| Introduction |
Recommendations to curtail sodium intake are based on the
observation that blood pressure levels in some people fall with a
reduction of 70-100 mmol/day in sodium intake.12 As lowering
blood pressure with drugs prevents cardiovascular events, it has
seemed reasonable to recommend that sodium intake, generally about
150 mmol/day, be restricted to less than 100 mmol/day.
However, we contend that no empirical data support the health value of
this logically appealing strategy, and, moreover, that a reduction
in dietary sodium has other effects which may cancel out its
beneficial blood pressure lowering effects. The most important of
these is an increase in plasma renin activity. As long ago as 1972, John
Laragh's group suggested,13 and subsequently
demonstrated,14 that plasma renin
activity is directly related to the occurrence of cardiovascular
events. The presumption is that this occurs through the generation of
angiotensin II. Angiotensin II levels are mediated by sodium intake,
and increase as sodium levels decrease. The interrelationship of
angiotensin II and sodium homoeostasis is shown in the Figure.
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Angiotensin II and cardiovascular events |
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It has been established that high blood pressure causes disability
and death through vascular damage. While the mechanical effects of
blood pressure must play a part, the same elevated blood pressure
level in different individuals can produce remarkably different
blood vessel lesions, ranging from vessels that are almost normal to
those with fibrinoid necrosis.15 This disparity suggests
that some factor other than blood pressure might be involved in the
vascular damage seen in hypertensive subjects,15 and
angiotensin II, perhaps acting with other vasoconstrictors such as
noradrenalin, is a favoured candidate.
Angiotensin II is atherogenic, causes endothelial damage, promotes
smooth muscle proliferation and increases medial thickness in
resistance vessels (arterioles).16,17 Some of these adverse
vascular effects can be reversed in humans by taking
angiotensin-converting enzyme inhibitors.18,19
The importance of angiotensin II in severe vessel damage was
emphasised by the animal experiments of Mohring et al,20 who
demonstrated that the syndrome and the vascular lesions of malignant
hypertension were reversed in rats that selected saline to drink
instead of water. This suppressed their high plasma angiotensin II
levels, and reversal of the features of malignant hypertension
occurred in spite of continuing very high blood pressure levels.
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Effects of sodium restriction |
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The various effects of sodium restriction have been studied in 83
randomised trials.12 A meta-analysis of these
trials (data from 1966 to 1997) by Graudal et al confirmed that a mean
reduction of 118 mmol/day in sodium intake caused a modest blood
pressure reduction (systolic/diastolic blood pressure 3.9/1.9
mmHg lower in hypertensive and 1.2/0.26 mmHg lower in
normotensive subjects).12 At the same time,
significantly increased levels of aldosterone, noradrenalin,
total and low density lipoprotein cholesterol, and triglycerides
were documented, as well as increased plasma renin activity. A
decrease in sodium intake of this magnitude (almost certainly more
than 50% of daily sodium intake) was found to generate a 3.6-fold
increase in plasma renin levels. A study by Alderman et al which linked
plasma renin activity to myocardial infarction in hypertensive
patients found that:21
- After controlling for other known cardiovascular risk factors each
increase in renin level of 2 ng/mL per hour was associated with a 25%
increase in the incidence of infarction.
- The mean plasma renin activity was 2.6 ng/mL per hour for whites and
1.5 ng/mL per hour for African Americans, who sustained fewer
infarctions.
Applying the results of Alderman et al to the plasma renin activity
increases reported in the meta-analysis by Graudal et al12 suggests that
the subjects with reduced sodium intake would have average plasma
renin activity increases of more than 4 ng/mL per hour, raising the
possibility of a 50% increase in vascular events.
Clearly, no evidence yet confirms the strong possibility that renin
has a causative role in myocardial infarction. Nevertheless,
clinical trial data consistently demonstrate the powerful
cardioprotective effect of blockade of the renin-angiotensin
system. Thus, if increased renin, and the associated angiotensin II
elevation, does have adverse cardiac consequences, it seems
reasonable to consider the possibility that this effect will swamp
the potential benefit associated with the modest blood pressure fall
produced by salt restriction. This, of course, does not take into
account the potential adverse effects of the associated increased
levels of aldosterone, noradrenalin, low density lipoprotein
cholesterol, total cholesterol and triglycerides with sodium
restriction.
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Net effect of sodium restriction |
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The issue, therefore, is the net effect of the beneficial and adverse
consequences of a sodium-restricted diet. A randomised controlled
clinical endpoints trial could resolve this question.
Unfortunately, few data associate sodium intake and health outcomes
measured by morbidity and mortality. In a treated hypertensive
population, 24-hour urinary sodium excretion, measured once at
baseline, was inversely associated with cardiovascular morbidity
and mortality.22 This association was
significant, continuous and independent of other known
cardiovascular risk factors. Among the 12 000 participants who were
followed up for 20 years in the first National Health and Nutrition
Examination Survey (NHANES I),6 sodium intake, estimated
from a single 24-hour dietary recall, was inversely associated with
all-cause and cardiovascular mortality. In this representative
sample of the non-institutionalised US population, the quarter of
subjects consuming the least sodium were roughly 20% more likely to
die than the quarter ingesting the most sodium. Finally, in the
Scottish Heart Health Study,23 sodium intake also had a
non-significant, but inverse, relation to mortality in men. By
contrast, no observational data suggest that consumption of a
low-sodium diet is associated with a longer or healthier life.
In the absence of evidence of benefit, and with reasonable concern
about safety because of effects on plasma renin activity,
noradrenalin and lipids, we contend that prudence dictates avoiding
any universal recommendation regarding sodium intake at this time.
Any future recommendation should be based upon compelling evidence
that a lower sodium intake is both associated with a health benefit and
free of safety concerns.
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Conflict of interest |
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None. We do not have any connection with or receive funds from the food
and salt industries or any related commercial interests.
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| Authors' details |
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Department of Pathology, University of Melbourne, Melbourne, VIC.
Priscilla Kincaid-Smith, AC, CBE, DSc, MD, FRACP, Emeritus
Professor.
Albert Einstein College of Medicine, Bronx, New York, NY.
Michael H Alderman, MD, Professor of Medicine and
Epidemiology and Social Medicine.
Reprints will not be available from the author.
Correspondence:
Professor P Kincaid-Smith, Department of Pathology, University of
Melbourne, Parkville, VIC 3052.
©MJA 1998
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The 100-year conflict: Introduction