Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, B304 Richards Building, 3700 Hamilton Walk, Philadelphia, PA, 19104-6021, USA.
Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, St. Vincent's Hospital, The Catholic University of Korea, Seoul, Republic of Korea.
Cardiovasc Diabetol. 2022 Jul 14;21(1):131. doi: 10.1186/s12933-022-01560-2.
Few studies have examined associations between genetic risk for type 2 diabetes (T2D), lifestyle, clinical risk factors, and cardiovascular disease (CVD). We aimed to investigate the association of and potential interactions among genetic risk for T2D, lifestyle behavior, and metabolic risk factors with CVD.
A total of 345,217 unrelated participants of white British descent were included in analyses. Genetic risk for T2D was estimated as a genome-wide polygenic risk score constructed from > 6 million genetic variants. A favorable lifestyle was defined in terms of four modifiable lifestyle components, and metabolic health status was determined according to the presence of metabolic syndrome components.
During a median follow-up of 8.9 years, 21,865 CVD cases (6.3%) were identified. Compared with the low genetic risk group, participants at high genetic risk for T2D had higher rates of overall CVD events, CVD subtypes (coronary artery disease, peripheral artery disease, heart failure, and atrial fibrillation/flutter), and CVD mortality. Individuals at very high genetic risk for T2D had a 35% higher risk of CVD than those with low genetic risk (HR 1.35 [95% CI 1.19 to 1.53]). A significant gradient of increased CVD risk was observed across genetic risk, lifestyle, and metabolic health status (P for trend > 0.001). Those with favorable lifestyle and metabolically healthy status had significantly reduced risk of CVD events regardless of T2D genetic risk. This risk reduction was more apparent in young participants (≤ 50 years).
Genetic risk for T2D was associated with increased risks of overall CVD, various CVD subtypes, and fatal CVD. Engaging in a healthy lifestyle and maintaining metabolic health may reduce subsequent risk of CVD regardless of genetic risk for T2D.
很少有研究探讨 2 型糖尿病（T2D）遗传风险、生活方式、临床危险因素与心血管疾病（CVD）之间的关系。本研究旨在探讨 T2D 遗传风险、生活方式行为以及代谢危险因素与 CVD 之间的关联及其潜在相互作用。
共纳入 345217 名无亲缘关系的白种英国人作为研究对象。T2D 的遗传风险通过构建一个基于>600 万个遗传变异的全基因组多基因风险评分来评估。生活方式是否良好通过四个可改变的生活方式因素来定义，代谢健康状况则根据代谢综合征成分的存在来确定。
在中位随访 8.9 年期间，共确定了 21865 例 CVD 病例（6.3%）。与低遗传风险组相比，T2D 遗传高风险组的整体 CVD 事件、CVD 亚型（冠状动脉疾病、外周动脉疾病、心力衰竭和心房颤动/扑动）以及 CVD 死亡率均较高。T2D 遗传风险极高的个体患 CVD 的风险比遗传风险低的个体高 35%（HR 1.35[95%CI 1.19 至 1.53]）。无论 T2D 遗传风险如何，CVD 风险均随着遗传风险、生活方式和代谢健康状况的升高而显著增加（趋势 P 值>0.001）。无论 T2D 遗传风险如何，具有良好生活方式和代谢健康状态的个体患 CVD 事件的风险均显著降低。这种风险降低在年轻参与者（≤50 岁）中更为明显。
T2D 的遗传风险与整体 CVD、各种 CVD 亚型以及致命性 CVD 的风险增加相关。无论 T2D 遗传风险如何，保持健康的生活方式和维持代谢健康都可能降低 CVD 的后续风险。
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