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BACKGROUND AND AIMS: The Mediterranean diet (MD) affects the risk of myocardial infarction and long-term prognosis after a coronary event. Limited data are available regarding the influence of MD on short-term prognosis. We assessed the impact of the MD adherence on in-hospital and short-term outcome in patients with first ST-elevation Myocardial Infarction (STEMI). METHODS AND RESULTS: As many as 533 European patients with STEMI and no previous history of coronary artery disease were included in this analysis. Previous dietary habits of each patient were collected with a food frequency questionnaire from which we calculated the FAMI Mediterranean Diet Score (FAMI MD Score), according to the MD adherence. A blood sample was drawn to each patient within 6 h of symptoms onset. Levels of high-sensitivity C-Reactive Protein (hsCRP), Interleukin-6 (IL-6) were measured. Clinical outcome at 180 days and myocardial reperfusion were assessed. Patients with higher FAMI MD Score had lower levels of hsCRP; there were no differences between IL-6 level among FAMI MD Score quintiles. There were no associations between adherence to MD and 180-day adverse events. Lower FAMI MD Score was associated with a higher risk of ineffective myocardial reperfusion after thrombolysis or percutaneous coronary intervention. Similar results were observed for daily consumption of ≥4 portions of fruit and vegetable. CONCLUSIONS: A positive effect of the Mediterranean diet, and fruit and vegetable intake was observed on hsCRP and the occurrence of effective myocardial reperfusion. These findings confirm the favorable impact of Mediterranean diet adherence not only in primary but also in secondary prevention.
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Dieta Saudável , Dieta Mediterrânea , Comportamento Alimentar , Cooperação do Paciente , Intervenção Coronária Percutânea , Comportamento de Redução do Risco , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Terapia Trombolítica , Idoso , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , Europa (Continente) , Feminino , Frutas , Humanos , Mediadores da Inflamação/sangue , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Valor Nutritivo , Intervenção Coronária Percutânea/efeitos adversos , Estudos Prospectivos , Fatores de Proteção , Recomendações Nutricionais , Medição de Risco , Fatores de Risco , Infarto do Miocárdio com Supradesnível do Segmento ST/sangue , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/fisiopatologia , Terapia Trombolítica/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , VerdurasRESUMO
BACKGROUND: The impact of incident sudden cardiac death (SCD) on the predictive accuracy of prognostic risk scores for patients with chronic heart failure (HF) has rarely been examined. We assessed the relationship between estimated probability of death and modes of death in this population, as well as the predictors of death and survival in prognostic outliers. METHODS AND RESULTS: The MAGGIC 3-year probability of death was estimated in 6,859 participants of the GISSI-HF trial (mean age 67±11 years, 78% men, 91% with ejection fraction <40%, mean follow-up 3.5±1.3 years, observed mortality 28.4%). The incidence of SCD progressively decreased with increased probability of death, and occurred in 52.5% of patients estimated at low-risk (N = 61 with probability <14%) vs. in 23.5% of the high-risk ones (N = 375 with probability >56%, P < .0001). On the contrary, death from worsening HF was significantly more frequent in the latter group (19.7% vs. 46.1%, P < .0001). The overall predictive accuracy of the MAGGIC model improved after excluding deaths from SCD (AUC from 0.731 to 0.760, P = .0034). Among patients estimated at low-risk (N = 61 dead, 743 alive), independent predictors of death were older age, longer history of HF, higher serum uric acid and chronic obstructive pulmonary disease. The only predictor of survival in patients estimated at high-risk (N = 210 alive, 375 dead) was higher systolic blood pressure. CONCLUSIONS: The MAGGIC risk score demonstrated its scarce ability to capture SCD, particularly in chronic HF patients estimated at low risk of death. Newer and better prognostic tools in the evolving horizon of HF are needed.
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Morte Súbita Cardíaca/epidemiologia , Insuficiência Cardíaca/mortalidade , Idoso , Área Sob a Curva , Causas de Morte , Feminino , Insuficiência Cardíaca/fisiopatologia , Humanos , Incidência , Masculino , Probabilidade , Prognóstico , Medição de Risco , Volume SistólicoRESUMO
Atherosclerotic cardiovascular disease still represents the leading cause of death in Western countries. A wealth of scientific evidence demonstrates that increased blood cholesterol levels have a major impact on the outbreak and progression of atherosclerotic plaques. Moreover, several cholesterol-lowering pharmacological agents, including statins and ezetimibe, have proved effective in improving clinical outcomes. This document focuses on the clinical management of hypercholesterolaemia and has been conceived by 16 Italian medical associations with the support of the Italian National Institute of Health. The authors discuss in detail the role of hypercholesterolaemia in the genesis of atherosclerotic cardiovascular disease. In addition, the implications for high cholesterol levels in the definition of the individual cardiovascular risk profile have been carefully analysed, while all available therapeutic options for blood cholesterol reduction and cardiovascular risk mitigation have been explored. Finally, this document outlines the diagnostic and therapeutic pathways for the clinical management of patients with hypercholesterolaemia.
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Although it is generally accepted that cardiac ischemic events develop when coronary atherosclerosis (coronary artery disease [CAD]) has reached a critical threshold, this is true only to a first approximation. Indeed, there are patients with severe CAD who do not develop ischemic events; conversely, at the other extreme, individuals with minimal CAD may do. Similar exceptions to this paradigm include patients with diffuse CAD with a low risk factor (RF) profile and others with multiple RFs who develop only mild or no CAD. Therefore, the CAPIRE project was designed to investigate whether the specific study of these extreme outlier populations could provide clues for identification of yet unknown risk or protective factors for CAD and ischemic events. In the CAPIRE study, 481 subjects without previous symptoms or history of ischemic heart disease and normal left ventricular systolic function undergoing coronary computed tomography angiography have been selected based on coronary computed tomography angiography findings and cardiovascular RF profile. Therefore, in the whole population, 2 extreme outlier populations have been identified: (1) subjects with no CAD despite multiple RFs, and (2) at the opposite extreme, subjects with diffuse CAD despite a low-risk profile. Each subject has been characterized by clinical, anatomical imaging variables of CAD and baseline circulating biomarkers. Blood samples were collected and stored in a biological bank for further advanced investigations. The project is designed as a prospective, observational, international multicenter study with an initial cross-sectional analysis of clinical, imaging, and biomolecular variables in the selected groups and a longitudinal 5-year follow-up.
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Aterosclerose/epidemiologia , Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico , Sistema de Registros , Medição de Risco , Tomografia Computadorizada por Raios X/métodos , Idoso , Aterosclerose/diagnóstico , Doença da Artéria Coronariana/epidemiologia , Estudos Transversais , Feminino , Seguimentos , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Morbidade/tendências , Estudos Prospectivos , Fatores de Risco , Índice de Gravidade de Doença , Fatores de TempoRESUMO
BACKGROUND: Cardiovascular disease is important in rheumatoid arthritis (RA). Tissue factor (TF) is expressed upon platelet activation and initiates coagulation. Anti-tumour necrosis factor-α (TNFα) agents seem to decrease RA-associated cardiovascular events. We investigated whether (1) TNFα activates human platelets and (2) TNFα pharmacological blockade modulates the platelet-leucocyte reciprocal activation in RA. DESIGN: The expression of platelet TNFα receptors has been assessed by flow cytometry and immunogold electron microscopy. Platelet and leucocyte activation has been assessed also in the presence of antibodies against the TNFα receptors 1 and 2 and of infliximab. TF expression, binding to fibrinogen and phosphatidylserine exposure, has been assessed by flow cytometry, TF activity by coagulation time and by endogenous thrombin generation. Markers of platelet and leucocyte activation have been assessed in 161 subjects: 42 patients with RA, 12 with osteoarthritis, 37 age-matched and sex-matched patients with chronic stable angina and 70 age-matched and sex-matched healthy subjects. RESULTS: TNFα elicited the platelet activation and the expression of TF, which in turn prompted thrombin generation and clot formation. Inhibition of the TNFα-induced activation restricted platelet ability to activate leucocytes and to induce leucocyte TF. TNFα inhibition did not influence platelet activation induced by collagen, ADP or thrombin receptor activating peptide-6. Platelets of patients with RA were more activated than those of controls. Activation was reduced in patients treated with TNFα inhibitors. CONCLUSIONS: TNFα-dependent pathways control platelet activation and TF expression in RA. Further studies will verify whether the protective effect of TNFα inhibitors on cardiovascular events involves their ability to modulate platelet function.
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Antirreumáticos/farmacologia , Artrite Reumatoide/sangue , Artrite Reumatoide/tratamento farmacológico , Ativação Plaquetária/efeitos dos fármacos , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Idoso , Idoso de 80 Anos ou mais , Antirreumáticos/uso terapêutico , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Adesão Celular/fisiologia , Feminino , Humanos , Contagem de Leucócitos , Leucócitos/fisiologia , Masculino , Pessoa de Meia-Idade , Selectina-P/fisiologia , Ativação Plaquetária/fisiologia , Proteínas Recombinantes/farmacologia , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/fisiologiaRESUMO
BACKGROUND: Granulocyte-colony stimulating factor (G-CSF) has been clinically tested in ST-elevation myocardial infarction (STEMI) with mixed results. Our 3-year follow-up data from STEM-AMI trial documented a sustained benefit of G-CSF on adverse ventricular remodeling after large anterior STEMI, when administered early and at a high-dose in patients with left ventricular (LV) dysfunction. The Aim of the present trial is to establish whether G-CSF improves hard clinical long-term outcomes. METHODS: The STEM-AMI OUTCOME is a prospective, multicenter, randomized, open-label, phase III trial. It will include 1,530 patients with anterior STEMI undergoing primary percutaneous coronary intervention 2 to 24 hours after symptoms onset and with LV ejection fraction ≤45% after successful reperfusion. Patients will be randomized 1:1 to G-CSF and/or standard treatment. The primary end point is a reduced occurrence of all-cause death, recurrence of myocardial infarction, or hospitalization due to heart failure in G-CSF-treated patients. Left ventricular remodeling will be assessed via cardiac ultrasound and a substudy with cardiac magnetic resonance will be carried out in 120 subjects. Accrual and follow-up periods will last 3 and 2 years, respectively. CONCLUSIONS: The STEM-AMI OUTCOME study is designed to be a rigorous controlled phase III trial with adequate statistical power to conclusively assess efficacy of G-CSF treatment in STEMI.
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Eletrocardiografia , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Infarto do Miocárdio/terapia , Intervenção Coronária Percutânea/métodos , Idoso , Angiografia Coronária , Feminino , Seguimentos , Humanos , Injeções Intra-Arteriais , Imagem Cinética por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/fisiopatologia , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento , Função Ventricular Esquerda , Remodelação VentricularRESUMO
RATIONALE: Four monocentric studies reported that circadian rhythms can affect left ventricular infarct size after ST-segment-elevation acute myocardial infarction (STEMI). OBJECTIVE: To further validate the circadian dependence of infarct size after STEMI in a multicentric and multiethnic population. METHODS AND RESULTS: We analyzed a prospective cohort of subjects with first STEMI from the First Acute Myocardial Infarction study that enrolled 1099 patients (ischemic time <6 hours) in Italy, Scotland, and China. We confirmed a circadian variation of STEMI incidence with an increased morning incidence (from 6:00 am till noon). We investigated the presence of circadian dependence of infarct size plotting the peak creatine kinase against time onset of ischemia. In addition, we studied the patients from the 3 countries separately, including 624 Italians; all patients were treated with percutaneous coronary intervention. We adopted several levels of analysis with different inclusion criteria consistent with previous studies. In all the analyses, we did not find a clear-cut circadian dependence of infarct size after STEMI. CONCLUSIONS: Although the circadian dependence of infarct size supported by previous studies poses an intriguing hypothesis, we were unable to converge toward their conclusions in a multicentric and multiethnic setting. Parameters that vary as a function of latitude could potentially obscure the circadian variations observed in monocentric studies. We believe that, to assess whether circadian rhythms can affect the infarct size, future study design should not only include larger samples but also aim to untangle the molecular time-dynamic mechanisms underlying such a relation.
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RATIONALE: At the onset of ST-elevation acute myocardial infarction (STEMI), patients can present with very high circulating interleukin-6 (IL-6(+)) levels or very low-IL-6(-) levels. OBJECTIVE: We compared these 2 groups of patients to understand whether it is possible to define specific STEMI phenotypes associated with outcome based on the cytokine response. METHODS AND RESULTS: We compared 109 patients with STEMI in the top IL-6 level (median, 15.6 pg/mL; IL-6(+) STEMI) with 96 in the bottom IL-6 level (median, 1.7 pg/mL; IL-6(-) STEMI) and 103 matched controls extracted from the multiethnic First Acute Myocardial Infarction study. We found minimal clinical differences between IL-6(+) STEMI and IL-6(-) STEMI. We assessed the inflammatory profiles of the 2 STEMI groups and the controls by measuring 18 cytokines in blood samples. We exploited clustering analysis algorithms to infer the functional modules of interacting cytokines. IL-6(+) STEMI patients were characterized by the activation of 2 modules of interacting signals comprising IL-10, IL-8, macrophage inflammatory protein-1α, and C-reactive protein, and monocyte chemoattractant protein-1, macrophage inflammatory protein-1ß, and monokine induced by interferon-γ. IL-10 was increased both in IL-6(+) STEMI and IL-6(-) STEMI patients compared with controls. IL-6(+)IL-10(+) STEMI patients had an increased risk of systolic dysfunction at discharge and an increased risk of death at 6 months in comparison with IL-6(-)IL-10(+) STEMI patients. We combined IL-10 and monokine induced by interferon-γ (derived from the 2 identified cytokine modules) with IL-6 in a formula yielding a risk index that outperformed any single cytokine in the prediction of systolic dysfunction and death. CONCLUSIONS: We have identified a characteristic circulating inflammatory cytokine pattern in STEMI patients, which is not related to the extent of myocardial damage. The simultaneous elevation of IL-6 and IL-10 levels distinguishes STEMI patients with worse clinical outcomes from other STEMI patients. These observations could have potential implications for risk-oriented patient stratification and immune-modulating therapies.
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Eletrocardiografia , Interleucina-10/sangue , Interleucina-6/sangue , Infarto do Miocárdio/imunologia , Infarto do Miocárdio/mortalidade , Idoso , Algoritmos , Inteligência Artificial , Análise por Conglomerados , Feminino , Humanos , Interleucina-10/imunologia , Interleucina-6/imunologia , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico , Valor Preditivo dos Testes , Prognóstico , Curva ROC , Fatores de Risco , Transdução de Sinais/imunologia , Sístole/imunologiaRESUMO
Pentraxin 3 (PTX3) plays cardioprotective and anti-atherogenic roles in murine models. PTX3 blood levels raise during early acute myocardial infarction (AMI). Neutrophils from healthy subjects physiologically contain PTX3 in secondary (also called specific) granules. In this study, we report that circulating neutrophils release preformed PTX3 in the early phase of AMI (within 6 h from the onset of clinical symptoms). Depletion of intracellular PTX3 correlates with increased plasma levels and with platelet-neutrophil heterotypic aggregates. Neutrophil PTX3 returns to normal values 48 h after the onset of symptoms; concentration does not vary in matched healthy controls or in patients with chronic stable angina. In vitro, recognition of activated P-selectin(+) platelets causes the formation of neutrophil-platelet heteroaggregates and the release of neutrophil PTX3. Purified or membrane-bound P-selectin triggers PTX3 release from resting neutrophils. Released PTX3 binds to activated platelets in vitro. Moreover, PTX3 binds to a substantial fraction of platelets from patients in the circulating blood. PTX3-bound activated platelets have a reduced ability to 1) form heterotypic aggregates with neutrophils and monocytes; 2) activate neutrophils, as evaluated assessing the upregulation of leukocyte ß(2) integrins; 3) aggregate with other platelets; and 4) bind to fibrinogen. Our results suggest that neutrophils early release prestored PTX3 in patients undergoing AMI. PTX3 binds to activated circulating platelets and dampens their proinflammatory and prothrombotic action, thus possibly contributing to its cardioprotective effects.
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Proteínas de Fase Aguda/metabolismo , Proteína C-Reativa/metabolismo , Infarto do Miocárdio/imunologia , Infarto do Miocárdio/prevenção & controle , Neutrófilos/imunologia , Neutrófilos/metabolismo , Componente Amiloide P Sérico/metabolismo , Proteínas de Fase Aguda/fisiologia , Adulto , Idoso , Proteína C-Reativa/fisiologia , Proteína C-Reativa/uso terapêutico , Comunicação Celular/imunologia , Trombose Coronária/imunologia , Trombose Coronária/patologia , Trombose Coronária/prevenção & controle , Grânulos Citoplasmáticos/imunologia , Grânulos Citoplasmáticos/metabolismo , Grânulos Citoplasmáticos/patologia , Feminino , Humanos , Mediadores da Inflamação/metabolismo , Mediadores da Inflamação/fisiologia , Mediadores da Inflamação/uso terapêutico , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/patologia , Ativação de Neutrófilo/imunologia , Neutrófilos/patologia , Ativação Plaquetária/imunologia , Fase de Repouso do Ciclo Celular/imunologia , Componente Amiloide P Sérico/fisiologia , Componente Amiloide P Sérico/uso terapêuticoRESUMO
Several lines of evidence suggest the involvement of infectious agents in the pathogenesis of atherosclerosis. Furthermore, a correlation between infection-driven inflammatory burden and acute manifestation of coronary artery disease has been hypothesized. The aim of this work was to assess whether human herpesvirus (HHV)-6 and HHV-8, two DNA viruses with a distinct tropism for endothelium and lymphocytes, may be associated with coronary instability. An age- and gender-matched cross-sectional study was undertaken in 70 patients with testing of plasma HHV-6 and HHV-8 DNA load in different cardiovascular clinical settings: 29 patients with acute myocardial infarction, 21 patients with stable coronary artery disease, and 20 patients without coronary and carotid artery atherosclerosis subjected to cardiac valve replacement. In all patients, HHV-6 and HHV-8 plasma DNA was tested by using highly sensitive, calibrated quantitative real-time PCR assays which employ a synthetic DNA calibrator to adjust for DNA extraction and amplification efficiency. HHV-8 viremia was undetectable in all three groups. HHV-6 viremia was detected in a substantial fraction of the samples examined (18.6%) without significant differences among the three groups (ST segment elevation myocardial infarction: 17.2%; stable coronary artery disease: 14.3%; patients without coronary and carotid artery atherosclerosis: 25%). Furthermore, no significant differences in plasma HHV-6 load were observed amongst the three groups of patients. These findings indicate that coronary instability is not associated specifically with active HHV-6 or HHV-8 infection. However, an unusually high rate of active HHV-6 infection was documented among patients without atherosclerosis admitted to hospital with cardiac disease.
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Doença da Artéria Coronariana/virologia , Vasos Coronários/patologia , DNA Viral/sangue , Infecções por Herpesviridae/patologia , Herpesvirus Humano 6/patogenicidade , Herpesvirus Humano 8/patogenicidade , Idoso , Doença da Artéria Coronariana/patologia , Vasos Coronários/virologia , Estudos Transversais , Feminino , Infecções por Herpesviridae/epidemiologia , Infecções por Herpesviridae/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/patologia , Infarto do Miocárdio/virologia , Prevalência , Reação em Cadeia da Polimerase em Tempo Real , Sensibilidade e Especificidade , Carga Viral , Viremia/patologia , Viremia/virologiaRESUMO
BACKGROUND: High mannose has previously associated with insulin resistance and cardiovascular disease (CVD). Our objective is to establish whether mannose is associated with anatomical evidence of coronary artery disease (CAD). METHODS: Plasma mannose concentrations were measured by liquid chromatography/tandem mass spectrometry in a discovery cohort (n = 513) and a validation cohort (n = 221) of carefully phenotyped individuals. In both cohorts CAD was quantitated using state-of-the-art imaging techniques (coronary computed coronary tomography angiography (CCTA), invasive coronary angiography and optical coherence tomography). Information on subsequent CVD events/death was collected. Associations of mannose with angiographic variables and biomarkers were tested using univariate and multivariate regression models. Survival analysis was performed using the Kaplan-Meier estimator. RESULTS: Mannose was related to indices of CAD and features of plaque vulnerability. In the discovery cohort, mannose was a marker of quantity and quality of CCTA-proven CAD and subjects with a mannose level in the top quartile had a significantly higher risk of CVD events/death (p = 3.6e-5). In the validation cohort, mannose was significantly associated with fibrous cap thickness < 65 µm (odds ratio = 1.32 per each 10 µmol/L mannose change [95% confidence interval, 1.05-1.65]) and was an independent predictor of death (hazard ratio for mannose≥vs < 84.6 µmol/L: 4.0(95%CI, 1.4-11.3), p = 0.006). CONCLUSION: The current data add novel evidence that high mannose is a signature of CAD with a vulnerable plaque phenotype, consistently across measures of severity of vessel involvement and independent of the traditional correlates of CVD, and that it is an independent predictor of incident adverse outcomes.
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Doença da Artéria Coronariana , Manose , Biomarcadores , Angiografia por Tomografia Computadorizada , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Humanos , Valor Preditivo dos Testes , Prognóstico , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
Activated platelets express ligands, which are recognized by counterreceptors on neutrophils. Here, we show that the ensuing cell-to-cell interaction programs neutrophil phagocytic function, resulting in activated platelet clearance. Neutrophils that have internalized platelets circulate in the blood of patients with acute myocardial infarction, and the extent of platelet clearance correlates with expression of platelet activation, including P-selectin. Activated platelets injected intravenously in experimental animals are detectable in circulating neutrophils 60 minutes after, and within 3 hours, more than 70% circulating neutrophils have internalized platelets. Platelet clearance comprises 2 events: adhesion to neutrophils, which requires divalent cations and depends on P-selectin, on the P-selectin glycoprotein ligand-1 (PSGL-1), and on the CD11b/CD18 beta2 integrin; and internalization, which is abrogated by the phosphatidylserine-binding protein annexin A5. Adhesion to platelets causes neutrophil degranulation and is blocked by antibodies specific for P-selectin and PSGL-1, either in a synthetic medium in vitro or in the whole blood, therefore in the presence of a physiologic array of plasma cofactors and opsonins. The data suggest that the interaction between circulating platelets and neutrophils influences innate immune functions, possibly contributing to regulate vascular inflammation.
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Plaquetas/imunologia , Antígenos CD18/imunologia , Neutrófilos/imunologia , Selectina-P/imunologia , Fagocitose , Fosfatidilserinas/imunologia , Comunicação Celular/imunologia , Degranulação Celular , Humanos , Imunidade Inata , Glicoproteínas de Membrana , Infarto do Miocárdio/sangue , Ativação Plaquetária/imunologiaRESUMO
Recent data indicated that adaptive immunity is involved in the process of atherogenesis. Oligoclonal recruitment of T lymphocytes has been described in coronary plaques of patients with acute coronary syndrome. However, the nature of immune response remains to be determined. In the present study, we examined the Ab response in six coronary plaques obtained by endoluminal directional atherectomy. The IgG1/kappa-coding gene repertoires of B lymphocytes present in circulating blood and in coronary plaques were cloned and analyzed. In all of the six plaques, we observed 1) a skewed usage of heavy and light IgG1/kappa Ab-coding genes, 2) an oligoclonal distribution of V(K), J(K), and V(H), D(H), and J(H) genes with overrepresentation of some rarely used IgG genes, and 3) the unequivocal signs of Ag-driven clonal expansion and evolution of B cells. The data document for the first time the presence of a local Ag-driven clonal evolution of B cells in human atherosclerotic plaques.
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Antígenos de Bactérias/fisiologia , Autoantígenos/fisiologia , Subpopulações de Linfócitos B/imunologia , Subpopulações de Linfócitos B/patologia , Doença da Artéria Coronariana/imunologia , Evolução Molecular , Imunoglobulina G/biossíntese , Cadeias kappa de Imunoglobulina/biossíntese , Adulto , Idoso , Subpopulações de Linfócitos B/microbiologia , Proliferação de Células , Células Clonais , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/patologia , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/genética , Cadeias kappa de Imunoglobulina/sangue , Cadeias kappa de Imunoglobulina/genética , Masculino , Pessoa de Meia-Idade , Família Multigênica/imunologiaRESUMO
BACKGROUND: Family history (FH) of cardiovascular disease (CVD) in first degree relatives (FDR) is a major risk factor, especially for premature events. Data are sparse on FH of different manifestations of CVD among FDRs of patients with premature myocardial infarction (MI), chronic stable angina (CSA) or peripheral vascular disease (PVD). METHODS: We obtained FHs from first degree relatives (parents or siblings) of 230 consecutive patients with premature (men < 60 and women < 65 years) CVD, including 79 wth MI, 39 CSA, 51 PVD and 61 blood donors. Among 1225 parents or siblings, 421 had MI, 222 CSA, 261PVD and 321 were among blood donors. RESULTS: FH of MI were 5.6% (18/321) among blood donors, 14.0% (59/421) among patients with premature MI, 14.4% (32/222) CSA, and 8.0% (21/261) PVD. (all p < 0.05). For FH of CSA the corresponding frequencies were 3.7% 5.2%, 11.3%, and 6.9%. (all p < 0.05). For PVD, the corresponding frequencies were 2.1%, 3.4%, 0.9% and 0.7%, respectively. (p = ns). CONCLUSIONS: These data are compatible with the hypothesis that FH of MI, CSA and PVD are significantly different for patients with premature MI or CSA but not PVD.
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Doenças Cardiovasculares , Infarto do Miocárdio , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/genética , Família , Feminino , Humanos , Masculino , Anamnese , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/genética , Fatores de RiscoRESUMO
BACKGROUND: Traditional cardiovascular risk factors (RFs) and coronary artery disease (CAD) do not always run parallel. We investigated functional-metabolic correlations of CAD, RFs, or neither in the CAPIRE (Coronary Atherosclerosis in Outlier Subjects: Protective and Novel Individual Risk Factors Evaluation) 2 × 2 phenotypic observational study. METHODS: Two hundred and fortyone subjects were included based on RF burden, presence/absence of CAD (assessed by computed tomography angiography), age and sex. Participants displayed one of four phenotypes: CAD with ≥3 RFs, no-CAD with ≥3 RFs, CAD with ≤1 RF and no-CAD with ≤1 RF. Metabolites were identified by gas chromatography-mass spectrometry and pathways by metabolite set enrichment analysis. RESULTS: Characteristic patterns and specific pathways emerged for each phenotypic group: amino sugars for CAD/high-RF; urea cycle for no-CAD/high-RF; glutathione for CAD/low-RF; glycine and serine for no-CAD/low-RF. Presence of CAD correlated with ammonia recycling; absence of CAD with the transfer of acetyl groups into mitochondria; high-risk profile with alanine metabolism (all p < 0.05). The comparative case-control analyses showed a statistically significant difference for the two pathways of phenylalanine, tyrosine and tryptophan biosynthesis and phenylalanine metabolism in the CAD/Low-RF vs NoCAD/Low-RF comparison. CONCLUSIONS: The present 2 × 2 observational study identified specific metabolic pathways for each of the four phenotypes, providing novel functional insights, particularly on CAD with low RF profiles and on the absence of CAD despite high-risk factor profiles.
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Doenças Cardiovasculares , Doença da Artéria Coronariana , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/epidemiologia , Fatores de Risco de Doenças Cardíacas , Humanos , Fenótipo , Fatores de RiscoRESUMO
BACKGROUND: Proteomics of atypical phenotypes may help unravel cardiovascular disease mechanisms. AIM: We aimed to prospectively screen the proteome of four types of individuals: with or without coronary artery disease (CAD), each with or without multiple risk factors. Associations with individual risk factors and circulating biomarkers were also tested to provide a functional context to the protein hits. MATERIALS AND METHODS: The CAPIRE study (ClinicalTrials.gov Identifier: NCT02157662) is a cross-sectional study aimed at identifying possible new mechanisms promoting or protecting against atherothrombosis. Quantification (by aptamer technology), ranking (using partial least squares), and correlations (by multivariate regression) of ~5000 plasma proteins were performed in consecutive individuals aged 45-75 years, without previous cardiovascular disease, undergoing computed tomography angiography for suspected CAD, showing either >5/16 atherosclerotic segments (CAD+) or completely clean arteries (CAD-) and either ≤ 1 risk factor (RF+) or ≥3 risk factors (RF-) (based on history, blood pressure, glycemia, lipids, and smoking). RESULTS: Of 544 individuals, 39% were atypical (93 CAD+/RF-; 120 CAD-/RF+) and 61% typical (102 CAD+/RF+; 229 CAD-/RF-). In the comparison with CAD+/RF- adjusted for sex and age, CAD-/RF+ was associated with increased atrial myosin regulatory light chain 2 (MYO) and C-C motif chemokine-22 (C-C-22), and reduced protein shisa-3 homolog (PS-3) and platelet-activating factor acetylhydrolase (PAF-AH). Extending the analysis to the entire cohort, an additional 8 proteins were independently associated with CAD or RF; by logistic regression, the 12-protein panel alone discriminated the four groups with AUCROC's of 0.72-0.81 (overall p = 1.0e-38). Among them, insulin-like growth factor binding protein-3 is positively associated with RF, lower BMI, and HDL-cholesterol, renin with CAD higher glycated hemoglobin HbA1c, and smoking. CONCLUSIONS: In a CCTA-based cohort, four proteins, involved in opposing vascular processes (healing vs. adverse remodeling), are specifically associated with low CAD burden in high CV-risk individuals (high MYO and C-C-22) and high CAD burden in low-risk subjects (high PS-3 and PAF-AH), in interaction with BMI, smoking, diabetes, HDL-cholesterol, and HbA1c. These findings could contribute to a deeper understanding of the atherosclerotic process beyond traditional risk profile assessment and potentially constitute new treatment targets.
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BACKGROUND: High-risk coronary atherosclerosis features evaluated coronary CT angiography (CCTA) were suggested to have a prognostic role. The present study aimed to evaluate the association of circulating biomarkers with high-risk plaque features assessed by CCTA. METHODS: A consecutive cohort of subjects who underwent CCTA because of suspected CAD was screened for inclusion in the CAPIRE study. Based on risk factors (RF) burden patients were defined as having a low clinical risk (0-1 RF with the exclusion of patients with diabetes mellitus as single RF) or an high clinical risk (≥3 RFs). In all patients, measurement of inflammatory biomarkers and CCTA analysis focused on high-risk plaque features were performed. Univariate and multivariate logistic regression analysis were used to evaluate the relationship between clinical and biological variables with CCTA advanced plaque features. RESULTS: 528 patients were enrolled in CAPIRE study. Older age and male sex appeared to be predictors of qualitative high-risk plaque features and associated with the presence of elevated total, non-calcified and low-attenuation plaque volume. Among circulating biomarkers only hs-CRP was found to be associated with qualitative high-risk plaque features (OR 2.02, pâ¯=â¯0.004 and 2.02, pâ¯=â¯0.012 for LAP and RIâ¯>â¯1.1, respectively) with borderline association with LAP-Vol (OR 1.52, pâ¯=â¯0.076); HbA1c and PTX-3 resulted to be significantly associated with quantitative high-risk plaque features (OR 1.71, pâ¯=â¯0.003 and 1.04, pâ¯=â¯0.002 for LAP-Vol, respectively). CONCLUSIONS: Our results support the association between inflammatory biomarkers (hs-CRP, PTX- 3), HbA1c and high-risk atherosclerotic features detected by CCTA. Male sex and older age are significant predictors of high-risk atherosclerosis.
Assuntos
Proteína C-Reativa/análise , Angiografia por Tomografia Computadorizada , Angiografia Coronária , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico por imagem , Hemoglobinas Glicadas/análise , Tomografia Computadorizada Multidetectores , Componente Amiloide P Sérico/análise , Fatores Etários , Idoso , Biomarcadores/sangue , Doença da Artéria Coronariana/epidemiologia , Estudos Transversais , Feminino , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica , Valor Preditivo dos Testes , Prevalência , Prognóstico , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Fatores SexuaisRESUMO
The purpose of this study was to test the hypothesis that specific epicardial adipose tissue (EAT) proinflammatory adipokines might be implicated in acute coronary syndrome (ACS). We compared expression and protein secretion of several EAT adipokines of male ACS with those of matched stable coronary artery disease (CAD) patients and controls with angiographically normal coronary arteries. The effect of supernatant of cultured EAT on endothelial cell permeability in vitro was also evaluated in the three study groups. EAT of ACS patients showed significantly higher gene expression and protein secretion of resistin than patients with stable CAD. Interleukin-6, plasminogen activator inhibitor-1, and monocyte chemoattractant protein-1 genes were also significantly overexpressed in ACS compared with the control group but not when compared with stable CAD. Immunofluorescence of EAT sections revealed a significantly greater number of CD68(+) cells in ACS patients than stable CAD and control groups. The permeability of endothelial cells in vitro was significantly increased after exposure to supernatant of cultured EAT from ACS, but not control or stable CAD groups, and this effect was normalized by anti-resistin antiserum. We found that EAT of patients with ACS is characterized by increased expression and secretion of resistin and associated with increased in vitro endothelial cell permeability.