 MACE 的风险也较高。
