INTERSALT: International Study of Sodium, Potassium, and Blood Pressure

BACKGROUND:

For decades diet, particularly high habitual sodium intake, has been implicated in the etiopathogenesis of high blood pressure. This concept has been based on clinical observations, including therapeutics and results of dietary trials; on animal experimentation, particularly induction of hypertension by salt feeding; and on epidemiologic findings. While considerable knowledge has been amassed in support of this concept, limitations and inconsistencies exist in the data base. This is especially true in regard to the findings from population studies. Thus, negative or inconsistent results have been reported from several cross-sectional studies of dietary sodium and blood pressure in which the unit of measurement has been the individual within a population. When INTERSALT began in 1984, no prospective data were available from population-based longitudinal investigations. A major problem in such studies, one possibly accounting for the negative and inconsistent findings, was the difficulty of validly measuring the habitual sodium intake of individuals within a population in which there was relative homogeneity in regard to this trait. This difficulty was due to large individual variation day-to-day in the sodium intake and output in most populations, so that the ratio of intra- to inter-individual variances was large. This led to high probability of misclassification and obscuring or weakening of true associations in any single population sample, unless multiple measurements were made for each person. Since dietary history methods such as 7-day food records, multiple 24-hour recalls, and dietary interviews were of limited validity for assessment of sodium intake, investigators had to rely on timed urine collections, especially 24-hour samples. But accurate collection of several such specimens per person by many individuals for population studies was a difficult undertaking. This was an important reason for the paucity of valid data on sodium and blood pressure from within-population studies.

INTERSALT was based on a common protocol and had a staff trained in standardized procedures in each center, thus permitting estimation of the sodium-blood pressure relationship within as well as across centers. INTERSALT originated as a Project of the Council on Epidemiology and Prevention of the International Society and Federation of Cardiology and has since its inception been jointly coordinated by the London School of Hygiene and Tropical Medicine and the Northwestern University Medical School. The main data analyses were performed in London. Overwhelmingly, funding for the work of the London Coordinating Center, the Central Laboratory, as well as for the 52 centers, had been organized independently. For example, support came from the Wellcome Trust, the World Health Organization, the International Society of Hypertension, the Council on Epidemiology and Prevention of the International Society and Federation of Cardiology, the Dutch Heart Foundation, the British Heart Foundation, the Canadian Heart Foundation, the Japanese Heart Foundation, as well as the private sector.

The grant to Northwestern University supported the Chicago share of training and coordination of the Chicago population sample of the Peoples Gas Company, assistance to six centers in developing countries, part of the Coordinating Center and the Central Laboratory, and some of the data analysis. The grant to the University of Mississippi supported the four population samples in Mississippi.

DESIGN NARRATIVE: