Culprit plaque morphology determines inflammatory risk and clinical outcomes in acute coronary syndrome

Aims Rupture of the fibrous cap (RFC) and erosion of an intact fibrous cap (IFC) are the two predominant mechanisms causing acute coronary syndromes (ACS). It is uncertain whether clinical outcomes are different following RFC-ACS vs. IFC-ACS and whether this is affected by a specific inflammatory response. The prospective, translational OPTIcal-COherence Tomography in Acute Coronary Syndrome study programme investigates the impact of the culprit lesion phenotype on inflammatory profiles and prognosis in ACS patients. Methods and results This analysis included 398 consecutive ACS patients, of which 62% had RFC-ACS and 25% had IFC-ACS. The primary endpoint was a composite of cardiac death, recurrent ACS, hospitalization for unstable angina, and target vessel revascularization at 2 years [major adverse cardiovascular events (MACE(+))]. Inflammatory profiling was performed at baseline and after 90 days. Patients with IFC-ACS had lower rates of MACE(+) than those with RFC-ACS (14.3% vs. 26.7%, P = 0.02). In 368-plex proteomic analyses, patients with IFC-ACS showed lower inflammatory proteome expression compared with those with RFC-ACS, including interleukin-6 and proteins associated with the response to interleukin-1 & beta;. Circulating plasma levels of interleukin-1 & beta; decreased from baseline to 3 months following IFC-ACS (P < 0.001) but remained stable following RFC-ACS (P = 0.25). Interleukin-6 levels decreased in patients with RFC-ACS free of MACE(+) (P = 0.01) but persisted high in those with MACE(+). Conclusion This study demonstrates a distinct inflammatory response and a lower risk of MACE(+) following IFC-ACS. These findings advance our understanding of inflammatory cascades associated with different mechanisms of plaque disruption and provide hypothesis generating data for personalized anti-inflammatory therapeutic allocation to ACS patients, a strategy that merits evaluation in future clinical trials.

Automated summary

This study investigates the clinical outcomes and inflammatory response in patients with acute coronary syndromes (ACS) caused by different mechanisms of plaque disruption. It found that patients with erosion of an intact fibrous cap (IFC-ACS) have a lower risk of major adverse cardiovascular events (MACE(+)) and a distinct inflammatory response compared to those with rupture of the fibrous cap (RFC-ACS). These findings provide hypothesis generating data for personalized anti-inflammatory therapeutic allocation in ACS patients.