Trials of Hypertension Prevention, Phases I and
II
Objectives:
Phase I of TOHP (TOHP I) was designed to test the
short-term feasibility and efficacy of seven nonpharmacologic interventions in
persons with high normal BP. These interventions included the lifestyle
interventions of weight loss, sodium reduction, and stress management, and the
nutritional supplement interventions of calcium, magnesium, potassium and fish
oil.
Phase II of TOHP (TOHP II) was designed to test the
efficacy of interventions to promote weight loss, sodium reduction, and the
combination of weight loss and sodium reduction in decreasing diastolic BP,
systolic BP, and the incidence of hypertension during a 3- to 4-year follow-up
period in moderately overweight men and women with a high-normal level of
diastolic BP.
Background:
Phase I: As much as one-third of cardiovascular
disease attributable to an above-optimal BP level occurs in the nonhypertensive
portion of the distribution, providing impetus for directing prevention efforts
at high normal levels of BP. Epidemiologic studies have identified several
dietary and other factors related to lifestyle as possible determinants of BP
levels. As of the mid-1980s, few trials had reported any results in subjects
with BP levels in the nonhypertensive range, and almost none included long-term
follow-up. The goals of Phase I of TOHP were to (1) test the short-term effect
on BP of selected nutritional and behavioral interventions, and (2) to
determine the feasibility of a long-term clinical trial of methods for reducing
the incidence of hypertension.
Phase II: Between 30% and 40% of all BP-related CVD
events occur in individuals with an average BP below currently defined
hypertensive levels but above the optimal level. A large body of information
from observational studies has identified several determinants of elevated BP.
The corresponding interventional data are less plentiful and much of what is
available reflects experience in small studies with relatively short periods of
follow-up. The initial phase of TOHP (TOHP I) tested the feasibility and
efficacy of 3 separate lifestyle interventions (weight loss, dietary sodium
reduction, and stress management) and 4 separate nutritional supplement
interventions (calcium, magnesium, potassium, and fish oil). The weight loss
and sodium reduction groups, but not the other groups, demonstrated significant
decreases in both systolic and diastolic BP. The second phase of TOHP was
designed to test the effect of the two most promising interventions over a
longer period of follow-up.
Subjects:
Phase I: Subjects were BP eligible if their mean
diastolic BP averaged over the three screening visits with three measurements
per visit was in the range 80-89 mmHg, and they had not taken antihypertensive
medication within the past two months. The entry weight criterion for the
weight loss intervention only was a BMI in the range 26.08 to 36.14 for men and
24.26 to 36.14 for women. Randomization began in September of 1987, and ended
in October of 1988. Of the 2,182 randomized participants, the average age at
randomization was 43 years, 70% were male, 82% were white, and 15% were black.
Collection of final visit data occurred throughout 1989, and ended on January
12, 1990.
Phase II: Participants were 30-54 years of age, with a
body mass index representing 110-165% of desirable body weight. BP was measured
at each of 3 screening visits with 3 measurements per visit. Eligible subjects
had an average diastolic BP in the range 83-89 mmHg, with systolic BP <140
mmHg, and were not on antihypertensive medication. A total of 2,382
participants were randomized into the trial. Average age at baseline was 44
years, 66% of participants were male, and 21% were minority.
Conclusions:
Phase I: The weight reduction intervention produced an
average weight loss of 3.9 kg, a diastolic BP change of -2.3 mm Hg, and a
systolic BP change of -2.9 mm Hg. The sodium reduction intervention lowered
urinary sodium excretion by 44 mmol/24 h, diastolic BP by 0.9 mm Hg, and
systolic BP by 1.7 mm Hg. Neither stress management nor nutritional supplements
reduced diastolic BP significantly. The weight reduction and sodium reduction
interventions were the most effective of those tested for reducing BP in
normotensive persons (JAMA 1992;267:1213-20). The long-term effects of these
require further evaluation.
Phase II: At six months, compared to usual care, BP
decreased 3.7/2.7 mm Hg in the weight loss group, 2.9/1.6 mm Hg in the sodium
reduction group, and 4.0/2.8 mm Hg in the combined group. At 36 months, BP
decreases remained greater in the active intervention groups than in the usual
care group (weight loss, 1.3/0.9 mm Hg; sodium reduction, 1.2/0.7 mm Hg;
combined, 1.1/0.6 mm Hg). The incidence of hypertension was significantly less
in each active intervention group than in the usual care group (Arch Intern Med
1997: 157:657-667). In overweight adults with high-normal BP, weight loss and
reduction in sodium intake, individually and in combination, were effective in
lowering systolic and diastolic BP, especially in the short-term. Although the
effects on average BP declined over time, reductions in hypertension incidence
were achieved.
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Study Website |
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Study Documentation |
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Data Distribution Agreement |
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