Natural history of premature coronary artery disease : impact of residual atherosclerosis on long-term prognosis

Abstract Background The long-term evolution of premature coronary artery disease (CAD) with no or non-significant residual atherosclerosis beyond the culprit lesion at diagnosis remains unknown. This study aimed to describe the evolution of coronary atherosclerosis in young patients based on their initial angiographic presentation. Methods Consecutive participants with obstructive CAD ≤ 45 years were included. Each participant was classified into three angiographic phenotypes after revascularization of the culprit lesion: no residual atherosclerosis (phenotype 0); mild residual atheroma, defined as a residual plaque with 10-50% stenosis (phenotype 1); severe atheroma, defined as an additional stenosis ≥50% (phenotype 2). Baseline and repeated coronary angiograms were reviewed by a dedicated core-lab. The primary endpoint was all-cause death, myocardial infarction, refractory angina requiring coronary revascularization, and ischemic stroke (MACE) at the longest available follow-up. Results Of 456 participants with premature CAD, 220 (48.2%) were classified as phenotype 0, 110 (24.2%) as phenotype 1 and 126 (27.6%) as phenotype 2. Over a median follow-up of 9 4.7; 12.8 years, 33.8% (n=154) of the participants experienced a first MACE involving 196 coronary lesions. The most frequent events were ACS and urgent coronary revascularization across all groups, while all-cause mortality occurred in 4.4% of the study population. An ascending gradient was observed between the presence and extent of residual atherosclerosis at baseline and ACS occurrence : patients with phenotype 2 experienced more frequently ACS (15 (11.9%) within 1.2 0.5; 4.0 years) compared with phenotype 1 and phenotype 0 (9 (8.2%) within 4.3 1.0; 6.7 years and 16 (7.3%) within 4.5 0.8; 9.5 years, respectively). Participants with phenotype 0 progressed to a multivessel disease burden comparable to that of phenotype 2 within a median delay of 9.3 4.6; 13.2 years and showed a cumulative MACE risk of 22.9%. While phenotype 1 and 2 displayed a similar two-fold higher risk progression over the long term than phenotype 0, phenotype 2 demonstrated the highest risk burden in the short term (Figure 1). MACE were predominantly attributable to a new lesion rather than recurrence at the initial culprit lesion in all three phenotypes with a cumulative risk of 16% versus 5.8% in phenotype 0, 29.8% versus 7.0% in phenotype 1, and 25.1% versus 10.4% in phenotype 2 (Figure 2). Conclusion Premature CAD is associated with a high incidence of recurrent events, mostly driven by new coronary lesions. Non-significant residual atherosclerosis carries a high long-term risk comparable to that of patients with initial multivessel disease.Figure 1 - Time to MACE in premature CAD Figure 2 - Initial versus culprit lesion