The Predictive Role of Urinary Proteomics in Blood Pressure Response of Obese Hypertensive Treated With Irbesartan or Eplerenone.

Background :

Hypertension remains the most prevalent modifiable risk factor associated with cardiovascular morbidity and mortality, however un-optimally treated hypertension prevalence remains alarmingly high. Variable blood pressure response to pharmacological treatment, physician inertia and lack of patient's compliance due to polypharmacy, are the main reasons behind non optimal blood pressure treatment. The multifactorial nature of hypertension has long been described, with various environmental, genetic and epi-genetic factors involved in its pathogenesis and progression. Therefore, scientific interest is starting to shift towards precision medicine, as a medical model for disease prevention and tailored treatment that incorporates individual, genetic, environmental and experiential variability. Το this end, proteomic analysis is an emerging representative in the research of predictive biomarkers.

Proteomic analysis consists of the qualitive and quantitative analysis of the final proteins in bodily fluids. A simplified approach constitutes of sample acquisition, protein extraction and separation through high-resolution electrophoresis and chromatography-based techniques, protein sequence determination with mass spectrometry-based analysis and protein identification with bioinformatic techniques in referential databases. Various small scale clinical trials have highlighted the clinical significance if proteomic analysis, ranging from identifying biomarkers able to determine the blood pressure response following treatment with spironolactone in patients with resistant hypertension, predicting pre-eclampsia through the urinary proteome even in early stages of gestation.

Obesity and essential hypertension are two pathological entities that often coexist. Data from the Framingham study suggesting a twofold risk of obese patients developing hypertension compared to underweight ones, while similar associations have been described by the NHANES III, MONICA, and Health, Aging and Body Composition Study studies, between increases in blood pressure, as a result of increases in BMI, waist circumference, and visceral fat, respectively. The mechanisms through which obesity leads to the development of hypertension, are a complex pathophysiological phenomenon under constant research and study, including the activation of the Sympathetic Nervous System, disorder of renal sodium excretion, excessive renin-angiotensin-aldosterone axis activation and endothelial dysfunction. Angiotensin 2 receptor blockers like Irbesartan, have long been used as first-line pharmacological treatment, however clinical trials including ASPIRANT, PATHWAY-2, and RALES study, have highlighted the role of aldosterone receptor blockers in obese hypertensive patients. Spironolactone and eplerenone are the main oral representatives of this group, with the latter showing less frequent side effects as well as higher binding specificity for the mineralocorticoid- receptor.

Aim of the study: