Evaluating the impact of communicating high polygenic risk for coronary artery disease on the health behaviour of young overweight adults: a pragmatic randomised controlled trial

Around 50% of the variation in cardiovascular disease (CVD) risk is attributable to heritable factors, and polygenic risk scores (PRS) can now capture part of that genetic component. As personalised public health advances, polygenic risk scores (PRS) may offer a useful tool for conveying overall CVD risk, particularly in younger populations, but require evaluation in real-world clinical trials. This study evaluated the effects of integrating coronary artery disease polygenic risk scores (CAD PRS) into CVD risk estimation and risk communication among young, overweight adults (25–44 years, BMI = 25.0–29.99 kg/m2). This was a parallel-group, double-blind, randomised controlled trial with a 12-month follow-up. A total of 1020 participants were randomised into intervention (n = 510) and control (n = 510) groups. The primary outcome measure was BMI; secondary outcomes included systolic and diastolic blood pressure, total, LDL and HDL cholesterol, waist circumference, 10-year CVD risk, preventive treatment prescription, smoking prevalence, alcohol consumption, diet, and physical activity. Per-protocol analyses used t-tests for continuous data, chi-square for categorical data, ANCOVA for adjusted outcomes, linear and logistic models for risk factors, with significance at p < 0.05. Over the 12-month follow-up, the intervention produced no statistically significant differences in BMI between groups (intervention: 27.9 ± 2.5 kg/m2; control: 27.7 ± 2.5 kg/m2; p = 0.291), waist circumference, systolic or diastolic blood pressure, lipid profile, blood glucose, or combined 10-year CVD risk (all p > 0.14). Self-reported behaviours showed limited impact on smoking prevalence and physical activity (p > 0.1). Prescribing and purchasing of lipid-lowering or antihypertensive medications did not differ between groups (IRR for lipid-lowering drugs 0.93; 95% CI 0.73–1.18), underscoring that the intervention had no measurable impact on either cardiometabolic parameters or preventive treatment patterns. This trial showed that communicating high CAD polygenic risk alone did not lead to behavioural changes or improvements in key cardiovascular risk factors. Future studies should assess interventions combining lifestyle counselling and preventive treatment to more effectively evaluate their potential for long-term cardiovascular risk reduction in individuals with high CAD polygenic risk. Trial registration: Prospectively registered on ClinicalTrials.gov NCT05603663 (03.11.2022).