(Hypertension. 1995;25:1153-1154.)
© 1995 American Heart Association, Inc.
Articles |
An Unexpected Result For Sodium— Causal Or Casual?
From the Division of Preventive Medicine, Brigham and Women's Hospital (N.R.C., C.H.H.), Boston, Mass, and the Division of Epidemiology and Clinical Applications, National Heart, Lung, and Blood Institute (J.A.C.), Bethesda, Md.
Key Words: cardiovascular disease • hypertension, sodium-dependent • blood pressure • sodium • myocardial infarction
 |
Introduction |
|---|
 Top Introduction References |
|---|
The study by Alderman et al1 in the current issue of Hypertension provides data that raise a question of whether a decrease in sodium intake lowers risk of cardiovascular disease. The National High Blood Pressure Education Program Working Group2 cited a reduction in sodium intake as one of the most effective approaches to preventing hypertension. They recommend a multifaceted approach to public education that includes limiting excess sodium intake as a key element. The Fifth Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure3 recommends lifestyle modifications, including sodium reduction, as a first-line treatment for mildly and moderately hypertensive individuals.
Much of the evidence concerning the benefit of a decrease in sodium intake is derived from studies of blood pressure. Observational data, from both between-population and within-population studies4 5 and particularly data from the INTERSALT study,6 7 show a consistent direct relationship of sodium excretion (UNaV) to blood pressure. Current estimates from INTERSALT7 suggest a 100-mmol decrease in sodium is associated with a decrease in systolic pressure of 3.1 mm Hg.
Randomized trial data have generally supported these observational results.8 9 The recent Trials of Hypertension Prevention, Phase I10 found that decreases in systolic/diastolic pressures of 1.7/0.9 mm Hg were associated with average sodium decreases of about 44 mmol/24 h, a finding comparable to other trials among normotensive subjects.9 The results in trials among hypertensive subjects tend to be even stronger. An overview9 suggests decreases in systolic/diastolic pressures of 4.9/2.6 mm Hg in trials among hypertensive subjects.
There are few data available on the impact of a reduction in sodium intake on subsequent morbidity and mortality, although there is some evidence linking sodium intake to certain disease manifestations, particularly left ventricular mass11 12 and renal stones.13 Based on the established relationship of a decrease in elevations of blood pressure by 5 to 6 mm Hg resulting in a lowered risk of stroke (by 38%) and coronary heart disease (by 16%),14 various projections have been made as to the effect of blood pressure reductions of the magnitude estimated with sodium reduction.8 15 16 Even the small blood pressure reductions in trials among normotensive subjects could reduce risks of stroke by 15% and coronary heart disease by 6%.16 The benefits among a hypertensive population such as Alderman et al's would be expected to be even greater.
In contrast, the current study raises the possibility of no reduction in disease rates among those with lower UNaV. In the hypertensive population studied, men with the lowest levels of UNaV actually had higher rates of cardiovascular events, including myocardial infarction, over an approximately 4-year follow-up period. This inverse association remained even after controlling for other well-known cardiovascular risk factors, such as blood pressure and cholesterol. This finding was only apparent in men; in women the expected direct relationship was seen, although the small number of events in women (only 21) precluded the ability to achieve statistical significance or further examination of the finding through multivariate analysis. This qualitative difference, however, deserves further study.
The population studied was one of hypertensive subjects who entered a treatment program at the workplace from 1981 to 1990. About 60% had previously been treated for hypertension, although they were removed from therapy for 3 to 4 weeks before UNaV was measured. Participants were then given medication as part of their treatment regimen and followed up for a median of 3.5 years (range, 0.2-9.5). Although prior treatment status was evenly distributed across quartiles of baseline UNaV and drug therapy appeared similar across quartiles, no information is given as to doses of treatment or multidrug regimens. It is possible that those in the lowest quartile had hypertension that was more difficult to control, particularly since they had higher systolic pressures at follow-up. If those in the lowest quartile were given higher diuretic doses before the short wash-out period, they may as a consequence have retained more sodium after diuretic withdrawal, a possibility consistent with their higher renin levels at baseline. Thus, an influence of drug therapy on excretions along with an unequal relationship with associated blood pressures remain plausible alternative explanations.
The authors indicated that there was no relationship of UNaV levels at baseline with systolic pressure and little relationship with diastolic pressure. This is in direct contradiction to the totality of evidence, in particular the observational data on UNaV and blood pressure cited above. The authors did not thoroughly examine these interrelationships, but they did control for blood pressure in their multivariate model and found that sodium remained predictive. Furthermore, after treatment mean systolic pressure was higher in the lowest sodium quartile in men. Because sodium intake is expected to directly affect blood pressure, further examination of this unexpected finding is necessary.
It is also plausible that the inconsistent relationship with blood pressure, as well as the overall relationship with cardiovascular disease, may be due to uncontrolled confounding among this group of men. Many important potential confounding variables, including prior cardiovascular disease, left ventricular hypertrophy, cholesterol (total cholesterol only), smoking (yes or no only), and renal function, were assessed with insensitive measures. No information is provided on diet or alcohol use. The lack of detailed information on smoking and alcohol use raises the possibility that those in the lowest quartile of UNaV were hypertensive due to heavy alcohol use and accordingly smoked more heavily. These and other uncontrolled confounders would also be expected to increase non–cardiovascular morbidity and mortality, as appears to be the case in these data.
A previous study in this same population showed a significant positive relationship between plasma renin activity and subsequent myocardial infarction.17 This finding was not supported by data in normotensive men,18 which showed no relationship. There is some suggestion in the latter report that there may be a slight positive relationship among those with high levels of blood pressure,18 although this is not as strong as that found previously in this population.17 This raises the possibility that the worksite population is unique and exhibits relationships that may not be representative of other populations. It also suggests that the relationship of plasma renin activity, and perhaps UNaV, may be different among severe hypertensive subjects. It is possible that there is a breakdown in the feedback control mechanisms, as suggested by Meade, in those with vascular damage. It is also possible that the relationship between sodium intake and excretion is altered among severely hypertensive individuals, perhaps influenced by sodium retention.
The finding of an inverse relationship of sodium and risk among drug-treated hypertensive subjects is intriguing; however, we have no evidence at present for a similar association among untreated hypertensive or normotensive individuals. In addition to the factors already mentioned, the extreme play of chance could account for this unexpected relationship,19 particularly since it appears to conflict with the totality of evidence from basic, epidemiologic, and clinical research. Further efforts must be made to corroborate or refute these findings in both hypertensive and normotensive individuals. Follow-up for disease end points is warranted in available cohorts that have shown a relationship with blood pressure to see if this is extended to disease outcomes. Further, follow-up of cohorts included in randomized trials of dietary sodium reduction for cardiovascular events would help address the important questions raised by Alderman et al. At present, the totality of evidence supports the likelihood that lowering sodium through dietary intervention will lead to a decreased risk of stroke and myocardial infarction primarily through a reduction in blood pressure.
|
Footnotes |
|---|
Reprint requests to Dr Nancy R. Cook, Brigham and Women's Hospital, 900 Commonwealth Avenue East, Boston, MA 02215
The opinions expressed in this editorial comment are not necessarily those of the editors or of the American Heart Association.
|
References |
|---|
|
TopIntroductionReferences |
|---|
1. Alderman MH, Madhavan S, Cohen H, Sealey JE, Laragh JH. Low urinary sodium is associated with greater risk of myocardial infarction among treated hypertensive men. Hypertension. 1995;25:1144-1152.
2.
National High Blood Pressure Education Program Working
Group. National High Blood Pressure Education Program Working
Group report on primary prevention of hypertension. Arch
Intern Med. 1993;153:186-208.
3.
Joint National Committee on Detection,
Evaluation, and Treatment of High Blood Pressure. The fifth
report of the Joint National Committee on Detection, Evaluation, and
Treatment of High Blood Pressure (JNC V). Arch Intern
Med. 1993;153:154-183.
4. Law MR, Frost CD, Wald NJ. By how much does dietary salt reduction lower blood pressure? I—Analysis of observational data among populations. Br Med J. 1991;302:811-815.
5. Frost CD, Law MR, Wald NJ. By how much does dietary salt reduction lower blood pressure? II—Analysis of observational data within populations. Br Med J. 1991;302:815-818.
6. 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.
7.
Dyer AR, Elliott P, Shipley M, for the INTERSALT
Cooperative Research Group. Urinary electrolyte excretion in 24
hours and blood pressure in the INTERSALT study. Am J
Epidemiol. 1994;139:940-951.
8. Law MR, Frost CD, Wald NJ. By how much does dietary salt reduction lower blood pressure? III—Analysis of data from trials of salt reduction. Br Med J. 1991;302:819-824.
9. Cutler JA, Follman D, Elliott P, Suh I. An overview of randomized trials of sodium reduction and blood pressure. Hypertension. 1991;17(suppl I):I-27-I-33.
10.
Trials of Hypertension Prevention Collaborative
Research Group. The effects of nonpharmacologic interventions on
blood pressure of persons with high normal levels: results of the
Trials of Hypertension Prevention, Phase I. JAMA. 1992;267:1213-1220.
11.
Ferrara LA, DeSimone G, Pasanisi F, Mancini M, Mancini
M. Left ventricular mass reduction during salt depletion in
arterial hypertension. Hypertension. 1984;6:755-759.
12. Prineas RJ, Grimm R, Grandits G, Liebson P, Neaton J, Stamler J, Elmer P, Cutler J, Rautaharju P, for the TOMHS Research Group. The effect of dietary sodium and body weight on echocardiographic measures of left ventricular mass among treated hypertensive men and women: Four-year change in the TOMHS study. Nieren-und Hochdruckkrankheiten. 1994;23(suppl 1):S14-S21.
13. Cirillo M, Laurenzi M, Panerelli W, Stamler J, on behalf of the Gubbio Population Study Research Group. Urinary sodium to potassium ratio and urinary stone disease. Kidney Int. 1994;46:1133-1139. [Medline] [Order article via Infotrieve]
14.
Hebert PR, Moser M, Mayer J, Glynn RJ, Hennekens CH.
Recent evidence on drug therapy of mild to moderate hypertension
and decreased risk of coronary heart disease. Arch Intern
Med. 1993;153:578-581.
15. Stamler R. Implications of the INTERSALT study. Hypertension. 1991;17(suppl I):I-16-I-20.
16.
Cook NR, Cohen J, Hebert P, Taylor JO, Hennekens CH.
Implications of small reductions in diastolic blood pressure for
primary prevention. Arch Intern Med. 1995;155:701-709.
17. Alderman MH, Madhavan S, Ooi WL, Cohen H, Sealey JE, Laragh JH. Association of the renin-sodium profile with the risk of myocardial infarction in patients with hypertension. N Engl J Med. 1991;324:1098-1104. [Abstract]
18.
Meade TW, Cooper JA, Peart WS. Plasma renin
activity and ischemic heart disease. N Engl J
Med. 1993;329:616-619.
19. Hennekens CH, Buring JE. Epidemiology in Medicine. Boston, Mass: Little, Brown & Co; 1987.
This article has been cited by other articles:
 |
|
 |
|
  N. R. Cook, E. Obarzanek, J. A. Cutler, J. E. Buring, K. M. Rexrode, S. K. Kumanyika, L. J. Appel, P. K. Whelton, and for the Trials of Hypertension Prevention Collabor Joint Effects of Sodium and Potassium Intake on Subsequent Cardiovascular Disease: The Trials of Hypertension Prevention Follow-up Study Arch Intern Med, January 12, 2009; 169(1): 32 - 40. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Meneton, X. Jeunemaitre, H. E. de Wardener, and G. A. Macgregor Links Between Dietary Salt Intake, Renal Salt Handling, Blood Pressure, and Cardiovascular Diseases Physiol Rev, April 1, 2005; 85(2): 679 - 715. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. He and P. K Whelton Commentary: Salt intake, hypertension and risk of cardiovascular disease: an important public health challenge Int. J. Epidemiol., April 1, 2002; 31(2): 327 - 331. [Full Text] [PDF]
|
|
|
|
 |
|
 D. A McCarron The dietary guideline for sodium: should we shake it up? Yes! Am. J. Clinical Nutrition, May 1, 2000; 71(5): 1013 - 1019. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. V. Chobanian and M. Hill National Heart, Lung, and Blood Institute Workshop on Sodium and Blood Pressure : A Critical Review of Current Scientific Evidence Hypertension, April 1, 2000; 35(4): 858 - 863. [Full Text] [PDF]
|
|
|
|
 |
|
 J. He, L. G. Ogden, S. Vupputuri, L. A. Bazzano, C. Loria, and P. K. Whelton Dietary Sodium Intake and Subsequent Risk of Cardiovascular Disease in Overweight Adults JAMA, December 1, 1999; 282(21): 2027 - 2034. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. K. Whelton, L. J. Appel, M. A. Espeland, W. B. Applegate, W. H. Ettinger Jr, J. B. Kostis, S. Kumanyika, C. R. Lacy, K. C. Johnson, S. Folmar, et al. Sodium Reduction and Weight Loss in the Treatment of Hypertension in Older Persons: A Randomized Controlled Trial of Nonpharmacologic Interventions in the Elderly (TONE) JAMA, March 18, 1998; 279(11): 839 - 846. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Lenfant High Blood Pressure: Some Answers, New Questions, Continuing Challenges JAMA, May 22, 1996; 275(20): 1604 - 1606. [Abstract] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||