Platelet biology and function: plaque erosion vs. rupture.

The leading cause of heart disease in developed countries is coronary atherosclerosis, which is not simply a result of ageing but a chronic inflammatory process that can lead to acute clinical events upon atherosclerotic plaque rupture or erosion and arterial thrombus formation. The composition and location of atherosclerotic plaques determine the phenotype of the lesion and whether it is more likely to rupture or to erode. Although plaque rupture and erosion both initiate platelet activation on the exposed vascular surface, the contribution of platelets to thrombus formation differs between the two phenotypes. In this review, plaque phenotype is discussed in relation to thrombus composition, and an overview of important mediators (haemodynamics, matrix components, and soluble factors) in plaque-induced platelet activation is given. As thrombus formation on disrupted plaques does not necessarily result in complete vessel occlusion, plaque healing can occur. Therefore, the latest findings on plaque healing and the potential role of platelets in this process are summarized. Finally, the clinical need for more effective antithrombotic agents is highlighted.

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-1ß. Circulating plasma levels of interleukin-1ß 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.

Toll-like receptor 2, hyaluronan, and neutrophils play a key role in plaque erosion: the OPTICO-ACS study.

BACKGROUND AND AIMS: In one-third of patients with acute coronary syndrome (ACS), thrombosis occurs despite an intact fibrous cap (IFC) (IFC-ACS, 'plaque erosion'). Recent studies emphasize neutrophils as the immediate inflammatory response in this pathology, but their exact molecular activation patterns are still poorly understood and may represent future therapeutic targets. METHODS AND RESULTS: Thirty-two patients with IFC-ACS and matched patients with ACS with ruptured fibrous cap (RFC) (RFC-ACS) from the OPTICO-ACS study were included, and blood samples were collected from the local site of the culprit lesion and the systemic circulation. Neutrophil surface marker expression was quantified by flow cytometry. Neutrophil cytotoxicity towards endothelial cells was examined in an ex vivo co-culture assay. Secretion of active matrix metalloproteinase 9 (MMP9) by neutrophils was evaluated using zymography in supernatants and in plasma samples. Optical coherence tomography (OCT)-embedded thrombi were used for immunofluorescence analysis. Toll-like receptor 2 (TLR2) expression was higher on neutrophils from IFC-ACS than RFC-ACS patients. TLR2 stimulation increased the release of active MMP9 from local IFC-ACS-derived neutrophils, which also aggravated endothelial cell death independently of TLR2. Thrombi of IFC-ACS patients exhibited more hyaluronidase 2 with concomitant increase in local plasma levels of the TLR2 ligand: hyaluronic acid. CONCLUSION: The current study provides first in-human evidence for distinct TLR2-mediated neutrophil activation in IFC-ACS, presumably triggered by elevated soluble hyaluronic acid. Together with disturbed flow conditions, neutrophil-released MMP9 might be promoting endothelial cell loss-triggered thrombosis and therefore providing a potential future target for a phenotype-specific secondary therapeutic approach in IFC-ACS.

Coronary Plaque Erosion: Epidemiology, Diagnosis, and Treatment.

Plaque erosion (PE), a distinct etiology of acute coronary syndromes (ACSs), is often overshadowed by plaque ruptures (PRs). Concerning its epidemiology, PE has garnered increasing recognition, with recent studies revealing its prevalence to be approximately 40% among ACS patients, challenging earlier assumptions based on autopsy data. Notably, PE exhibits distinct epidemiological features, preferentially affecting younger demographics, particularly women, and often manifesting as a non-ST-segment elevation myocardial infarction. There are seasonal variations, with PE events being less common in winter, potentially linked to physiological changes and cholesterol solidification, while peaking in summer, warranting further investigation. Moving to molecular mechanisms, PE presents a unique profile characterized by a lesser degree of inflammation compared to PR, with endothelial shear stress emerging as a plausible molecular mechanism. Neutrophil activation, toll-like receptor-2 pathways, and hyaluronidase 2 expression are among the factors implicated in PE pathophysiology, underscoring its multifactorial nature. Advancements in intravascular imaging diagnostics, particularly optical coherence tomography and near-infrared spectroscopy coupled with intravascular ultrasound, offer unprecedented insights into plaque composition and morphology. Artificial intelligence algorithms show promise in enhancing diagnostic accuracy and streamlining image interpretation, augmenting clinician decision-making. Therapeutically, the management of PE evolves, with studies exploring less invasive approaches such as antithrombotic therapy without stenting, particularly in cases identified early through intravascular imaging. Additionally, the potential role of drug-coated balloons in reducing thrombus burden and minimizing future major adverse cardiovascular events warrants further investigation. Looking ahead, the integration of advanced imaging modalities, biomarkers, and artificial intelligence promises to revolutionize the diagnosis and treatment of coronary PE, ushering in a new era of personalized and precise cardiovascular care.

Differential Proteoglycan Expression in Atherosclerosis Alters Platelet Adhesion and Activation.

Proteoglycans are differentially expressed in different atherosclerotic plaque phenotypes, with biglycan and decorin characteristic of ruptured plaques and versican and hyaluronan more prominent in eroded plaques. Following plaque disruption, the exposure of extracellular matrix (ECM) proteins triggers platelet adhesion and thrombus formation. In this study, the impact of differential plaque composition on platelet function and thrombus formation was investigated. Platelet adhesion, activation and thrombus formation under different shear stress conditions were assessed in response to individual proteoglycans and composites representing different plaque phenotypes. The results demonstrated that all the proteoglycans tested mediated platelet adhesion but not platelet activation, and the extent of adhesion observed was significantly lower than that observed with type I and type III collagens. Thrombus formation upon the rupture and erosion ECM composites was significantly reduced (p < 0.05) compared to relevant collagen alone, indicating that proteoglycans negatively regulate platelet collagen responses. This was supported by results demonstrating that the addition of soluble biglycan or decorin to whole blood markedly reduced thrombus formation on type I collagen (p < 0.05). Interestingly, thrombus formation upon the erosion composite displayed aspirin sensitivity, whereas the rupture composite was intensive to aspirin, having implications for current antiplatelet therapy regimes. In conclusion, differential platelet responses and antiplatelet efficacy are observed on ECM composites phenotypic of plaque rupture and erosion. Proteoglycans inhibit thrombus formation and may offer a novel plaque-specific approach to limit arterial thrombosis.

New Concepts on the Pathophysiology of Acute Coronary Syndrome.

Acute coronary syndrome (ACS) is the most severe form of ischemic heart disease. Although it is caused by atherosclerotic plaque thrombosis or nonatherosclerotic causes, its pathophysiological mechanism of ACS is not fully understood, and its concept is constantly updated and developed. At present, the main pathophysiological mechanisms include plaque rupture, plaque erosion, calcified nodules (CN) and non-atherosclerotic causes such as coronary vasospasm and myocardial bridging (MB). These mechanisms may overlap and coexist in some ACS patients. Therefore, the pathophysiological mechanism of ACS is complex, and is of great significance for the diagnosis and treatment of ACS. This review will discuss the pathophysiological mechanisms of ACS to provide new thoughts on the pathogenesis, diagnosis and treatment of ACS.

Associations of Culprit Vessel Size and Plaque Characteristics in Patients with ST-Segment Elevation Myocardial Infarction.

Background: Small vessel disease (SVD) widely exists in patients with acute coronary syndrome. However, the plaque characteristic of SVD has not been investigated. Methods: Optical coherence tomography (OCT) of culprit lesion was examined in 576 patients with ST-segment elevation myocardial infarction (STEMI) and finally 404 patients with qualified images were analysed of plaque phenotypes and microstructure. The cohort was divided into three groups according to vessel diameters of culprit lesion which were measured by OCT. Major adverse cardiac events (MACEs) were recorded of each patient and compared among patients with different vessel diameters and plaque phenotypes. Results: Gender, age and body mass index (BMI) were significantly different among patients with different diameters of culprit vessels (98.4% vs. 85.7% vs.71.4%, p < 0.001; 40.0 ± 7.0 vs. 54.9 ± 6.6 vs. 68.9 ± 5.8, p < 0.001; 28.4 ± 4.0 vs. 25.8 ± 2.9 vs. 25.2 ± 3.0, p < 0.001, respectively). Moreover, patients with diameters of culprit lesion > 3 mm presented with more incidence of plaque rupture and macrophage (57.7% vs. 42.1% vs. 46.2%, p = 0.015, 55.1% vs. 41.0% vs. 36.9%, p = 0.010). Total MACE did not differ among groups of different vessel diameters and plaque phenotypes. Conclusions: Vessel size of culprit lesion is significantly associated with plaque phenotype in patients with STEMI. However, patients with different diameters and plaque phenotypes showed no significant difference of clinical outcomes. Clinical Trial Registration: NCT03593928.

Diagnostic Performance of 60 MHz High-Definition Intravascular Ultrasound versus Fourier Domain Optical Coherence Tomography for Identifying Plaque Rupture, Plaque Erosion, and Thrombosis in a Rabbit Model.

Background: Most acute coronary syndromes occur due to coronary thrombosis caused by plaque rupture (PR) and plaque erosion (PE). Precise in vivo differentiation between PR and PE is challenging for intravascular imaging. This study is the first to determine the diagnostic performance of the novel 60 MHz high-definition intravascular ultrasound (HD-IVUS) for differentiating atherosclerotic plaque morphology influenced by local hemodynamic flow in rabbits. This study evaluated the diagnostic performance of 60 MHz HD-IVUS in identifying thrombosis in rabbits. Methods: We established 60 rabbit models of atherosclerosis with left common carotid artery (LCCA) stenosis and 30 FeCl 3 -induced LCCA thrombosis. Intravascular imaging was assessed with 60 MHz HD-IVUS and fourier-domain optical coherence tomography (FD-OCT). The present study investigated the diagnostic accuracy of 60 MHz HD-IVUS for PR and PE, as well as thrombosis, using OCT-diagnosis as a standard reference. Results: 60 MHz HD-IVUS for identifying atherosclerotic plaque morphology using plaque cavity and minor intimal irregularities showed high sensitivity and specificity; 92.0 and 90.0% for identifying OCT-defined PR, and 80.0 and 70.0% for OCT-defined PE, respectively. In a rabbit thrombus model, 60 MHz HD-IVUS showed high sensitivity (88.0%) and specificity (80.0%) in identifying OCT-defined thrombosis. Conclusions: 60 MHz HD-IVUS can accurately identify PR and thrombosis. Further studies should confirm the clinical value of this novel technique in PE diagnosis.

Utility of optical coherence tomography in acute coronary syndromes.

Studies utilizing intravascular imaging have replicated the findings of histopathological studies, identifying the most common substrates for acute coronary syndromes (ACS) as plaque rupture, erosion, and calcified nodule, with spontaneous coronary artery dissection, coronary artery spasm, and coronary embolism constituting the less common etiologies. The purpose of this review is to summarize the data from clinical studies that have used high-resolution intravascular optical coherence tomography (OCT) to assess culprit plaque morphology in ACS. In addition, we discuss the utility of intravascular OCT for effective treatment of patients presenting with ACS, including the possibility of culprit lesion-based treatment by percutaneous coronary intervention.

The Contribution of Vascular Proteoglycans to Atherothrombosis: Clinical Implications.

The vascular extracellular matrix (ECM) produced by endothelial and smooth muscle cells is composed of collagens and glycoproteins and plays an integral role in regulating the structure and function of the vascular wall. Alteration in the expression of these proteins is associated with endothelial dysfunction and has been implicated in the development and progression of atherosclerosis. The ECM composition of atherosclerotic plaques varies depending on plaque phenotype and vulnerability, with distinct differences observed between ruptured and erodes plaques. Moreover, the thrombi on the exposed ECM are diverse in structure and composition, suggesting that the best antithrombotic approach may differ depending on plaque phenotype. This review provides a comprehensive overview of the role of proteoglycans in atherogenesis and thrombosis. It discusses the differential expression of the proteoglycans in different plaque phenotypes and the potential impact on platelet function and thrombosis. Finally, the review highlights the importance of this concept in developing a targeted approach to antithrombotic treatments to improve clinical outcomes in cardiovascular disease.

Sex Differences in Coronary Atherosclerosis.

PURPOSE OF REVIEW: The importance of cardiovascular disease (CVD) in women has long been underestimated. Therefore, we need to understand the impact of sex differences on CVD. RECENT FINDINGS: Traditional risk factors contribute to coronary artery disease (CAD) differently in women and men. There are female-specific risk factors and comorbid conditions that affect the risk of CAD. Plaque erosion is frequently seen in younger women who smoke, while plaque rupture is common in older women and men who have elevated blood cholesterol. Coronary artery calcification is also different in both sexes. Thus, coronary artery calcification score-based risk stratification in women is challenging. A deeper understanding of the sex differences in the risk factors and plaque morphology of coronary atherosclerosis may lead to improved outcomes of CVD in women.

Culprit and Non-Culprit Plaque Characteristics With vs. Without a Healed Phenotype in Patients With Acute Myocardial Infarction Caused by Plaque Erosion　- A 3-Vessel OCT Study.

BACKGROUND: Plaque erosion can occur quietly without causing clinical symptoms, followed by a healing process resulting in healed plaque. This study aimed to assess culprit and non-culprit plaque characteristics of patients with acute myocardial infarction (AMI) caused by plaque erosion with vs. without healed phenotype at the culprit plaque using optical coherence tomography (OCT).Methods and Results: A total of 117 AMI patients caused by plaque erosion who underwent OCT imaging of 3 coronary arteries were included. Patients were divided into 2 groups based on presence or absence of a healed phenotype at the culprit site. Culprit and non-culprit plaque characteristics were compared between the 2 groups. A healed phenotype at the culprit lesion was identified in 47.9% of AMI patients caused by plaque erosion. Patients with a healed phenotype at the culprit site were more frequently with hyperlipidemia, and had a higher prevalence of macrophage infiltration, microchannels, cholesterol crystals, and calcification at the culprit lesion. Moreover, patients with a healed phenotype at the culprit site had more non-culprit plaques and more characteristics of plaque vulnerability at the non-culprit lesion. In addition, patients with a healed phenotype at the culprit site presented with more severe luminal stenosis at both the culprit and non-culprit lesion. CONCLUSIONS: A healed phenotype was identified in 47.9% of AMI patients caused by plaque erosion at the culprit site. A healed phenotype within eroded culprit plaque was associated with signs of pancoronary vulnerability and advanced atherosclerosis.

Potent platelet inhibition with peri-procedural tirofiban may attenuate progression of atherosclerosis in patients with acute coronary syndromes.

Organization of platelet-rich thrombus at the site of plaque disruption may contribute to rapid progression of atherosclerosis. This study was conducted to investigate if potent platelet inhibition therapy in patients with acute coronary syndromes (ACS) mitigates plaque progression. Patients enrolled in the EROSION study who presented with ACS caused by plaque erosion and underwent serial imaging of the culprit lesion by optical coherence tomography at baseline, 1 month, and 1 year were included. Among 49 patients, 32 (65.3%) patients were treated with glycoprotein IIb/IIIa inhibitor (GPI) in addition to aspirin and ticagrelor. The increase in area stenosis from baseline to 1-year follow-up was significantly smaller in patients treated with GPI, compared to those without GPI therapy (4.8% [- 1.6 to 10.9] vs. 9.6% [4.0 to 21.3], p = 0.031). The cohort was divided into 2 groups based on culprit lesion phenotype at 1 year: Group A, new layer formation at 1-year that was not present at baseline (n = 18); Group B, no new layer formation (n = 31). A new layer was less frequently found at 1 year in patients treated with GPI than in those without GPI (25.0% vs. 58.8%, p = 0.019). Group A, compared to Group B, was associated with a greater increase in area stenosis (19.0 ± 16.4% vs. 3.7 ± 7.1%; p < 0.001). Potent platelet inhibition with GPI in patients with ACS caused by plaque erosion was associated with lower incidence of new layer formation and less plaque progression.

Predictors of Coronary Plaque Erosion in Current and Non-Current Smokers With ST-Segment Elevation Myocardial Infarction　- An Optical Coherence Tomography Study.

BACKGROUND: Smoking is an important risk factor of plaque erosion. This study aimed to investigate the predictors of plaque erosion in current and non-current smokers presenting with ST-segment elevation myocardial infarction (STEMI).Methods and Results:A total of 1,320 STEMI patients with culprit plaque rupture or plaque erosion detected by pre-intervention optical coherence tomography were divided into a current smoking group (n=715) and non-current smoking group (n=605). Plaque erosion accounted for 30.8% (220/715) of culprit lesions in the current smokers and 21.2% (128/605) in the non-current smokers. Multivariable analysis showed age <50 years, single-vessel disease and the absence of dyslipidemia were independently associated with plaque erosion rather than plaque rupture, regardless of smoking status. In current smokers, diabetes mellitus (odds ratio [OR]: 0.29; 95% confidence interval [CI]: 0.10-0.83; P=0.021) was negatively associated with plaque erosion as compared with plaque rupture. In non-current smokers, minimal lumen area (MLA, OR: 1.37; 95% CI: 1.16-1.62; P<0.001) and nearby bifurcation (OR: 3.20; 95% CI: 1.98-5.16; P<0.001) were positively related to plaque erosion, but not plaque rupture. CONCLUSIONS: In patients with STEMI, the presence of diabetes mellitus significantly increased the risk of rupture-based STEMI but may not have reduced the risk of plaque erosion-based STEMI in current smokers. Nearby bifurcation and larger MLA were associated with plaque erosion in non-current smokers.

Plaque erosion causing ST-elevation myocardial infarction after consumption of cannabis and N2O in a 27-year old man: a case report.

BACKGROUND: The recreational drugs cannabis and nitrous oxide (N2O) are known for pro-atherogenic effects and are associated with an elevated risk of myocardial infarction. These cardiovascular effects might be underestimated by the public. Culprit-lesion composition of myocardial infarctions associated with cannabis and N2O has been unknown so far. This case report aims to raise the awareness of the adverse cardiovascular effects of cannabis and N2O and reports, for the first time, optical coherence tomography (OCT) findings of the culprit lesion. CASE PRESENTATION: This is a case report of a 27-year old man with anterior ST-segment-elevation myocardial infarction (STEMI) after intoxication with cannabis and N2O. Coronary angiography and OCT revealed plaque erosion with subsequent subtotal thrombotic occlusion of the left anterior descending artery that was successfully treated with 1 drug-eluting stent. The patient was symptom free at 6 months follow-up and had been able to abstain from drug consumption. CONCLUSIONS: This is the first case to demonstrate the association between cannabis and N2O abuse and plaque erosion on OCT in a young man with STEMI. In contrast to smoking, whose adverse effects are well-known, the cardiovascular effects of cannabis and N2O might be underestimated. These adverse effects should gain more awareness in the public to prevent early vascular events in young adults.

Circadian variations in pathogenesis of ST-segment elevation myocardial infarction: an optical coherence tomography study.

Previous studies have reported a circadian variation in the onset of ST-segment elevation myocardial infarction (STEMI). However, underlying mechanisms for the circadian variation have not been fully elucidated. We investigated the relationship between onset of STEMI and the underlying pathology using optical coherence tomography (OCT). Patients with a diagnosis of STEMI were selected from a multicenter OCT registry. Patients were divided into 4 groups based on the estimated time of onset (00:00-05:59, 06:00-11:59, 12:00-17:59, or 18:00-23:59). Underlying pathologies of MI (plaque rupture, plaque erosion, and calcified plaque) were compared among the 4 groups. Among 648 patients, plaque rupture was diagnosed in 386 patients (59.6%), plaque erosion in 197 patients (30.4%), and calcified plaque in 65 patients (10.0%). A marked circadian variation was detected in the incidence of plaque rupture with a peak at 09:00, whereas it was not evident in plaque erosion or calcified plaque. The probability of plaque rupture significantly increased in the periods of 06:00-11:59 [odds ratio (OR) 2.13, 95% confidence interval (CI) 1.30-3.49, p = 0.002] and 12:00-17:59 (OR 2.10, 95% CI 1.23-3.58, p = 0.005), compared to the period of 00:00-05:59. This circadian pattern was observed only during weekdays (p = 0.010) and it was not evident during the weekend (p = 0.742). Plaque rupture occurred most frequently in the morning and this circadian variation was evident only during weekdays. Acute MI caused by plaque rupture may be related to catecholamine surge.

Degree of luminal narrowing and composition of thrombus in plaque erosion.

As the degree of luminal narrowing increases, shear stress increases, and high shear stress is known to activate platelets. However, the relationship between the degree of luminal narrowing and the composition of thrombus in patients with plaque erosion has not been studied. A total of 148 patients with plaque erosion and thrombus detected by optical coherence tomography were divided into tertiles based on the minimum lumen area (MLA) at the culprit lesion. Thrombus was categorized as platelet-rich or fibrin-rich. Among 148 patients, 50 (34%) were in the mild stenosis group, 49 (33%) were in the moderate stenosis group, and 49 (33%) were in the severe stenosis group. The composition of thrombus was significantly different among the 3 groups (prevalence of platelet-rich thrombus was 60% in the mild stenosis group; 78% in the moderate stenosis group; and 84% in the severe stenosis group; P = 0.021). The pattern of fibrin-rich thrombus showed the opposite: 40%, 22%, and 16%, respectively. In the multivariate analysis, current smoking was independently associated with fibrin-rich thrombus (odds ratio [OR] 2.364 [95% CI 1.004-5.567], P = 0.049). This study demonstrated that platelet-rich thrombus was the predominant type of thrombus in plaque erosion. The prevalence of fibrin-rich thrombus was highest in the mild stenosis group.

Determinants of ST-segment elevation myocardial infarction as clinical presentation of acute coronary syndrome.

Antiplatelet agents and statin therapies are widely used in patients with known cardiovascular disease. Plaque rupture (PR) and plaque erosion (PE) are the most frequent underlying mechanisms of acute coronary syndromes (ACS). The conditions and medications that are associated with ST-segment elevation myocardial infarction (STEMI) following PR or PE have not been systematically studied. A total of 838 ACS patients (494 with STEMI, 344 with NSTE-ACS) who were diagnosed with PR or PE by optical coherence tomography were included. The patients were categorized into two groups based on underlying pathology, and the baseline characteristics and culprit plaque morphology associated with STEMI were investigated within each group. Among 838 patients, 467 (55.7%) had PR, and 371 (44.3%) were diagnosed with PE. Among patients with PR, older age, hyperlipidemia, no antiplatelet therapy, higher level of low-density lipoprotein cholesterol, and greater lipid burden and macrophage infiltration were associated with increased probability of STEMI. Among patients with PE, no dual antiplatelet therapy and no statin therapy were associated with increased probability of STEMI. The incidence of STEMI caused by PR was significantly lower on antiplatelet therapy (P < 0.001), and the incidence of STEMI caused by PE was significantly lower on antiplatelet therapy (P < 0.001) or on statin therapy (P < 0.001). Antiplatelet therapy is associated with lower probability of STEMI, regardless of underlying pathology, and statin therapy is associated with lower probability of STEMI in PE as clinical presentation of ACS. Statin therapy prior to the onset of acute coronary syndromes (ACS) may reduce the probability of plaque rupture. Antiplatelet therapy prior to the onset of ACS is associated with reduced probability of ST-segment elevation myocardial infarction (STEMI) following both plaque rupture and plaque erosion, and dual antiplatelet therapy offers additional protection compared to a single antiplatelet agent in plaque erosion. The combination of statin and antiplatelet therapy may have an additive effect on reducing the probability of STEMI caused by plaque erosion. Yellow: lipid pool(necrotic core); red: fibrin-rich thrombus; gray; platelet-rich thrombus.

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

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.

The association between glucose-related variables and plaque morphology in patients with ST-segment elevated myocardial infarction.

BACKGROUND: Plaque rupture (PR) and plaque erosion (PE) are main causes of acute myocardial infarction with different demographic and histology characteristics and need different treatment strategy. PR and PE can be identified with optical coherence tomography (OCT) accurately, but convenient and effective noninvasive markers for them are rarely found. History of diabetes mellitus (DM) was reported to be a potential predictor of PR in ST-segment elevated myocardial infarction (STEMI) patients, but the predictive value of other glucose-related variables for it is still uncertain. Present study aimed to clear the relationship between some glucose-related variables and plaque morphology in patients with STEMI. METHODS: We consecutively enrolled 872 STEMI patients and divided them into PR group (n = 616) and PE group (n = 256) based on OCT diagnostic criteria. The relationship of glucose-related variables, including random plasma glucose on admission (ARPG), glycosylated hemoglobin (HbA1c), post-PCI fasting plasma glucose (PFPG), DM history, glucose variable tendency (GVT) and the acute-to-chronic glycemic ratio (A/C), to the PR risk of STEMI patients was analyzed. The correlation between the glucose-related variables and plaque morphology was analyzed meanwhile. RESULTS: Among the glucose-related variables, ARPG and GVT were confirmed to be independent predictors for PR after adjusting for other traditional risk factors in nondiabetic patients. The higher the ARPG level, the more PR risk the STEMI patients had. And high HbA1c and APPG were demonstrated to have a weak and positive correlation with lipid constituents and stenosis degree of culprit vessel. CONCLUSIONS: Compared to HbA1c, DM history, and some other glucose-related variables, ARPG and GVT were risk factors for PR in STEMI patients, especially those without DM. And high HbA1c and ARPG were positively correlated with the development of vulnerable plaque in culprit vessels. Trial registration Present study is a retrospective one and the population came from the EROSION study of our center previously. It was approved by the Ethics Committee of the Second Affiliated Hospital of Harbin Medical University (Approval reference number, KY2017-249), and all patients provided written informed consent prior to the inclusion in the study and the investigation conformed to the principles outlined in the Declaration of Helsinki.