Symptomatic patients without coronary artery disease do not have excess cardiovascular risk compared to the general population

Abstract Background Patients with stable angina with no coronary atherosclerosis by coronary computed tomography angiography (CCTA) have a lower cardiovascular risk compared to CCTA patients with greater atherosclerotic burden. However, it remains unknown whether these symptomatic patients have excess cardiovascular risk when compared to the general population and if any excess risk is sex or age dependent. Purpose To examine the 10-year cardiovascular risk and mortality in patients with no coronary atherosclerosis by CCTA compared to a matched general population comparison cohort. Methods We included every symptomatic CCTA patient with no coronary artery disease (CAD), defined as no coronary plaques and Agatston calcium score of 0, in Western Denmark from 2008-2021. Each patient was matched by age and sex with 5 individuals with no previous history of ischemic heart disease from the Western Danish general population. Maximum follow-up was 10 years. Outcomes were myocardial infarction, ischemic stroke, and all-cause death. We estimated 10-year risk difference (RD) and incidence rate ratios (IRR) using a conditional Poisson regression, comparing patients with no CAD to the general population cohort. Additionally, we performed age- (<45 year, 45-65 years, and ≥65 years) and sex stratified analyses. Results We included 39,223 patients with no CAD who were matched with 196,115 individuals from the general population. Median age was 54 and 60% were women. Baseline use of anti-thrombotic agents, statins, and anti-hypertensive drugs was higher in patients with no CAD than the general population. Median follow-up was 6.1 years. CCTA patients with no CAD had lower risk of myocardial infarction [RD -0.2%, IRR 0.75 (95% CI 0.65-0.85)] and death [RD -3.3%, IRR 0.51 (95% CI 0.48-0.55)], but similar risk of ischemic stroke [RD 0.0%, IRR 0.93 (95% CI 0.84-1.02)] compared to the general population (Figure 1). However, patients <45 years had higher 10-year risk of both myocardial infarction and ischemic stroke despite absence of CAD by CCTA compared the general population (Figure 2). Conclusions Symptomatic patients without CAD by CCTA do not have excess cardiovascular risk when compared to a general population cohort without known ischemic heart disease. Future cardiovascular risk management of these patients should therefore follow primary prevention guidelines. However, patients <45 years did exhibit higher risk of ischemic outcomes and may require intensified preventative treatment.Figure 1Figure 2