体重指数和遗传因素与心血管疾病的联合和交互关联：英国生物库的前瞻性研究。

Joint and interactive associations of body mass index and genetic factors with cardiovascular disease: a prospective study in UK Biobank.

机构信息

Department of Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.

Department of Epidemiology and Biostatistics, College of Public Health, Temple University, Philadelphia, PA, 19122, USA.

出版信息

BMC Public Health. 2024 Sep 2;24(1):2371. doi: 10.1186/s12889-024-19916-6.

DOI:10.1186/s12889-024-19916-6

PMID:39223569

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11367834/

Abstract

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/m), overweight (25.0-29.9 kg/m), and obesity (≥ 30.0 kg/m). 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.

摘要

背景

体重指数（BMI）和遗传因素都独立导致心血管疾病（CVD）。然而，尚不清楚遗传风险是否会改变 BMI 与 CVD 风险之间的关联。本研究旨在调查 BMI 类别和遗传风险是否共同且相互作用导致 CVD 事件的发生，包括高血压（HTN）、心房颤动（AF）、冠心病（CHD）、中风和心力衰竭（HF）。

方法

纳入了来自英国生物银行的 496851 名有一个或多个新发 CVD 事件的参与者，对他们进行分析。BMI 分为正常体重（<25.0 kg/m）、超重（25.0-29.9 kg/m）和肥胖（≥30.0 kg/m）。采用多基因风险评分将每种结局的遗传风险定义为低（最低三分位）、中（第二三分位）和高（最高三分位）。使用 Cox 比例风险模型探讨 BMI 类别和遗传风险与 CVD 发病的联合关联。此外，还评估了相加性交互作用。

结果

在 496851 名参与者中，270726 名（54.5%）为女性，平均（SD）年龄为 56.5（8.1）岁。中位（IQR）随访时间为 12.4（11.5-13.1）年期间，102131 名（22.9%）参与者发生 HTN，26301 名（5.4%）发生 AF，32222 名（6.9%）发生 CHD，10684 名（2.2%）发生中风，13304 名（2.7%）发生 HF。与低遗传风险的正常体重相比，高遗传风险的肥胖者发生 CVD 的风险最高：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）、中风（HR：1.44；95%CI：1.31-1.57）和 HF（HR：2.47；95%CI：2.27-2.69）。BMI 类别和遗传风险之间存在 HTN、AF 和 CHD 的显著相加性交互作用，超额相对危险度分别为 0.53（95%CI：0.43-0.62）、0.67（95%CI：0.51-0.83）和 0.37（95%CI：0.25-0.49）。