Population Dietary Salt Reduction and the Risk of Cardiovascular Disease: A Commentary on Recent Evidence

Raised blood pressure (BP) is the leading cause of death and disability in adults worldwide, mainly due to cardiovascular disease (CVD). The risk of CVD increases progressively with increasing BP. However, the majority of CVD deaths and morbidity attributable to BP occur at a level around or below 140/90 mm Hg, because there are so many individuals in the population with BP below these levels. Based on recommendations from clinical guidelines, the majority of these individuals would not be treated with drugs. Furthermore, there is a graded relationship between BP and CVD down to at least 115/75 mm Hg. Therefore, a population-approach through nonpharmacological measures (diet and lifestyle) is the most feasible option to prevent BP-related adverse outcomes and is recommended by the World Health Organization and adopted under a United Nations resolution of the 66th World Health Assembly in 2013. High salt intake is associated with high BP and a moderate reduction in salt consumption causes a significant reduction in BP. Furthermore, in wellconducted cohort studies and in few intervention trials, lower salt consumption is associated with reduced cardiovascular events. A recent publication in The Lancet has reported that low salt intake is associated with a high risk of CVD. The paper methodology suffers from flaws that have been repeatedly addressed in the medical literature in recent years and that are ignored. First, the study reported in The Lancet used a morning spot urine sample to estimate usual salt intake. The use of sodium concentrations from a single morning urine fasting sample extrapolated to 24-hour urinary sodium excretion using the Kawasaki formula is an inappropriate method for estimating salt intake in individuals. The authors’ reference to their validation, critiqued at the time of its publication, neglects the presence of a significant bias when estimating individuals’ sodium excretion, as shown in the Bland-Altman plots, results superimposable to other validations. They also do not mention that a similar validation in the Chinese cohort of the Prospective Urban Rural Epidemiology (PURE) study presents the results with less confidence. The authors insist on the concept (uncritically repeated in the editorial) that the method could be useful to assess group means. However, they use data on individuals when assessing risk prediction in a cohort study design. This is misleading as it has been long established that several 24-hour urine collections are needed to approximate an individual’s salt intake with a high degree of confidence (ie, within 10%) and without bias. In contrast, cohort studies that use the method of repeated 24-hour urine collections to assess salt intake show beyond doubt a linear graded relationship between sodium excretion and cardiovascular outcomes with no increase at lower sodium intakes. Second, the present study is a republication of previous data from the Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial (ONTARGET) and Telmisartan Randomized Assessment Study in ACE Intolerant Subjects With Cardiovascular Disease (TRANSCEND) and from the PURE study, with the addition of EpiDREAM (study of screenees from the DREAM trial). Not surprising, the results in this “larger” sample are confirmatory of their previous results. There are several considerations to make. The authors split a continuously distributed biological variable in the population (BP) in a biological meaningless dichotomy of “hypertension” and “normotension.” By doing that, they reduced the statistical power of detecting relationships, particularly when studying trends. Similarly, in randomized controlled trials, salt reduction was shown not to impact cardiovascular events when dichotomized into hypertensive and normotensive categories but had a statistically significant impact on cardiovascular events in the studies overall. An important point is the consistent use of sick populations and patient groups to study the implications of a moderate reduction in salt consumption in the general population. The ONTARGET/TRANSCEND study selected 28,800 participants from a high-risk population to undergo randomized clinical trials of antihypertensive treatments. Patients were old (66.5 7.2 years, with patients 2.4 years older in the low sodium group), 71% were men of white European background (but the low sodium group included 54% women), all with significant previous disease (48% with myocardial infarctions, 21% cerebral vascular accidents, 70% hypertension, and 37% diabetes), and all highly medicated with b-blockers (57%), diuretics Address for correspondence: Francesco P. Cappuccio, MD, University of Warwick, Warwick Medical School, Gibbet Hill Road, Coventry, CV4 7LA, UK E-mail: f.p.cappuccio@warwick.ac.uk