Salt sensitivity (changes in blood pressure in response to alterations in salt intake) may be a risk factor for hypertension. In the present study, we examined the prevalence of salt sensitivity based on two different classifications in healthy black male and female adolescents (aged 13 to 16 years). A total of 135 black adolescents participated in a 50 mmol/24 h low sodium diet for 5 days and a 150 mmol/24 h NaCl supplement for 10 days. Dietary compliance was defined as sodium excretion less than or equal to 50 mmol/24 h for the low sodium diet and greater than or equal to 165 mmol/24 h for the high NaCl supplement. Salt sensitivity was defined by two classifications: (1) as a decrease in mean blood pressure greater than or equal to 5 mm Hg from baseline to the low sodium diet, and (2) as an increase in mean blood pressure greater than or equal to 5 mm Hg from the low sodium diet to the high NaCl supplement. With classification 1, 14% of boys were identified as salt sensitive compared with 22% of girls. With classification 2, however, 31% of boys were identified as salt sensitive compared with 18% of girls. Analyses based on changes in systolic pressure demonstrated similar findings across sex, although overall classifications based on systolic pressure yielded a greater percentage of salt-sensitive subjects. These sex differences in classification patterns were not due to differences in other important variables, such as changes in sodium excretion, potassium excretion, or Quetelet index. These results suggest that the prevalence of salt sensitivity differs by sex depending on the type of protocol used for the classification of salt sensitivity in a black pediatric population.
A number of investigators have suggested that SS (changes in BP in response to alterations in Na+ intake) is an important factor in BP regulation. Previous studies have indicated that the prevalence of SS in normotensive adults ranges from 15% to 42%1 2 and in hypertensive adults from 28% to 74%.1 3 4 5 6 7 8 9 A greater prevalence of SS has also been demonstrated among black compared with white adults and children.10 11 To date, only a few studies have examined sex differences in SS. Although sex differences in SS have been inconsistent, several studies have suggested that among adolescents, girls are more likely than boys to show BP reductions in response to low Na+ diets.12 13 The purpose of the present study was to compare the prevalence of SS in healthy black adolescent boys versus girls across two different SS classifications. The first SS classification was defined as a decrease in MBP from baseline to a low Na+ diet (50 mmol/24 h), and the second SS classification was defined as an increase in MBP from a low Na+ diet (50 mmol/24 h) to a high Na+ diet (150 mmol/24 h NaCl supplement).
The study protocol was approved by the University of Tennessee, Memphis; Le Bonheur Children's Medical Center; and the Medical College of Virginia Institutional Review Boards. Written informed parental consent was obtained before participation. One hundred and thirty-five healthy black adolescents were recruited into the study primarily from schools and churches and through radio and newspaper advertisements. Each child participated in a health screening conducted by a trained nurse at the Clinical Research Center. The screening included BP assessment, urine specimen (to rule out hematuria, glucosuria, or proteinuria), and measurement of height (centimeters) and weight (kilograms). Only normotensive children who did not have preexisting cardiovascular or chronic disease and who were not currently taking medications (including oral contraceptives) were allowed to participate in the program. All participants were within 25% of ideal weight for their height.
Ninety-five adolescents (70%; 35 boys and 60 girls) successfully completed the protocol, and the remaining 40 adolescents (30%) dropped out of the program. Subjects ranged in age from 13 to 16 years old. Analyses comparing compliant versus dropped subjects revealed no differences in demographic variables including age, sex, annual family income, education, and marital status. The final sample was composed of two cohorts: 28 subjects were recruited and run in Memphis, Tenn, from August 1992 to July 1993; the remaining 67 subjects were recruited in Richmond, Va, from August 1993 to the present. Preliminary analyses revealed that the only significant difference among the two cohorts was that the subjects recruited in Richmond were slightly older (14.6 versus 14.1 years, P<.05). Subjects were pooled in subsequent analyses.
Subjects arrived at the Clinical Research Center where they participated in the health screening described above. Next, several questionnaires were administered to the participants and their parents for assessment of demographic and background information. Each child's height and weight were measured by a trained nurse using a standard hospital balance beam scale. BP measurements were obtained by a trained research technician as outlined by the Second Task Force on Blood Pressure Control in Children.14 During measurements, subjects were seated in a relaxed position with their legs uncrossed, and care was taken to select the proper size of cuff for each subject. For all participants, the BP cuff was placed on the nondominant arm throughout BP testing during each visit. A Dinamap automated BP machine (Critikon Inc) was used to obtain BP measures. Before BP assessment, each subject's BP measurements were obtained from the Dinamap and compared with measurements made with a sphygmomanometer to assure accuracy. Only subjects whose SBP measurements were within ±5 mm Hg were allowed to participate in the study. After a 5-minute rest period, a total of five SBP, DBP, and heart rate measurements were taken, with a 30-second interval between readings. The average of these five measurements was used as the BP value for data analyses. MBP values were computed as SBP+2 DBP/3 and were used to define SS based on the two different classifications.
Demographic and Background Information
Parents provided information regarding their child's family history of essential hypertension and related illnesses. Parents indicated in a yes/no format whether anyone in the child's immediate family (father, mother, brother, sister, grandparents, uncles, and aunts) had hypertension, had died of a stroke or heart attack before the age of 50 years, or had died suddenly because of natural causes. For assessment of parental level of education, respondents indicated the highest level of education that the head of the household (the person who financially supported the family) had completed (1=less than 8th grade, 2=8th grade, 3=some high school, 4=high school graduate, 5=some college, 6=college graduate, and 7=professional or graduate school). Parents also indicated their total annual family income (1=less than $10 000, 2=$10 000 to $19 000, 3=$20 000 to $29 000, 4=$30 000 to $39 000, 5=$40 000 to $49 000, 6=$50 000 to $59 000, and 7=$60 000 or more).
Low Na+ Diet
Subjects participated in a 5-day low Na+ diet (50 mmol/24 h). This 5-day protocol was based on a previously published protocol used by Sullivan and Ratts15 which indicated that the decrement in BP during Na+ depletion typically occurred gradually over a 3- to 4-day period. After BP had been assessed, a trained technician gave each child and their parent guidelines for maintaining the low Na+ diet. For example, subjects were told to eat fresh meats (ie, no cured or processed meats), fresh vegetables (no canned vegetables), and fresh fruits. They were also instructed to abstain from eating fast foods and other prepackaged or processed foods. Subjects were also provided with several foods to help them maintain the diet (apple juice, low Na+ peanut butter, low Na+ tuna fish, low Na+ potato chips, and low Na+ margarine). Each family was given examples of breakfast, lunch, and dinner menus that met their individual food preferences. Suggestions were also given for adhering to the diet (consuming very limited, if any, amounts of condiments, dairy products, salad dressings, and foods with baking powder or baking soda). Participants were encouraged to use herbs and fresh spices in lieu of condiments. All child participants were required to keep a food diary to track their Na+ intake each day. To assist the participants in maintaining the low salt diet, an Na+ counter was provided to each family and instructions were given for its use in tracking the dietary goals.
High Na+ Diet
After completing the 5-day low Na+ diet, subjects participated in a 10-day high Na+ diet (NaCl supplement of 150 mmol/24 h). Supplement levels were chosen with the use of the recommended daily allowances of the National Academy of Sciences and were well within established safety limits. The participants were instructed to distribute the supplements across their two heaviest meals and to take the supplements only with a full stomach. In a few cases, the participants were instructed on how to reach the goal of approximately 240 mmol/24 h of dietary Na+ without taking the NaCl supplements. In these cases, subjects were instructed to eat high Na+ foods such as pizza, submarine sandwiches, pickles, and fast foods. Participants were also instructed to add extra table salt to their food.
For determination of compliance, UNaV, UKV, and creatinine excretion were examined from 24-hour urine collections. One 24-hour collection was performed on day 5 of the low Na+ diet. On days 8 and 9 of the high Na+ diet, each subject completed two consecutive 24-hour urine collections. Subjects who had a 24-hour urine volume greater than or equal to 500 mL and creatinine excretion greater than or equal to 10 mg/kg per 24 h met the criteria of having an adequate urine collection. Subjects were considered compliant if their low Na+ diet UNaV was less than or equal to 50 mmol/24 h and their high NaCl diet UNaV was greater than or equal to 165 mmol/24 h. Subjects whose UNaV was less than or equal to 50 mmol/24 h and who showed a threefold or higher increase in their UNaV during the NaCl load were also considered as compliant and were included in the analyses. Urine containers with boric acid preservative were provided for the 24-hour specimens. Urine samples were analyzed for Na+ and potassium with a NOVA 13 analyzer (NOVA Biomedical). Creatinine was measured with a Creatinine Analyzer 2 (Beckman Instruments, Inc).
For SS classification 1, subjects were classified as SS if they showed a decrease in MBP of greater than or equal to 5 mm Hg from baseline to the low Na+ diet. Subjects who showed a decrease of less than 5 mm Hg or who showed an increase in MBP were classified as SR. For classification 2, subjects were classified as SS if they showed an increase in MBP of greater than or equal to 5 mm Hg from the low Na+ diet to the high NaCl supplement diet. Subjects who showed an increase of less than 5 mm Hg or a decrease in MBP were classified as SR.
Approximately 78% of the boys and 73% of the girls had a positive family history of essential hypertension. The average Quetelet index for boys was 21±2 kg/m2 and for girls was 21±3 kg/m2. For boys and girls, the majority of parents had completed high school or some college or had graduated from college. The majority of families of both boys and girls had an annual family income between $10 000 and $50 000. A two-way ANOVA with sex and SS classification in the model was performed for examination of group differences in demographic and baseline variables. The groups did not differ significantly in age, Quetelet index, or baseline heart rate. χ2 analyses also demonstrated no group differences in annual family income, parental education, or family history of essential hypertension. Thus, SS was unrelated to any of these demographic and baseline variables.
Urinary Electrolyte Excretion
Table 1⇓ shows UNaV, UKV, and creatinine excretion for boys and girls separately. A repeated measures ANOVA revealed a significant period effect of UNaV (P<.0001). For both boys and girls, UNaV significantly increased from the low to the high Na+ diet. A repeated measures ANOVA also revealed a significant period effect of UKV (P<.001). For both boys and girls, UKV significantly decreased from the low to the high Na+ diet.
Repeated measures ANOVA indicated a significant period effect for the low Na+ diet on MBP (P<.003) and SBP (P<.0001). MBP and SBP dropped from baseline (72±6 and 104±9 mm Hg, respectively) to the low Na+ diet (70±5 and 101±7 mm Hg, respectively). There was also a significant period effect for the high Na+ diet (NaCl supplement) on SBP (P<.0001). SBP increased from the low to high Na+ diet (101±7 versus 105±9, mm Hg). No other effects were significant.
Table 2⇓ presents BP data by sex and SS based on classification 1 (Na+ depletion). At baseline, SS subjects had greater MBP and SBP than SR subjects (P<.01), and boys had greater SBP than girls (P<.05). Boys also showed greater SBP than girls on the low and high Na+ diets (P<.05). Table 3⇓ presents BP data by sex and SS based on classification 2 (Na+ loading). Boys showed greater SBP than girls at baseline (P<.05). In addition, boys had greater SBP than girls during the low and high Na+ diets (P<.05 for both). SS subjects had lower MBP and SBP than SR subjects during the low Na+ diet (P<.05 for both) and higher MBP and SBP than SR subjects during the high Na+ diet (P<.05 for both).
Classifications Based on MBP
Fig 1⇓ shows the percentage of boys and girls who were identified as SS based on the two classifications by MBP. Overall, boys and girls showed a different prevalence of SS depending on the classification scheme. The prevalence of SS for boys was greater when the classification was defined by an increase in MBP in response to Na+ loading rather than by a decrease in MBP in response to Na+ depletion. For girls, however, the prevalence of SS was fairly equal for both classification schemes. Comparison by sex indicated that the prevalence of SS was greater for boys in response to the NaCl load but greater for girls in response to Na+ depletion.
We conducted further analyses to determine whether there was overlap in classifications (Fig 2⇓). A χ2 analysis indicated that only 6% of the subjects were identified as SS across the two classifications regardless of sex. The overlap was much greater for subjects who were identified as SR. Sixty percent of the boys and 66% of the girls showed an overlap between the two classifications when identified as SR.
Classifications Based on SBP
Fig 3⇓ shows the percentage of boys and girls who were identified as SS based on the two different classifications of SBP. Overall, classifications based on SBP yielded a greater percentage of SS subjects than classifications based on MBP. Boys and girls again showed a different pattern of results depending on the classification scheme. The prevalence of SS for boys was greater when the classification was defined as an increase in SBP in response to Na+ loading. For girls, however, the prevalence of SS was fairly equal across both classifications. Comparison by sex indicated that the prevalence of SS was greater for boys in response to the NaCl load and greater for girls in response to Na+ depletion.
We conducted further analyses to determine whether there was overlap in classifications by SBP (Fig 4⇓). Overall, the overlap increased for SS classifications but decreased for SR classifications when the classifications were based on SBP rather than MBP. A χ2 analysis indicated that 26% of the boys and 15% of the girls were identified as SS across the two classifications. Thirty-seven percent of the boys and 33% of the girls showed an overlap between the two classifications when identified as SR.
Analysis of Covariables
We conducted further analyses to determine whether the above sex differences in SS classifications were influenced indirectly by changes in other important variables, such as UNaV, UKV, or Quetelet index. Change scores for boys and girls were computed separately for each of these variables. UNaV and UKV were only obtained during the low and high Na+ diets. The results indicated that there were no significant differences between boys and girls for classification 1 relative to change in Quetelet index. For classification 2, however, girls tended to show a greater increase than boys in Quetelet index from the low to high Na+ diet (0.6±0.4 versus 0.4±0.4, respectively; P<.05). However, UNaV and UKV did not change significantly in boys versus girls for classification 2.
We performed a series of repeated measures ANCOVAs with Quetelet index, UNaV, and UKV as the covariates in the model to determine whether MBP was influenced by any of these variables. None of the covariates significantly influenced MBP over time, and the adjusted means demonstrated that MBP was not different when controlling for these variables in the analyses.
The results of the present study demonstrate that overall, both boys and girls showed a decrease in MBP and SBP during the low Na+ diet and an increase in SBP in response to the NaCl supplement. Boys, however, were more likely to be classified as SS in response to NaCl loading. The pattern of results for girls looked very similar across both Na+ classification protocols. Comparisons by sex revealed a greater rate of SS for boys to NaCl loading and a greater rate of SS for girls in response to Na+ depletion. Overall, similar sex differences were demonstrated when these classifications were examined for SBP; however, overall, a greater percentage of SS subjects was identified on the basis of SBP classifications. These sex differences in classification patterns were not attributable to changes in other variables, such as UNaV, UKV, or Quetelet index. The data further indicate that there was relatively little overlap in SS classifications across the two protocols.
The finding that boys but not girls showed a greater prevalence of SS in response to NaCl supplementation expands on previous research. In general, research examining sex differences in SS to Na+ loading has been limited and only correlational in nature. For example, some correlational studies have shown that the association between UNaV and BP was unrelated to sex,16 17 whereas other correlational studies have shown a greater positive association among women than men.18 The majority of laboratory studies have focused on sex differences in response to Na+ depletion, with some investigators finding greater rates of SS among women than men.13 19 The findings in the present study suggest the importance of identifying prevalence rates of SS across the sexes in response to both Na+ loading and depletion protocols.
Our data show that a greater percentage of girls than boys were identified as SS in response to the low Na+ diet across MBP and SBP measures. These findings are consistent with a growing literature which indicates that girls are more likely to show BP reductions in response to Na+ depletion than are boys.12 13 19 20 Wilson et al13 examined the prevalence of SS in black male and female adolescents defined as a decrease in MBP greater than or equal to 5 mm Hg in response to a 7-day low Na+ diet (50 mmol/24 h). The results demonstrated that a significantly greater proportion of girls (43%) were SS than boys (23%). Miller et al12 examined BP changes in response to a 3-month Na+-restricted diet (60 mmol/24 h). Girls, but not boys, showed a significant drop in DBP and MBP in response to the diet. Sinaiko et al19 examined the influence of a 3-year Na+-restricted diet (70 mmol/24 h) in 6th- to 8th-grade boys and girls. Girls in the low Na+ group showed a greater negative slope than girls in a placebo condition, whereas no association was found for boys, suggesting that girls were more sensitive to changes in Na+ than boys. Similar findings are also available from epidemiological studies. For example, INTERSALT,18 one of the largest interpopulation studies on Na+ excretion and BP, showed a stronger positive association between Na+ excretion and SBP in women than in men. In that study, the size of the regression coefficients for women was twice that of the regression coefficients for men. Our data, in conjunction with these previous studies, suggest that girls may be more easily identifiable as SS than boys in response to Na+ depletion.
An important question underlying the concept of SS is to understand whether the condition is reproducible across different Na+ protocols; however, research examining this issue is scarce.21 In the present study, we found that only 6% of SS individuals were consistently classified as SS across both classifications for MBP, and only 15% to 26% of SS individuals were consistently classified as SS for SBP. Thus, there was relatively little overlap in detecting SS individuals with either of the two approaches. These findings are consistent with Flack et al,22 who reported a 17% (8 of 48) overlap when subjects were classified as SS based on a bidirectional change of 2 mm Hg or more in DBP. The variability in findings with regard to the prevalence of SS may in part be due to the inconsistent use of protocols and definitions of SS. For example, Weinberger et al9 examined SS among hypertensive and normotensive subjects using an Na+ infusion (0.9% saline at a rate of 500 mL/h for 4 hours) followed by a low Na+ diet (10 mmol/d) the subsequent day. SS was defined as a decrease in mean arterial pressure from the high to the low Na+ diet of at least 10 mm Hg. Conversely, Sullivan and Ratts15 defined SS as an increase in mean arterial pressure of 5% or greater from a low Na+ diet (4 days of 10 mmol/24 h) to a high Na+ diet (4 days of 200 mmol/24 h). In their study of young black adults, Falkner et al23 used only an Na+ loading protocol (435 mmol NaCl daily for 14 days). They defined SS as an increase in mean arterial pressure of 5 mm Hg or greater after the Na+ load. Thus, the minimal overlap in classifying individuals across various Na+ depletion and loading protocols may be partly attributable to procedural differences that vary in the magnitude of NaCl intake, duration of NaCl manipulation, and magnitude of BP change required. Sullivan and Ratts have also suggested that the variation in BP responses across SS and SR subjects may largely be accounted for by differences in vascular resistance and renin-aldosterone functioning. Thus, the lack of overlap in classifying SS individuals across protocols may also be related to individual differences in vascular resistance and/or neurohumoral responses to Na+ depletion/supplementation.
The present study has several limitations. First, baseline measures of UNaV and UKV were not available in this study population. Previous work by our group, however, has demonstrated that among a comparable group of healthy black adolescents (n=37 boys and 38 girls; mean age, 14 years; mean Quetelet, 22), the average baseline UNaV was 146±46 mmol/24 h and baseline UKV was 35±14 mmol/24 h. Thus, the UNaV and UKV rates reflected in the present study during the low and high Na+ protocols seem appropriately responsive on the basis of these previous averages. A second potential limitation involves whether the 5-day low Na+ diet is of sufficient duration to adequately identify SS individuals. Previous research by a number of investigators indicates that the decrement in BP from Na+ depletion occurs within 3 to 4 days.10 24 25 Furthermore, our data demonstrated that as a group, these adolescents showed significant decreases in both SBP and MBP in response to the 5-day low Na+ diet. Taken together, these results suggest that a 5-day period of Na+ depletion should be sufficient to adequately identify the majority of SS individuals. A final limitation to the present study concerns the decrease in UKV during the Na+ loading protocol. Although our analyses demonstrated that the sex differences in Na+ classifications were not influenced by changes in UKV, it is still noteworthy that UKV decreased from the low to high NaCl diet. Given that this study was based on an outpatient protocol, it is difficult to know exactly what this change in UKV may be attributable to. Children in our program have reported a higher intake of potassium-rich foods such as fresh fruits and vegetables during the low Na+ diet; thus, this decrease may reflect a change in the diet back to normal lower levels of intake in response to discontinuation of Na+ depletion. Given that the previous baseline average of UKV in similar populations approximates 35 mmol/24 h, the average intakes ranging from 34 to 39 mmol/24 h during the high Na+ diet in the present study seem quite normal.
In conclusion, this study provides evidence suggesting that the prevalence of SS differs by sex depending on the type of Na+ protocol used. In particular, black adolescent boys are more likely to be identified as SS based on Na+ loading rather than Na+ depletion. However, for black adolescent girls, the prevalence of SS was relatively equal across the two Na+ classification schemes, although compared with boys, girls showed a greater rate of SS in response to Na+ depletion. SS may be an important marker in the identification of children for hypertension prevention programs; however, further research is needed to better understand the underlying mechanisms that may be associated with different prevalence rates in boys versus girls. Further research should investigate neurohormonal correlates of SS in black male versus female adolescents.
Selected Abbreviations and Acronyms
|DBP||=||diastolic blood pressure|
|MBP||=||mean blood pressure|
|SBP||=||systolic blood pressure|
|SS||=||salt sensitivity, salt-sensitive|
|UKV||=||urinary potassium excretion|
|UNaV||=||urinary sodium excretion|
This project was supported by a First Independent Research Support and Transition Award grant HL-46736 from the National Institutes of Health to D.K.W.
Reprint requests to Dawn K. Wilson, PhD, Department of Internal Medicine, Division of Clinical Pharmacology and Hypertension, Medical College of Virginia, PO 980160, Richmond, VA 23298. E-mail email@example.com.
- Received February 2, 1996.
- Revision received March 1, 1996.
- Revision received March 25, 1996.
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