Evaluation of diagnostic accuracy of extreme cardiovascular risk definitions in acute coronary syndrome patients

Abstract Background In 2022 the European Society of Cardiology published a consensus paper with six definitions of extreme cardiovascular (CV) risk. In secondary the gold standard is definition 2: two cardiovascular events within two years. Commonly used are also acute coronary syndrome (ACS) combined with peripheral or polyvascular disease (definition 3) and ACS with multivessel coronary artery disease (definition 4). The aim of our study was to evaluate the diagnostic accuracy of definitions 3 and 4 compared to the gold standard in a population of ACS patients. Methods The study included 1061 ACS patients admitted to the intensive cardiac care unit (ICCU) of our hospital from 2014 to 2020. The primary composite outcome was time to first ischaemic events (myocardial infarction or stroke or peripheral artery event) or CV death. The follow-up was updated in June 2021 and events in the first 2 years since diagnosis were registered. Results Among the 1061 ACS patients analyzed, the primary composite outcome was observed in 225 (21%) patients, with a higher incidence in patients fulfilling criteria of definitions 3 and 4 compared to the general ACS cohort. At multivariate analysis, the increased risk was still significant only for definition 4 (HR 1.44; 95% CI 1.03 - 2.01, p=0.031) while the increase in risk was not significant for definition 3 (HR 1.31; 95% CI 0.94 - 1.82, p=0.114;). When definitions 3 and 4 were compared to definition 2 in order to test their discrimination accuracy for early recurring events, we found that they both presented poor predictive performance (definition 3: sensitivity 23.5%, specificity 87.5%, positive predictive values 35.7%; definition 4: sensitivity 25.5%, specificity 85.3%, positive predictive values 32.1%; the percentage of correctly classified patients was 73% for both definitions). Conclusion Among the current definitions of extreme CV risk the one based on the presence of ACS combined with multivessel coronary artery disease most effectively identifies subjects likely to experience early (within 2 years) recurrence. Both definitions, however, showed higher specificity than sensitivity, highlighting their limitations in detecting all individuals at extreme risk within ACS populations. These findings underscore the need for refinement of extreme risk criteria to improve prognostic accuracy and guide targeted interventions.