- Lawrence J Appel, professor of medicine, epidemiology, and international health (human nutrition)
- 1Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins University, 2024 East Monument Street, Suite 2-618, Baltimore, MD 21205-2223, USA
Excess intake of salt (sodium chloride) has an important and probably predominant role in the pathogenesis of raised blood pressure. The evidence is indisputable—on average, as salt intake increases, blood pressure increases. Animal studies, migration studies, ecological studies, longitudinal observational studies, clinical trials, and meta-analyses of trials have confirmed this association.1 The importance of this association cannot be overstated—blood pressure is an aetiologically relevant and modifiable cardiovascular risk factor, which has guided policy makers for decades.
Worldwide, raised blood pressure accounts for around 62% of strokes and 49% of coronary heart disease events.2 Large scale trials and meta-analyses of trials have conclusively shown that several treatments that reduce blood pressure prevent stroke and coronary heart disease.3 This compelling evidence has led numerous authoritative bodies to conclude that salt reduction, through its effects on blood pressure, should also prevent stroke and coronary heart disease. Direct evidence to support calls for salt reduction has been limited, however, so the linked meta-analysis of cohort studies by Strazzullo and colleagues (doi:10.1136/bmj.b4567) is a useful and welcome addition to the medical literature.4
The projected benefits of salt reduction are substantial. Several studies have estimated the societal benefits of population-wide salt reduction. Asaria and colleagues estimated that across 23 countries with a high burden of chronic disease, 850 000 lives would be saved each year from a reduction in salt intake to 5 g a day, the recommended limit set by the World Health Organization.5 In a recent analysis, reducing average sodium intake to the upper limit of recommended intake in the United States (5.8 g a day of salt, equivalent to 100 mmol a day or 2300 mg a day of sodium) should reduce the prevalence of hypertension by 11 million, save $18bn (£10.8bn; €12bn) in healthcare costs, and gain 312 000 quality adjusted life years.6 Nonetheless, this line of reasoning is indirect. Salt reduction lowers blood pressure (this has been proved), and lowering blood pressure prevents cardiovascular events (so has this).
Evidence of a direct association between salt intake and cardiovascular disease in humans has been sparse, however, owing largely to methodological challenges in conducting appropriate studies. Direct evidence has come from the results of clinical trials and prospective observational studies with cardiovascular disease events as outcomes. To date, three trials conducted in general populations have reported the effects of reduced sodium interventions on such outcomes. Two of these trials tested lifestyle interventions that focused on reducing salt intake,7 8 and one trial tested the effects of reduced sodium salt that is high in potassium.9 In each instance, clinically important cardiovascular disease events were reduced by 21-41% in people who received an intervention to reduce sodium intake (significant reduction in two trials,8 9 non-significant trend in the third7). Hence, direct evidence from trials, albeit limited, is consistent with indirect evidence on the health benefits of salt reduction.
The most perplexing body of evidence on the health effects of dietary salt intake comes from prospective observational studies that relate estimated salt intake to subsequent stroke and cardiovascular disease. A host of methodological problems plague this literature. Major concerns are random and systematic errors in the measurement of dietary salt intake. Because of large day to day variation in salt consumption, imprecise and inaccurate measurement techniques, and incomplete assessment of dietary intake, results from prospective observational studies have been inconsistent and occasionally paradoxical.
In this setting, the meta-analysis by Strazzullo and colleagues is a useful and welcome addition to the medical literature.4 In their analysis of 13 cohort studies with 19 independent samples, a higher salt intake was associated with an increased risk of stroke, and, probably, cardiovascular disease. Specifically, an 86 mmol/day increase in sodium intake (~5 g a day of salt) was associated with a 23% higher risk of stroke (P=0.007). The association between cardiovascular disease and salt intake was of borderline significance (14% greater risk of cardiovascular disease, P=0.07). However, in sensitivity analyses that excluded one study with particularly unreliable estimates of sodium intake, the corresponding effect size was 17%, and the association was significant (P=0.02).
The disparate and often poor quality of measurements of dietary salt probably contributed to the significant heterogeneity in the study results seen by Strazzullo and colleagues. The gold standard to assess dietary salt intake is urinary excretion of sodium, as assessed from multiple complete 24 hour urine collections. Yet in only four of the 13 studies were 24 hour urine samples collected, and in none of these studies was more than one collection obtained. More importantly, several studies had evidence of substantial non-systematic under-reporting of salt intake,10 11 12 and most other studies provided no data on the completeness of dietary assessment.
Policy makers have previously dismissed the results from prospective observational studies in favour of the considerably more robust body of evidence that links salt intake with blood pressure. At a minimum, Strazzullo and colleagues’ analyses should dispel any residual belief that salt reduction might be harmful (a canard resulting from misinterpretation of studies, often with flawed analyses). The case for population-wide salt reduction is now stronger. A reduced intake of salt not only lowers blood pressure but also prevents its major sequelae—stroke and other cardiovascular diseases.
Cite this as: BMJ 2009;339:b4980
Competing interests: The author has completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and has (1) No financial support for the submitted work from anyone other than his employer; (2) No financial relationships with commercial entities that might have an interest in the submitted work; (3) No spouses, partners, or children with relationships with commercial entities that might have an interest in the submitted work; (4) No Non-financial interests that may be relevant to the submitted work.”
Provenance and peer review: Commissioned; not externally peer reviewed.