Dietary Compliance Among Salt-Sensitive and Salt-Insensitive Normotensive Adults

Dietary Compliance Among Salt-Sensitive and Salt-Insensitive Normotensive Adults RICHARD D. MATTES, MPH, PHD, RD; BONITA FALKNER, MD

ERIC WESTBY;

ABSTRACT: Little is known about the customary level of sodium intake by salt-sensitive. people and the nature of obstacles they face in the adoption of a reduced-sodium diet. These issues were addressed with 12 salt-sensitive (SS) and 9 salt-insensitive (SI) normotensive adults. Information about sodium consumption, taste, and blood pressure and concerns about following a diet reduced in sodium were collected at baseline and monthly while participants followed a 100 mmol Na/day diet for 4 months. Mean sodium intakes of both groups were comparable at baseline and were reduced significantly during diet. The principal dietary concerns were reduced food availability, increased food costs, and reduced food palatability. There were no group differences. Ratings declined over time, but only the food palatability issue did so significantly because of a shift by the SI only. While the predictive value of SS classification remains uncertain, these data indicate that dietary change is feasible in SS subjects. KEY INDEXING TERMS: Salt sensitivity; Human, Diet; Sodium; Compliance [Am J Med Sci 1999;317(5):287-94.]

T

he health benefits associated with maintenance of normal blood pressure are widely recognized. Accumulating evidence indicates this may be best achieved through adherence to a multifac-

From the Monell Chemical Senses Center, Philadelphia, Pennsylvania (RDM, EW), Purdue University, W. Lafayette, Indiana (RDM, RD), and Medical College of Pennsylvania, Philadelphia, Pennsylvania (BF). This work was supported by Grant P50-DC00214 from the National Institute on Deafness and Other Communication Disorders. Submitted June 2, 1998; accepted in revised form September 4, 1998. Correspondence: Richard Mattes, Ph.D., R.D., Purdue University, Department of Foods and Nutrition, 209 Stone Hall, W. Lafayette, IN 47907-1264. (E-mail: [email protected]) THE AMERICAN JOURNAL OF THE MEDICAL SCIENCES

RAFAEL DE CABO;

eted dietary and lifestyle pattern.1- 6 Nevertheless, moderation of dietary sodium remains a cornerstone of all dietary recommendations. Mean sodium consumption in the general population is 142 mmol/day (3266 mg/day),7 a level that is higher than recommended by numerous expert panels and policy-makers.8 Despite addressing many of the factors hindering adoption of a diet lower in sodium, 6 meeting goal levels in the normotensive population has proven difficult. The Trials of Hypertension Prevention (TOHP) were specifically designed to definitively determine the feasibility of reducing sodium consumption to 60 mmol/day (1400 mg/day) in this groUp.9 The intensive IS-month intervention resulted in a reduction from 154.6 mmol/day to 99.4 mmol/day, falling far short of the goaL Only 19.5% of the 246 participants reduced intake to < 60 mmol/ day and only 56% had intakes below 100 mmol/day. Although extrapolation to the general population yields potentially important public health benefits,lO,11 the associated reductions of diastolic and systolic blood pressure were modest, 0.009 mm Hg and 0.014 mm Hg SBP, respectively, per 1 mmol/day reduction. TOPH and other studies indicate that reduction of dietary sodium is difficult, that feasible reductions result in small mean changes of blood pressure and that elevations of blood pressure occur in some people with moderate restriction. Consequently, there have been numerous calls to identify the subset of people most likely to benefit from a dietary intervention. 12- 15 Salt-sensitivity classification stemmed from these observations. When someone's blood pressure rises or falls with increased or decreased sodium consumption, respectively, that person is deemed salt-sensitive (SS). Estimates on the prevalence of this trait vary widely, from 20% to 60% of the U.S. population.15- 17 Those whose blood pressure is not responsive to changes of dietary sodium are defined as salt-insensitive (SI). Another estimated 15% of the population are termed reverse salt-sensitive, because they experience a rise of blood pressure with adherence to a reduced sodium diet. 18 Classification has been based on blood pressure responses to short-term salt chal-

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lenges. Most commonly, this has entailed measurement of a 10% or 5 mm Hg change of mean arterial blood pressure (MAP) from the end of a I-week period of low sodium diet (eg, 20 mmol/day) to the end of a week of high-sodium diet (eg, 220 mmol/ day). Issues regarding SS classification reliability, sensitivity, and specificity aside,18a questions regarding the clinical utility of identifying this trait in a normotensive subject remain unexplored. To our knowledge, there are no data regarding the feasibility of implementing a reduced sodium diet in this group. Subgroups of the population with a high incidence of SS, such as African Americans, are reported to achieve lower levels of compliance with a sodium reduction regimen, in part because of differences in customary dietary intake. 9 This raises questions about the optimal dietary intervention approach for SS subjects. A primary aim ofthe present study was to evaluate the compliance of SS and SI subjects to a diet reduced in sodium and to identify the principal obstacles to chronic dietary change in the SS. Methods

General protocol. A nonrandom sample of healthy, normotensive adults was recruited by public advertisement. To ensure inclusion of an adequate number of SS subjects, particular efforts were made to enroll those who had a positive family history of hypertension, who were of African American descent, and who were overweight since these characteristics are linked with SS.15,19-23 Other eligibility criteria included no chronic or acute health disorder, no use of medications , not pregnant or lactating, 18 -70 years of age, no special diet, no history of high or low blood pressure, stable body weight (no change >3kg over the previous 3 months), stable activity level, ratings of concern about dietary sodium intake, heart disease and hypertension of 5 or less on a 9-point category scale (1 = not at all, 9 = extreme), control of over 50% of food 'purchasing and preparation, and blood pressure consistently < 140/90 mm Hg. The first ~7 weeks of the study involved repeat salt challenge trials to diagnose SS and assessments of glucose tolerance, diuretic response to a saline load, measurement of salivary flow, and composition and taste testing. The results of this work are reported elsewhere.1 8a After these activities, participants were placed on a reduced sodium diet (target was 100 mmol N a/day) as described by the American Dietetic Association. 24 At monthly intervals, participants collected two 24-hour urine samples, participated in taste tests, had body weight and composition measured, and completed health and dietary questionnaires. Blood pressure was monitored every other week. Subjects. Table 1 contains selected characteristics of the study participants. Sixty-six people were re-

288

Table 1. Characteristics of the 21 Participants who Tested Reliably as SS or S1.

Number Age (years, mean :+: SE) Sex (men, women) Ethnicity (Afr Am, Cauc, Other) BM1 (kg/m 2 ) Waistlhip ratio MAP (mmHg) Sodium intake (excretion) (mmolld) Fam hist of hypertension (Y,N) Smoking (Y,N) Alcohol use (Y,N)

SS

S1

12 32.8:+: 3,8 10,2 4, 8, 0

9 29.8 :+: 2.4 7, 2 0,8,1

25.3:+: 0.82 :+: 80.0 :+: 157.1 :+:

1.5 0.02 2.3 25.9

8,4 2,10 6,6

21.5 0.79 78.7 152.4

:+: :+: :+: :+:

0.7 0.03 3.2 24.1

4,5 0,9 8, 1

cruited initially. Based on urine excretion values, 21 were deemed noncompliant during salt challenge trials, thus precluding determination of their saltsensitivity status. Fifteen people met all study conditions, but upon repeat testing, were not classified consistently. Consistent SS test results were obtained from 17 participants, and 13 participants were consistently diagnosed as SI. Of these 30 people, 21 volunteered to adopt the reduced sodium diet for 4 months and are the focus of this report. There were no statistically significant differences for the listed variables between the subjects not following the protocol, testing inconsistently, classified as SS or SI or volunteering for the reduced sodium diet trial. The SS and SI subjects described in this report were comparable for all of the listed attributes, although the body mass index of SS participants tended to be higher than that of the SI participants (t = 2.084, P = 0.051). Blood pressure. Systolic (phase I) and diastolic (phase V) blood pressure values were determined with a random-zero sphygmomanometer (Hawksley; W.A. Braun Co., Inc., Copiague, NY) and an appropriately sized cuff after subjects had been standing, sitting, and supine for at least 5 minutes. MAP was determined as the diastolic pressure plus one-third of the pulse pressure. Blood pressure readings were taken in duplicate four times during screening and bi-monthly during the diet trial. Body weight and composition. Body weight was measured by clinical scale (Scale-Tronix, Inc., Wheaton, IL). Body composition was determined by bioelectrical impedance analysis using a model 101 analyzer (RJL Systems, Detroit, MI). Height was measured by stadiometer (Holtain Ltd., Crymych, Dyfed, UK). Urinary collection and analysis. Participants were provided with 2-liter, wide-mouth plastic containers with 2 g of boric acid (a preservative) for the 24-hour collections conducted twice at the end of the May 1999 Volume 317 Number 5

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salt challenge periods, twice before the initiation of the diet, and at the end of each of the four diet months. The samples were returned to the laboratory within 3 days of collection. The total volume was determined and a 100-ml aliquot was frozen (-20°C) for later analysis. Samples were analyzed for sodium and potassium by flame photometry and creatinine by a colorimetric method (diagnostic kit 555; Sigma, St. Louis, MO). Dietary compliance. Urinary sodium excretion was the principal means by which dietary compliance was assessed during the salt challenge and diet periods. A difference greater than 100 mmol/day between the ends of the low and high salt periods of the salt challenge trials was the minimal criteria for compliance. Diet records were also kept on the final 3 days (including 2 weekdays and 1 weekend day) of each month during the dietary period and were analyzed for sodium using the Nutritionist III nutrient database (ver. 5.1; N-Squared Computing, Salem, OR). Questionnaires addressing problems with dietary compliance were administered monthly during the diet. Sensory tests. Suprathreshold intensity ratings were obtained by magnitude matching25 for samples of: • V-8 juice (Campbell's Soup Co, Camden, NJ) containing five graded levels of NaCI (0.8, 0.4, 0.2, 0.1, and 0.05 mollL), • cherry-flavored Kool-Aid (2.1g/L; General Foods Corp., White Plains, NY) containing 5 levels of sucrose (0.8, 0.4, 0.2, 0.1, and 0.05 mollL), • lemonade [12.5% (v/v) lemon extract and 0.25 mollL sucrose] containing five levels of citric acid (0.02, 0.01, 0.005, 0.0025, and 0.00125 mollL) and • tonic water (0.26 mollL sucrose and 0.02 mollL citric acid) with five concentrations of urea (4.00, 2.00, 1.00, 0.50, and 0.25 mollL). Ten-milliliter samples were presented at room temperature in a random order in duplicate. A rinse with deionized water was interspersed between all samplings of taste solutions. Intensity responses were made on a 200-mm line scale with end anchors of "no salty (sweet, sour, bitter) taste" and "extremely salty (sweet, sour, bitter) taste." Tones were interspersed with taste solutions. The 100-Hz 30, 45, 60,75, and 90dB tones were delivered in a predetermined random order in duplicate by a Maico MA-27 audiometer (Maico Hearing Instruments, Inc., Minneapolis, MN) for 3 seconds. Taste responses were normalized to the auditory responses and plotted against stimulus concentration. The slopes and Yintercepts of the best fitting regression lines served as estimates of perceived intensity. Participants also indicated how much they liked each sample on a line THE AMERICAN JOURNAL OF THE MEDICAL SCIENCES

scale with anchors of "extremely unpleasant" and "extremely pleasant." The order of taste qualities was counter-balanced. Participants were also presented samples of regular and reduced-sodium (or sugar) versions of 12 commercially available products and asked to indicate on a line scale how pleasant they tasted. The foods included: dill pickles (Vlasic Foods Inc., Camden, NJ), tuna (light, in water; Starkist Seafood Co., Newport, KY), potato chips (Herr Foods, Nottingham, PA), crackers (Wheat Thins; Nabisco Foods, Inc., East Hanover, NJ), green beans (Del Monte Foods, San Francisco, CA), cocktail peanuts (Planters, Nabisco Foods Inc., Winston-Salem, NC), V-8 juice (Campbell's Soup Co., Camden, NJ), cheddar cheese (Heluva Good Cheese, Sodus, NY), margarine (Fleishman's; Nabisco Foods Co), white bread (Schafer Bakeries, Inc., Lansing, MI), chicken bouillon (Herb-Ox; Hormel Food Corp., Austin, MN), and grape jelly (J.M. Smucker Co, Orrville, OR). Salt-challenge period. Participants ingested a diet containing 40 mmol of sodium for 4 days. This was followed immediately by a return to each subject's customary diet supplemented with N aCl. The extra sodium was provided as slow-sodium tablets (CIBA Laboratories, Horsham, West Sussex, UK). To minimize gastric complications the dose was 87 mmol on day 1, 130 mmol on day 2, and 174 mmol on days 3-7. A MAP rise of at least 5 mm Hg from the end of the low salt diet period to the end of the high salt diet period was used as the criteria for SS. Reduced sodium dietary period. Subjects were placed on diets containing about 100 mmol Na/day for 4 months. To enhance dietary compliance, subjects were provided guidance by a registered dietitian using food models and printed materials. They were also provided with low-sodium recipes. Statistical analyses. Repeated measures analysis of variance with SS status as a between-groups factor was used to assess changes of sodium excretion, dietary intake, blood pressure, taste preferences, and dietary concerns over the diet period. Pearson correlation coefficients were computed to assess the associations between variables (eg, urinary sodium excretion, reported sodium ingestion, and blood pressure). Analyses were conducted with the Statistical Package for the Social Sciences for Windows (ver. 7.5; SPSS, Chicago, IL). A value of P < 0.05 was used to determine statistical significance. Data are expressed as mean ± standard error (SE). Results

Dietary compliance. Figure 1 shows the mean of two 24-hour urinary sodium excretion values conducted at baseline and the end of each month of the reduced sodium diet for SS and SI participants. Urinary sodium excretion (intake) was comparable 289

Salt Sensitivity and Dietary Compliance

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MONTHS ON DIET among the SS and SI groups before initiating the diet; averaged over the diet period, both groups achieved approximately 50% reductions [change from baseline F(4,64) = 9.72, P < 0.001]. Values were significantly different from baseline for each of the diet months, but there were no statistically significant differences between months. The individual data also showed strong compliance. Whereas only three SS and 1 SI participants had urinary sodium concentrations < 100 mmol/day at baseline, by the end of the diet, 9 of 12 SS participants excreted (ingested) less than 100 mmol Na/day, as did eight of nine SI participants. Urinary sodium excretion and reported dietary sodium ingestion were not significantly correlated and the estimates of sodium intake from diet records were only 65% and 86% of the urinary excretion values for the SS and SI participants, respectively. This suggests that the diet records were probably incomplete. Blood pressure change. MAP was consistently reduced in the SS, although not significantly so relative to pre-diet values. The mean (± SE) reduction of MAP was -2.56 ± 2.14 mm Hg. Nine of the 12 SS subjects had a drop in blood pressure by the end of the period. The SI subjects had smaller and less consistent changes of blood pressure, with means oscillating between small reductions and increases. At the end of the diet period, the SI group had a mean increase of MAP equal to 0.43 ± 2.42 mm Hg. Three of the 9 SI subjects had a reduction. There was no statistically significant difference in blood pressure changes between the SS and SI participants. Urinary sodium excretion was not signifi-

290

cantly correlated with blood pressure response in either group. Hedonic shift. Mean hedonic ratings were computed for the reduced sodium foods and for their normal sodium counterparts at each of the assessed time points. In the pooled sample, repeated-measures analysis of variance revealed a significant effect of salt concentration [F(1,13) = 23.06, P < 0.001], time [F(4,52) = 5.32, P = 0.001] and a salt by time interaction [F(4,52) = 3.03, P = 0.025]. The foods showing the greatest hedonic shift were beans, bread, cheese, potato chips, and margarine (all time effects, P :5 0.05). Lesser effects were observed for tuna fish, chicken, tomato juice, pickles, peanuts and crackers. For the latter three, however, there was also no significant difference in ratings for the regular and reduced sodium versions. The withingroup analyses indicated that only the effect of salt was significant [F(1,7) = 12.49, P = 0.01] among the SS, whereas there was a significant effect of salt [F(1,6) = 16.47,P = 0.007], time [F(5,30) = 5.85,P = 0.001] and a salt-by-time interaction [F(5,30) = 2.53, P = 0.05] among the SI. These results are presented in Figure 2. Thus, the SS showed no change in hedonic ratings for either the low or normal salt foods over time and ratings between them were significantly different at every time point. In contrast, the SI rated the reduced sodium foods as significantly less pleasant than their regular sodium counterparts at baseline, but their ratings rose to levels comparable with the regular versions by the end of the diet period. The hedonic shift was specific May 1999 Volume 317 Number 5

Mattes et 01

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291

Salt Sensitivity and Dietary Compliance

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rating did not change during the 4-month diet period and ratings were comparable for the SS and SI at all time points. Figure 3 depicts the least-square regression lines for the NaCI intensity ratings by SS and SI participants at baseline and the end of the 4-month diet. Hedonic ratings also showed significant concentration effects (all P < 0.001), but there were no time, group, or interaction effects. Obstacles to dietary compliance. Data on baseline reported concerns associated with diet adherence are presented in Figure 4. In absolute terms, the issue rated as most potentially difficult (ie, reduced food availability) received ratings indicative of only moderate concern. In the total sample, reduced food availability was rated significantly higher than increased food preparation time and feeling less healthy (P < 0.005 for both). Concern about feeling less healthy was rated significantly lower than all of the other listed concerns (all P < 0.03), although this was the one issue where a group difference approached significance. The SS tended to rate this as a larger potential problem (P = 0.063). The magnitude of concern for each item tended to decline over the 4-month diet period, but only ratings for decreased palatability of food decreased significantly [F(3,36) = 2.85, P = 0.05]. No statistically significant group differences were observed for the rated Issues. Discussion

A primary motivation for classifying normotensive subjects as salt-sensitive is to implement dietary and lifestyle interventions with the aim of prevent292

Food Prep

Healthy

ing or delaying a rise of blood pressure in this group. Studies with unclassified normotensive subjects indicate moderation of dietary sodium consumption is difficult,6,12 but there are no data on the dietary experiences of SS subjects specifically. Should they face different or more resistant obstacles to dietary change than SI subjects, alternative intervention approaches could be warranted. Although the sample size was modest, the present data provide the first insights on the dietary experiences of reliably classified SS and SI subjects prescribed a reduced-sodium diet. Before dietary intervention, the SS and SI participants consumed comparable quantities of sodium. This is consistent with data from previous studies isolating these groups26,27 ; however, sample sizes from previously published studies have also been too limited to draw firm conclusions on this point. The absolute levels were also comparable with those reported in the general population. 7 Thus, to the extent that our baseline estimates of dietary sodium ingestion captured the participants' customary level of intake, the SS do not seem to habitually consume diets higher in sodium than the S1. When confronted with the prospect of reducing dietary sodium intake, a number of issues were raised. However, the magnitudes of concern were low to moderate. The most highly rated in both groups was the problem of limited availability of foods composing such a diet. Indeed, this issue was viewed as the most difficult throughout the study. The level of concern declined for all potential problems over the course of the diet period, but signifiMay 1999 Volume 317 Number 5

Mattes et al

cantly so only for the issue of decreased palatability offood. This observation was consistent with data on the food ratings, which also revealed a significant group difference. Both groups preferred the regular sodium foods to the reduced-sodium counterparts and preferred them to a similar degree at the start of the diet. We had obtained similar findings in an earlier study of SS and SI African American adolescents. 28 However, the SI showed a hedonic shift over time, so that by the end of the 4-month diet, the reduced-sodium foods were rated equally palatable to the regular sodium versions. Consistent with the literature, the most dynamic phase of the shift occurred over the first 8-12 weeks of the diet29 .3o and the change was specific for preferred saltiness responses,29.31 because no hedonic change was observed for the regular and reduced sugar jelly. It is also noteworthy that the hedonic shift largely involved increased acceptability of the reduced-sodium foods rather than a decline in pleasantness of foods higher in sodium content. In earlier work, there was convergence because of hedonic changes in both types offoods. 31 Contrary to widely held lay beliefs, the hedonic shift was not associated with a change of salt taste responsiveness. Other studies have also reported hedonic changes occur independently of the ability to report on the intensity of suprathreshold salty stimuli. Blais et a}3o and Chan et a}32 observed no changes, and Bertino et al 29 noted an increased intensity rating on only one of two test foods. Thus, the SI displayed a hedonic shift over the course of the study with features largely consistent with previously reported findings. In contrast, no hedonic shift was observed with the SS. Whether a shift just takes longer to occur in the SS or requires more extreme restriction of sensory exposure to salt cannot be answered with the present data. If the SS are resistant to a hedonic shift and diet palatability influences dietary compliance, the SS may find it more difficult to chronically adhere to a reduced sodium diet. The SS achieved a marked reduction in dietary sodium consumption that was comparable with that ofthe SI. Indeed, the target reduction to 100 mmol Na/day was met or exceeded by 9 of 12 SS and eight of nine SI participants (81%). This indicates food palatability was not a prepotent influence on compliance. However, participants in this trial were aware that the diet would be of finite duration rather than a life-long change; as a consequence, they may have been more tolerant of the dietary manipulation. Monitoring SS subjects over a longer period of dietary sodium restriction than used here will be required to address this issue. The SS participants experienced a small but consistent reduction of blood pressure. The absolute magnitude is comparable with that previously reported after moderate sodium restriction in normotensive adults. 33 The SI participants had more variTHE AMERICAN JOURNAL OF THE MEDICAL SCIENCES

able changes as reported elsewhere. 33 Given the high level of dietary compliance with this group of subjects testing reliably for salt-sensitivity status, the lack of a consistent reduction of MAP among the SS and instances of MAP reductions among the SI suggests that the classification lacks sensitivity and specificity. Whether this is attributable to shortcomings in the testing methodology and/or reflects the multifaceted regulation of blood pressure is not known. Until this issue is clarified, it will be difficult to develop dietary recommendations specific for SS subjects. In summary, the SS and SI participants had similar customary intakes of sodium and held similar concerns about adopting a diet reduced in sodium. However, these concerns were not overwhelming and members of both groups were able to meet the goal level of 100 mmol Na/day. Thus reduction of dietary sodium seems feasible among the SS. Although it did not hinder dietary change during this 4-month study, the SS did not exhibit as strong a sensory acclimation to the diet as the SI. Whether this holds implications for longer-term dietary change warrants further study. The poor acceptability offoods included in a reduced-sodium diet among the SS may require different or more intensive dietary intervention strategies to achieve a sustained change of sodium consumption. Should unique interventions prove advantageous, there will also be a need for improved methods to identify SS subjects. In the present study involving reliably classified SS and SI subjects, classification status was not highly predictive of blood pressure changes associated with dietary modification. Acknowledgments

We thank Leslie Bormann, Doreen Dimeglio, Gian Gonzaga, Sarah Kirkmeyer, and Michael Singelton for their invaluable assistance in the conduct of this study. References 1. The fifth report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. Arch Intern Med. Arch Intern Med 1993;153:154-83. 2. National High Blood Pressure Education Program Working Group report on primary prevention of hypertension. Arch Intern Med 1993;153:186-208. 3. 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;267:121320. 4. Stamler J, Caggiula A, Grandits GA, et aI. Relationship to blood pressure of combinations of dietary macronutrients. Findings of the Multiple Risk Factor Intervention Trial (MRFIT). Circulation 1996;94:2417-23. 5. Sacks FM, Obarzanek E, Windhauser MM, et aI.Rationale and design of the Dietary Approaches to Stop Hypertension trial (DASH). A multicenter controlled-feeding study of dietary patterns to lower blood pressure. Ann Epidemiol 1995;5:108-18.

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6. Kumanyika S. Behavioral aspects of intervention strategies to reduce dietary sodium. Hypertension 1991;17(1 Suppl): 1190-5. 7. Food Surveys Research Group, Beltsville Human Nutrition Research Center. Results from USDA's 1996 continuing survey of food intakes by individuals; and, 1996 diet and health knowledge survey. Riverdale (MD): US Department of Agriculture; 1997. 8. Kumanyika SK, Cutler JA. Dietary sodium reduction: is there cause for concern? J Am Coll Nutr 1997;16:192-203. 9. Kumanyika SK, Hebert PR, Cutler JA, et al. Feasibility and efficacy of sodium reduction in the trials of hypertension prevention, phase I. Hypertension 1993;22:502-12. 10. Stamler R. Implications of the INTERSALT study. Hypertension 1991;17(1 Suppl):116-20 11. Kuller LH. Salt and blood pressure: population and individual perspectives. Am J Hypertens 1997;10:29S-36S. 12. Miller JZ, Cohen SJ, Weinberger MH, et al. Effects of sodium restriction in hypertensive outpatients. J Hypertens 1986;4(Suppl 6):S654-6. 13. Horan MJ, Blaustein MP, Dunbar JB, et al. NIH report on nutrition and hypertension. Hypertension 1985;7:818-23. 14. Dustan HP, Kirk KA. Corcoran lecture: the case for or against salt in hypertension. Hypertension 1989;13:696-705. 15. Weinberger MH, Miller JZ, Luft FC, et al. Definitions and characteristics of sodium sensitivity and blood pressure resistance. Hypertension 1986;8:127-34. 16. Laragh JH, Peeker MS. Dietary sodium and essential hypertension: some myths, hopes, and truths. Ann Intern Med 1983;98(Part 2):735-43. 17. Sullivan JM, Prewitt RL, Ratts TE. Sodium sensitivity in normotensive and borderline hypertensive humans. Am J Med Sci 1988;295:370-7. 18. Ruppert M, Overlack A, Kolloch R, et al. Neurohormonal and metabolic effects of severe and moderate salt restriction in non-obese normotensive adults. J Hypertens 1993;11: 743-9. 18a.Mathes RD, Falkner B. Salt-sensitivity classification in normotensive adults. Clin Sci 1999;96:449-59. 19. Grim CE, Luft FC, Miller JZ, et al. Effects of sodium loading and depletion in normotensive first-degree relatives of essential hypertensives. J Lab Clin Med 1979;94:764-71. 20. Luft FC, Miller JZ, Grim CE, et al. Salt sensitivity and

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21.

22. 23.

24. 25. 26. 27. 28. 29. 30. 31. 32.

33.

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May 1999 Volume 317 Number 5