Download Dietary Salt and Blood Pressure

1-97
Dietary Salt and Blood Pressure
A Perspective
Mark S. Pecker and John H. Laragh
Downloaded from http://hyper.ahajournals.org/ by guest on June 17, 2017
Although dietary salt restriction is often valuable as sole or adjunctive therapy of hypertensive
disorders, it is abundantly clear that hypertensive patients comprise a heterogeneous group
with regard to salt sensitivity of blood pressure. This is apparent despite the many methodological obstacles to defining salt sensitivity in an individual patient Currently, dietary trial is
the only sure means of defining a given patient as responsive to salt restriction. Easily definable
markers of salt sensitivity would allow appropriate targeting of this rather ponderous therapy.
Promising leads include the assessment of membrane ion transporters such as sodium-lithium
exchange and of the activity of the renin-angiotensin system, including the phenomenon of
"non-modulating" hypertension and other volume regulatory hormones such as atrial natriuretic factor. Although less intensively studied than in hypertensive patients, the blood pressure
response of normal subjects to salt restriction is also marked by great variability. Given the
possibility of deleterious consequences of population-wide salt restriction for at least some
people in a setting such as the United States, it seems imprudent to recommend such a policy
before its proven worth has been demonstrated by clinical trial. Pending such evidence and the
development of markers, salt restriction should be reserved for those in whom it is of
demonstrated efficacy. {Hypertension 1991;17[suppl I]:I-97-I-99)
S
ince the introduction of dietary sodium chloride restriction as a therapy of essential hypertension, it has been recognized that hypertensive patients comprise a heterogeneous group
with regard to the property of salt sensitivity of blood
pressure,1-2 a fact amply borne out by animal models
of hypertension.1 The basis of this heterogeneity
among patients with essential hypertension is poorly
understood, and we have only a limited ability to
select salt-sensitive and salt-resistant individuals
without rigorous clinical trial. The definition of salt
sensitivity itself is not clear and may be different for
different purposes. As with blood pressure in the
general population, the distribution of changes in
blood pressure with changes in dietary salt, while
markedly skewed, is not bimodal, and any cutoff
criterion must be dictated by other than physiological
considerations. It is also not clear whether denning
salt sensitivity in short-term studies identifies the
same subjects as those who are responders to longterm therapy. Given the methodological difficulties
of definition and the biases inherent in the selection
of subjects for study combined with the intrinsic
heterogeneity of essential hypertension, it becomes
quite difficult to ascertain the incidence of this phe-
Frora the Hypertension Center, Cornell University Medical
College, New York, N.Y.
Address for correspondence: Mark S. Pecker, MD, Hypertension Center, Cornell University Medical College, New York, NY
10021.
nomenon in the general hypertensive or normotensive population.
A universally acceptable definition, together with
the development of markers of this phenomenon,
would be of great value not only for targeting this
rather ponderous diet therapy but also for obtaining
pathophysiological insight into its mechanisms.
Among the potential markers with some promise are
those evaluations of the renin-angiotensin-aldosterone system that define low renin hypertension,34
perhaps including plasma prorenin levels as an additional, more reliable indicator,5 or non-modulating
hypertension.6 Atrial natriuretic factor is part of a
volume-sensing and volume-regulating hormonal system whose assessment may also provide an indicator
of salt sensitivity.5'7 Assessment of the activity of ion
transport systems is another area of research that
may prove useful in identifying salt-sensitive people.
Of these, sodium-lithium exchange activity seems to
be promising, and importantly is not dependent on
salt intake (A. Weder, personal communication, December 1989).
The existence of significant salt sensitivity among
normal subjects, short of the extremes of shock with
volume depletion and toxic levels of salt, is uncertain.
Intervention studies of normal subjects show variable, usually small changes in blood pressure with
some experiencing a decline and others a rise.8 The
reproducibility of these changes in a given individual
is uncertain, and some of the changes may reflect
1-98
Supplement I
Hypertension
Vol 17, No 1, January 1991
Downloaded from http://hyper.ahajournals.org/ by guest on June 17, 2017
variability of blood pressure. However, several studies show that changes in blood pressure in both
directions exist even with intra-arterial monitoring
under controlled circumstances,9 suggesting that
both pressor and depressor responses to short-term
(1-2 weeks) salt loading indeed occur in normotensive subjects. Beyond individual variability, there is
also very likely to be considerable heterogeneity in
the response of populations to changes in salt intake
based on adaptations to differing environments.10
In addition to the heterogeneous responses to salt
restriction, a second aspect of the heterogeneity of
hypertension of potential significance to the phenomenon of salt sensitivity is the variability in prognosis.
In the recent past the ability to stratify patients as to
prognosis has improved greatly. Factors other than
blood pressure per se, such as left ventricular mass,
micToalbuminuria, plasma renin, fasting blood sugar,
lipid profile, previous heart attack, or tobacco use,
have been shown to have an important influence on
the outcome of patients with hypertension.11-12 In this
context, it is important to know whether types of
hypertension characterized by the presence or absence of salt sensitivity have any unusual prognostic
features, as is suggested by some studies showing
better prognosis in patients with lower renin values,12-13 who are more likely to be salt-sensitive.
Observational studies comparing the relation of
salt intake with blood pressure in different populations have suggested that effects of salt intake on
mean blood pressure or on the increase of blood
pressure with age, although statistically significant,
are small. These relations weaken further when
analyses of variables such as body mass index or
alcohol intake are included. Thus, the INTERSALT
study, the most comprehensive cross-cultural study of
salt excretion and blood pressure, suggests that a
reduction of salt intake of 100 mmol/day would lower
the mean systolic pressure of a population by 2
mm Hg and the diastolic pressure by 0.1 mm Hg.14
Projections that even these small changes in blood
pressure could have profound effects on the incidence of cardiovascular disease in the United States
raise the possibility that universal salt restriction
would result in a dramatic decrease in cardiovascular
disease.15 Several scientific and legislative committees have already suggested that all Americans reduce their salt intake to less than 3 g (105 meq) per
day (see Reference 16). The INTERSALT data have
led some investigators to suggest that such reductions
in salt intake should be even more stringent.15
We believe that universal salt restriction is inappropriate for several reasons. The magnitude of
benefits remains uncertain despite the multiple attempts made to quantify them. Biological meaning
rests on more than statistical correlation. In this
regard, the trials of the treatment of mild hypertension are instructive in that actual benefits regarding
coronary protection fell far short of statistical projections based on epidemiological studies.
Furthermore, the failure of most people to benefit
becomes important when the discomforts and possible dangers of salt restriction are taken into consideration. It is routinely assumed that the marvelous
capability of the kidneys to attain external sodium
balance over wide ranges of intake make salt restriction a therapy without significant hazard and thus
universally applicable as a preventive measure. We
believe that this view is unproven and that there are
several important cautions in this regard.
Sodium chloride is the major currency of the
extracellular fluid (ECF) volume, and external sodium balance in the face of changes in salt intake is
accompanied by fluctuations in the ECF volume. The
ability to adapt to very low salt diets is usually studied
in healthy young people or observed in non-Western,
traditionally living people whose lifestyles and life
expectancy differ substantially from our own. This
ability does not appear to be uniform even within our
society. For example, age appears to have an important influence on the ability to conserve sodium.
Healthy older people have greater negative sodium
balance and take longer when coming into sodium
balance than do younger persons.17
Decreased availability of salt in the diet would
have at least two potentially detrimental effects beyond "quality of life" issues. First, a person on a low
salt diet might be closer to a critical deficit of ECF
and therefore have less reserve in the face of a
salt-depleting stress. Second, a persistent low salt
diet would make it more difficult to reconstitute
losses after an acute salt-depleting stress.
Such stresses are not rare and include many acute,
otherwise self-limited illnesses accompanied by diarrhea, vomiting, or fever with anorexia and diaphoresis. The seriousness of these illnesses is most often
related to circulatory derangements caused by salt
deficits. The very young and elderly are particularly
vulnerable. The marked vulnerability of even the
healthy elderly person to salt depletion was demonstrated in a study of healthy young and old men, in
which both groups tolerated 60° head-up tilt when
salt replete, but only the young subjects tolerated the
stress after short-term salt depletion.18 The older
subjects all had pronounced falls in pressure and half
fainted under the latter condition.
Another large group of people who may be vulnerable to salt depletion are healthy persons who exercise intermittently, especially in hot weather. Weekend warriors who spend most of their time in
temperature-controlled environments may have large
sodium losses in sweat. Few follow regimens rigorous
enough to provide maximal acclimatization,19 and
even with acclimatization, sodium losses in sweat can
be considerable, up to 10-25 meq/hr. Salt depletion
in this setting may predispose to heat stress, in
addition to the other problems associated with hypovolemia. Rhabdomyolysis and acute renal failure
are well described consequences of exertion in the
context of hypovolemia.
Pecker and Laragh Dietary Salt aad Blood Pressure
Downloaded from http://hyper.ahajournals.org/ by guest on June 17, 2017
These important derangements come to medical
attention only in their most severe form, and the
treatment is saline administration. The value of
liberal dietary salt intake in buffering these problems
is poorly researched but may be quite important in
maintaining people during milder versions of these
stresses and preventing them from coming to medical
attention.
In addition to these conditions, several investigators have suggested that liberal salt intake may afford
protection from toxemia and is advantageous in
several medical conditions, including poorly controlled diabetes mellitus, adrenal insufficiency, and
some forms of chronic renal insufficiency.
These dangers of salt restriction, while extremely
well-known qualitatively, have not been subject to
quantitation in a population such as ours. Given the
broad variety of dietary habits in the population, even
a policy of universal moderate salt restriction
achieved by markedly restricting the salt content of
prepared foods may subject large numbers of people
to diets severely restricted in salt. Thus, problems
related to salt depletion may well exist even with a
program of moderate salt restriction.
Therefore, it would seem appropriate to recommend universal salt restriction only after its benefits
have been proven and carefully weighed against its
other costs to society as well as its dangers, to which
even cursory analysis reveals that large groups of
people may be susceptible. This should involve carrying out the same type of rigorous trials to which
antihypertensive medications have been subject in
both hypertensive and normotensive people. Meanwhile, pending the development of markers of salt
sensitivity, salt restriction as a safe and effective
treatment of hypertension should be reserved for
those hypertensive subjects in whom it has been
demonstrated by clinical trial to be effective. Its use
for the prevention of hypertension in the general
population must remain an interesting speculation
without enough evidence to justify its inclusion as
part of a national program.
References
1. Laragh JH, Pecker MS: Dietary sodium and essential hypertension: Some myths, hopes and truths. Ann Intern Med
1983;98:735-743
2. Kawasaki T, Delea CS, Barrier FC, Smith H: The effect of
high-sodium and low-sodium intakes on blood pressure and
other related variables in human subjects with idiopathic
hypertension. Am J Med 1978;64:193-198
3. Longworth DL, Drayer JI, Weber MA, Laragh JH: Divergent
blood pressure responses during short-term sodium restriction
in hypertension. Clin Pharmacol Ther 1980;27:544-546
1-99
4. Niarchos AP, Weinstein DL, Laragh JH: Comparison of the
effects of diuretic therapy and low sodium intake in isolated
systolic hypertension. Am J Med 1984;77:1061-1068
5. Pecker MS, James GD, Sealey JE, Jackson ST, Difabio B,
Carroll L, Orlic S, Blake M, Alderman MJ, Pickering TG,
Schnall P, Atlas SA, Laragh JH: Predictors of sodium sensitivity in mild hypertension (abstract). Am J Hypertens 1989;
2:85a
6. Hollenberg NK, Moore T, Shoback D, Redgrave J, Rabinowe
S, Williams GH: Abnormal renal sodium handling in essential
hypertension: Relation to failure of renal and adrenal modulation of responses to angiotensin II. Am J Med 1986;81:
412-418
7. Kohno M, Yasunari K, Murakawa K, Kanayama Y, Matsuura
T, Takeda T: Effects of high-sodium and low-sodium intake on
circulating atrial natriuretic peptides in salt-sensitive patients
with essential hypertension. Am J Cardiol 1987^9:1212-1213
8. Miller JZ, Weinberger MH, Daugherty SA, Fineberg NS,
Christian JC, Grim CE: Heterogeneity of blood pressure
response to dietary sodium restriction in normotensive adults.
/ Chron Dis 1987;40:245-250
9. Egan B, Weder A: Deleterious effects of NaCl restriction
(abstract). Circulation 1989;80(suppl n):D-415
10. James GD, Baker PT: Human population biology and hypertension: Evolutionary and ecological aspects of blood pressure, in Laragh JH, Brenner BM (eds): Hypertension: Pathophysiology, Diagnosis, and Management New York, Raven
Press, Publishers, 1990, pp 137-145
11. Kannel WB: Hypertension and the risk of cardiovascular
disease, in Laragh JH, Brenner BM (eds): Hypertension:
Pathophysiology, Diagnosis, and Management. New York,
Raven Press, Publishers, 1990, pp 101-117
12. Alderman M, Madhavan S, Ooi WL, Cohen H, Sealey J,
Laragh JH: High renin/sodium phenotype predicts myocardial
infarction: Renin hypothesis confirmed (abstract). Circulation
1989-,80:II-101
13. Brunner HR, Laragh JH, Baer L, Newton MA, Goodwin FT,
Krakoff LR, Bard RH, Buhler FR: Essential hypertension:
Renin and aldosterone, heart attack and stroke. N Engl J Med
1972;286:441-449
14. INTERSALT Cooperative Research Group: INTERSALT:
An international study of electrolyte excretion and blood
pressure: Results for 24 hour urinary sodium and potassium
excretion. Br Med J 1988;297:319-328
15. Stamler J, Rose G, Stamler R, Elliott P, Dyer A, Marmot M:
INTERSALT study findings: Public health and medical care
implications. Hypertension 1989;14i570-577
16. National Research Council: Diet and Health: Implications for
Reducing Chronic Disease Risk. Report of the Committee on
Diet and Health, Food and Nutrition Board. Washington, DC,
National Academy Press, 1989
17. Epstein M, Hollenberg NK; Age as a determinant of renal
sodium conservation in normal man. / Lab Clin Med 1976;87:
411-417
18. Shannon RP, Wei JY, Rosa RM, Epstein FH, Rowe JW: The
effect of age and sodium depletion on cardiovascular response
to orthostasis. Hypertension 1986;8:438-443
19. Smiles KA, Robinson S: Sodium ion conservation during
acclimatization of men to work in the heat. / Appl PhysUA
1971;31:63-69
KEY WORDS • diet • salt • sodium • blood pressure •
sodium-dependent hypertension • public policy
Dietary salt and blood pressure. A perspective.
M S Pecker and J H Laragh
Hypertension. 1991;17:I97
doi: 10.1161/01.HYP.17.1_Suppl.I97
Downloaded from http://hyper.ahajournals.org/ by guest on June 17, 2017
Hypertension is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright © 1991 American Heart Association, Inc. All rights reserved.
Print ISSN: 0194-911X. Online ISSN: 1524-4563
The online version of this article, along with updated information and services, is located on the
World Wide Web at:
http://hyper.ahajournals.org/content/17/1_Suppl/I97
Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published in
Hypertension can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial
Office. Once the online version of the published article for which permission is being requested is located, click
Request Permissions in the middle column of the Web page under Services. Further information about this
process is available in the Permissions and Rights Question and Answer document.
Reprints: Information about reprints can be found online at:
http://www.lww.com/reprints
Subscriptions: Information about subscribing to Hypertension is online at:
http://hyper.ahajournals.org//subscriptions/