Re: Effect of longer term modest salt reduction on blood pressure: Cochrane systematic review and meta-analysis of randomised trials
Graudal and Jürgens claim that our meta-analysis (1) is similar to theirs (2), however, this claim is wrong. Graudal and colleagues’s meta-analysis included a large number of metabolic studies with many trials having a duration of only 5 days and the median duration of all of the studies in the normotensives was only 7 days. In addition, they included salt-loading trials where very large amounts of salt had been given, e.g. up to 20 g/d and then reduced suddenly to less than 1 g/d for only 5 days. These short-term metabolic studies are completely irrelevant to the public health recommendations for longer-term modest reductions in salt intake, yet Graudal and colleagues persist in drawing public health conclusions about the benefits of population salt reduction from these types of studies. Salt reduction, like blood pressure lowering drugs, takes time to work and all drug regulatory agencies require evidence that, for drugs lowering blood pressure, the trials must be for a month or ideally longer. It is well established that diuretics, which work in a similar way to salt restriction, take at least a month or longer, to have a maximum blood pressure lowering effect.
Our meta-analysis, in contrast to Graudal’s, only included trials with a modest reduction in salt intake for at least 4 weeks, and is of public health relevance. These longer term modest reductions in salt intake of the same amount as the public health recommendations do lower blood pressure significantly in both hypertensive and normotensive individuals by amounts that are of great public health importance, given that blood pressure is the single biggest cause of death in the world (3,4). The risks start at blood pressure of 115/75 mmHg (5) (i.e. over 80% of the UK adult population have blood pressure above this level). Our meta-analysis also showed that the greater the reduction in salt intake the greater the fall in blood pressure.
Our current meta-analysis (1) also has the following new findings: (a) 68% of the variance of the change in systolic blood pressure could be explained by four variables, i.e. age, ethnic group, blood pressure levels and the change in 24 hour urinary sodium; (b) the effects of salt reduction on systolic blood pressure are significant in both whites and blacks, men and women; (c) with a longer-term modest reduction in salt intake, there is only a small physiological increase in plasma renin activity, aldosterone and noradrenaline. There is no significant change in adrenaline, cholesterol, low-density lipoprotein, high-density lipoprotein or triglycerides. In our view, the results of our meta-analysis provide strong further support for a reduction in population salt intake, which will lower population blood pressure and, therefore, reduce strokes, heart attacks and heart failure.
Graudal and Jürgens tried to imply that an increase in plasma renin activity and aldosterone with salt restriction is harmful. They do not seem to be aware that there is a reciprocal relationship between sodium balance and the renin-angiotensin-aldosterone system, and that with long term modest reductions in salt intake there are only very small increases in plasma renin activity and aldosterone, and this is an entirely normal physiological response to the changes in sodium balance. Indeed diuretics, which cause a small loss of sodium from the body and a reduction in sodium balance, also cause increases in plasma renin activity, angiotensin II and aldosterone, to a much greater extent than modest salt reduction. Diuretics have been demonstrated in outcome trials to reduce cardiovascular disease mortality in individuals with raised blood pressure (6).
Graudal and Jürgens also imply that salt reduction has deleterious effects on sympathetic activity, but this only occurs when there are sudden large changes in salt intake and, thereby, large changes in extracellular volume. It does not occur with modest salt reduction over a long period of time (7).
Graudal and Jürgens claim that salt reduction has adverse effects on blood lipids (2). However, these changes only occurred in their meta-analysis with acute and large reductions in salt intake, where there is a contraction in plasma volume and, thereby, a small increase in the concentration of lipids. Our meta-analysis clearly demonstrated that there were no significant changes in lipid levels (1). Indeed, Graudal and Jürgens’s own meta-analysis, when they only considered studies of more than 4 weeks, showed no significant change in lipids, although in their paper they tried to imply that these were of borderline significance, which they were not.
Graudal and Jürgens continue to believe that there is a J-shaped association between salt intake and mortality. However, close examination of these studies shows that nearly all of them were done in patients who had severe cardiovascular disease or other diseases and were on multiple drug therapy. A careful analysis by the American Heart Association (8) concluded that these studies have many methodological flaws e.g. measurement error in assessing daily salt intake such as the use of spot urines which are notoriously inaccurate in measuring salt intake, other confounding factors not controlled for, and reverse causality, i.e. patients who are ill do not eat as much and therefore have a lower salt intake, but because of their illness, they are more likely to die.
Finally, Graudal and Jürgens make the astonishing claim that the benefits of salt reduction on cardiovascular disease is based on "unproven blood pressure hypothesis". This claim is incorrect. Firstly, blood pressure throughout the range starting from 115/75 mmHg is a major cause of cardiovascular disease (5), responsible for 62% of all strokes and 49% of coronary heart disease (9). Secondly, there is evidence from both prospective cohort studies (10) and, importantly, outcome trials (11) that a lower salt intake is related to a reduced risk of cardiovascular disease. For example, a recent meta-analysis of outcome trials demonstrated a significant reduction in cardiovascular events by 20% (P<0.05) in spite of only a small reduction in salt intake of 2.0-2.3 g/d (11). Unsurprisingly, Graudal and Jürgens choose to ignore such evidence.
The totality of evidence for a causal relationship of chronic high salt intake with raised blood pressure and cardiovascular disease is very strong (12). The question now is not ‘should’ we reduce salt intake, but ‘how’ to do it. Many countries are now adopting a policy of reducing salt intake, and indeed the UK is leading the world with a structured, coherent salt reduction policy by getting the food industry to slowly take out the excessive amounts of salt in food. A reduction in population salt intake will have major beneficial effects, firstly by reducing blood pressure in the whole population (1,13) and by reducing cancer of the stomach (14), and it is likely that it will have a beneficial effect on bone demineralisation (15,16). Many studies have demonstrated major cost savings in all countries around the world with salt reduction (17-19). Indeed, it is one of the most cost-effective public health policies.
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19. National Institute for Health and Clinical Excellence (NICE). Guidance on the prevention of cardiovascular disease at the population level. http://guidance.nice.org.uk/PH25.
Competing interests: Feng He is a member of Consensus Action on Salt & Health (CASH) and World Action on Salt & Health (WASH). Both CASH and WASH are nonprofit charitable organisations and Feng He does not receive any financial support from CASH or WASH. Graham MacGregor is board member of World Hypertension League (WHL), Chairman of Blood Pressure Association (BPA), Chairman of Consensus Action on Salt & Health (CASH) and Chairman of World Action on Salt & Health (WASH). WHL, BPA, CASH and WASH are nonprofit charitable organisations. Graham MacGregor does not receive any financial support from any of these organisations.