Proyectos Integrados de Excelencia en los IIS

Proyectos Integrados de Excelencia en los IIS


Código identificativo: PIE16/00043

Investigador principal: JAVIER ESCANED

Duración: 3 años (2017-2019) Objetivo: Cardiovascular diseases constitute the single leading cause of death worldwide. The morbidity, mortality, and socioeconomic impact of stable coronary artery disease (CAD) make accurate diagnosis and cost-effective management of the utmost importance. The treatment of stable CAD is largely based on a paradigm that gives epicardial coronary stenoses a central role in the generation of myocardial ischaemia. However, microcirculatory dysfunction (MCD) is a major and frequently ignored cause of ischaemia that, according to retrospective studies, influences the outcomes of patients with stable CAD. Prospective evaluation of the prevalence and extension of MCD in clinical populations of patients considered for revascularization is still pending. In addition to the prognostic implications of MCD-derived myocardial ischaemia, patients with MCD may not experience symptomatic relief with myocardial revascularization or non-specific pharmacological treatment. This may explain the high prevalence of persistent angina after revascularization,

causing not only an impairment of the quality of life and higher consumption of healthcare resources, but potentially disorders like depression, which has been found to be associated with CAD and with prognosis. Despite being recommended in clinical practice guidelines, available diagnostic tools for the diagnosis of MCD are seldom used, and therefore its diagnosis leading to tailored treatment is seldom reached. Development of new techniques that do not require intracoronary instrumentation might lead to a more widespread diagnosis of MCD. Available studies suggest that the presence and extension of MCD in patients with stable CAD is variable. It has not been investigated whether this variability is linked to factors like systemic inflammation or platelet function. It also remains largely unknown whether MCD in stable CAD is organ-specific only or rather indicative of involvement of other vital organs. While this seems to be the case in the kidney, the relationship between MCD in the heart and the brain has not been studied. Cardiovascular risk factors linked to the development of MCD have been also associated with a higher risk of neuro-degenerative disease, including Alzheimer’s disease and cerebral small vessel disease (CSVD). Systemic endothelial dysfunction, which can be also linked to inflammation, could constitute a link between microcirculatory involvement in both organs.

The objectives of this prospective, analytic, double-blind study are: a) to establish the prevalence and extension of MCD in a clinical cohort of patients with stable CAD; b) to investigate its influence on patient prognosis, angina symptoms and mental health; c) to explore the relationship of MCD with the presence and development of cerebral small vessel disease; d) to investigate the relationship of MCD with systemic inflammation and platelet function; and e) to validate and develop novel indices of microcirculatory function based on both magnetic resonance imaging and computational analysis of coronary angiography that

could facilitate a more widespread identification of patients with MCD without intracoronary instrumentation.

Estos proyectos están financiados por el Instituto de Salud Carlos III, Ministerio de Economía, Industria y Competitividad y cofinanciados por la Unión Europea