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Genetic Based Analysis in Hypertensive Patients

2020-03-31 04:04:36 | BioPortfolio

Summary

Many attempts to identify predictors of blood pressure response after renal denervation failed to identify a meaningful determination of blood pressure response.

These attempts have been based on demographic parameters, clinical parameters, endocrine inflammatory and other biochemical variables, comorbidities and disease factors. So far the only predictor of blood pressure response is the pre-treatment blood pressure. According to Wilder`s law the pre-treatment baseline value is always a determinant for any change due to an intervention, irrespective which biological variable is examined.

The investigators propose a genetic approach to identify predictors of blood pressure response after renal denervation. Genetic factors are not subject to changes of clinical parameters, previous or current antihypertensive therapy, hypertension associated organ damages, comorbidities and other potential clinical variables.

Description

Background:

Up to now numerous attempts to identify predictors of blood pressure response after renal denervation failed to identify a meaningful and consistent determinant of blood pressure response. These approaches have been based on demographic parameters, clinical parameters, comorbidities and disease factors as well as numerous endocrine inflammatory and other biochemical variables. Only the pre-treatment blood pressure emerged as a predictor of blood pressure response which is no surprise since according to Wilder's law the pre-treatment baseline value is always a determinant for any change due to an intervention, irrespective which biological variable is examined, e.g. blood pressure, LDL cholesterol, HbA1c and so on.

The investigators suggest a genetic approach to identify predictors of blood pressure response after renal denervation. The rationale is quite simple: Genetic factors are not subject to changes of clinical parameters, previous or current antihypertensive therapy, hypertension associated organ damages, comorbidities, and other potential clinical variables. By such an approach the investigators previously were very successful to identify several parameters of modulators hypertensive organ damage that could not have been identified by pathophysiological or pharmaceutical maneuvers. THE INVESTIGATORS PREFER TO RUN A GENOM WIDE ASSOCIATION STUDY AND THE PARTNERS IN GLASGOW AND EDINBURGH HAVE THE DEEP KNOWLWEDGE; EXPERIENCE AND CAPACITY TO RUN A NGS (next generation sequencing, so that's the complete genome)) INCLUDING ALL BIOINFORMATICS AND OTHER ANALYSIS

Objective:

The investigators attempt to identify predictors of blood pressure response to renal denervation by using a GWAS (genome wide association study) approach. This allows to identify various suspected and unexpected polymorphism that are of interest and potentially being strong predictors of blood pressure response. By that approach the investigators will identify novel mechanism of action that are important for blood pressure response (by identifying polymorphism that are beyond the classical thinking how renal denervation may exert blood pressure lowering effects).

Study design:

In collaboration with the Homburg Group (Prof. Dr. Felix Mahfoud), the investigators will extract DNA from stored samples of patients with uncontrolled treatment resistant hypertension and perform a genome wide association study analysis (GWAS) in two cohorts: no/low responders vs. high/excellent responders. NGS will be applied by the partners in Glasgow and Edinburgh. All patients with renal denervation will be categorized according to their pretreatment adjusted blood pressure response and the investigators will compare the upper quartile vs. the lower quartile of all patients that has been so far studied in Homburg and Erlangen. By excluding those patients with a medium or average blood pressure response, the investigators will have two distinct response patterns: low/no response vs. high/excellent response.

By applying standard biostatistics analysis, the investigators will come up with a pattern of polymorphism that are significantly different between the two groups. These identified polymorphisms (or a pattern of it) may be refer, not unexpectedly, to renin angiotensin aldosterone system, sodium and water balance, sympathetic nervous system or other endocrine parameters related to hypertension. In addition to that, the investigators may find significant results of polymorphisms involved in other pathophysiologic pathways not related to hypertension (by our current knowledge) and that the Investigators have not thought about to be related to uncontrolled hypertension. These novel mechanism need to be subsequently further analyzed, but they will offer the opportunity to find novel predictors of blood pressure response.

Study Design

Conditions

Hypertension

Intervention

Genetic based analysis of identifying predictors of blood pressure in patients after renal denervation

Location

Klinik für Innere Medizin III, Kardiologie, Angiologie Und Internistische Intensivmedizin, Saarland University Hospital, Saarla
Homburg
Saarland
Germany
66421

Status

Active, not recruiting

Source

University of Erlangen-Nürnberg Medical School

Results (where available)

View Results

Links

Published on BioPortfolio: 2020-03-31T04:04:36-0400

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Medical and Biotech [MESH] Definitions

Method in which repeated blood pressure readings are made while the patient undergoes normal daily activities. It allows quantitative analysis of the high blood pressure load over time, can help distinguish between types of HYPERTENSION, and can assess the effectiveness of antihypertensive therapy.

Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.

Analysis based on the mathematical function first formulated by Jean-Baptiste-Joseph Fourier in 1807. The function, known as the Fourier transform, describes the sinusoidal pattern of any fluctuating pattern in the physical world in terms of its amplitude and its phase. It has broad applications in biomedicine, e.g., analysis of the x-ray crystallography data pivotal in identifying the double helical nature of DNA and in analysis of other molecules, including viruses, and the modified back-projection algorithm universally used in computerized tomography imaging, etc. (From Segen, The Dictionary of Modern Medicine, 1992)

A method of chemical analysis based on the detection of characteristic radionuclides following a nuclear bombardment. It is also known as radioactivity analysis. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)

A response by the BARORECEPTORS to increased BLOOD PRESSURE. Increased pressure stretches BLOOD VESSELS which activates the baroreceptors in the vessel walls. The net response of the CENTRAL NERVOUS SYSTEM is a reduction of central sympathetic outflow. This reduces blood pressure both by decreasing peripheral VASCULAR RESISTANCE and by lowering CARDIAC OUTPUT. Because the baroreceptors are tonically active, the baroreflex can compensate rapidly for both increases and decreases in blood pressure.

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