Hypertension Clinical Trial
To analyze the genetic and environmental contributions of juvenile hemodynamic determinants of blood pressure, including cardiac output and systemic vascular pressure, to adult cardiovascular risk.
BACKGROUND:
Identifying individuals at a young age who are at risk for future development of
hypertension in adult life is a public health issue of great importance. The imperfect
nature of blood pressure tracking throughout childhood and adolescence, and the fact that
the genes which determine blood pressure in childhood may not be the same ones which operate
in adulthood make it clear that improved predicting models are needed. The twin-parent study
design allowed testing more subtle genetic and environmental hypotheses than was possible
with nuclear families or twins alone. The longitudinal component permitted an analysis of
developmental changes in the genetic expression of the hemodynamic determinants of blood
pressure. The inclusion of unlike sex twins permitted an analysis of the consistency of
genetic and environmental effects across the sexes.
DESIGN NARRATIVE:
The longitudinal comparison of the cardiovascular responses of adolescent twins and their
parents was initialed in 1983. Three cohorts of twin families were enrolled, each cohort
beginning 18 months apart. Both monozygotic and dizygotic twins were included. Variables
measured included demographics, family history, personality, blood pressure, anthropometry,
stage of puberty, dynamic exercise, isometric exercise, psychological stress,
echocardiography, genotyping, and lipid profiles. Each cohort revisited every 18 months.
A fourth cohort of 330 preadolescent twin pairs stratified by sex and zygosity was recruited
from an established population-based twin registry. The hemodynamic determinants of blood
pressure were assessed by non-invasive measurements of cardiac function including
echocardiography and response to isometric and dynamic exercise. Zygosity was determined by
questionnaire and confirmed by dermatoglyphic analysis and blood group tests. Anthropometric
and hemodynamic measurements in the parents were compared to those in the children. The
study included up to five sets of longitudinal measurements, thereby permitting an
evaluation of whether the same or different genes operated at different ages encompassing
pre-puberty, puberty, and post-puberty.
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