Trials of Hypertension Prevention (TOHP)
Condition: Cardiovascular Diseases; Heart Diseases; Hypertension; Vascular Diseases
MeSH terms: Hypertension; Cardiovascular Diseases; Heart Diseases; Vascular Diseases
Study type: Interventional
Phase: Phase 3

Summary: 
      To determine if nonpharmacological interventions, including diet and lifestyle change, could
      prevent increases in arterial blood pressure leading to systemic hypertension.
    

Detailed description: 
      BACKGROUND:

      High blood pressure affects between 15 and 30 percent of the adult population in the United
      States, and is a major contributor to some of the leading causes of death including coronary
      artery and cerebrovascular diseases. A substantial body of evidence from both population and
      laboratory studies indicates that a number of dietary and lifestyle factors are associated
      with the chronic and progressive increase in blood pressure with age, commonly observed in
      populations of industrialized countries. There are also an increasing number of reports of
      important reductions in blood pressure in persons with hypertension following treatment with
      a number of different non-pharmacological interventions. These observations have led to
      interest in the possibility of the primary prevention of hypertension through
      non-pharmacological intervention on factors related to the development of high blood
      pressure.

      In 1979, the main results of the NHLBI-supported Hypertension Detection and Follow-up Program
      (HDFP), then the largest of the randomized clinical trials of antihypertensive drug
      treatment, were reported. This trial compared the effects of intensive systematic
      Stepped-Care drug treatment with Referred-Care in the community. These results confirmed
      findings of earlier and subsequently reported placebo-controlled trials that effective
      blood-pressure lowering in hypertensive individuals reduces the occurrence of stroke,
      congestive heart failure, and other complications of hypertension, and for the first time
      demonstrated a significant reduction of total mortality. The implications of the findings
      regarding recommendations for long-term drug treatment for tens of millions of Americans led
      several groups of investigators to consider alternative approaches to the control of
      hypertension. To the concerns of these clinicians about drug-related symptoms and economic
      costs were added additional questions regarding the safety of common antihypertensive agents
      in some hypertensive subgroups, based on the results of the Multiple Risk Factor Intervention
      Trial and on other evidence.

      A number of small to moderate-sized randomized clinical trials of non-pharmacologic
      intervention in hypertension have been initiated during the past 5 years with NHLBI support.
      The Hypertension Prevention Trial (HPT) was the largest program studying the effectiveness of
      intervening in a non-hypertensive population. The HPT was a feasibility study to establish
      the ability to enroll in sufficient numbers men and women with diastolic blood pressure of
      78-89 mm Hg; to determine if dietary intervention alone could achieve sustained weight
      reduction, and/or a decrease in sodium intake, or an increase in potassium intake along with
      sodium reduction in these subjects; and to study the effects of the interventions on blood
      pressure. If feasibility were demonstrated, the plan was to conduct a full-scale trial with
      incidence of frank hypertension as the outcome measure.

      The HPT achieved its feasibility goals regarding recruitment of participants and weight
      reduction, but not for dietary sodium reduction and potassium increase. Some of the other
      dietary trials among non-hypertensive subjects have also achieved relatively small sodium
      changes (20-25 percent); a few have produced much larger changes, but only with short-term
      follow-up. Other experience has also shown that it is difficult to increase potassium intake
      by dietary means alone.

      The importance of further work in this area has meanwhile been reinforced by conclusions of
      several expert groups convened by NHLBI. These have included the participants in the 1984 NIH
      Workshop on Nutrition and Hypertension and the 1984 Joint National Committee on Detection,
      Evaluation, and Treatment of High Blood Pressure, whose report addressed in some detail
      non-pharmacologic intervention and primary prevention.

      DESIGN NARRATIVE:

      Phase I was a pilot study to test the feasibility of providing and obtaining compliance with
      selected nutritional-behavioral, non-pharmacologic interventions and to measure the
      short-term effectiveness of the interventions on reducing or preventing an increase in
      diastolic blood pressure. Ten clinical centers, and a coordinating center, which included two
      central laboratories and a nutrient data center, participated. Each clinic tested a subset of
      the interventions. The lifestyle arm of the trial, which included weight loss, sodium
      restriction, and stress management, had an open design with untreated controls. The two-stage
      supplement arm of the trial, which tested magnesium and calcium in Stage I, and fish oil and
      potassium in Stage II, was double-blinded and placebo-controlled. Three clinics tested only
      lifestyle interventions, two tested only supplements, and five participated in both arms of
      the trial. Recruitment began in August 1987 and randomization was completed by October 1988.
      Endpoint data collection was completed in January 1990. The average follow-up was
      approximately 18 months.

      Phase II had a 2x2 factorial design to test the effectiveness of weight loss and sodium
      restriction alone and in combination in reducing blood pressure and decreasing the incidence
      of definite hypertension. Lifestyle interventions were administered through counseling
      sessions at each center. Blood pressure, weight, body mass index, skin fold thickness, and
      urine electrolytes were measured at baseline and at six month intervals for a minimum of 36
      months. Recruitment began at the end of 1990 and was completed in March 1992. Intervention
      and follow-up were completed in March 1995. Data analysis continued through June 1998 under
      U01-HL-37852, the coordinating center.

      The main results were presented at the 1995 American Heart Association Scientific Sessions.
      The Phase II main results paper was published in March 1997.

      The study completion date listed in this record was obtained from the "End Date" entered in
      the Protocol Registration and Results System (PRS) record.
    

Intervention name(s): diet, sodium-restricted (Phase III) diet, sodium-restricted; diet, reducing (Phase III)
Intervention type(s): Behavioral; Behavioral
Intervention model: Factorial Assignment
Primary purpose: Prevention