背景:体重指数(BMI)和遗传因素都独立地与心血管疾病(CVD)有关。然而,目前尚不清楚遗传风险是否改变了BMI与心血管事件风险之间的关联.这项研究旨在调查BMI类别和遗传风险是否共同和交互地导致CVD事件。包括高血压(HTN),心房颤动(AF),冠心病,中风,心力衰竭(HF)。
方法:来自英国生物银行的496,851名具有一个或多个新发CVD事件的参与者被纳入分析。BMI被归类为正常体重(<25.0kg/m2),超重(25.0-29.9kg/m2),和肥胖(≥30.0kg/m2)。每个结果的遗传风险被定义为低(最低三分位数),中间(第二三元),和高(最高三位数)使用多基因风险评分。使用Cox比例风险模型研究了BMI类别和遗传风险与CVD事件的联合关联。此外,对加性相互作用进行了评估。
结果:在496,851名参与者中,270,726(54.5%)为女性,平均年龄(SD)为56.5(8.1)岁。在12.4(11.5-13.1)年的中位随访(IQR)中,102,131(22.9%)参与者开发了HTN,26,301(5.4%)开发了AF,32,222(6.9%)患有冠心病,10,684(2.2%)发生中风,和13,304(2.7%)开发的HF。与正常体重相比,遗传风险较低,具有高遗传风险的肥胖具有最高的CVD风险:HTN(HR:3.96;95CI:3.84-4.09),AF(HR:3.60;95CI:3.38-3.83),冠心病(HR:2.76;95CI:2.61-2.91),中风(HR:1.44;95CI:1.31-1.57),和HF(HR:2.47;95CI:2.27-2.69)。BMI类别和HTN的遗传风险之间存在显著的累加相互作用,AF,CHD,相对超额风险为0.53(95CI:0.43-0.62),0.67(95CI:0.51-0.83),和0.37(95CI:0.25-0.49),分别。
结论:BMI和遗传因素共同且相互作用地导致CVD的发生,特别是在具有高遗传风险的参与者中。这些发现对确定更有可能从减肥干预措施中获得心血管益处的人群具有公共卫生意义。
BACKGROUND: Both body mass index (BMI) and genetic factors independently contribute to cardiovascular disease (CVD). However, it is unclear whether genetic risk modifies the association between BMI and the risk of incident CVD. This study aimed to investigate whether BMI categories and genetic risk jointly and interactively contribute to incident CVD events, including hypertension (HTN), atrial fibrillation (AF), coronary heart disease (CHD), stroke, and heart failure (HF).
METHODS: A total of 496,851 participants from the UK Biobank with one or more new-onset CVD events were included in the analyses. BMI was categorized as normal weight (< 25.0 kg/m2), overweight (25.0-29.9 kg/m2), and obesity (≥ 30.0 kg/m2). Genetic risk for each outcome was defined as low (lowest tertile), intermediate (second tertile), and high (highest tertile) using polygenic risk score. The joint associations of BMI categories and genetic risk with incident CVD were investigated using Cox proportional hazard models. Additionally, additive interactions were evaluated.
RESULTS: Among the 496,851 participants, 270,726 (54.5%) were female, with a mean (SD) age was 56.5 (8.1) years. Over a median follow-up (IQR) of 12.4 (11.5-13.1) years, 102,131 (22.9%) participants developed HTN, 26,301 (5.4%) developed AF, 32,222 (6.9%) developed CHD, 10,684 (2.2%) developed stroke, and 13,304 (2.7%) developed HF. Compared with the normal weight with low genetic risk, the obesity with high genetic risk had the highest risk of CVD: HTN (HR: 3.96; 95%CI: 3.84-4.09), AF (HR: 3.60; 95%CI: 3.38-3.83), CHD (HR: 2.76; 95%CI: 2.61-2.91), stroke (HR: 1.44; 95%CI: 1.31-1.57), and HF (HR: 2.47; 95%CI: 2.27-2.69). There were significant additive interactions between BMI categories and genetic risk for HTN, AF, and CHD, with relative excess risk of 0.53 (95%CI: 0.43-0.62), 0.67 (95%CI: 0.51-0.83), and 0.37 (95%CI: 0.25-0.49), respectively.
CONCLUSIONS: BMI and genetic factors jointly and interactively contribute to incident CVD, especially among participants with high genetic risk. These findings have public health implications for identifying populations more likely to have cardiovascular benefit from weight loss interventions.