hypothesis discrepancy between intra- and interpopulation studies of the relationship between...
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CLIN. AND EWER. HYPER.-THEORY AND PRACTICE, A6(4) , 897-903 (1984)
HYPOTHESIS DISCREPANCY BETWEEN INTRA- AND INTERPOPULATION STUDIES OF THE RELATIONSHIP BETWEEN DIETARY SALT AND BLOOD PRESSURE:
FACT OR FICTION?
Per Omvik Medical Department
University of Bergen 5016 Haukeland Sykehus
Bergen Norway
Kev-words:
Hypertension, hypothesis, population study, salt intake.
ABSTRACT
show significant correlation between sodium excretion and blood pressure while a clear relationship exists in cross- cultural studies. Since daily variation of sodium excre- tion is high, the discrepancy between the two observations could be due to non-comparable data on sodium excretion. This is a discussion of the hypothesis that the finding o f a significant correlation or not between sodium excretion a n d blood pressure depends on the statistical analysis of the data.
It is a paradox that intra-population studies fail to
Cross-cultural studies have shown a highly significant
positive correlation between mean daily sodium excretion
and both blood pressure level ( 1 , 2 ) and occurrence of
hypertension ( 3 , 4 ) . This and other findings ( 5 ) has led to
the hypothesis of a cause- and effect relationship between
sodium intake and development of hypertension ( 6 ) .
However, it is a paradox that most studies fail to show
897
Copyright 0 1984 by Marcel Dekker, Inc. 07304077/84/06044897$3.50/0
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a positive correlation between sodium excretion and blood
pressure within each separate society ( 7 , 8 , 9 ) . One hypo-
thesis claims that higher levels of dietary sodium in
high-salt societies might trigger genetic or other factors
initiating the development of hypertension in "salt-
sensitive" individuals while "salt-resistants" would
remain normotensive, enduring the strain of the high-salt
diet (10,ll). In a low-salt society a smaller fraction of
the population would become hypertensive because o f less
stimulation o f the salt-sensitive mechanism. According to
this hypothesis, no significant intra-population corre-
lation between sodium excretion and blood pressure would
be expected since both normotensives and hypertensives
would be exposed to the same amount of salt as part of the
dietary habits o f their society.
An alternative hypothesis is that the discrepancy
between the intra- and the interpopulation studies of the
relationship between sodium excretion and blood pressure
is due to non-comparable data on sodium excretion: In most
intrapopulation studies individual sodium excretion rates
are determined by one or a few 24-hour urine samples
( 7 , 8 , 9 , 1 2 ) whereas in cross cultural comparisons the mean
sodium excretion rates are calculated from large groups o f
subjects, thereby minimizing the effect of the intra-
individual variability o f sodium excretion.
In each subject sodium excretion varies widely from one day to another depending on a number o f factors including
neurRhumora1 activity, blood pressure and sodium intake.
The m o s t powerful determinant is sodium intake: following
a change in dietary salt the sodium excretion rapidly
readjusts to match the new level of sodium intake ( 1 3 , 1 4 1 .
At the extreme ranges of salt intake the sodium excretion
can be altered by a hundred - or even a thousand fold
( 1 5 ) . Thus, it is not astonishing that the individual day-to-day variation o f sodium excretion is high with a
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RELATIONSHIP BETWEEN SALT AND BLOOD PRESSURE? 899
coefficient of variation of 4 0 % ( 9 , 1 2 , 1 6 , 1 7 ) and with
correlation coefficients between two 24-hour observation
periods ranging between 0 . 4 0 and 0.60 ( 9 , 1 7 1 . I n compari- son the daily variation of blood pressure is small ( 1 8 ) .
As shown by Stamler et al. (12) a large number of urine
samples from each subject is needed to minimize the large
intra-individual variation of sodium excretion. After 14
24-hour collections this variation was less than the
inter-individual variability and the "true" relationship
between sodium excretion and blood pressure, became
apparent.
Alternatively, as discussed by Watt et al, the
number o f subjects needed to detect a significant corre-
lation between the two parameters would be high (in the order of six thousand) if single urine collections were
used for each individual ( 1 9 ) . However, the group mean
level of sodium excretion is essentially the same whether
single or multiple urine samples from each rubject are
used in the calculation; by both methods t h e total number
of urine collections is high. Similarly the reproduci-
bility o f the mean rate of sodium excretion within a
population is remarkably good ( 9 , 1 7 , 2 0 ) , possibly because of the large number of samples masking the intra-
individual variability. Thus, although studies based on
single urine collections fail to demonstrato significant
correlations between individual sodium excretion rater and blood pressure, the mean rates of sodium excretion are
close to the true level of sodium intake within the society and might be used for cross-cultural comparison.
B y analogy the same analysis would apply if subgroups
within a single population were compared: despite lack of
'overall correlation between blood pressure and sodium
excretion within the whole population mean values of sodium excretion for subgroups might still be correlated
t o the mean blood pressure of each subgroup. This was
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900 OPNIK
shown in a recent study of blood pressure and daily sodium
excretion among middle-aged men living in three districts
of different geographical location in the Sogn county of
Western Norway (17).
The above analysis suggests that the discrepancy
between intra- and inter-population studies of the
relationship between dietary salt and blood pressure is a
fiction due to non-comparable data on sodium excretion.
Thus, it is probable that blood pressure is interrelated
with sodium excretion within communities as well as
between different communities. However. it is important to
note that the demonstration of a positive correlation
between the two variables in population studies does not
prove a cause-and-effect relationship between salt and
hypertension. From acute studies both in man and in
experimental animals it is well known that changes i n
blood pressure might induce large changes in sodium
excretion by the pressure natriuresis mechanism (21,22,23)
while even monstrous increments in sodium intake might
cause only minor alterations in blood pressure ( 1 5 ) .
Furthermore, most studies have shown that essential
hypertensives are in either perfect sodium and body fluid
volume balance (24,251 or slightly hypovolemic (26,27,26)
rather than hypervolemic.The higher levels o f sodium
intake in Western societies might therefore reflect more
craving for salt in order to maintain sodium balance in
the face of higher levels of sodium losses due to pressure
natriuresis (14).
REFERENCES 1. Prior I A M , Evans J G , Harvey HP8, Oavidson F , Lindsey
M: Sodium intake and blood pressure in two Polynesian populations. New Engl J Med 2 7 9 : 5 1 5 . 1968.
2. Page LE: Epidemiological evidence on the etiology of human hypertension and its possible prevention. hm Heart J 91.527, 1976.
Clin
Exp
Hyp
erte
ns D
ownl
oade
d fr
om in
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ahea
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y Fr
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RELATIONSHIP BETWEEN SALT AND BLOOD PRESSURE? 901
3.
4 .
5.
6.
7.
8 .
9.
10.
1 1 .
12.
13.
14.
Dahl L K , Love RM: P o s s i b l e role o f chronic excess salt consumption i n t h e pathogenesis of essential hypertension. Am J C a r d i o l 8:571, 1961.
Isaacson L C , Modlin M , Jackson WPU: Sodium intake and hypertension. Lancet 1:946, 1963.
Freis ED: S a l t , volume and prevention o f hypertension. Circulation 53:589, 1976.
Dahl L K , Love RM: Evidence f o r relationship between sodium ( c h l o r i d e ) i n t a k e and human hypertension. Arch ' *
Intern Med 9 4 : 5 2 5 , 1954.
M i a l l WE: F o l l o w - u p study o f arterial pressure in t h e population o f a W e l s h . m i n i n g valley. Brit Med J 2:1205, 1959.
*li
Langford H , Watson RL: Electrolytes and hypertension. Epidemiology and C o n t r o l of Hypertension. Ed. P a u l 0. Stratton Interco n t i n e n t a l Medical Book Corporation, N e w York 119, 1975.
Ljungma n S , Aurell M , Hartford M , Wikstrand J , Wilhelmsen L , Berglund G: Sodium excretion and blood pressure. Hypertension 3 : 318, 1981.
dewarde n e r H E , MacGregor GA: Dahl's hypothesis that a saluretic s u b s t a n c e m a y be responsible for a sustained r i s e i n a r t e r i a l pressure: Its possible r o l e in e s s e n t i a l hypertension. Kidney Int 18:1, 1980.
Luft F C , Weinberger MH: Sodium intake and essential hypertension. Hypertension 4 ( S u p p l 1 1 1 1 : 111-14, 1982.
Liu K , Cooper R , McKeever J , McKever P , Byington R , S o l t e r o I , S t a m l e r R , Gooch F , Stevens E , Stamler J : Assessment o f t h e association between habitual salt intake and high blood pressure: methodological problems. A m J E p i d e m i o l 110:219, 1979.
Wesson LG J r , L a u l e r DP: D i u r n a l c y cle of glomerular filtration r a t e and s o d i u m chloride excretion during respon s e s t o altered salt and water balance in man. J C l i n Invest 40:1967, 1961.
Kiil F: Pressure diu r e s i s and hypertension. Scand J Clin L a b Invest 35:289, 1975.
Clin
Exp
Hyp
erte
ns D
ownl
oade
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ahea
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902 OMVIK
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
Luft FC, Rankin L I , Henry DP, Bloch R , Grim CE, Weyman AE, Murray RH, Weinberger MH: Plasma and urinary norepinephrine values at extremes of sodium intake in normal man. Hypertension 1:261, 1979.
Joosens J V , Claessens J , Geboers J , Claess J H ; Electrolytes and creatinine in multiple 24-hour urine collections (1970-1974). Epidemiology o f Arterial Blood Pressure. Eds. Kesteloot H , Joosens J V , Hague, Martinus Nijhoff Publishers, 45, 1980.
Omvik P , Lund-Johansen P , Eide R: Sodium excretion and blood pressure i n middle aged men i n the Sogn county: a n intra- and interpopulation study. J Hypertension 1:77, 1983.
Clement D L , Bogaert M G , Pannier R: Effects of beta-adrenergic blockade on blood pressure variation in patients with moderate hypertension, Eur J Clin Pharmacol II:325, 1977.
Watt GCM, Foy JW: Dietary sodium and arterial pressure: problems o f studies within a single population. J Epidemiol Commun Health 36:197, 1982.
Liu K , Cooper R , Soltero I , Stamler J: Variability in 24-hour urinary sodium excretion in children. Hypertension 1:631, 1979.
Eisinger RP: Augmented natriuretic response to infusion o f saline in d o g s rendered acutely hypertensive with metaraminol. Proc SOC Exp Biol Med 122:804, 1966.
Raeder M , Omvik P jr, Kiil F : Effect of acute hypertension on the natriuretic response to saline loading. Am J Physiol 226:989, 1974.
Omvik P, Tarazi RC. Bravo El: Regulation o f sodium balance in hypertension. Hypertension 2:515, 1980.
Hansen J: Blood volume and exchangeable sodium in essential hypertension. Acta Med Scand 184:517, 1968.
Schalekamp M A D H , Lebel M , Beevers DG, Fraser R , Kolsters G , Birkenhager WH: Body fluid volume in low-renin hypertension. Lancet 2:310, 1974.
Tarazi RC, Frolich ED, Dustan H P : Plasma volume in men with essential hypertension. New Engl J Med 278:762, 1968.
Clin
Exp
Hyp
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ns D
ownl
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ahea
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27. Julius S , Pascual AW, Reilly K , London R : Abnormalities o f plasma volume in borderline hypertension. Arch Intern Med 127:116, 1971.
28. Ibsen H , Leth A: Plasma volume and extracellular fluid volume in essential hypertension. Acta Med Scand 194:93, 1973.
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