Vulnerable plaques and patients: state-of-the-art

Abstract

Despite advanced understanding of the biology of atherosclerosis, coronary heart disease remains the leading cause of death worldwide. Progress has been challenging as half of the individuals who suffer sudden cardiac death do not experience premonitory symptoms. Furthermore, it is well-recognized that also a plaque that does not cause a haemodynamically significant stenosis can trigger a sudden cardiac event, yet the majority of ruptured or eroded plaques remain clinically silent. In the past 30 years since the term ‘vulnerable plaque’ was introduced, there have been major advances in the understanding of plaque pathogenesis and pathophysiology, shifting from pursuing features of ‘vulnerability’ of a specific lesion to the more comprehensive goal of identifying patient ‘cardiovascular vulnerability’. It has been also recognized that aside a thin-capped, lipid-rich plaque associated with plaque rupture, acute coronary syndromes (ACS) are also caused by plaque erosion underlying between 25% and 60% of ACS nowadays, by calcified nodule or by functional coronary alterations. While there have been advances in preventive strategies and in pharmacotherapy, with improved agents to reduce cholesterol, thrombosis, and inflammation, events continue to occur in patients receiving optimal medical treatment. Although at present the positive predictive value of imaging precursors of the culprit plaques remains too low for clinical relevance, improving coronary plaque imaging may be instrumental in guiding pharmacotherapy intensity and could facilitate optimal allocation of novel, more aggressive, and costly treatment strategies. Recent technical and diagnostic advances justify continuation of interdisciplinary research efforts to improve cardiovascular prognosis by both systemic and ‘local’ diagnostics and therapies. The present state-of-the-art document aims to present and critically appraise the latest evidence, developments, and future perspectives in detection, prevention, and treatment of ‘high-risk’ plaques occurring in ‘vulnerable’ patients.

Immune and Inflammation in Acute Coronary Syndrome: Molecular Mechanisms and Therapeutic Implications

“…Therefore, the molecular mechanism of plaque rupture and erosion differ in phenotypical and functional aspects, which can explain why plaque erosion is not accompanied by detectable systemic inflammation. In general, superficial plaque erosion is mainly initiated by endothelial cell damage caused by various factors, including hemodynamic disturbance, oxidative stress, and TLR activation mediated by hyaluronic acid [ 2 , 42 ]. Injured endothelial cells covering the plaque progressively detach from the basement membrane.…”

OCT-Derived Plaque Morphology and FFR-Determined Hemodynamic Relevance in Intermediate Coronary Stenoses

“…Morphological assessment of ruptured plaques revealed that fibrous cap thickness and a combination of large plaque burden and small lumen area result in ACS [30]. Although PCI for vulnerable coronary atherosclerotic plaques seems to be a safe procedure, a systemic pharmacotherapy rather than individual 'plaque sealing' remains the key intervention in the treatment of TCFA in non-flow limiting coronary lesions [31][32][33].…”

Systemic Vulnerability, as Expressed by I-CAM and MMP-9 at Presentation, Predicts One Year Outcomes in Patients with Acute Myocardial Infarction—Insights from the VIP Clinical Study

“…The systemic vulnerability of patients that have suffered an acute coronary event is still a hot topic in cardiovascular research, as several predictive markers are still arising. The concept of a cardiovascular vulnerable patient refers to systemic vulnerability including systemic inflammation and increased thrombogenicity, and also local vulnerability, that encompasses unstable coronary plaques and vulnerable myocardium [ 67 ]. Both systemic and local coronary vulnerability should be included in models that can predict patient outcomes, both in the short and long term, following AMI.…”