Trials of Hypertension Prevention (TOHP)

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.