dietary salt and blood pressure

PREVENTIVE MEDICINE 12, 133- 137 (1983)

Dietary Salt and Blood Pressure1,2,3

M. TREVISAN, R. COOPER, R. STAMLER, F. GOSCH, A. ALLEN, K. LIU, D. OSTROW, AND J. STAMLER

Northwestern University, Medical School, Chicago, Illinois 60611

Research evidence on the role of dietary sodium in the etiology and pathogenesis of hypertension is briefly reviewed. This matter is assuming new importance at present, given new data on the efficacy of normalization of blood pressure for adults with so-called “mild” hypertension (average diastolic 90-104 mm Hg), hence the need for safe nutritional-hygienic alternatives to years-long drug treatment for millions of people with such hypertension. Two trials by the authors deal with some unresolved questions in this area. The first, a preliminary study, involved 21 lacto-ovo-vegetarian high school students living in a boarding school. With decrease in daily Na intake from 216 to 72 meq for the experimental compared with the control group, red blood cell Na concentration was significantly lower in the former; systolic pressure was slightly but not significantly lower. The second trial, the Primary Prevention of Hypertension, involves over 200 hypertension-prone persons aged 30-44, and explores the ability in the experimental group to reduce blood pressure and prevent development of hypertension by safe nutritional-hygienic means (weight reduction, dietary Na decrease, avoidance of excess alcohol, rhythmic exercise). Initial results at 6 months are presented. Trials on the prevention and control of hypertension by nonpharmacologic means, including reduced Na intake, and involving analyses of the interrelationships among dietary Na, other dietary factors, Na metabolism, and blood pressure in samples from different population strata, are an important present-day research need.

DIETARY SALT AND BLOOD PRESSURE

Dietary sodium was first implicated in the etiology and pathogenesis of hypertension early this century (1). Our research group in Chicago has been concerned with this problem for over 30 years (15). The data supporting a causative relationship between dietary sodium (Na), sodium metabolism, and hypertension come from clinical, animal-experimental, epidemiologic, and anthropologic research (2, 3, 6, 10); they include limited evidence from controlled experiments in human nutrition. This article deals with this aspect of controlled human experiments in dietary sodium and hypertension.

This matter has assumed increased importance recently with demonstration of the ability of sustained effective antihypertensive drug treatment to reduce mor-

’ Presented at the International Symposium on Epidemiology and Prevention of Atherosclerotic Disease, June 24-26, 1981, Anacapri, Italy.

2 This work was supported by grants from the National Heart, Lung and Blood Institute, National Institutes of Health (HL21823-03, HL24999, HL23468), the Research Career Development Award for Kiang Liu, Ph.D. (HL00577), the postdoctoral training in cardiovascular epidemiology, nutrition, and biostatistics for Arline McDonald Allen, Ph.D. (HL07113-05), and a grant from the Chicago Health Research Foundation.

3 Address reprint requests to: Maurizio Trevisan, M.D., Research Associate, Department of Com- munity Health and Preventive Medicine, Northwestern University, Medical School, 303 E. Chicago Avenue, Chicago, Illinois 60611.

133 0091-743.5/83/010133-05$03.00/O Copyright 0 1983 by Academic Press, Inc. All rights of reproduction in any form reserved.

134 TREVISAN ET AL.

bidity and mortality of individuals with high blood pressure, including so-called “mild” hypertensives (average diastolic pressure 90- 104 mm Hg) (8). Such persons number in the tens of millions, and a perspective of years-long drug treatment for them must evoke serious concerns and active searches for alternative approaches. The primary and secondary prevention of high blood pressure by nutritional means, including the moderation of sodium intake, offers this possibility, therefore its particular relevance at the present time.

BRIEF REVIEW OF EARLIER WORK

In the 1940s Kempner reported that the rice diet brought about a substantial sustained fall in blood pressure in a sizable proportion of severe hypertensives (9). Watkin et al. subsequently confirmed that the very low sodium content of this diet, less than 10 meq of sodium per day (less than 0.6 g salt), was of critical importance in terms of the blood pressure-reducing effects (18). The early data indicated that very low sodium intake was critical for the antihypertensive effects, at least for severe hypertensives. This severely limited the large-scale practical application of low-sodium diets. With the development of oral diuretics, this nutritional approach received little further attention for years. However, it was recognized that high sodium intake interfered with the effectiveness of oral diuretics as antihypertensive agents.

In 1958, Dahl presented data on eight obese hypertensive persons, studied under controlled metabolic ward conditions, indicating that reduced sodium intake was a crucial component in the fall in blood pressure occurring with weight loss (4). Strazzullo et al. found that sodium restriction markedly enhanced the fall in blood pressure of obese hypertensives on a very low calorie weight reducing diet in Naples (16). Yet, Reisen et al. recently presented evidence that weight reduction with a high sodium diet was effective in lowering blood pressure in hypertensive persons; details of the frequency of measurement of 24-hr urinary sodium were not given (13). As Stamler et al. showed based on data from the Chicago Coronary Prevention Evaluation Program, moderate weight reduction over 5 years for men with both moderate and marked obesity is significantly correlated with sustained lowering of blood pressure (14). However, this study collected no dietary or urinary sodium data. Hunt reported years-long experience from the Mayo Clinic apparently indicating that for the great majority of persons with “mild” hypertension, sodium intake less than 75 meq per day (4.4 g salt) was effective in achieving and maintaining normalization of blood pressure (7). Details were not given, e.g., with respect to concomitant weight loss.

In a randomized trial, Morgan et al. showed a beneficial effect of moderate Na restriction on blood pressure in hypertensives with an average diastolic blood pressure (DBP) between 95 and 109 mm Hg, from 191 (baseline) to 157 meq of sodium/day over 2 years (11).

De Wardener et al. (5) and Morgan et al. (12) independently presented evidence for an inhibitory effect of salt feeding on the Na-K pump. Such inhibition in- creases intracellular Na concentration that could result in an increase in blood pressure.

SYMPOSIUM: ATHEROSCLEROTIC DISEASE 135

This brief review of the literature indicates the following unresolved problems in the area of controlled trials on dietary Na and blood pressure:

(a) Is there a linear or curvilinear relationship between dietary Na and blood pressure for most people, or is the relationship a threshold one, as the original studies of severe hypertensives indicated? That is, is moderation of Na intake (e.g., 60- 100 meq/day instead of 200) effective in controlling blood pressure for sizable numbers of people?

(b) Is reduced Na intake an important component of weight reducing diets for lowering blood pressure of obese hypertensive persons?

(c) Are there synergistic effects between Na reduction and other nutrients-e.g., protein, sucrose, in the control of blood pressure?

(d) What roles do pathophysiologic mechanisms and genetic factors play in modulating the electrolytic, metabolic, and blood pressure responses to dietary Na?

(e) What is the role of dietary Na moderation in the primary prevention of hypertension and the maintenance over the life span of optimal low-normal blood pressure?

EXPERIMENTAL STUDIES BY OUR GROUP

Two trials recently undertaken by our group in Chicago attempt to register progress in clarifying the foregoing questions. One is a short-term preliminary primary prevention study on teenagers. The second is a long-term trial on the primary prevention of hypertension in adults.

The Broadview study. In this preliminary controlled experiment, 21 lacto-ovo- vegetarian high school students, living in a boarding school in the Chicago area, concluded a 24-day randomized salt moderation trial. Specially prepared food was served to the experimental group, resulting in a decrease in sodium intake of about 70% (from 216 to 72 meq/day); the control group continued to eat the usual cafeteria food. Level of salt restriction was checked by chemical analysis of random food duplicates and random collection of 24-hr urinary excretion. Blood pressure was measured at the beginning and at the end of the study with the use of an automatic device (VITA-STAT). The values are the mean of two consecutive readings, 1 min apart, after 5 min rest. Five milliliters of venous blood was collected at the beginning and at the end of the study for determination of red blood cell Na concentration, by a method described in detail elsewhere (17).

Table 1 shows the values (mean + standard deviation) for systolic blood pressure, weight, and red blood cell Na concentration (RBC [Na] ) for both experimental and control groups at the beginning and at the end of the study. A signifi- cant decrease occurred in the experimental group in the RBC [Na], while there was virtually no change in the control group; the two groups were significantly different in regard to change in this variable. Both SBP and weight decreased slightly, but nonsignificantly, in the experimental group. These results should be interpreted with caution because of the small sample size in this preliminary study. Furthermore, the relatively short period of the experiment and the level of salt restriction may account for the lack of statistical significance for the blood pressure change.

136 TREVISAN ET AL.

TABLE 1 SALT MODERATION TRIAL IN YOUNGSTERS:

THE BROADVIEW STUDY MEAN LEVEL BY GROUP AND TIME

Variable

Experimental group (n = 12)

Baseline Final

Control group (n = 9)

Baseline Final

SBP (mm Hg) Weight (kg) RBC [Na]

(meq/liter RBC)

a x k S.D. * P < 0.01.

108.4 2 11.6” 107.2 2 13.1 110.7 ? 10.5 110.7 + 7.6 64.1 + 8.3 63.3 t 8.1 61.7 2 8.4 61.7 k 8.3

8.0” 1.1 7.4 2 1.0* 8.7 2 1.9 8.6 k 2.1

The Primary Prevention of Hypertension study. This randomized controlled trial investigates the possibility of influencing blood pressure through nutritional- hygienic measures in a group of hypertension-prone individuals. The effort especially involves sodium moderation, weight loss, a regimen of regular physical exercise, and alcohol moderation when indicated for persons randomly allocated to the Intervention Group. Through screening in industries in Chicago, 200 participants are being recruited into the study. The criteria for eligibility are age 30-44 years, relative weight not more than 50% above desirable weight; average DBP SO-89 mm Hg at the second screening; for individuals with DBP averaging 80-84 mm Hg, additional criteria are rapid heart rate (>80/min) and/or lo-49% above desirable weight. Individuals with previous history of coronary heart disease, insulin dependent diabetes, or on current treatment with medication influencing blood pressure are not admitted into the study.

Dietary pattern and sodium intake are being monitored with the use of 7-day food records and 4-7 consecutive overnight urine collections, on a semiannual basis for the intervention group, and annually for the control group. Blood pressure is measured every 6 months in all participants. Table 2 shows initial results of intervention for participants completing the first 6 months in the trial. A reduction of about 33% has been achieved in the sodium consumption, and an average weight loss of about 7 pounds.

CONCLUSION

The data available in the literature and our preliminary data support the evidence for a beneficial effect of salt reduction on blood pressure level and justify

TABLE 2 CHANGE IN WEIGHT, RELATIVE WEIGHT, AVERAGE DAILY URINARY Na EXCRETION,

INTERVENTION PARTICIPANTS, ~-MONTH DATA, CHICAGO PRIMARY PREVENTION OF HYPERTENSION PROGRAM

Variable Baseline 6 months Change

Weight (Ibs) 188.9 180.3 -8.6” Relative weight 123.5 117.8 -5.7 Na (mg/24 hr) 4,495 3,353 -1,142

a N for weight and relative weight: 78 people; 47.4% lost lO+ lbs, 64.1% lost 6+ Ibs. N for Na: 65 people.

SYMPOSIUM: ATHEROSCLEROTIC DISEASE 137

the emergence of wide interest in this matter. The intense activity in this field may provide more insight into the link between Na in the diet, Na metabolism, and blood pressure, and eventually their relationship with other nutrients as well.

There is need for large-scale trials in this area using modern methods and accurate standardized procedures. In addition, we feel that attention should be paid by public health authorities to this matter in terms of preventive approaches.

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