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Abstract: Post-mortem observations demonstrated that plaque fissure was the final event leading to coronary thrombosis and occlusion in about two-thirds of cases of sudden coronary death. Plaques prone to fissure have, therefore, been defined “vulnerable plaques” and are identified by specific anatomic features including thin inflamed fibrous cap, large lipidic core and positive remodeling. Accordingly, elegant imaging modalities have been developed in order to identify this “holy grail”. However, the results of prognostic studies based on the identification of vulnerable plaques have not been encouraging because of the low positive predictive value for major cardiovascular events. This observation is not surprising as the pathogenesis of acute coronary syndromes is complex and multifactorial. In this review we propose a pathogenetic classification of acute coronary syndromes in the attempt to identify homogeneous groups of patients with a common mechanism of coronary instability which can be identified by using specific biomarkers and imaging techniques, and become a specific therapeutic target. [Copyright &y& Elsevier]

Abstract: Aims: Coronary atherosclerosis is a chronic inflammatory disease, but different inflammatory biomarkers may reflect different phases of atherosclerotic plaque evolution. We aimed at assessing the role of eosinophil cationic protein (ECP), a sensitive marker of eosinophil activation, and C-reactive protein (CRP) in coronary artery disease (CAD). Methods and results: Consecutive anginal patients with angiographic evidence of CAD [stable angina (SA) or non-ST-elevation acute coronary syndrome (NSTE-ACS)], or with angiographically normal coronary arteries (NCA) were enrolled. The severity of CAD was graded according to Bogaty''s score and coronary lesion morphology was defined as smooth or complex. Baseline ECP and high sensitivity CRP were measured in all patients. Of 198 patients (64±10 years, male 74%), 91 had SA, 57 had NSTE-ACS and 50 had NCA. ECP levels were significantly higher in SA [30μg/L (13.8–46.9), p <0.001] and NSTE-ACS [21.8μg/L (5.5–46.3), p =0.016] compared to NCA [9.7μg/L (6.1–13.6)], without significant difference between SA and NSTE-ACS (p =0.45). CRP levels were significantly higher in NSTE-ACS [2.38mg/L (1.11–11.94)] compared to SA [1.48mg/L (0.82–2.83), p =0.03], and NCA [1.09mg/L (0.8–2.1), p <0.001], without significant difference between SA and NCA (p =0.20). The addition of ECP to main cardiovascular risk factors improved the area under the curve from 0.88 to 0.92, p =0.007 for the angiographic diagnosis of CAD; further addition of CRP increased the area to 0.94, p =0.014. At multiple linear regression analysis ECP levels independently predicted CAD severity (p =0.001), whereas CRP levels independently predicted lesion complexity (p =0.01). Conclusions: Our study shows that ECP is a marker of CAD and that different inflammatory biomarkers reflect different phases of atherosclerotic plaque evolution. [Copyright &y& Elsevier]

Abstract: Background: Cytotoxin-associated gene-A (CagA) antigen is expressed by some virulent strains of Helicobacter pylori (H. pylori). The role of CagA antigen in coronary instability is unknown. We performed a clinico-pathological study and a meta-analysis in the attempt to shed new light on this complex issue. Methods: In the clinico-pathological study, 38 patients with unstable angina (UA), 25 patients with stable angina (SA), 21 patients with normal coronary arteries (NCA) and 50 age and sex matched healthy volunteers were enrolled. Serology for CagA was assessed in all patients. Specimens of atherosclerotic plaques were obtained from all patients by directional coronary atherectomy, and prepared for immunohistochemistry using anti-CagA monoclonal antibodies. The meta-analysis includes 9 studies assessing the association between seropositivity to CagA strains and acute coronary events. Results: The titre of anti-CagA antibodies was significantly higher in patients with unstable angina (161±90RU/ml) compared to those with stable angina (83±59RU/ml p <0.02), NCA (47.3±29RU/ml p <0.01) and healthy controls (73±69 p <0.02). Anti-CagA antibodies recognized antigens localized inside coronary atherosclerotic plaques in all specimens from both stable and unstable patients. In the meta-analysis, seropositivity to CagA was significantly associated with the occurrence of acute coronary events with an odds ratio (OR) of 1.34 (95% CI, 1.15–1.58, p =0.0003). Conclusions: Taken together these findings suggest that in a subset of patients with unstable angina, an intense immune response against CagA-positive H. pylori strains might be critical to precipitate coronary instability mediated by antigen mimicry between CagA antigen and a protein contained in coronary atherosclerotic plaques. [Copyright &y& Elsevier]

Reactive oxygen species (ROS) induce nuclear factor erythroid 2–related factor 2 (Nrf2) activation as an adaptive defense mechanism, determining the synthesis of antioxidant molecules, including heme-oxygenase-1 (HO-1). HO-1 protects cells against oxidative injury, degrading free heme and inhibiting ROS production. HO-1 is highly expressed in macrophages during plaque growth. Macrophages are morpho-functionally heterogeneous, and the prevalence of a specific phenotype may influence the plaque fate. This heterogeneity has also been observed in monocyte-derived macrophages (MDMs), a model of macrophages infiltrating tissue. The study aims to assess oxidative stress status and Nrf2/HO-1 axis in MDM morphotypes obtained from healthy subjects and coronary artery disease (CAD) patients, in relation to coronary plaque features evaluated in vivo by optical coherence tomography (OCT). We found that MDMs of healthy subjects exhibited a lower oxidative stress status, lower Nrf2 and HO-1 levels as compared to CAD patients. High HO-1 levels in MDMs were associated with the presence of a higher macrophage content, a thinner fibrous cap, and a ruptured plaque with thrombus formation, detected by OCT analysis. These findings suggest the presence of a relationship between in vivo plaque characteristics and in vitro MDM profile, and may help to identify patients with rupture-prone coronary plaque. [ABSTRACT FROM AUTHOR]

Air pollution is emerging as an important risk factor for acute coronary syndrome (ACS). In this study, we investigated the association between short-term air pollution exposure and mechanisms of coronary plaque instability evaluated by optical coherence tomography (OCT) imaging in ACS patients. Patients with ACS undergoing OCT imaging were retrospectively selected. Mechanism of culprit lesion instability was classified as plaque rupture (PR) or intact fibrous cap (IFC) by OCT. Based on each case's home address, the mean daily exposures to several pollutants, including particulate matter 2.5 (PM 2.5), on the same day of ACS and in the immediate days (up to 6 days) prior to the index ACS, were collected. 139 ACS patients were included [69 (49.6%) had PR and 70 (50.4%) IFC]. Patients with PR, compared to those with IFC, had higher PM 2.5 exposure levels on the same day of ACS, without differences in the immediate 6 days before index ACS. At multivariate analysis, PM 2.5 exposure on the same day of ACS was the only independent predictor of PR [OR = 1.912 per SD (8.6 μg/m3), CI95 % (1.087–3.364), p = 0.025]. Patients with PR presented a steady increase in PM 2.5 daily exposure levels in the days preceding the occurrence of ACS, with a peak the day of ACS (p for trend = 0.042) This study demonstrates for the first time that a higher short-term PM2.5 exposure, on the same day of ACS, is associated with an increased risk of PR as a pathobiological mechanism of coronary plaque instability. [Display omitted] • Air pollution is emerging as an important risk factor for acute coronary syndrome (ACS). • Acute PM 2.5 exposure, especially on the same day of ACS, is associated with an increased risk of plaque rupture as mechanism of coronary plaque instability. • Mitigation strategies are crucial to reduce the burden of ischemic heart disease, especially in patients with a higher risk of cardiovascular events. [ABSTRACT FROM AUTHOR]