the microbiome as a target for precision medicine in atherosclerosis

Conditions: Acute Coronary Syndrome; Atherosclerosis

Summary: cardiovascular diseases are the main cause of death in industrialized countries. among them, atherosclerosis has the highest prevalence and constitutes a common pathological pathway responsible for the majority of cases of chronic ischemic heart disease, acute myocardial infarction, heart failure and cerebrovascular disease. classic studies have confirmed well-established etiopathogenic factors of atherosclerosis based on genetic and immunological components and environmental modifying agents such as diet and exercise. but in addition, recent experimental studies have shown that dysbiosis (alteration of the microbiota) may be an additional factor that participates in the onset and progression of atherosclerosis. the objective of this study is to identify the potential interactions between changes in the microbiota, changes in the immune status, the clinical evolution and the instability and progression of atherosclerosis.

the study will prospectively study two groups of patients : 1) patients with acute coronary syndrome and 2) age and sex matched patients with chronic stable documented atherosclerosis. immune cell populations and immune-related metabolites will be characterized, the genetic profile of the main known functional variants will be determined, and the oral, gastrointestinal, and blood microbiota will be compared in both groups in a transversal observational design. in addition, 1-year clinical follow-up will be performed and correlation with the evolution of the microbiota and immune response in a longitudinal design will be conducted. besides, an angiographic substudy, for those patients included in the study but that require revascularization of culprit artery according to clinical indication, will be 1 year follow-up and functional assessment and intravascular imaging and the degree of remodelling of the atherosclerotic plaque will be correlated with the evolution of the microbiota and immune response in a longitudinal design.

Eligibility criteria:
inclusion criteria acute coronary syndrome group: * diagnosis of acute coronary syndrome * signature of informed consent for the study (annex i). exclusion criteria acute coronary syndrome group: * previous ejection fraction of vi less than 30%. * history of heart failure * systemic inflammatory diseases * in treatment with corticosteroids or immunomodulators * in treatment with antibiotics during the last month aditional inclusion criteria for angiographic substudy group: * clinical indication of coronary angiography in the acute phase (in the first 72 hours after its hospital diagnosis). * at least one non-causal coronary lesion in a coronary segment with reference diameter\> 2 mm, stenosis between 40-80%, and timi 3 flow in this vessel (angiographic criteria, only confirmed after performing coronary angiography) * signature of informed consent for the substudy (annex ii). aditional exclusion criteria for angiographic substudy group: * renal insufficiency with creatinine clearance less than 30 ml / h * hepatic insufficiency: patients with cirrhosis in child b or c stages will be excluded. inclusion criteria chronic atherosclerosis group: * angiographic diagnosis, using catheterization or computed tomography of coronary atherosclerotic disease. * clinical situation of stable chronic ischemic heart disease. * signature of informed consent for the study (annex iii). exclusion criteria chronic atherosclerosis group: * previous ejection fraction of vi less than 30%. * history of heart failure * systemic inflammatory diseases * in treatment with corticosteroids or immunomodulators * in treatment with antibiotics during the last month

Keywords: microbiota immunity genetics atherosclerosis