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European Project on Genes in Hypertension (EPOGH)

Description


THE PROTOCOL OF THE STUDY



Background:  Hypertension (HT) comes about through interaction between genetic, environmental and life-style factors. However, the literature on the presumed associations between genetic variability and HT is conflicting and difficult to interpret because of unstandardized definitions, divergent epidemiological methods and insufficient sample size.

Objective: 
EPOGH sets out (1) to measure the genetic determination of blood pressure (BP) and HT and its cardiovascular complications; (2) to identify polymorphisms significantly associated with HT or cardiovascular risk; (3) to produce a database, which describes the genetic background and cardiovascular phenotypes of 4 Eastern and 2 Western European populations; (4) and to establish a permanent pool of genetic material, which is immediately accessible to address emerging issues in genetic research.

Methodology:  Via random population sampling and enrolment at specialized HT clinics, EPOGH will recruit 600 nuclear families (nearly 2400 subjects) in 6 European countries (Belgium, Bulgaria, Italy, Poland, Romania and Russia). In subjects aged 18-59 years, the relationship between BP, HT and genetic variation in the renin system will be investigated using linkage analysis. Strictly standardized epidemiological methods, subjected to rigorous quality control, will be used to determine complex phenotypes consisting of BP in combination with other traits. The conventional BP will be measured at 2 separate home visits (2 ´ 5 readings). Modern methods to define complex phenotypes will include 24‑h ambulatory BP monitoring, power spectral analysis of heart rate variability as index of the autonomic nervous modulation of the cardiovascular system, and measurement of the endogenous lithium clearance as index of sodium sensitivity. A validated questionnaire will inquire into personal and familial medical his­tory and important life-style factors. In addition to usual measurements, blood biochemistry will also include plasma renin activity, angiotensinogen concentration and angiotensin converting-enzyme activity. The electrolyte and aldosterone excretion will be measured in timed 24‑h urine samples.

Expected outcomes:  HT affects 15% of the adult European population. Beyond age 65, its complications explain over 50% of total mortality. This project will enable the pharmaceutical industry to develop, produce and commercialize simple diagnostic tests to determine genetic predisposition and responsiveness to drug treatment. This, in turn, will lead to the more rational prevention and treatment of HT and its incapacitating complications and will help to curb the epidemic of cardiovascular disease in Eastern Europe. This project will promote genetic and cardiovascular research in 4 Eastern European countries and define new goals and markets for the European pharmaceutical industry.


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