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PhD Thesis

dc.contributor.advisorCruz Fernández, José Maríaes
dc.contributor.advisorSabaté Díaz, Juanes
dc.creatorRecio Mayoral, Alejandroes
dc.date.accessioned2016-04-07T06:51:48Z
dc.date.available2016-04-07T06:51:48Z
dc.date.issued2016-01-05
dc.identifier.urihttp://hdl.handle.net/11441/39641
dc.description.abstractLa disfunción microvascular coronaria asociada a disfunción endotelial está presente en diferentes contextos de la enfermedad cardiovascular, incluyendo los factores de riesgo cardiovascular clásicos, y la inflamación podría jugar un papel esencial en todo este epifenómeno. De hecho, actualmente la aterosclerosis es vista como un proceso inflamatorio activo e inmuno-mediado en el cual leucocitos y factores solubles (anticuerpos, factores de complemento activados, citoquinas) participan en el progreso de la enfermedad. Los pacientes con enfermedades inflamatorias sistémicas autoinmunes, como la artritis reumatoide y el lupus eritematoso sistémico presentan una elevada morbilidad y mortalidad de origen cardiovascular secundaria a aterosclerosis acelerada y enfermedad coronaria prematura. El exceso de riesgo observado en estos pacientes parece estar relacionado con los efectos deletéreos de la inflamación sistémica en la vasculatura. Por otro lado se especula que un estado inflamatorio de bajo grado podría ser relevante en la patogénesis del síndrome X cardiaco, enfermedad caracterizada por episodios anginosos típicos con isquemia miocárdica transitoria a pesar de no presentar lesiones angiográficas en la coronariografía, en los cuales la disfunción microvascular se ha mostrado como causante de la isquemia miocárdica. El objetivo de la presente tesis es demostrar la posible relación entre inflamación crónica y disfunción microvascular coronaria. Especulamos con que el grado de disfunción de la microcirculación está directamente relacionado con el tiempo de exposición a la inflamación e incluso contemplamos el potencial papel de la inflamación en la modulación de la respuesta microvascular coronaria en algunos pacientes.es
dc.description.abstractBackground. Coronary microvascular dysfunction associated with endothelial dysfunction is often found in many cardiac conditions, including cardiovascular risk factors, and inflammation would be playing a key role in all this epiphenomenon. Actually, atherosclerosis is seen as an active inflammatory and immune-mediated process in which leukocytes and soluble factors (antibodies, activated complement, cytokines) play a role in accelerating vessel pathology. Patients with systemic inflammatory, autoimmune disease, such as rheumatoid arthritis (AR) and systemic lupus erythematosus (SLE), suffer from increased cardiovascular morbidity and mortality owing to accelerated atherosclerosis and premature coronary disease. The excess risk observed in these patients appears to be driven by the damaging effects of systemic inflammation on the vasculature. A low grade of inflammation could also play a role in the pathogenesis of cardiac syndrome X (ie typical angina and transient myocardial ischemia despite normal coronary arteries) in which coronary microvascular dysfunction has been show to lead myocardial ischemia. Aims. To demonstrate that exposure to chronic inflammation results in coronary microvascular dysfunction (CMD). We speculate that the degree of CMD is directly related to time exposed to inflammation and also hypothesise a potential role of inflammation in the modulation of coronary microvascular responses in some patients. Methods. We carried out 2 separated studies in which systemic inflammatory (AR and LES) patients and CSX patients were analyzed by using positron emission tomography. Resting and hyperaemic (adenosine, 140 μg/Kg/min) myocardial blood flow (MBF) was measured in both groups of patients and in matched healthy volunteers as controls. Results. Although resting MBF was similar in patients (AR/LES and CSX) and controls, abnormalities of the coronary microvascular function were found in both studies, with reduced coronary flow reserve (CFR). CSX patients with C reactive protein levels higher of 3 mg/L at study entry had more severe impairment of CFR. In AR/SLE patients, CFR was inversely related to disease duration (r=-0.65; p<0.001). In both groups of patients, we also found that patients showing ischaemic electrocardiographic changes during adenosine induced hyperaemia, had lower CFR and longer disease duration (AR/LES patients) or higher CRP levels (CSX patients) when compared with patients without changes. Conclusions. Chronic inflammation in the absence of significant coronary disease and traditional cardiovascular risk factors is associated with severe abnormalities of coronary microcirculation, and the degree of this CMD is related with the exposure time to inflammation. We suggest a role for inflammation in the modulation of coronary responses in patients with CSX. This may represent an early marker of cardiovascular disease which precedes and contributes to accelerated atherogenesis.es
dc.formatapplication/pdfes
dc.language.isospaes
dc.rightsAtribución-NoComercial-SinDerivadas 4.0 España
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectCoronary circulationes
dc.subjectInflammationes
dc.subjectMyocardial blood flowes
dc.subjectRheumatoid arthritises
dc.subjectSystemic Lupus Erythematosuses
dc.subjectCardiac Syndrome Xes
dc.subjectPositron emission tomographyes
dc.titleDisfunción microvascular coronaria e inflamación crónicaes
dc.typeinfo:eu-repo/semantics/doctoralThesises
dcterms.identifierhttps://ror.org/03yxnpp24
dc.type.versioninfo:eu-repo/semantics/publishedVersiones
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses
dc.contributor.affiliationUniversidad de Sevilla. Departamento de Farmacología, Pediatría y Radiologíaes
dc.identifier.idushttps://idus.us.es/xmlui/handle/11441/39641

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Except where otherwise noted, this item's license is described as: Atribución-NoComercial-SinDerivadas 4.0 España