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Updated: Jan 24, 2026

In Silico Clinical Trials for Cardiovascular Disease
Published on: May 27, 2022
Hypothetical Interventions on Multiple Cardiometabolic Risk Factors for Cardiovascular Disease Prevention: A Target
Xue Xia1, Shuohua Chen2, Xue Tian3
1Department of Epidemiology, Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Department of Clinical Epidemiology and Clinical Trial, Capital Medical University, Beijing, China.
Objective:
To evaluate cardiovascular benefits associated with sustained intensive and moderate interventions targeting body mass index (BMI), systolic blood pressure (SBP), fasting blood glucose (FBG) level, and total cholesterol (TC) concentration.
Methods:
Using longitudinal data (from June 2006-October 2007 to December 2017) of 94,661 cardiovascular disease (CVD)-free participants aged 30 years and older from the Kailuan cohort, we emulated a target trial to assess the long-term effectiveness of intensive (BMI <25 kg/m2, SBP <120 mm Hg, FBG <5.6 mmol/L, TC <5.2 mmol/L) and moderate (BMI <30 kg/m2, SBP <140 mm Hg, FBG <7.0 mmol/L, TC <6.2 mmol/L) interventions on 10-year risk of incident CVD. The target trial emulation framework with the parametric g-formula was used to simulate counterfactual outcomes under dynamic interventions, accounting for time-varying confounders and competitive events.
Results:
Compared with the natural course CVD risk of 6.48%, intensive interventions yielded a 49% decrease in relative risk (risk ratio, 0.51; 95% CI, 0.49 to 0.54), translating to approximately 3 fewer CVD cases per 100 individuals during 10 years (absolute risk reduction, -3.15%; 95% CI, -3.36% to -2.98%), which extended the restricted mean CVD-free time from 9.32 to 9.51 years. Of all the individual risk factors, SBP control yielded the largest benefits. Notably, even moderate interventions produced a 25% relative reduction in CVD risk, with the average proportion intervened on decreasing from 74.8% to 37.6%. Greater absolute risk reductions were observed in male participants and adults aged 60 years and older.
Conclusion:
Long-term interventions addressing cardiometabolic risk factors have considerable public health implications for primary prevention of CVD in China and other Western Pacific countries, where suboptimal cardiometabolic risk profiles remain prevalent.
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