Influence of home monitoring on compliance with a reduced sodium intake diet.

To test the utility of a qualitative chloride titrator strip in facilitating compliance with a reduced sodium intake diet, we enrolled 32 patients into a randomized crossover trial comprising two study periods of four weeks each. The study periods were begun after the patients had undergone extensive instruction in the diet and the use of the strip. A high degree of correlation between the patient's and the laboratory's interpretation of the strip result was identified in 29 of the subjects. Ability to use the strip was not related to level of education. A total of 12 patients achieved compliance with the diet when using the strips. Of these, nine were able to achieve compliance without the strips. Ten patients (30%) had significantly lower sodium intake when using the strips than when they did not use them. We conclude that the use of the chloride titrator strip can be mastered by most patients and, in conjunction with dietary counseling, can facilitate compliance with a reduced sodium intake diet.

Role of physical activity in the development of skeletal mass in children.

A group of 118 children, aged 5.3-14 years, were enrolled in a prospective study of calcium supplementation and bone mass. At entry to the study, questionnaires regarding the child's usual physical activity were administered to the children and their mothers. Repeated activity assessments at 6 month intervals indicated good within-person agreement for total activity and for most individual activities. Consistent positive associations were observed between bone mineral densities (BMD) in the radius, spine, and hip and most activities. A summary measure (total hours of weight-bearing activity) was significantly related to BMD in the radius and hip, independently of age or gender effects. Self-reported sports and play activities were associated with BMD, but neither time spent watching television nor hours of physical education classes were associated either positively or negatively with skeletal mass. These data suggest that important increments in skeletal mass may result from physical activity during childhood.

Blood pressure response to potassium supplementation in normotensive adults and children.

To investigate the effect on blood pressure of a modest increase in dietary potassium intake, 38 healthy, free-living families were enrolled in a study involving 4 weeks of potassium supplementation. This was preceded by collection of five baseline measurements of blood pressure and urinary electrolyte excretion and followed by a 4-week recovery period. Although there was a significant increase in urinary potassium excretion during supplementation in both adults and children (p less than 0.001), there were no significant changes in systolic, diastolic, or mean arterial blood pressure. Height and weight increased significantly in children (p less than 0.001), and weight increased in adults (p less than 0.01) over the course of the study. Multivariate analysis of variance of blood pressure controlling for these confounding variables failed to reveal any effect of the potassium supplementation on blood pressure. These results suggest that increasing intake of dietary potassium alone in a healthy, free-living normotensive population is unlikely to have a discernible effect on blood pressure.

Association of blood groups with essential and secondary hypertension. A possible association of the MNS system.

Persons participating in a 5-day diagnostic protocol were routinely typed for ABO, Rh, MNS, Kell, Kidd, Duffy, P, Haptoglobin, phosphoglucomutase-1 (PGM-1), and acid phosphatase (AcP). The study population was composed of 164 normotensive whites, 34 normotensive blacks, 161 whites and 43 blacks with essential hypertension, and 52 whites with secondary forms of hypertension (18 atherosclerotic renovascular hypertensives, 17 patients with fibromuscular disease, and 17 patients with primary aldosteronism). There were no significant differences in phenotype frequencies in ABO, Rh, Kidd, Kell, Duffy, P, Haptoglobin, PGM-1 or AcP in any of the comparisons. However, there was a significantly different distribution of MNS phenotypes in comparisons of essential and atherosclerotic renovascular hypertensives with normotensive controls. Essential hypertensives had a lower frequency of the S gene and a higher frequency of s in whites (X2 = 12.21, p less than 0.005). Atherosclerotic renovascular hypertensives differed from the normotensive population in the frequencies of both MN (X 2 = 4.34, p less than 0.05) and Ss (X2 = 4.21, p less than 0.05). The finding of disease-blood group associations supports the hypothesis that there may be significant physiological differences between individuals of different blood types.

Aldosterone excretion rates in children and adults during sleep.

The present study undertook to examine aldosterone excretion during sleep as an integrated measurement of aldosterone production. A 24-hour urine collection was divided into awake and sleep fractions. Urinary aldosterone and electrolyte excretion were measured in 26 healthy children (mean age, 8.9 +/- 1.9 [SD] years) and 28 adults (mean age, 29.9 +/- 9.5 years). Aldosterone excretion in children was 5.6 +/- 3.9 (SD) micrograms/g creatinine during the awake period, which was significantly different from the 3.9 +/- 4.1 micrograms/g creatinine value recorded during sleep (p less than 0.002). In adults, awake aldosterone excretion was significantly greater than that during sleep; 4.9 +/- 2.7 versus 3.2 +/- 1.6 micrograms/g creatinine (p less than 0.001). Sleep aldosterone excretion values were highly correlated with the corresponding 24-hour aldosterone excretion values (r = 0.85, p less than 0.001) in children and in adults (r = 0.64, p less than 0.001). Sleep aldosterone excretion was correlated with 24-hour potassium excretion (p less than 0.02) only in children. Sleep aldosterone excretion correlated with neither sleep nor 24-hour sodium excretion in children or adults. Sleep electrolyte excretion rates were highly correlated with 24-hour excretion rates in both children and adults. Dexamethasone, 1 mg, administered the night before to suppress the normally high morning levels of endogenous adrenocorticotropic hormone, had no discernible effect on sleep aldosterone excretion. These results indicate that measurement of aldosterone excretion in an easily collected sleep urine sample provides a reliable index of aldosterone production in children and adults.

Definitions and characteristics of sodium sensitivity and blood pressure resistance.

Sensitivity and resistance to the effects of sodium were evaluated in normotensive and hypertensive humans by two approaches. Blood pressure was measured after an intravenous infusion of 2 L of normal (0.9%) saline and after sodium and volume depletion induced by a low sodium diet and furosemide administration in 378 normal volunteers and 198 subjects with essential hypertension. Those in whom mean arterial blood pressure decreased by at least 10 mm Hg after sodium and volume depletion were considered sodium-sensitive, and those with a decrease of 5 mm Hg or less (including an increase in pressure) were considered sodium-resistant. The second study utilized the blood pressure response to modest dietary sodium restriction in 74 normotensive subjects to identify sodium sensitivity and resistance. In both studies the responses were heterogeneous. In the first study significantly more hypertensive subjects were sodium-sensitive, as compared with those in the normotensive group (p less than 0.001). Plasma renin activity (low, normal, or high) did not predict sodium responses. In both groups sodium-sensitive individuals were significantly older (p less than 0.001) and had lower baseline renin values than sodium-resistant subjects. Factors related to the change in mean arterial blood pressure after sodium and volume depletion included baseline pressure (r = -0.54, p less than 0.001) and age (r = -0.16, p = 0.002 in the normotensive group; r = -0.28, p less than 0.001 in the hypertensive group). The response to dietary sodium restriction was also correlated with baseline pressure (r = 0.61, p less than 0.001) and the initial urinary sodium excretion (r = 0.27, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Genetic influences on the urinary excretion of aldosterone in children.

Several studies have shown an inverse relation between blood pressure and plasma aldosterone levels. Since blood pressure is in part genetically regulated, we looked for evidence that genetic factors might also affect aldosterone production. The nocturnal urinary excretion rate was used to estimate aldosterone production, and electrolyte excretion rates were used to estimate sodium and potassium intakes. Studies were carried out in monozygotic (MZ) (n = 37 pairs) and dizygotic (DZ) (n = 26 pairs) twins, aged 6-17 years. Both groups of twins were white. The intraclass correlation coefficient for aldosterone excretion was 0.686 (p = 0.0001) for MZ twins, and 0.290 (p = 0.079) for DZ twins, indicating high heritability for the aldosterone excretion rate. In a second study, we looked for a racial effect on the genetic regulation of aldosterone excretion. Siblings from both black and white families (72 black siblings and 157 white siblings) were selected from an ongoing longitudinal study. Mean values for nocturnal aldosterone excretion, rates measured every 6 months over 1.5-3.5 years, were used in the analysis. The intraclass correlation coefficient for aldosterone excretion, adjusted for sodium and potassium excretion, was 0.510 (p = 0.001) for black siblings and 0.087 (p = 0.228) for white siblings, indicating a strong familial aggregation for aldosterone excretion in black children. In conclusion, studies in twins showed that regulation of urinary aldosterone excretion in children is determined partially by genetic factors. A familial component affecting the aldosterone excretion rate appears to be much stronger in blacks than in whites.

Genetic influences on renin, aldosterone, and the renal excretion of sodium and potassium following volume expansion and contraction in normal man.

To investigate the influence of hereditary on plasma renin activity (PRA), plasma aldosterone concentrations (PAC), blood pressure, and the renal excretion of sodium and potassium following volume expansion and contraction in normal man, we studied 37 pairs of monozygotic (MZ) and 18 pairs of dizygotic (DZ) twins. Volume expansion was achieved by the intravenous infusion of 2L normal saline; volume contraction was accomplished by a low-sodium diet and 120 mg oral furosemide. The presence of genetic variance was tested by calculating the within pair and among component estimates of genetic variance. Outpatient 24-hour-urine collections suggested that MZ and DZ twins ingested diets similar in sodium and potassium content, and failed to reveal genetic influences on the dietary preferences for these electrolytes. The PRA values suggested heritable influences during both the volume expanded and contracted state with the added stimulus of upright posture. Heritable influences were observed on PAC and were most apparent in the basal state on the day of volume expansion. An influence of heredity on blood pressure was most apparent during volume contraction. Urinary sodium excretion (UNaV), urinary potassium excretion (UKV), fractional excretion of sodium (FENa), and fractional excretion of potassium (FEK) revealed evidence of significant genetic variance under the condition of volume expansion. in that state, systolic blood pressure was directly correlated with PRA, PAC, and inversely with FENa. The data suggest that the renal regulation of sodium and potassium excretion is in part influenced by heritable factors that may in turn contribute to the development of hypertension in some individuals.

An approach to the evaluation of genetic influences on factors that regulate arterial blood pressure in man.

To assess the influence of heredity on factors that help regulate the arterial blood pressure in man, we conducted sodium-loading and depletion studies in monozygotic and dizygotic twins, normotensive first-degree relatives of essential hypertensives, and in normotensive control subjects matched for age, sex, and race. Following sodium-loading, we found evidence for the influence of genetic variance on the natriuretic responses, plasma renin activity (PRA), plasma aldosterone concentrations (PA), and plasma and urinary norepinephrine. Relatives of hypertensives differed from controls in that they had higher blood pressures, greater renin values, and relatively sluggish natriuretic responses. Since renin and fractional sodium excretion values were inversely correlated in all subject groups, it is possible that the heritable influences we observed on sodium excretion were mediated by the renin-angiotensin-aldosterone system.

Genetic influences on plasma and urinary norepinephrine after volume expansion and contraction in normal men.

Heritable influences on venous plasma norepinephrine (PNe) and urinary norepinephrine (UNe) values were examined in normotensive monozygotic and dizygotic twins during volume expansion and contraction. The presence of genetic variance was tested by calculating the within-pair estimate of genetic variance. Significant genetic variance was found to influence PNe during recumbency before and after a 4-h iv infusion of 2 liters saline. Similarly, heritable influences on UNe excretion were observed in a 10-h urine collection after the sodium load. Heritable influences on PNe or UNe were not observed after postural stimulation or volume contraction. The data suggest that sympathetic nervous system activity is influenced by heritable factors which may contribute to the development of hypertension in some individuals.

Association of haptoglobin with sodium sensitivity and resistance of blood pressure.

Sodium sensitivity and resistance of blood pressure were examined in 117 normotensive and 85 hypertensive subjects by means of a protocol using rapid extracellular fluid volume expansion with intravenously administered saline (2 L over 4 hours) followed by a day of low dietary sodium intake (10 mEq) and volume contraction induced by a diuretic (furosemide, 120 mg orally). Genetic markers were also examined. Both hypertensive and normotensive subjects with haptoglobin 1-1 phenotype were significantly more (p less than 0.05) likely to be sodium-sensitive than were those with 2-1 or 2-2 phenotypes, and subjects with 2-2 phenotypes were more apt to be sodium-resistant. A second population was examined in which both adults and children with haptoglobin 1-1 phenotype were found to have significantly (p less than 0.05) higher casual systolic and diastolic blood pressures. These two studies independently confirm a relationship between haptoglobin phenotypes and blood pressure and suggest an environmental factor (sodium) as well.

Salt sensitivity and resistance of blood pressure. Age and race as factors in physiological responses.

To identify characteristics that may contribute to salt sensitivity, we conducted studies of normal subjects who are at risk for hypertension, namely blacks, subjects older than 40 years of age, and first-degree relatives of subjects with essential hypertension. We also formulated definitions for salt sensitivity and resistance with a short-term volume expansion and contraction protocol and additionally from data derived from studies of long-term reduced dietary salt intake. We examined the effects of augmented potassium and calcium intake and also those of sodium as the chloride or the bicarbonate salt. Finally, we sought genetic markers that are associated with salt sensitivity. We found that salt sensitivity is a function of age and is more common in blacks than whites. These groups also have relatively delayed acute salt excretion compared with controls. We were unable to identify effects of gender. Haptoglobin phenotypes (HP 1-1) may facilitate identification of salt-sensitive individuals. A high potassium intake may make individuals less salt sensitive. Sodium chloride and sodium bicarbonate differ in their effects on blood pressure. Sodium chloride augments urinary calcium excretion, but sodium bicarbonate does not. Differences between susceptible and nonsusceptible groups, together with improved knowledge of electrolyte interactions, may facilitate our understanding of salt-sensitive hypertension.

Blood pressure response to dietary sodium restriction in normotensive adults.

Sixteen healthy, normotensive husband-wife pairs participated in a study to investigate the effect of reduction of dietary sodium intake (goal less than or equal to 60 mEq/day) on blood pressure. Sodium excretion decreased from a control average of 152.7 +/- 10.1 (SE) mEq/day to 69.5 +/- 4.5 mEq/day (p less than 0.001). Results indicated significant decreases in both systolic (p less than 0.001) and diastolic (p less than 0.001) blood pressure after a period of sodium restriction. In the entire group, there was no significant change in potassium excretion (58.4 +/- 3.2 vs 54.6 +/- 3.5 mEq/day) or body weight (76.0 +/- 2.8 vs 75.3 +/- 2.7 kg). Although there was variability in the blood pressure response, the decrease in blood pressure was significantly correlated with the magnitude of sodium restriction (r = 0.36, p less than 0.03). These results indicate that the blood pressure response to sodium restriction may not be limited to individuals with hypertension and that the response is heterogeneous in normotensive subjects.

Calcium absorption from calcium carbonate and a new form of calcium (CCM) in healthy male and female adolescents.

Calcium absorption from two Ca salts was investigated in a crossover design using stable isotopic tracers in 12 healthy adolescents (6 males, 6 females). A Ca supplement in the form of Ca carbonate or Ca citric and malic acids (CCM) was ingested with a standardized breakfast and the order of administration was randomized. The oral supplement contained 250 mg elemental Ca, 21.8 mg of which was highly enriched 44Ca tracer. Thirty minutes later subjects received 3.6 mg 42Ca tracer intravenously. The molar concentrations of 42Ca and 44Ca tracers in a urine sample obtained 24 h after tracer administration were quantified by fast-atom-bombardment mass spectrometry and used to determine fractional absorption of the Ca from the supplement. Ca in the form of CCM had an increased fractional absorption (p less than 0.03) relative to Ca carbonate in healthy adolescents (36.2 vs 26.4%). This increase was not related to body size, sex, or indices of Ca metabolism.

Blood pressure response to dietary sodium restriction in healthy normotensive children.

To examine the effect of dietary sodium restriction on blood pressure, 149 healthy, normotensive children (64 males, 85 females) participated in a study designed to lower Na intake and maintain Na excretion at less than or equal to 75 mmol/d or half usual intake for 12 wk. Na excretion was decreased during the study period in both males (112.9 +/- 6.3 vs 53.4 +/- 3.6 mmol, p less than 0.001) and females (91.1 +/- 3.2 vs 41.1 +/- 1.9 mmol, p less than 0.001). Changes in systolic blood pressure were not significant in either sex but females showed a decrease (p less than 0.05) in diastolic and mean arterial blood pressures. Because blood pressure in children is correlated with age and body size, multiple linear regression was used to adjust blood pressure levels for age and weight. These analyses yielded small but significant decreases in systolic, diastolic, and mean arterial pressure measurements. The blood pressure response was heterogeneous but this variable response could not be attributed to varying degrees of compliance within families. These results suggest that compliance with modest Na restriction does not consistently lower blood pressure in normotensive children.

Effects of age on renal sodium homeostasis and its relevance to sodium sensitivity.

Age-related changes in blood pressure, renal function, and sodium homeostasis suggest that sodium sensitivity of blood pressure may also be influenced by age. Blood pressure was measured in 378 normal volunteers and 198 patients with essential hypertension after an intravenous infusion of normal saline and after sodium and volume depletion. Those whose mean arterial blood pressure decreased more than 10 mm Hg after sodium and volume depletion were considered sodium-sensitive, whereas those with a decrease of less than 5 mm Hg were considered sodium resistant. The normal and hypertensive subjects were divided into groups of those above and those below 40 years of age. The blood pressure responses of both older and younger groups were normally distributed, indicating that blood pressure could either decrease or increase following volume depletion. Older hypertensive and normotensive subjects are more likely to be sodium sensitive. They usually have lower renin values than do younger subjects, but substantial heterogeneity is found. Age and renin status do not reliably predict sodium sensitivity. Volume contraction and dietary sodium restriction are more likely to decrease blood pressure in older than in younger subjects, but regimens must be tailored individually.

Race and gender influence hemodynamic responses to psychological and physical stimuli.

To evaluate factors influencing hemodynamic responses to psychological and physical stress, 117 normotensive college students were studied. The standardized tests included arithmetic, Stroop word-color, mirror draw, isometric handgrip and cold pressor challenges. The responses of blood pressure and pulse during the tests were compared to the baseline measurements. All the challenges produced a significant (P less than 0.01) increase in systolic and diastolic pressure and pulse rate, with the greatest increase being seen with the isometric handgrip test. The increases in the systolic and diastolic pressure and the heart rate to the psychological stressors were highly correlated (P less than 0.001). The responses to the physical stressors were correlated for the diastolic pressure (P less than 0.01) and the heart rate (P less than 0.001), but not for the systolic pressure. The responses of the systolic and diastolic pressure, but not the heart rate, to the isometric handgrip correlated with the responses to the psychological stressors. The responses of the diastolic pressure and the heart rate, but not the systolic pressure, to the cold pressor stimulus correlated with the responses to the psychological stressors. The gender influenced the response to all the stressors with males having a greater (P less than 0.05) blood pressure response and a lesser (P less than 0.001) heart rate response than females. Black subjects had greater blood pressure responses to the cold pressor test and a greater diastolic pressure response to the handgrip, but there were no observed racial differences in the responses to the psychological stressors.(ABSTRACT TRUNCATED AT 250 WORDS)

Estimation of dietary sodium intake in children.

To examine the utility of nocturnal urine collections in the estimation of dietary sodium intake in children, 29 families who agreed to lower their dietary sodium intake to less than 65 mEq/d were studied. A total of 58 adults and 95 children collected urine specimens weekly or biweekly before and after being instructed in a dietary sodium restriction regimen. Urine collections were fractionated into a diurnal and nocturnal portion. Sodium was measured directly, and estimated by measuring chloride excretion with a chloride titrator stick. Nocturnal chloride and 24-hour sodium excretion were highly correlated in adults (r = .75), and slightly less so (r = .56) in children. The slopes of the relationships were not different. Discriminant analysis showed that two or more chloride estimates permitted classification of both adults and children into the low sodium intake category with 100% accuracy, and into the normal sodium intake category with 75% accuracy. It was concluded that nocturnal chloride estimates are as useful in estimating compliance to a reduced sodium intake in children as in adults.

Heritable aspects of salt sensitivity.

Dietary salt reduction is an important nonpharmacologic remedy for mild hypertension as well as a useful adjunct to drug treatment. However, a reduced salt intake diet is not effective in reducing the blood pressure of all hypertensive patients. Several lines of evidence indicate that some patients are salt-sensitive whereas others are salt-resistant. A series of investigations have been conducted showing that the blood pressure responses to either acute salt and volume loading or to a reduced dietary salt intake are normally distributed. Blood pressure, humoral regulators of blood pressure and renal sodium handling are each found to be influenced by genetic variance. The change in blood pressure from dietary salt reduction is influenced by genetic variance as well. Definitions of salt sensitivity and resistance were formulated, and salt sensitivity of blood pressure was found to occur significantly more often in black than in white Americans. Furthermore, preliminary data suggest that measurement of phenotypes of haptoglobin in blood may assist in identifying salt-sensitive and salt-resistant subjects. Trials of a reduced salt intake diet in pharmacologically treated hypertensive patients are currently being conducted. The data suggest that at least half of the patients are salt-sensitive and that their medications may be reduced in response to the intervention. Results of this study may be of relevance to many of the 60 million Americans with hypertension, particularly to those who are black and elderly.

Calcium absorption in children estimated from single and double stable calcium isotope techniques.

In order to determine whether the specific activity in a single serum sample estimates calcium absorption, six healthy children participated in a study using stable isotopic calcium tracers, one given orally and the second intravenously. High-resolution, fast atom bombardment mass spectrometry was used to quantify the 44Ca and 42Ca tracers in serum and urine. Subjects ingested 250 mg of calcium (215 mg calcium enriched with 35 mg 44Ca) in the form of a chewable calcium citrate malate tablet with a standard meal, followed 30 min later with an i.v. injection of 42Ca tracer. Blood for tracer determinations was obtained at 90, 120, 150, 180, and 300 min after oral ingestion, and a urine sample was obtained 24 h after oral calcium tracer administration. The average calcium absorption estimated from the ratio of urinary tracers was 41.4 +/- 8.2%. This study indicates that the level of oral tracer in serum taken 150 min post-ingestion is significantly correlated (r = 0.85, p less than 0.05) with calcium absorption, as determined by the tracer levels in the urine. These results show that an oral stable isotopic tracer coupled with a single blood sample can be used to estimate calcium absorption in children.