Hypertension Clinical Trial
To determine the pathophysiology of different types of essential hypertension by identifying the discrete effects of major genes and environmental variables as determinants of the subtypes of essential hypertension.
BACKGROUND:
Essential hypertension is believed to be a heterogeneous group of disorders, the subtypes of
which could be related to sodium sensitivity, obesity, diabetes, calcium intake and
metabolism, the renin-angiotensin balance, or membrane cation transport. Essential
hypertension aggregates in families. The syndromes leading to hypertension may involve
shared genes, shared environmental factors, or both.
DESIGN NARRATIVE:
In 1980 a series of biochemical and physiological tests were initiated in the 2,548 persons
in 98 extended pedigrees in Utah. Most of the subjects were obtained from three major
pedigree types: stroke cluster pedigrees; coronary heart disease cluster pedigrees; and
pedigrees of Utah Hypertension Detection and Follow-up Program high blood pressure probands.
Data were collected on personal history, medical family history and genealogy,
anthropometrics, standard and 32-lead electro- cardiograms, multiple blood pressure
measurements during sitting, standing, lying, tilting, isometric hand grip exercise, bicycle
exercise, venipuncture and mental arithmetic. Cation tests included sodium-lithium
countertransport, lithium-potassium co-transport, intracellular sodium, potassium,
magnesium, sodium-potassium ATP-ase pump activity and binding sites and plasma levels of
sodium, potassium, magnesium, ionized calcium and digoxin-like pump inhibitor. Information
was also collected on stress, exercise, plasma renin activity, and urinary kallikrein.
Statistical and pedigree analysis were conducted.
The same tests were also performed on 600 new population-based hypertensive subjects on drug
therapy and again four months after interruption of drug therapy. Tests were conduced for
specific subtypes of high blood pressure among the 600 subjects using individual variables
and multivariate combinations of variables. Three hundred nuclear families were screened to
test for familiality of subtype indicators and to identify those high blood pressure subtype
indicator variables needing detailed pedigree analysis.
One thousand sequentially-sampled persons were studied for major genes, DNA probe linkage,
and gene-environment interactions as determinants of specific types of hypertension.
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