Impact of diet on blood pressure and age-related changes in blood pressure in the US population: analysis of NHANES III.

BACKGROUND: The impact of diet on blood pressure and the age-related changes in blood pressure have been difficult to detect within one population. We designed this analysis to study the association of major dietary factors with blood pressure and with age-related changes in blood pressure in a representative sample of the US population. METHODS: Data were obtained on all individuals 20 years or older (n = 17 030) surveyed in the Third National Health and Nutrition Examination Survey (NHANES III), including demographic data, anthropometric data, dietary intake (sodium, potassium, calcium, magnesium, protein, alcohol, and total energy) based on 24-hour recall, and blood pressure. Multivariate models relating diet to blood pressure were constructed using stepwise regression, best subset regression, and multiple regression. RESULTS: Systolic blood pressure was positively associated with higher sodium, alcohol, and protein intakes (P<.05) and negatively associated with potassium intake (P =.003). Diastolic blood pressure was negatively associated with potassium and alcohol intakes (P<.001). Pulse pressure was positively associated with sodium, protein, and alcohol intakes (P<.001). A higher intake of calcium (P =.01) was associated with a lower rate of rise in systolic blood pressure with age. CONCLUSION: A diet low in sodium, alcohol, and protein is associated with lower systolic blood and pulse pressure. Potassium intake was associated with lower systolic and diastolic blood pressure, whereas alcohol intake was associated with lower diastolic blood pressure. In addition, the age-related changes in systolic blood pressure were attenuated by higher calcium and protein intakes. Magnesium was not associated with any changes in blood pressure.

Detection of adrenal tumors by computerized tomographic scan in endocrine hypertension.

Localization of adrenal lesions in various adrenal disorders can be difficult. An attempt to identify the adrenal tumors in ten patients with pheochromocytoma, Cushing's syndrome, or primary aldosteronism was made using computerized tomographic (CT) scans. The adrenal tumor was visualized in eight patients. The CT scan appears to be a promising noninvasive technique for localization of adrenal tumors.

Rapid blood pressure control with minoxidil: acute and chronic effects on blood pressure, sodium excretion, and the renin-aldosterone system.

Changes in blood pressure, heart rate, electrolyte excretion, and the renin-angiotensin-aldosterone system were monitored before and after minoxidil was added to a regimen of a diuretic and propranolol hydrochloride in 12 severely hypertensive patients. None required more than 40 mg of minoxidil daily for control. On a constant intake, urinary sodium excretion decreased, while urinary potassium excretion remained stable. Heart rate, body weight, and plasma volume increased, while creatinine clearance did not change. Although plasma renin activity increased fourfold, the plasma aldosterone concentration did not increase. Six subjects were restudied after two months of minoxidil treatment. Although blood pressure control continued to be excellent in these subjects, plasma renin values and plasma volume had returned to pretreatment levels. These studies suggest that minoxidil rapidly and effectively lowers blood pressure. Although sodium retention accompanies minoxidil administration acutely, the effect is independent of aldosterone and may be transient.

Dilevalol in severe hypertension. A multicenter trial of bolus intravenous dosing.

Dilevalol, the R-R optical isomer of labetalol, a nonselective beta-antagonist with vasodilation from selective beta 2 agonism, was administered in sequential multiple bolus intravenous injections of 10 to 100 mg in total doses ranging from 35 to 585 mg (mean dose, 414 mg) to 101 patients with supine diastolic blood pressures above 120 mm Hg. Mean blood pressure was reduced from 200 (+/- 3)/129 (+/- 1) mm Hg to 149 (+/- 2)/101 (+/- 1) mm Hg, a mean reduction of 51/28 mm Hg. The therapeutic goal was established as a reduction in supine diastolic blood pressure to less than 100 mm Hg or a reduction of at least 30 mm Hg. This was achieved in 62 (61%) of 101 patients, with an additional 7 patients having a final supine diastolic blood pressure of 100 mm Hg. Treatment with dilevalol was less successful in black male patients than in the group at large. There was a tendency for older patients to respond better than younger patients. Prior recent treatment of patients with beta-adrenergic antagonists decreased the effectiveness of the drug. Significant orthostatic hypotension was not noted. Sixty-four patients were transferred to oral dilevalol treatment in combination with a diuretic, and blood pressure in this group averaged 160/100 mm Hg after 1 month of therapy. Dilevalol appears to be a safe and effective drug that can be used intravenously successfully in the majority of patients with severe hypertension and provides an alternative to therapy with other agents. It also is a useful agent for oral treatment of these patients after successful intravenous therapy.

Biohistory of slavery and blood pressure differences in blacks today. A hypothesis.

Genetic factors are known to play an important role in the variations in blood pressure levels. However, genetic factors that explain the higher average blood pressure levels of western hemisphere blacks when compared with African blacks have not been seriously considered. Because the genetic makeup of a population is largely determined by biological and ecological forces in the past, an examination of the biohistory of blacks, specifically the slavery era, was conducted. An overview of the salient findings of that investigation is included in this article. The published historical evidence on the transatlantic slave trade and New World slavery (from the 16th century to the 19th century) reveals that conditions existed for "natural selection," and therefore, genetic changes were virtually inevitable in the slave populations. During this period of history, mortality was extremely high, and fertility (or reproductive success) was so low among the survivors that most plantation societies in the western hemisphere depended on a constant importation of captives (over 12 million) from Africa for the viability of the plantation communities. Because the major causes of death were salt-depletive diseases such as diarrhea, fevers, and vomiting, it is argued that individuals with an enhanced genetic-based ability to conserve salt had a distinct survival advantage over others and were, therefore, more likely to bequeath their genotype to subsequent generations of Western hemisphere blacks. Thus, it is predicted that blacks in the Americas have a greater frequency of individuals with an enhanced genetic-based ability to conserve salt than African blacks.(ABSTRACT TRUNCATED AT 250 WORDS)

Suppression of renin and aldosterone by small amounts of DOCA in normal man.

Previous investigators have suggested that low renin hypertension may be due to an unknown mineralocorticoid. This investigation was designed to simulate the effect of an unknown mineralocorticoid by administration of small amounts of desoxycorticosterone acetate (DOCA) in three normal subjects. The response of 2-h upright plasma renin activity (PRA), plasma aldosterone concentration (PA), and urinary aldosterone excretion (UA), as well as extracellular fluid volume, (ECFV) was determined on a high and low salt diet before and during the administration of DOCA for 13 days. After 9 days of DOCA, ECFV increased approximately 2 liters and PRA decreased to levels found in our patients with LRH. PA and UA decreased appropriately as PRA was suppressed. We would expect an unknown mineralocorticoid to have similar effects on the reninangiotension-aldosterone system. Thus, these results would suggest that in LRH the normal levels of PA and UA are inappropriately elevated in relation to the low PRA.

Systolic blood pressure levels in black populations in sub-Sahara Africa, the West Indies, and the United States: a meta-analysis.

Average systolic blood pressure levels from epidemiological studies conducted on black populations in sub-Sahara Africa were pooled and compared with pooled systolic blood pressure levels from black populations in the northern portion of the Western hemisphere (the West Indies and the United States). Studies published in English that listed systolic blood pressure means and standard deviations and sample sizes in 40-49-year-old men and women were included. Overall, systolic blood pressure levels were higher (p less than 0.05) in blacks from the northern Western hemisphere than in blacks from sub-Sahara Africa for both men (12 mm Hg higher) and women (13 mm Hg higher). The analysis was also conducted on regions within sub-Sahara Africa and in rural and urban subgroups. Systolic blood pressure was lower (p less than 0.05) in East Africa than in the other three regions within Africa for both sexes. Overall, urban blacks within Africa had higher systolic blood pressures (p less than 0.05) than rural blacks for both sexes. In the northern Western hemisphere, rural blacks had higher systolic blood pressures (p less than 0.05) than urban blacks for both sexes. Studies should be designed with standardized methods to unravel these intraracial differences in blood pressure levels.

Minoxidil increases aldosterone metabolic clearance in hypertensive patients.

It has been shown that despite an effect of minoxidil to increase PRA, plasma levels of aldosterone do not change. We observed similar findings in seven hypertensive patients undergoing treatment with minoxidil; PRA activity increased markedly, whereas the plasma aldosterone concentration showed no consistent change. The aldosterone MCRs in these patients increased by 41% in response to minoxidil, from 1110 +/- 91 to 1570 +/- 180 (SEM) liters/day; this appeared to explain why plasma aldosterone levels did not increase in parallel with renin activity. Hepatic blood flow (estimated from the clearance of indocyanine green) in a group of patients receiving minoxidil was greater than that in an otherwise comparable group (P less than 0.02). This increase in hepatic perfusion may, at least in part, have accounted for the increase in aldosterone MCR.

Rapid cyclic fluctuations of blood pressure associated with an adrenal pheochromocytoma.

We present a patient with an adrenal pheochromocytoma with an unusual pattern of periodic alternating hypertension and hypotension. Alpha-adrenergic blockade alone failed to affect this pattern, which was abolished only after fluid repletion. The efficacy of volume expansion in ultimately correcting the wide fluctuations of blood pressure implicates a possible reflex neurogenic mechanism for the cyclic changes in blood pressure attributable to intravascular volume contraction.

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.

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)

The effect of posture and saline loading on plasma renin activity and aldosterone concentration in pregnant, non-pregnant and estrogen-treated women.

The effect of contraceptive ingestion and pregnancy on components of the renin-angiotensin-aldosterone system was compared in 17 non-pregnant women, 8 non-pregnant women taking oral contraceptives, and 11 pregnant women. Plasma renin substrate concentrations and the dynamic responses of plasma renin activity and aldosterone concentrations to upright posture and iv saline infusion were evaluated. Renin substrate was significantly higher in those women taking oral contraceptives and among the pregnant subjects than the other non-pregnant group. No significant differences in plasma renin activity or aldosterone concentrations were seen before or after postural stimulation among the 2 non-pregnant groups. After saline loading renin was higher and aldosterone lower in the contraceptive-treated group. In contrast, the pregnant group had significantly higher values at every point. The response to posture and saline among the pregnant subjects was similar in direction and magnitude to those of the non-pregnant groups. The urinary excretion of sodium before and after saline infusion was significantly lower in the pregnant group than in the non-pregnant groups. These observations suggest that estrogen-induced increases in renin substrate do not alone account for the increases in the renin-angiotensin-aldosterone system observed during pregnancy, but rather such increases appear to represent a physiological response to increased sodium need during pregnancy.

PIP: The effect of posture and saline loading on plasma renin activity (PRA) and aldosterone concentration in 11 pregnant, 17 nonpregnant, and 8 estrogen-treated women was investigated. Following saline loading, renin was higher and aldosterone lower in the contraceptive-treated group, while the pregnant group has markedly higher values at every point. The response to posture and saline was similar in direction and magnitude in all groups. The urinary excretion of sodium before and after saline infusion was singificantly lower (p less than .005) in the pregnant group than in the nonpregnant groups. The contraceptive group had a significantly higher (p less than .001) mean plasma renin substrate (PRS) than the nonpregnant group. The pregnant group had an even higher PRS when compared to those taking contraceptives (p less than .05). No marked differences in PRA or aldosterone concentrations were seen before or aft postural stimulation among the 2 nonpregnant groups. These results suggest that estrogen-induced increases in renin substrate do not alone account for the increase in the renin-angiotensin-aldosterone system observed during pregnancy, but rather such increases appear to represent a physiological response to increased sodium need during pregnancy.

Differing effects of metoclopramide and adrenocorticotropin on plasma aldosterone levels in glucocorticoid-suppressible hyperaldosteronism and other forms of hyperaldosteronism.

To investigate possible dopaminergic effects on aldosterone production, we administered the dopamine antagonist metoclopramide to 11 normal subjects, 8 patients with primary aldosteronism due to adenoma or hyperplasia, and 5 other patients with the glucocorticoid-suppressible form of hyperaldosteronism (GSH). All subjects except for those with GSH responded to metoclopramide with an increase in plasma aldosterone concentration even when endogenous ACTH was suppressed by dexamethasone pretreatment. This increase occurred without apparent mediation of other recognized stimuli for aldosterone secretion. In contrast, the patients with GSH failed to show any aldosterone response while receiving dexamethasone, but demonstrated a rise in plasma aldosterone concentration when dexamethasone was withheld. The responses in the patients with both forms of primary aldosteronism were greater in magnitude than in the normal subjects or in the subjects with GSH when not receiving dexamethasone. These studies, while demonstrating differences between the subtypes of hyperaldosteronism in their responsiveness to metoclopramide, indicate that ACTH or some other factor may exert a permissive effect in GSH for the aldosterone response to metoclopramide. A graded infusion of ACTH revealed a greater aldosterone response in GSH compared to that in the other groups, further suggesting the importance of ACTH in this disorder.

Genetic and pathophysiologic studies of a new kindred with glucocorticoid-suppressible hyperaldosteronism manifest in three generations.

This report describes investigations in a new kindred with dexamethasone-suppressible hyperaldosteronism affecting three successive generations. The presumptive diagnosis was first made in a 7-yr-old boy and led to the identification of the disorder in his mother and grandmother. Several other members of the family were investigated. Genotyping and HLA typing were also performed. To further explore the nature of this unusual disorder, urine from the three patients documented to have the syndrome was assayed for an aldosterone-stimulating factor recently reported to be found in patients with idiopathic aldosteronism. None of these patients showed measurable activity of such a urinary factor. The identification of members in three generations strongly supports the heritable nature of the disorder and probable autosomal dominant type of transmission. The absence of urinary aldosterone-stimulating factor in these patients further supports the tenet that the disorder is pathogenetically distinct from idiopathic aldosteronism, since both disorders are usually associated with bilateral adrenal hyperplasia.

Norepinephrine in urine and plasma following provocative maneuvers in normal and hypertensive subjects.

Urinary norepinephrine (UNE) excretion rate and venous plasma norepinephrine (PNE) concentrations were studied in 266 normotensive and 107 essential hypertensive men and women under conditions of volume expansion with 2 liters of intravenous normal saline over 4 hours, and volume contraction with a 10 mEq sodium diet and 120 mg oral furosemide. The UNE excretion rate was correlated with age in normal women only. In men, and in hypertensives of both sexes, the relationship appeared to be biphasic. The PNE concentration was not correlated with age in the hypertensive subjects. Insufficient numbers of older subjects were available to exclude absolutely such a relationship among normals. The UNE and PNE were influenced by volume expansion and contraction in both normals and hypertensives; however, normals exhibited a correlation between UNE and blood pressure as well as consistent correlations between UNE and PNE, neither of which were observed in the hypertensives. Hypertensive women generally had greater UNE and PNE values than normal women or hypertensive men. Hypertensive women may have altered sympathetic activity.

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.

Blood pressure in blacks. Twin studies in Barbados.

We have recently reported that there are significant genetic influences on the population variation in blood pressure in black twins in Los Angeles. The present cross-sectional study was undertaken to replicate these findings in a black twin population that lives in a different biosocial environment. We chose the Caribbean island nation of Barbados, where 96% of the population is black, the literacy rate is 99%, and the access to health care is guaranteed. The goals were 1) to test the feasibility of twin studies in blood pressure research in a developing country and 2) to estimate the relative contribution of genes and environment to blood pressure variability in blacks in the Caribbean. The names of 200 twin sets were obtained with the assistance of community resources including a twin club, by media advertisement, and by asking people at public blood pressure screenings if they knew any twins. By using these methods, we identified 200 sets of twins. Of these, 37.5% (75/200) met our criteria for study. Although 97% of the sets of twins (73/75) said they were willing to participate, only 69% (52/75) were able to be scheduled during the 1 week of the study when the full team of investigators was in Barbados. Of those scheduled, 83% (43/52) were examined. Examination included medical history, physical examination, recumbent blood pressure measurements by two observers, anthropometric measurements, 24-hour urine collections for sodium and potassium tests, and blood tests for zygosity.(ABSTRACT TRUNCATED AT 250 WORDS)

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.