Tulane University, School of Public Health and Tropical Medicine and School of Medicine, New Orleans, LA, USA.
Jiang He, Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, 1430 Tulane Avenue, SL 18, New Orleans, LA 70112, USA. E-mail: jhe{at}tulane.edu
Accepted 22 November 2001
Hence if too much salt is used for food, the pulse hardens ...
Huang Ti Nei Ching Su Wen, 26982598 BC (the Yellow Emperor's classic on internal medicine).
Although ancient Chinese medical literaturethe Yellow Emperor's classic on internal medicinereported that a high intake of dietary salt (sodium chloride) might produce a hardened pulse nearly 5000 years ago, the first meaningful scientific evidence for a positive association between salt consumption and level of blood pressure was published by Dahl in 1960.1 Dahl described a remarkable linear relationship between average sodium intake and prevalence of hypertension across five population groups.1 Since then, abundant evidence of a causal association between dietary sodium intake and high blood pressure has emerged from animal experiments and from observational epidemiological studies and randomized controlled clinical trials.2,3
Animal Experiments
Studies in a variety of laboratory animals have demonstrated that a high dietary intake of salt results in hypertension.4 Recently, Denton et al. reported the findings of a 3-year experiment conducted in 26 chimpanzees with a baseline diet which was very low in sodium and high in potassium content.5 Following a year of baseline observations, salt was added to the diet of 13 animals in increasing amounts (5 g/day for 19 weeks, 10 g/day for 3 weeks, and then 15 g/day for 67 weeks) during an 89-week period of active intervention. Dietary intake of salt remained unaltered in the other 13 control animals. The average level of blood pressure did not change significantly during the intervention phase in the control group. However, in the 13 animals assigned to the active intervention mean systolic blood pressure (SBP) increased by 12 mmHg compared to the corresponding baseline level (P < 0.05) after the first 19 weeks of supplementary salt intake (5 g/day). Following the 39 weeks of supplementation with 10 g/day salt (3 weeks) and 15 g/day salt (36 weeks), mean SBP was increased by 26 mmHg (P < 0.001) and mean diastolic blood pressure (DBP) was increased by 5 mmHg (P > 0.05). Following a further 26 weeks of supplementation with 15 g of salt/day (a total of 84 weeks of supplementation with dietary salt), mean SBP was increased by 33 mmHg (P < 0.001) and DBP was increased by 10 mmHg (P < 0.01). Twenty weeks after the end of the period of salt addition, the animals' average level of blood pressure returned its baseline level. This experiment, conducted in the species that is phylogenetically closest to humans, provides direct evidence in favour of a causal relationship between high salt intake and hypertension.5
Observational Epidemiological Studies
Studies in low blood pressure populations and in migrants from these societies to more westernized environments provide strong evidence for a causal relationship between high salt intake and hypertension. More than 30 populations with an average blood pressure that is lower than in westernized societies and in whom blood pressure does not rise or rises very little with age, and hypertension is virtually absent, have been reported in the scientific literature.6,7 Typically, these populations live in fairly isolated settings, eat unprocessed foods, are lean, physical active, and consume less dietary sodium than their counterparts in westernized societies.6,7 Migration from relatively isolated societies to more westernized environments has been associated with an increase in the average level of blood pressure, a steeper slope of blood pressure with increasing age and a higher prevalence of hypertension.6,7 We examined the effect of lifestyle change including dietary sodium intake on blood pressure in the Yi people, an ethnic minority group in Southwestern China.7,8 Blood pressure rose very little with increasing age after puberty in the Yi farmers who lived in their natural environment in remote mountainous areas and consumed a diet low in sodium content. In contrast, Yi migrants and Han people who lived in urban areas consumed a diet which was higher in sodium content and experienced a much greater increase in blood pressure with progressive ageing.7,8 In a sample of 417 men, we documented a positive relationship between sodium intake and higher blood pressure and also demonstrated the importance of other factors, such as increasing body mass index, in the higher prevalence of hypertension. These findings suggest that changes in lifestyle, including a higher intake of dietary sodium, contribute to the higher blood pressure among Yi migrants.8
INTERSALT, a cross-sectional study of 10 074 participants from 52 populations in 32 countries reported a strong, positive association between urinary sodium excretion and blood pressure.9 In within-population analyses, after adjustment for age and sex and correction for regression dilution bias, a 100 mmol higher 24-hour urinary sodium was associated with a 4.3 mmHg higher SBP and a 1.8 mmHg higher DBP. After additional adjustment for 24-hour urinary potassium and alcohol intake, the corresponding differences in SBP and DBP were 6.0 and 2.5 mmHg, respectively. After further adjustment for body mass index, the differences in blood pressure were 3.1 mmHg for SBP and 0.1 mmHg for DBP. Estimates of the association were larger for older compared to younger participants. In cross-population analyses, a 100 mmol higher 24-hour urinary sodium was associated with a 4.5 mmHg higher SBP and 2.3 mmHg higher DBP after adjustment for several important potential confounding variables.9 These estimates of the association between sodium intake and blood pressure are similar to those for the same age groups published in a meta-analysis of data from studies other than INTERSALT.10,11
Randomized Controlled Trials
Randomized controlled clinical trials provide unbiased evidence for a causal relationship between dietary sodium intake and blood pressure. During the past 30 years, more than 80 randomized controlled trials have been conducted to explore the efficacy and effectiveness of changes in sodium consumption on blood pressure in hypertensive and normotensive participants.1214 The findings from these trials have been summarized in three recent meta-analyses.1214 There were differences in the eligibility criteria and statistical methods employed in the three meta-analyses but in each case a reduced intake of dietary sodium was associated with a significant diminution in blood pressure. As expected, the effect was smaller in normotensive people compared to hypertensive patients. For example, compared to the control group, the reported mean reduction in blood pressure was 3.9 to 5.9 mmHg for SBP and 1.9 to 3.8 mmHg for DBP in hypertensives; 1.2 to 1.9 mmHg for SBP and 0.3 to 1.1 mmHg for DBP in normotensives.1214 Despite differences in study design, sample size, participant characteristics, initial level of blood pressure, and baseline dietary sodium intake among the trials, a significant dose-response relationship between net change in urinary sodium and net change in blood pressure was detected in both the hypertensive and normotensive trials.12,13
Several recently published trials which were not included in these meta-analyses deserve mention.1517 The Trial of Nonpharmacologic Interventions in the Elderly (TONE) was a randomized controlled trial designed to determine whether weight loss and/or a reduction in dietary sodium intake enhance blood pressure control and reduce the need for antihypertensive drug therapy in older people with hypertension. The trial was conducted in 975 hypertensives, aged 6080 years, with baseline SBP <145 mmHg and DBP <85 mmHg on one antihypertensive medication.15 Using a factorial design, those meeting the National Center for Health Statistics criteria for overweight were randomly assigned to either counselling aimed at a reduction in sodium consumption, weight loss, combined sodium reduction and weight loss, or usual care. Those who were in the normal weight category were randomly assigned to either counselling aimed at sodium reduction or usual care. Those assigned to usual care received counselling in health-related topics remote to the goals of the trial but had the same investigator contact schedule as their counterparts who were assigned to the sodium reduction and/or weight loss counselling intervention arms. Mean 24-hour urinary sodium excretion was reduced by 40 mmol in those assigned to counselling in sodium reduction (alone) and by 24 mmol for those assigned to counselling in the combination of sodium reduction and weight loss. Prior to attempting tapering or withdrawal of antihypertensive medication a significant reduction in blood pressure was noted in those assigned to the active intervention groups compared to their counterparts in the usual care group. For example, average SBP in those assigned to counselling in sodium reduction alone was further reduced by 3.4 mmHg compared to the corresponding value in the usual care group. After 30 months, the per cent of participants who were free of an endpoint (blood pressure >150/90 mmHg, resumption of antihypertensive medication, or a blood pressure-related clinical complication) was 38% in those assigned to counselling in sodium reduction versus 24% in those assigned to usual care (P < 0.001). Cappuccio and colleagues conducted a double-blind crossover trial, in which 47 untreated elderly people (age range: 6078 years, blood pressure range: 123205/64112 mmHg) were randomly assigned to a usual salt intake (10 g/day) or modestly reduced dietary salt intake (5 g/day) group for a 2-month period.16 In this trial, a reduction in sodium intake of 83 mmol/day was significantly associated with a reduction of 7.2 mmHg in SBP and 3.2 mmHg in DBP. In the DASH-Sodium trial conducted in 412 people with average SBP of 120159 mmHg and average DBP of 8095 mmHg, reduction in sodium intake from a high (142 mmol/day) to an intermediate (107 mmol/day) level reduced SBP by 2.1 mmHg (P < 0.001) during consumption of a usual American control diet and by 1.3 mmHg (P = 0.03) during consumption of a DASH diet which was high in fruits and vegetables as well as low in dairy fat products.17 Reducing sodium intake from the intermediate to a lower level (65 mmol/day) resulted in an additional reduction in SBP of 4.6 mmHg during consumption of the control diet (P < 0.001) and 1.7 mmHg during consumption of the DASH diet (P < 0.01). Compared to the combination of the control diet and a high level of sodium, the combination of the DASH diet and a low level of sodium resulted in an average reduction in SBP of 11.5 mmHg in hypertensive patients and 7.1 mmHg in normotensives.17 These findings are consistent with the current US national recommendations for consumption of a moderately low intake of dietary sodium (<2400 mg or <100 mmol sodium per day) by all Americans18 and suggest that a lower level of dietary sodium intake might result in an even greater reduction in blood pressure.
Sodium Sensitivity
The magnitude of the blood pressure reduction resulting from a lowering of dietary sodium varies among different population subgroups. The proportion of salt-sensitive and salt-resistant individuals has varied from one study to another based on the definition of salt-sensitivity and the methods used to assess its presence or absence.19 Both genetic and environmental factors may play an important role in determining salt-sensitivity.19,20 Results from several prospective cohort studies have suggested that salt-sensitivity increases the risk of cardiovascular disease and all-cause morality.21,22 Morimoto and colleagues followed 62 salt sensitive hypertensive patients and 94 non-salt sensitive patients for an average of 7.3 years.21 Salt-sensitivity was defined as a difference of more than 10% in mean blood pressure between a lower-salt (13 g sodium chloride per day) and higher-salt (1215 g sodium chloride per day) diet. Salt-sensitivity was associated with 3-fold increase (RR = 3.05; 95% CI : 1.346.89) in the risk of cardiovascular disease.21 Weinberger et al. followed a cohort of 278 hypertensive and 430 normotensive participants for up to 27 years.22 Salt-sensitivity, determined at baseline by an individual's blood pressure response to sodium loading and depletion, was associated with a 73% increase (RR = 1.73; 95% CI : 1.022.94) in all-cause mortality.22 Due to the technical difficulties of performing such studies, population-based investigations to assess the frequency of salt-sensitivity in the general population have not been conducted. Based on the available data, however, a majority of hypertensive and normotensive people respond to sodium reduction. Therefore, one could expect that salt-sensitivity is a common phenomenon in human populations.
Salt Intake and the Risk of Cardiovascular Disease
Two studies published by the same investigative team have been cited as providing evidence for an adverse effect of low sodium diet on human health.23,24 In the first of these studies, Alderman and colleagues reported the presence of a significant inverse association between urinary sodium excretion and incidence of myocardial infarction in a prospective cohort study conducted in 2937 treated hypertensive patients.23 As indicated in an accompanying editorial and in subsequent letters to the editor,25,26 however, unmeasured variables and imprecision in the measurement of potentially confounding variables might have contributed to the occurrence of this unexpected finding. In addition, urinary sodium excretion was measured after 5 days of reduced dietary sodium intake. This is likely to have resulted in an invalid assessment of an individual's habitual intake of dietary sodium. Finally, the study was conducted in hypertensive patients who were enrolled in a work-site treatment programme making it difficult to know whether the findings have general application. Given these and other considerations, we agree with others that the findings in this study are difficult, if not impossible to interpret.25,26 In a second study, Alderman and colleagues examined the relationship between dietary sodium intake and mortality from cardiovascular disease and all causes in the National Health and Nutrition Examination Survey I Epidemiologic Follow-up Study.24 They identified an inverse relationship between sodium intake and mortality from cardiovascular disease (P = 0.09) and all causes (P < 0.007) and a positive relationship between sodium/calorie ratio and mortality from cardiovascular diseases (P = 0.006) and all causes (P < 0.001). Again, however, methodological concerns make it difficult to interpret the findings in this study. For instance, the authors did not exclude participants with a baseline history of cardiovascular diseases in their main analysis, albeit such participants might be expected to have changed their dietary intake of sodium. In addition, they did not exclude participants who were already on a low sodium diet due to their health concerns at baseline. Acute rheumatic fever, chronic rheumatic heart disease and diseases of the pulmonary circulation were included as cardiovascular disease mortality outcomes although there is no obvious biological basis for a relationship between sodium intake and these outcomes. Perhaps of greatest concern is the fact that they included sodium intake, caloric intake, and sodium/calorie ratio as continuous variables in the same multivariate model. Given that an interaction term was included in their analysis model, it is not possible to interpret the main effect of sodium intake alone on the outcomes of interest. The inconsistency of the association between the two indicators of sodium intake (sodium alone and sodium/calorie ratio) and the corresponding outcomes of interest in Alderman's study might reflect the heterogeneity of this relationship in a study population with different body weights.
In an independent examination of data from the National Health and Nutrition Examination Survey I Epidemiologic Follow-up Study, we found a consistent and positive relationship between dietary sodium intake and risk of cardiovascular diseases and total mortality in overweight people.27 For an average caloric intake, a 100 mmol higher intake of dietary sodium was associated with a 32% increase (RR = 1.32; 95% CI : 1.071.64) in stroke incidence, an 89% increase (RR = 1.89; 95% CI : 1.312.74) in stroke mortality, a 44% increase (RR = 1.44; 95% CI : 1.14 1.81) in coronary heart disease mortality, a 61% increase (RR = 1.61; 95% CI : 1.321.96) in cardiovascular disease mortality, and a 39% increase (RR = 1.39; 95% CI : 1.231.58) in mortality from all causes in the overweight. Dietary sodium intake was not significantly associated with risk of cardiovascular disease in participants with a normal weight. In a recently published prospective cohort study conducted in 1173 Finnish men and 1263 women aged 2564 years, the hazard ratios for coronary heart disease, cardiovascular disease, and all-cause mortality, associated with a 100 mmol higher level of 24-hour urinary sodium excretion, were 1.51 (95% CI : 1.142.00), 1.45 (95% CI : 1.141.84), and 1.26 (95% CI : 1.061.50), respectively.28 There was a significant interaction between sodium excretion and body mass index for cardiovascular and total mortality, with sodium intake being a significant predictor of mortality in men who were overweight. These data support the premise that a lower intake of dietary sodium reduces the risk of subsequent cardiovascular disease, especially in those who are also concurrently overweight.
Public Health Implications of Reducing Dietary Salt
An intervention to lower blood pressure in the general population should not only result in a substantial reduction in the prevalence of hypertension but also a large decrease in cardiovascular risk. Cook and colleagues examined the potential impact of a population-wide reduction in blood pressure using data from the Framingham Heart Study and the National Health and Nutrition Examination Survey II.29 According to their estimates, a population-wide reduction in DBP of as little as 2 mmHg should result in a 17% reduction in the prevalence of hypertension, a 15% reduction in the risk of stroke and transient ischaemic attack and a 6% reduction in the risk of coronary heart disease.29 Further, they estimated that this blood pressure reduction should prevent 93% of the strokes and transient ischaemic attacks, as well as 100% of the incident coronary heart disease events that could be prevented by treatment of all hypertensive patients with antihypertensive drug therapy.29 The results underscore the potential value of complementing traditional hypertension detection and treatment approaches with public health interventions aimed at achieving a slight downward shift in the blood pressure of the general population.30
Conclusion
Evidence from animal experiments, observational studies, and randomized controlled trials provide overwhelming support for a causal relationship between dietary sodium intake and elevated blood pressure. Three large meta-analyses have provided consistent evidence of blood pressure lowering following a reduction in dietary sodium intake.1214 In addition, results from the large TONE and DASH community-based trials and a recent trial by Cappuccio et al., provide additional confirmation that sodium reduction significantly lowers blood pressure in both hypertensive and normotensive populations.1517 Recent prospective cohort studies indicate that a high dietary intake of salt increases the risk of cardiovascular disease.28,29 The increasingly strong body of scientific evidence related to the relationship between dietary sodium and cardiovascular disease should lay to rest the long-standing controversy over whether sodium reduction lowers blood pressure and improves cardiovascular health in general population.
References
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9
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17
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27
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