Years: 1984 - 1997
Location: Multiple Locations Worldwide
Principal Investigator: Stamler, Jeremiah
The INTERSALT Study focused on high sodium intake as one of several exposures producing high blood pressure in adults aged over 35 years. The INTERSALT study was completed to fill the gap in the research left by small-scale, short-term preceding studies that often lacked valid measures of salt intake. The hypotheses explored by the INTERSALT study were that, among a large number of participants, systolic and diastolic blood pressure would be related to 24 hour urinary sodium excretion, the ratio of sodium to potassium excreted, body mass index and alcohol intake both directly and independently. Potassium excretion was hypothesized to be inversely related.
The INTERSALT study used a cross sectional design. The study population consisted of 10,079 men and women aged 20-59 years from 52 diverse sites in 32 countries worldwide. Data collection began in 1984, and further analysis was periodically performed on the data through 1997. At each of the 52 study centers, researchers would collect data from 200 participants, 25 from each sex-decade strata. Five blood pressure endpoints were established: sample median SBP and DBP, sample slope of SBP and DBP with age and sample prevalence of high BP. Urine samples were taken once to be assessed for sodium and potassium excretion, and a random sample of participants would be asked to provide a second sample to correct for regression-dilution bias. Data on potential confounding variables such as urinary excretion of magnesium and calcium, pulse rate, ethnicity, education, physical activity level, smoking, medication use and postmenopausal status were also gathered. Interview techniques were standardized with a single system of equipment and procedures, protocol and manual of operations.
For 24-hour sodium excretion and SBP/DBP, a significant independent relationship was found. Estimates of the sodium-SBP/DBP relation were 3.1-6.0/0.1-1.25 mmHg lower on average with 100-mmol/d lower sodium intake (632S). High BMI and alcohol use also yielded a direct and independent relation with increased blood pressure. The test of potassium excretion also revealed an inverse relationship to high blood pressure. Favorable sodium to potassium ratios were associated with blood pressure values 6.5/2.0 to 9.3/4.1 mmHg lower than those with poor excretion ratios. The study also found that sodium and blood pressure results for participants under forty years of age had multivariate coefficients about two to three times smaller than participants aged 40 years or older. Further examination of potential confounders uncovered an inverse relationship between education level and high blood pressure. Further population analysis was performed to compare results across the sites internationally.
The study found a linear relationship between high sodium intake universally with increased SBP and DBP. Although data could not be collected on mortality for the INTERSALT cohort, when the cohort data were compared to that of the MRFIT study, ischemic heart disease and other CVD death rates were lower by 13% and all cause mortality was lower by 9% with sodium intake lower by each 100 mmol. The study’s results were met with some controversy, however, as a number of peer responses were sent to the British Medical Journal soon after the first publication of results. The study was criticized on the basis of its generalization that a reduced sodium intake will decrease hypertension across ethnic groups and for using epidemiological and biostatistical methods that did not adequately reduce error (LeFanu 484). Stamler articulates the need for more long-term studies that focus on linking greater sodium intake and cardiovascular diseases, as causality can not yet adequately be inferred. (HB)
 Stamler, J., 1997. The INTERSALT Study: background, methods, findings, and implications. American journal of clinical nutrition 65 (2 Suppl), 626S-642S.
 Lefanu, J., 1997. Cross cultural studies such as Intersalt study cannot be used to infer causality. British medical journal, 315, 484.