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To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.amjmed.2010.02.016 Byline: Luigi Marzio Biasucci (a), Francesca Graziani (a), Vittoria Rizzello (a), Giovanna Liuzzo (a), Caterina Guidone (b), Alberto Ranieri De Caterina (a), Salvatore Brugaletta (a), Gertrude Mingrone (b), Filippo Crea (a) Keywords: Endothelial function; Inflammation; Obesity Abstract: Obesity is associated with a high risk of coronary artery disease morbidity and mortality. Yet, postmortem studies have shown that severely obese subjects exhibit smooth coronary arteries, thus suggesting that they may be protected from atherosclerosis. We assessed vascular function and its possible determinants in a cohort of normal-weight to severely obese insulin-sensitive subjects (body mass index [BMI] 23.2-49 kg/m.sup.2). Author Affiliation: (a) Institute of Cardiology, Catholic University of the Sacred Heart, Rome, Italy (b) Institute of Internal Medicine, Catholic University of the Sacred Heart, Rome, Italy Article Note: (footnote) Funding: The study was funded by grant 70200400 from Catholic University of the Sacred Heart, Rome, Italy., Conflict of Interest: None of the authors have any conflicts of interest associated with the work presented in this manuscript., Authorship: All authors had access to the data and played a role in writing this manuscript.

ObjectivePatients with Takotsubo syndrome (TTS) present an acute microvascular dysfunction that leads to an impaired myocardial perfusion and, in more severe forms, an impaired epicardial flow. However, clinical relevance of a delayed coronary flow, the coronary slow flow (CSF), has never been investigated. We studied the prognostic value of CSF occurring in the acute phase of TTS.MethodsThis cohort study prospectively evaluated patients with a diagnosis of TTS. CSF was defined as angiographically non-obstructive coronary arteries with thrombolysis in myocardial infarction-2 flow. The incidence of overall mortality and major adverse cardiovascular events (MACEs), defined as the composite of TTS recurrence, cardiac rehospitalisation, cerebrovascular events and mortality, was assessed at follow-up.ResultsWe enrolled 101 patients (mean age 71.0±11.1 years, 86 (85.1%) female); CSF occurred in 18 (17.8%) patients. At admission, patients with CSF presented more frequently with Killip class III/IV, moderate-to-severe left ventricle systolic dysfunction and right ventricle dysfunction. During the index admission, patients with CSF had a higher rate of intrahospital complications (12 (66.7%) vs 28 (33.7%), p=0.01). At long-term follow-up, patients with CSF had a significantly higher occurrence of overall mortality (9 (50%) vs 19 (22.9%), p=0.011), mainly due to non-cardiac causes (89.3%), and a higher rate of MACE (10 (55.5%) vs 27 (32.5%), p=0.06). At multivariable Cox regression, CSF was independently associated with death from any causes.ConclusionsPatients with TTS presenting with CSF have a worse clinical presentation with a higher rate of intrahospital complications and a poor long-term clinical outcome.

IMPORTANCE: At one end of the coronary artery disease (CAD) spectrum, there are patients with multiple recurrent acute coronary syndromes (rACS), and at the other end there are those with long-standing clinical stability. Predicting the natural history of these patients is challenging because unstable plaques often heal without resulting in ACS. OBJECTIVE: To assess in vivo the coronary atherosclerotic phenotype as well as the prevalence and characteristics of healed coronary plaques by optical coherence tomography (OCT) imaging in patients at the extremes of the CAD spectrum. DESIGN, SETTING, AND PARTICIPANTS: This is an observational, single-center cohort study with prospective clinical follow-up. From a total of 823 consecutive patients enrolled in OCT Registry of the Fondazione Policlinico A. Gemelli–IRCCS, Rome, Italy, from March 2009 to February 2016, 105 patients were included in the following groups: (1) patients with rACS, defined as history of at least 3 acute myocardial infarctions (AMIs) or at least 4 ACS with at least 1 AMI; (2) patients with long-standing stable angina pectoris (ls-SAP), defined as a minimum 3-year history of stable angina; and (3) patients with a single unheralded AMI followed by a minimum 3-year period of clinical stability (sAMI). Data were analyzed from January to August 2018. EXPOSURES: Intracoronary OCT imaging of nonculprit coronary segments. MAIN OUTCOMES AND MEASURES: Coronary plaque features and the prevalence of healed coronary plaques in nonculprit segments as assessed by intracoronary OCT imaging. RESULTS: Of 105 patients, 85 were men (81.0%); the median (interquartile range) age was 68 (63-75) years. Median (interquartile range) time of clinical stability was 9 (5.0-15.0) years in the ls-SAP group and 8 (4.5-14.5) years in the sAMI group. Patients in the rACS and sAMI groups showed similar prevalence of lipid-rich plaque and thin-cap fibroatheroma, which was significantly higher than in those with ls-SAP (lipid-rich plaque 80.0% [n = 24 of 30] vs 76.3% [n = 29 of 38] vs 37.8% [n = 14 of 37], respectively; P < .001; thin-cap fibroatheroma 40.0% [n = 12 of 30] vs 34.2% [n = 13 of 38] vs 8.1% [n = 3 of 37], respectively; P = .006). Spotty calcifications were more frequently observed in patients with rACS than in those with ls-SAP and sAMI (70.0% [n = 21 of 30] vs 40.5% [n = 15 of 37] vs 44.7% [n = 17 of 38], respectively; P = .04). Healed coronary plaques were rarely observed in patients with rACS, whereas their prevalence was significantly higher in patients with ls-SAP and sAMI (3.3% [n = 1 of 30] vs 29.7% [n = 11 of 37] vs 28.9% [n = 11 of 38], respectively; P = .01). CONCLUSIONS AND RELEVANCE: Patients with rACS have a distinct atherosclerotic phenotype compared with those with ls-SAP, including higher prevalence of thin-cap fibroatheroma and lower prevalence of healed coronary plaques, suggesting that atherosclerotic profile and plaque healing may play a role in leading the natural history of patients with CAD.

Recent reports have suggested a link between blood concentrations of C reactive protein and the risk of cardiovascular disease. The ECAT study (European Concerted Action on Thrombosis and Disabilities Angina [...]

Statins, inhibitors of 3-hydroxy-3-methylglutaryl-CoA are best known for their lipid-lowering effects but they also possess immunomodulatory properties that are, at least in part, independent of changes in serum cholesterol. Some recent clinical trials (eg. PROVE-IT) have shown that statins exert beneficial cardiovascular effects independently of the resultant level of LDL cholesterol. These “pleiotropic” effects seem to be due to inhibition of prenylation of several proteins such as the small GTP-binding proteins Ras and Rho, and to the disruption, or depletion, of cholesterol rich membrane micro-domains (membrane rafts). Through these pathways statins are able to modulate immune responses by modulating cytokine levels and by affecting the function of cells involved in both innate and adaptive responses. Over the past decade, a large number of studies reported a prominent role of inflammation and immune response in atherosclerosis, thus, the ability of statins to modulate immune-inflammatory processes could explain their cardiovascular beneficial effects beyond lipid-lowering effects. Moreover, various studies demonstrated beneficial effects of statins in inflammatory and auto-immune diseases, such as rheumatoid arthritis, multiple sclerosis, and others. The purpose of this review is to summarize clinical and experimental evidence of immunomodulatory properties of these drugs, highlighting their clinical and, thus, therapeutic implications.

La inflamación desempeña un papel fundamental en la patogenia de la aterosclerosis y de sus complicaciones. La aterosclerosis es un proceso activo y el componente inflamatorio parece estar particularmente correlacionado con el desarrollo de los síndromes coronarios agudos. Los datos que se han ido recogiendo demuestran que, en los síndromes coronarios agudos, las concentraciones elevadas de marcadores circulantes de inflamación, como la proteína C reactiva, predicen una respuesta cardiovascular desfavorable. Aumentar el conocimiento de los mecanismos moleculares y celulares de la inflamación puede no solamente redundar en una mejor estratificación pronóstica, sino también permitir la identificación de nuevas dianas terapéuticas. En esta revisión se resumen los mecanismos de la respuesta inflamatoria en los síndromes coronarios agudos, sus implicaciones clínicas y las potenciales estrategias terapéuticas para contrarrestar este fenómeno.

Acute coronary syndromes (ACS) are complications of atherosclerotic vascular disease that are triggered by the sudden rupture of an atheroma. Atherosclerotic plaque stability is determined by multiple factors, of which immune and inflammatory pathways are critical. Unstable plaque is characterized by an infiltrate of T cells and macrophages, thereby resembling a delayed hypersensitivity reaction. On activation, T cells secrete cytokines that regulate the activity of macrophages, or the T cells may differentiate into effector cells with tissue-damaging potential. Constitutive stimulation of T cells and macro-phages in ACS is not limited to the vascular lesion but also involves peripheral immune cells, suggesting fundamental abnormalities in homeostatic mechanisms that control the assembly, turnover, and diversity of the immune system as a whole. This review gives particular attention to the emergence of a specialized T-cell subset, natural killer T cells, in patients with ACS. Natural killer T cells have proinflammatory properties and the capability of directly contributing to vascular injury.

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Objectives. This study sought to assess neutrophil activation in acute coronary syndromes and its relation to ischemic episodes.

A growing body of evidence suggests that inflammation plays a major role in the pathogenesis of unstable angina; this evidence is mainly derived from the prognostic role of the acute phase reaction proteins, such as C-reactive protein (CRP) and fibrinogen. Since the production of acute phase protein is under the control of the pro-inflammatory cytokines, it is probable that citokines, such as tumour-necrosis factor (TNF)-α, interleukin (IL)-1 and IL-6 are involved in the same process. Indeed, elevated levels of IL-1 and IL-6 have been found by our group and by others, in patients with acute coronary syndromes. Cytokines may have procoagulant effects, directly or via endothelial dysfunction, and may induce plaque vulnerability or rupture. They may also be responsible for the activation of other cells, as neutrophils or mast-cells. Although it is conceivable that activated lymphocytes, via interferon-γ production, are responsible for macrophage activation and cytokine production in unstable angina, the trigger and the precise mechanism of this event are still unknown. The multiple roles of cytokines in unstable angina suggest that a targeted anti-inflammatory therapy might be a novel approach in the future for the treatment of this syndrome.

Objectives. The aim of this study was to assess the relations between inflammation, specific immune response and clinical course in unstable angina (UA).

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Troponin T (TT), a specific marker of myocardial cell damage, and C reactive protein (CAP), an acute phase reactant, were found to be prognostic of outcome in unstable angina (UA) in different studies. We assessed the sensitivity and specificity of these markers for myocardial infarction (MI), death (D) and for the need of revascularization within a week after admission (R) in a group of 90 pts with UA. Blood samples for n and CAP measurement were taken on admission.

Elevated levels of C-reactive protein (CRP), a sensitive marker of inflammation, are independent predictors of short-term prognosis in patients (pts) with unstable angina (UA). The causes of the acute phase response in UA, however, are still unknown. Percutaneous transluminal coronary angioplasty (PTCA) is an useful model for the assessment of the effects of plaque disruption and myocardial ischemia on the acute phase response. Serum levels of CRP were measured in 21 pts with chronic stable angina (SA) (G 1) and in 22 pts with UA refractory to maximal medical treatment (G2), undergoing single-vessel PTCA. Venous blood samples were taken immediately before PTCA and 6, 24, 48, 72 hours after the end of the procedure. CRP values are expressed as median and range.