IJE Advance Access originally published online on September 5, 2005
International Journal of Epidemiology 2005 34(5):975-978; doi:10.1093/ije/dyi179
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Commentary |
Commentary: Role of salt intake in the development of high blood pressure
Department of Epidemiology and Public Health, Faculty of Medicine, St Mary's Campus, Imperial College London, Norfolk Place, London W2 1PG, UK
E-mail: p.elliott@imperial.ac.uk
Louis Dahl's famous graph in 1960 showing a positive linear relationship between prevalence of hypertension and mean salt intake across five population groups caught the imagination of the blood pressure research community, and it remains influential to this day. It led to an intensification of research on the role of salt in hypertension spanning anthropology, epidemiology, animal studies, studies of mechanisms and clinical trials. In his 1960 paper, Dahl encompasses much of the basic thinking underpinning current-day public health efforts to reduce sodium consumption in the population. First, he notes that daily intakes of salt among Americans and other populations were well in excess of physiological need 
1 g salt/day (17 mmol sodium) compared with the 10 g (170 mmol sodium) or more being consumed on average by a white American man, and >26 g (440 mmol sodium) by northern Japanese farmers (rates of hypertension and stroke were exceptionally high in northern Japan at that time). He remarks that an individual's dietary salt intake is highly variable and difficult to measure (noting that 24 h urinary excretion was the preferred method); also that salt appetite in humans is induced rather than innate, such that people on a low sodium diet (in some cases as low as a few mmol sodium/day) could rapidly adapt, and furthermore suffered no ill effects. In addition, his animal experiments (and those of Meneely et al.1) had shown that hypertension in rats could be induced by sodium ingestion, in a dose-dependent way over a prolonged period. Though not an epidemiologist by training, he understood and expounded the concept that an environmental risk factor (salt intake) could increase the risk of disease (high blood pressure) in a group, while acknowledging that the risk for any given individual also depended on other factors, including genetic susceptibility. Therefore, the experiment of choice was to examine disease occurrence (rates of hypertension) in different populations with wide variations in exposure (salt intake, measured by 24 h urinary sodium excretion), rather than to compare blood pressures and sodium intakes of individuals within a population.
Later, through a series of breeding experiments Dahl expanded on the concept of gene–environment interaction with respect to an animal model of salt and hypertension; he in-bred a strain of rats (Dahl-S rats), which were ‘sensitive’ to salt intake—fed a diet high in salt, the rats would go on to develop hypertension and stroke. In contrast Dahl-R rats (‘resistant’) could tolerate high salt intake without developing hypertension.2 In his 1960 paper, Dahl postulated that humans would show a range of responses to a high salt intake, but that at the group level, hypertension would be uncommon below an intake of 4–5 g salt/day (68–85 mmol sodium/day).
Other authors subsequently extended Dahl's observations on five populations to other population groups. These studies generally confirmed the Dahl relationship, but, to a greater or lesser extent, suffered from a number of uncertainties and potential biases. Often, the data were not derived from one source, but from a variety of studies in the published literature in which unstandardized and often unspecified methods were used, and few data on confounding variables were available. Perhaps the best known of these reports was by Gleibermann, an anthropologist, who examined the relationship between sodium intake and blood pressure across 27 populations.3 In contrast to Dahl's reliance on 24 h urinary data to estimate sodium intake, in six of Gleibermann's populations, the author's own estimates of sodium intake (6 g salt/day) were used, while in a further ten ‘a quantitative value for mean salt consumption was reported with or without indications as to how it was calculated’.3
One of the most comprehensive of these cross-cultural (ecological) studies of salt and blood pressure, following Dahl, was reported by Froment et al. in 19794 using published data from 28 populations around the world. Data on sodium intake were mostly based on 24 h urinary sodium excretion (although not necessarily from the same studies as the blood pressure data)—except in two studies where ‘spot’ (casual) urine collections were used. Data were presented separately by sex and at approximate ages of 20 and 50 years. An example is given in Figure 1a, which shows the scatter plot for systolic blood pressure and mean sodium excretion among men aged 50. Fitted regression lines are shown for all 28 populations, and for 19 populations excluding nine with salt intakes <2 g/day (34 mmol sodium)—as these isolated, low sodium populations probably had the least adequate data for both sodium intakes and blood pressure,5 and may have differed from the remainder in many ways other than sodium intake. Figure 1b shows a similar analysis for slope of systolic blood pressure with age (estimated from data at approximate ages of 20 and 50 years). Across all 28 populations, the regression coefficient indicates systolic blood pressure lower by 7.7 mm Hg over a 30 y period for sodium intake lower by 100 mmol/day.
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As Dahl had noted in his 1960 paper, sodium intake of the individual is extremely variable: ‘salt consumption may vary so widely from day to day that a single or even several consecutive 24 h collections will hardly give an accurate index of a person's average intake’. This variability leads to misclassification of individuals with respect to their usual intakes when sodium is estimated from a single 24 h urine collection. As a result, in contrast to the generally positive cross-population associations between sodium and blood pressure noted by Dahl and subsequent authors, within-population associations (often based on small numbers of individuals) were—in the late 1970s to the early 1980s—largely considered to be negative: the so-called ‘regression-dilution’ problem (though when these so-called negative studies were subsequently pooled into a meta-analysis, highly significant direct associations of sodium intake to blood pressure were found6).
Because of these apparent inconsistencies in the epidemiological literature on salt and blood pressure at the time (1982) of the First Advanced Seminar on Cardiovascular Epidemiology (held under the auspices of the International Society and Federation of Cardiology) participants were given the task of devising an international study to investigate the salt–blood pressure association: the INTERSALT study was born. INTERSALT collected data on over 10 000 men and women aged 20–59 years from 52 population samples in 32 countries.7 It was designed both to address cross-population comparisons of blood pressure with salt intake (measured by 24 h urinary sodium excretion) and within-population associations (taking into account the known regression dilution problem). Accordingly 8% of the study sample collected two 24 h urinary collections allowing estimates of, and statistical corrections for, the reliability of measurement of sodium (due to the large day-to-day variability in intake) in the within-population analyses.7 Figure 2 illustrates results of the cross-population association of the systolic blood pressure slope with age and average sodium excretion. As with the analysis of data from 28 populations in Froment et al.,4 there is a highly significant direct association across all 52 populations, such that sodium lower by 100 mmol/day was associated with lower rise in systolic blood pressure over a 30 year period (e.g. age 25 to age 55) of 10.2 mm Hg. (This result was robust to the method of calculating rise in blood pressure with age8). In the within-population analysis, with adjustment for confounding variables and correction for reliability (the regression dilution problem), 100 mmol lower sodium intake was associated with systolic blood pressure lower by 3.1–6.0 mm Hg and diastolic by 0.1–2.5 mm Hg,8 with findings larger in women than in men9—results similar to the meta-analysis of the previous within-population studies.6
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Dahl mentions in his 1960 review the advent of the thiazide diuretics (that promote sodium loss), as well as the benefits of sodium restriction for the treatment of high blood pressure. Since then a number of studies have documented the benefits of more moderate sodium reduction in reducing or obviating the need for anti-hypertensive therapy,10 and a large number of randomized controlled trials of sodium reduction and blood pressure have been carried out. These were summarized in three meta-analyses published in the mid-1990s to the late-1990s.11–13 Although the meta-analyses differed according to their inclusion criteria (e.g. the meta-analysis of Graudal et al.13 included many short-term trials with large fluctuations of sodium intake) their results were similar in reporting lower blood pressure for lower sodium intake. Subsequently the DASH-sodium study has reported,14 with particular attention to adherence to dietary intervention among those assigned to the DASH diet (high in fruit and vegetables and low-fat dairy products) and reduced sodium diets, as all food was supplied to participants. Its design provided for three levels of sodium—higher (141 mmol/day), intermediate (106 mmol/day), and lower (64 mmol/day)—as verified by analyses of 24 h urine samples. For hypertensive participants eating usual American diet, lower compared with higher sodium produced an 8 mm Hg fall in systolic pressure. For non-hypertensive DASH-sodium participants—systolic/diastolic pressures 120–139/80–89 mm Hg—lower vs higher sodium (i.e. 77 mmol/day lower) produced a 5.5 mm Hg fall in systolic pressure. For all DASH-sodium participants, lower vs higher sodium reduced systolic/diastolic pressure by 6.7/3.5 mm Hg. Further, the effect on blood pressure of salt reduction in the DASH-sodium trial was greater for lower vs intermediate sodium than for intermediate vs higher sodium: –4.6 vs –2.1 mm Hg systolic, for sodium lower by 42 and 35 mmol/day, respectively.
Sodium intakes of Americans and many other populations around the world remain too high—in particular, the average 10 g salt (170 mmol sodium) intake per day Dahl reported for American men in 1960 is similar to the median 24 h urinary sodium excretion of 174 mmol/day for American men in the INTERMAP study (1996–99).15 The most recent Dietary Guidelines for Americans (2005)16 recommends dietary intake of no more than 2300 mg sodium/day (100 mmol) except for individuals with hypertension, blacks, and middle-aged and older adults, for whom no more than 1500 mg sodium/day (65 mmol) is recommended. In the UK, the Food Standards Agency has entered into discussions with the food industry for the reduction of sodium in processed foods, and has embarked on a national advertising campaign highlighting the dangers of high sodium intake. Today, 45 years after Dahl's insightful observations on the key role of salt intake in the development of population high blood pressure, the public health message is clear.
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