Emulated Effects of Glucagon-Like Peptide 1 Receptor Agonist Therapy in the General Population.

However, their benefit in primary prevention remains unclear.

然而，它们在初级预防中的益处仍不清楚。

This study aims to emulate GLP-1RA use for primary prevention by applying risk factor changes observed in the SELECT (Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes) trial to obese individuals at risk of but without established CVD.

本研究旨在通过应用在SELECT（Semaglutide和心血管结果在没有糖尿病的肥胖症患者中）试验中观察到的风险因素变化，模拟GLP-1RA用于初级预防，针对有心血管疾病（CVD）风险但尚未确立的肥胖个体。

Methods

In 610,789 CVD-free individuals from European and North American Global Cardiovascular Risk Consortium cohorts, a model to estimate 10-year incidenceof CVD and death from any cause was fitted using prespecified risk factors: body mass index (BMI), glycosylated hemoglobin, systolic blood pressure, high-sensitivity C-reactive protein, and non-high-density-lipoprotein cholesterol.

在来自欧洲和北美全球心血管风险联盟队列的610,789名无心血管疾病（CVD）的个体中，使用预先设定的风险因素：体重指数（BMI）、糖化血红蛋白、收缩压、高敏C反应蛋白和非高密度脂蛋白胆固醇，拟合了一个用于估计10年心血管疾病（CVD）发生率和任何原因死亡的模型。

This model was applied to 200,012 individuals from 2 contemporary health examination surveys to emulate GLP-1RA therapy by using sex-stratified, placebo-adjusted changes in the 5 risk factors observed with GLP-1RA therapy in SELECT.

该模型应用于来自2项当代健康检查调查的200,012名个体，通过使用性别分层、安慰剂校正的5个风险因素变化来模拟GLP-1RA治疗，这些风险因素变化是根据SELECT研究中观察到的GLP-1RA治疗效果。

Primary analyses included individuals with a BMI ≥27 kg/m2 and a SCORE2 (Systematic Coronary Risk Evaluation 2)-derived baseline risk ≥7.5%.

主要分析包括BMI ≥27 kg/m2且SCORE2（系统性冠状动脉风险评估2）导出的基线风险≥7.5%的个体。

Secondary analyses examined nonobese and lower SCORE2 groups and accounted for reduced compliance.

二次分析考察了非肥胖和低 SCORE2 组，并考虑了遵从性降低的影响。

Results

In the surveys, 21,720 individuals had a BMI ≥27 kg/m2 and a SCORE2-derived baseline risk ≥7.5%.

在调查中，有 21,720 名个体的 BMI ≥27 kg/m2 以及 SCORE2 导出的基线风险 ≥7.5%。

Observed 10-year CVD incidencewas 13.82% (95% CI: 11.94%-15.71%).

观察到的10年心血管疾病（CVD）发病率为13.82%（95% 置信区间：11.94%-15.71%）。

Emulated GLP-1RA therapy lowered projected CVD incidenceto 10.83% (95% CI: 9.27%-12.39%), an absolute reduction of 2.99% (95% CI: 2.67%-3.31%) and a relative reduction of 22%.

模拟的GLP-1RA治疗将预测的心血管疾病（CVD）发病率降低到10.83%（95% 置信区间：9.27%-12.39%），绝对降低2.99%（95% 置信区间：2.67%-3.31%），相对降低22%。

Absolute reductions were larger in men than in women (3.14% [95% CI: 2.82%-3.47%] vs 2.7% [95% CI: 2.23%-3.16%]), with similar potential relative reductions across sexes (21% vs 23%).

绝对降低在男性中比女性更大（3.14% [95% 置信区间: 2.82%-3.47%] 对比 2.7% [95% 置信区间: 2.23%-3.16%]），两性之间潜在的相对降低相似（21% 对比 23%）。

Modeled risk reductions were attenuated in nonobese and lower SCORE2 groups and diminished further with lower compliance assumptions.

在非肥胖和低 SCORE2 组中，模拟的风险降低减弱，并且随着遵从性假设的降低进一步减弱。

Conclusions

In appropriately selected individuals at high CVD risk, GLP-1RA therapy may complement existing primary prevention strategies, supporting the rationale for future randomized studies.

在适当选择的高心血管疾病（CVD）风险个体中，GLP-1RA治疗可能补充现有的初级预防策略，支持未来随机研究的合理性。