Normal coronary computed tomography angiography and long-term cardiovascular risk: implications for SCORE2–guided primary prevention

Background In primary prevention, treatment decisions are guided by the predicted 10-year cardiovascular risk estimated by the Systematic COronary Risk Evaluation 2 (SCORE2) model, as endorsed by the European Society of Cardiology (ESC). Primary preventive therapy is recommended for patients categorized as high risk. Many patients referred for coronary evaluation have no coronary artery disease (CAD) on CCTA. Whether these patients should continue to be viewed as high-risk is unknown. Aims We investigated the 10-year cardiovascular risk in patients referred for coronary computed tomography angiography (CCTA) with suspected stable angina pectoris but no evidence of CAD. We hypothesized that patients with a normal CCTA would not reach the SCORE2 high-risk threshold. Methods We included all statin-naïve patients <70 years without diabetes who were referred for CCTA between 2008 and 2021 for suspected stable angina pectoris and who had an Agatston calcium score of 0 with no coronary plaque. The 10-year cumulative incidence of major adverse cardiovascular events (MACE: non-fatal myocardial infarction, non-fatal stroke, or cardiovascular death) was estimated by age group (<50 year and 50-69 years) and further stratified by baseline risk factors (male sex, hypertension, LDL-cholesterol >2.6 mmol/L, smoking, and body mass index). The observed risks were compared with the age-dependent 10-year high-risk thresholds (<50 years: >2.5% and 50-69 years: >5.0%). Results Among 21,655 patients without CAD on CCTA, median age was 51 years (Q1-Q3 44-58) and 60% were women. Median follow-up was 8.4 years (Q1-Q3 5.6-10.0). The overall 10-year risk of MACE was low and increased with age [<50 years: 1.9% (95% CI 1.6-2.3) and 50-69 years: 3.1% (95% CI 2.7-3.5)]. No subgroup exceeded the age-specific high-risk threshold, except patients <50 years who were current smokers (3.3%) or had hypertension (3.1%) (Figure). Patients with multiple cardiovascular risk factors did not exceed the high-risk threshold, except young patients with ≥3 risk factors. Conclusions In symptomatic patients without diabetes referred for coronary evaluation but no CAD on CCTA have a low observed 10-year risk of MACE that generally remains below the ESC SCORE2 high-risk threshold. A normal CCTA therefore supports classification into a lower risk category, in which routine initiation of preventive pharmacotherapy is not indicated, while continued emphasis on lifestyle modification and targeted risk factor management remains appropriate in younger patients with hypertension or active smoking.