RESUMO
INTRODUCTION: The vascular cell adhesion molecule (VCAM-1) is a transmembrane sialoglycoprotein detected in activated endothelial and vascular smooth muscle cells involved in the adhesion and transmigration of inflammatory cells into damaged tissue. Widely used as a pro-inflammatory marker, its potential role as a targeting molecule has not been thoroughly explored. AREAS COVERED: We discuss the current evidence supporting the potential targeting of VCAM-1 in atherosclerosis, diabetes, hypertension and ischemia/reperfusion injury. EXPERT OPINION: There is emerging evidence that VCAM-1 is more than a biomarker and may be a promising therapeutic target for vascular diseases. While there are neutralizing antibodies that allow preclinical research, the development of pharmacological tools to activate or inhibit this protein are required to thoroughly assess its therapeutic potential.
Assuntos
Aterosclerose , Traumatismo por Reperfusão , Humanos , Molécula 1 de Adesão de Célula Vascular/metabolismo , Molécula 1 de Adesão de Célula Vascular/uso terapêutico , Aterosclerose/tratamento farmacológico , Endotélio VascularRESUMO
Atrial Fibrillation (AF) is the most common sustained arrhythmia and is highly prevalent in elderly patients. It confers a higher risk for ischemic stroke, heart failure and death. The diagnosis and treatment of AF has been extensively studied and remain under constant revision. This article reviews the recent European guidelines and the advances observed with the introduction of direct oral anticoagulants in the last ten years. This new family of drugs has clear benefits in terms of efficacy and safety compared with traditional vitamin K antagonists. Treatment of most common comorbidities in patients with AF such as advanced age, heart failure, diabetes, renal failure, and others are also analyzed. New therapies for AF will be shortly available.
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Humanos , Idoso de 80 Anos ou mais , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/tratamento farmacológico , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/tratamento farmacológico , Diabetes Mellitus/tratamento farmacológico , Insuficiência Cardíaca/tratamento farmacológico , Comorbidade , Administração Oral , Anticoagulantes/efeitos adversosRESUMO
Atrial Fibrillation (AF) is the most common sustained arrhythmia and is highly prevalent in elderly patients. It confers a higher risk for ischemic stroke, heart failure and death. The diagnosis and treatment of AF has been extensively studied and remain under constant revision. This article reviews the recent European guidelines and the advances observed with the introduction of direct oral anticoagulants in the last ten years. This new family of drugs has clear benefits in terms of efficacy and safety compared with traditional vitamin K antagonists. Treatment of most common comorbidities in patients with AF such as advanced age, heart failure, diabetes, renal failure, and others are also analyzed. New therapies for AF will be shortly available.
Assuntos
Fibrilação Atrial , Diabetes Mellitus , Insuficiência Cardíaca , Acidente Vascular Cerebral , Humanos , Idoso , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/tratamento farmacológico , Anticoagulantes/efeitos adversos , Comorbidade , Diabetes Mellitus/tratamento farmacológico , Insuficiência Cardíaca/tratamento farmacológico , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/tratamento farmacológico , Administração OralRESUMO
RESUMEN: Se presenta una semblanza del Dr. Bernard Lown, uno de los más destacados cardiólogos del siglo XX. Muy relevantes fueron sus estudios sobre arritmias ventriculares e isquemia miocárdica, como también la influencia del estrés sobre el umbral de la fibrilación ventricular. Simultáneamente con otros investigadores europeos desarrolló el cardiovertor eléctrico. Se releva particularmente su condición de gran clínico y el trato humano con sus pacientes. Finalmente, se destaca su contribución a evitar una guerra nuclear por lo cual, junto al Dr Chazov, recibió el Premio Nobel de la Paz.
ABSTRACT: This is a biographical note on Bernard Lown MD, recently deceased. He was one of the foremost cardiologist in the XXth century. Relevant were his studies on ventricular arrhythmias and myocardial ischemia, as well the effect of mental stress in lowering the ventricular arrhythmia threshold. Along with European researchs he developed the electric cardiovertor. Special emphasis is placed on his skills as a clinician and is humane approach to patient care. He contributed to international efforts to prevent nuclear war. For this effort he was awarded, along with Dr Chazov, the Nobel Peace Price.
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História do Século XX , Cardiologia/história , Cardiologistas/história , LituâniaRESUMO
The vascular cellular adhesion molecule-1 (VCAM-1) is a protein that canonically participates in the adhesion and transmigration of leukocytes to the interstitium during inflammation. VCAM-1 expression, together with soluble VCAM-1 (sVCAM-1) induced by the shedding of VCAM-1 by metalloproteinases, have been proposed as biomarkers in immunological diseases, cancer, autoimmune myocarditis, and as predictors of mortality and morbidity in patients with chronic heart failure (HF), endothelial injury in patients with coronary artery disease, and arrhythmias. This revision aims to discuss the role of sVCAM-1 as a biomarker to predict the occurrence, development, and preservation of cardiovascular disease.
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Biomarcadores/metabolismo , Doenças Cardiovasculares/metabolismo , Molécula 1 de Adesão de Célula Vascular/metabolismo , Animais , Humanos , Miocardite/metabolismoRESUMO
BACKGROUND: Soluble vascular cell adhesion molecule-1 has been associated with long-term cardiovascular mortality in patients with stable coronary artery disease and to the development of new atrial fibrillation in subjects with cardiovascular risk factors but no evidence of cardiac disease. HYPOTHESIS: Preoperative soluble vascular cell adhesion molecule-1 predicts the risk of future all-cause death and cardiovascular death among patients submitted to elective coronary artery bypass surgery. METHODS: From a cohort of 312 patients who underwent elective coronary artery bypass surgery prospectively followed for a median of 6.7 years, we evaluated the prognostic role of preoperative soluble vascular cell adhesion molecule-1, inflammatory markers, CHA2DS2-VASc score and development of postoperative atrial fibrillation (POAF). Univariable and multivariable Cox regression analyses were performed to establish an association of these parameters with long term all-cause death and cardiovascular death. RESULTS: During 2112 person-years of follow-up, we observed 41 deaths, 10 were cardiovascular deaths. Independently increased levels of preoperative soluble vascular cell adhesion molecule-1, POAF, and CHA2DS2-VASc score were associated with all-cause mortality. After multivariate adjustment, elevated preoperative soluble vascular cell adhesion molecule-1 and POAF were the only independent predictors of all-cause death. Also, preoperative soluble vascular cell adhesion molecule-1, POAF, and CHA2DS2-VASc score resulted in being independent predictors of cardiovascular mortality. CONCLUSIONS: Increased circulating levels of preoperative soluble vascular cell adhesion molecule-1, together with POAF and CHA2DS2-VASc score, were significantly associated with future all-cause death and cardiovascular death among patients submitted to coronary artery bypass surgery.
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Ponte de Artéria Coronária/mortalidade , Doença da Artéria Coronariana/cirurgia , Complicações Pós-Operatórias , Medição de Risco/métodos , Molécula 1 de Adesão de Célula Vascular/sangue , Biomarcadores/sangue , Chile/epidemiologia , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Período Pré-Operatório , Estudos Prospectivos , Curva ROC , Taxa de Sobrevida/tendências , Fatores de TempoRESUMO
BACKGROUND: Cardiorespiratory fitness (CRF) is a powerful predictor of mortality. This study evaluated the predictive value of CRF for mortality in Chilean subjects without atherosclerotic disease compared with the Framingham, European Systematic Coronary Risk Evaluation (SCORE), and 2013 ACC/AHA risk scores and determined the incremental predictive value of CRF when added to these scores. HYPOTHESIS: CRF improves prediction of all-cause and cardiovascular disease (CVD)-related mortality of the standard international risk scores. METHODS: Cross-sectional study, which evaluated 4064 subjects between 2002 and 2016. Cardiovascular (CV) risk factors, anthropometric and biochemical parameters, and blood pressure were measured. CRF was determined by metabolic equivalents during maximum stress test. The Framingham, SCORE, and ACC/AHA risk scores were calculated for all subjects. After a median follow-up of 9 years, all-cause and CVD-related mortality were assessed. Receiver operating curves were built to determine mortality prediction for CRF, the risk scores, and CRF added to the scores. RESULTS: As of August 2016, 99 deaths were reported, 33 of which were CVD-related. All risk scores and CRF predicted CVD-related mortality, with CRF identified as the best predictor: CRF: C = 0.88 (95% CI: 0.82-0.93) vs Framingham: C = 0.68 (95% CI: 0.60-0.76), SCORE: C = 0.76 (95% CI: 0.70-0.83), and ACC/AHA: C = 0.79 (95% CI: 0.73-0.85). Predictive power of the three scores improved when CRF was added to the model, but this was only significant for the Framingham score. CONCLUSIONS: CRF is a good predictor of both, all-cause and CV mortality and a better predictor of CVD-related deaths than standard risk scores in this population.
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Aptidão Cardiorrespiratória/fisiologia , Doenças Cardiovasculares/terapia , Medição de Risco/métodos , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/fisiopatologia , Causas de Morte/tendências , Chile/epidemiologia , Estudos Transversais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Padrões de Referência , Fatores de Risco , Taxa de Sobrevida/tendênciasRESUMO
AIMS: Non-vitamin K antagonist oral anticoagulants represent a new option for prevention of embolic events in patients with atrial fibrillation (AF). However, little is known about the impact of non-cardiac comorbidities on the efficacy and safety profile of these drugs. METHODS AND RESULTS: In a post hoc analysis of the ENGAGE AF-TIMI 48 trial, we analysed 21 105 patients with AF followed for an average of 2.8 years and randomized to either a higher-dose edoxaban regimen (HDER), a lower-dose edoxaban regimen, or warfarin. We used the updated Charlson Comorbidity Index (CCI) to stratify the patients according to the burden of concomitant disease (CCI = 0, 1, 2, 3, and ≥4). The treatment groups were then compared for safety, efficacy, and net clinical outcomes across CCI categories. There were 32.0%, 7.3%, 42.1%, 12.7%, and 6.0% of patients with CCI scores of 0, 1, 2, 3, and ≥4, respectively. A CCI score ≥4 was associated with significantly higher rates of thromboembolic events, bleeding, and death compared to CCI = 0 (P < 0.05 for each). The annualized rates of the primary net clinical outcome (stroke/systemic embolism, major bleeding, or death) for CCI = 0, 1, 2, 3, or ≥4 were 5.9%, 8.7%, 6.6%, 10.3%, and 13.6% (Ptrend < 0.001). There were no significant interactions between treatment with HDER vs. warfarin and efficacy, safety, and net outcomes across the CCI groups (P-interaction > 0.10 for each). CONCLUSION: Although increasing CCI scores are associated with worse outcomes, the efficacy, safety, and net clinical outcomes of edoxaban vs. warfarin were independent of the degree of comorbidity present.