Divergent hemodynamic and hormonal responses to varying salt intake in normotensive subjects. A randomized trial on sodium reduction in two developing countries. Neurohormonal and metabolic effects of severe and moderate salt restriction in non-obese normotensive adults. Moderate salt restriction effectively lowers blood pressure and degree of salt sensitivity is related to baseline concentration of renin and N-terminal atrial natriuretic peptide in plasma. Effect of modest salt reduction on blood pressure, urinary albumin, and pulse wave velocity in white, black, and Asian mild hypertensives. BP changes in obese hypertensive subjects during rapid weight loss. Comparison of restricted v unchanged salt intake. Salt restriction among hypertensive patients: modest blood pressure effect and no adverse effects. A pilot study to test the feasibility of salt restriction in a community. Two-way factorial study of alcohol and salt restriction in treated hypertensive men. Salt-induced increases in systolic blood pressure affect renal hemodynamics and proteinuria. Double-blind randomised trial of modest salt restriction in older people. Effects of weight loss and sodium reduction intervention on blood pressure and hypertension incidence in overweight people with high-normal blood pressure. The Trials of Hypertension Prevention, phase II. The Trials of Hypertension Prevention Collaborative Research Group. Salt-sensitivity testing in patients with borderline hypertension: reproducibility and potential mechanisms. Effects of dietary sodium reduction on blood pressure in subjects with resistant hypertension: results from a randomized trial. Metabolic effects of strict salt restriction in essential hypertensive patients. Effects of reduced sodium intake on hypertension control in older individuals: results from the Trial of Nonpharmacologic Interventions in the Elderly (TONE). Effects of dietary sodium on blood pressure in IDDM patients with nephropathy. Effects of comprehensive lifestyle modification on blood pressure control: main results of the PREMIER clinical trial. Normal responses of atrial natriuretic factor and renal tubular function to sodium loading in hypertension-prone humans. Sodium sensitivity in essential hypertension: role of the renin-angiotensin-aldosterone system and predictive value of an intravenous frusemide test. Prediction of salt sensitivity. Adjunctive effect of salt restriction on antihypertensive efficacy.
Blood pressure responses to 1 week of low-salt (20 mmol sodium/d) and high-salt (300 mmol sodium/d) intake were investigated in a single-blind randomized study in 163 white, nonobese normotensive subjects (65 women and 98 men; mean age, 38 +/- 1.2 years). The individuals were classified as salt sensitive when mean arterial blood pressure rose by at least 5 mm Hg during high-salt intake, as salt resistant when mean arterial blood pressure changed by less than 5 mm Hg, and as "counterregulator" when mean arterial blood pressure fell by at least 5 mm Hg during the high-salt diet. Reexamination of 31 subjects showed that this approach to the testing of salt sensitivity was reliable and reproducible. Thirty subjects (18.4%) were classified as salt sensitive, 108 (66.3%) as salt resistant, and 25 (15.3%) as counterregulators. Multiple regression analysis revealed that age, body weight, and family history of hypertension contributed significantly to the change in blood pressure after the diets. Salt sensitivity was more frequent in older subjects and in those with a positive family history of hypertension. An increase in blood pressure after salt restriction was more likely in younger individuals and in those with a negative family history of hypertension. Plasma renin activity and plasma aldosterone concentrations were lower in salt-sensitive compared with salt-resistant and counterregulating subjects. The rise in plasma renin activity during salt restriction was most pronounced in counterregulating subjects. Plasma norepinephrine concentrations were not different among the groups.(ABSTRACT TRUNCATED AT 250 WORDS) Hypertension remains the most common cardiovascular risk factor in developing countries, yet the majority of patients have no access to pharmacological therapy. Population-wide preventive strategies, such as salt restriction, are an attractive alternative, but experience in resource-poor settings is limited. To address this question, we conducted a randomized crossover study of salt restriction in adults living in Nigeria and Jamaica in order to estimate the mean blood pressure (BP) response. After a 4-week run-in period to determine willingness to adhere to a low-salt diet, 56 Jamaicans and 58 Nigerians completed an 8-week crossover study of low-salt and high-salt intake. Baseline BPs were in the normotensive range (systolic=125 mmHg in Jamaica, 114 mmHg in Nigeria). Baseline urinary sodium excretion was 86.8 and 125.6 mEq/day in Nigeria and Jamaica, respectively. The mean difference between urinary sodium excretion at baseline and at the end of the 3-week low-sodium phase was 33.6 mEq/day in Nigeria and 57.5 mEq/day in Jamaica. During the high-sodium phase, mean change in urinary sodium excretion from baseline to week 3 was 35.0 and 5.5 mEq/day in Nigeria and Jamaica, respectively. The mean change in systolic BP ('high' vs 'low' sodium phase) was approximately 5 mmHg in both groups. This study suggests that the efficacy of sodium reduction in developing countries equals those noted in more affluent cultures. If promoted on a wide scale, sodium reduction could be used to treat persons with established hypertension, and more importantly, to prevent age-related increases in BP in poor communities. The effects of severe and moderate sodium restriction on blood pressure, neurohormonal activity and serum lipids were studied in non-obese normotensive adults.
                In the first part of the study, 163 subjects were randomly assigned to a diet of 20 or 300 mmol/day sodium for 1 week each. In the second part, 25 subjects were given a diet of 85 or 200 mmol/day sodium for 4 weeks each in random order.
                After severe salt restriction 19% of the subjects had a significant decline (salt-sensitive group), 15% showed a significant rise (counter-regulator group) and 66% exhibited no change in blood pressure (salt-resistant group). Severe sodium restriction increased plasma renin activity and noradrenaline concentration, as well as serum total and low-density lipoprotein-cholesterol and triglycerides. After correction for haematocrit, only the changes in total and low-density lipoprotein-cholesterol remained significant. The rise in plasma renin activity during salt restriction was steeper in the counter-regulator group than in the other groups, whereas the changes in plasma noradrenaline concentrations were similar in all groups. During moderate salt restriction, plasma renin activity and noradrenaline concentration were significantly increased, but serum lipid concentrations and blood pressure did not change.
                In non-obese normotensive adults, severe and moderate salt restriction stimulates neurohormonal activity. In contrast to severe salt restriction, a moderate reduction in dietary salt intake does not influence blood lipids in normotensive subjects. The effect of salt restriction on blood pressure is under intense debate. We tested the effect of 100 mmol salt reduction on ambulatory blood pressure (ABP) in 46 Swedish individuals, 39 of whom completed the study, using a double-blind, placebo-controlled, cross-over design. Furthermore, we tested whether the basal plasma concentration of renin or N-terminal atrial natriuretic peptide (Nt-proANP) predict the degree of salt sensitivity.
                Participants received all meals and drinks with a total daily NaCl content of 50 mmol during 8 weeks. In addition, NaCl capsules (100 mmol/day) and corresponding placebo capsules were administered for 4 weeks each in random order. ABP after high-salt intake (150 mmol/day) was compared with ABP after low-salt intake (50 mmol/day). Salt sensitivity was defined as the difference between 24-h systolic ABP at the high-salt versus the low-salt periods. Baseline renin and Nt-proANP were related to salt sensitivity.
                Lowering of salt intake from 150 to 50 mmol/day induced significant blood pressure reductions (mean reduction, 95% confidence interval) in systolic and diastolic 24-h ABP (5.8, 3.4-8.2 and 2.6, 0.91-4.4 mmHg), daytime ABP (5.5, 2.9-8.1 and 2.3, 0.42-4.1 mmHg) and night-time ABP (6.4, 3.5-9.3 and 3.4, 1.4-5.5 mmHg). Baseline ln(renin) correlated inversely with salt sensitivity (r = -0.50, P = 0.001) whereas baseline ln(Nt-proANP) correlated directly (r = 0.33, P = 0.04).
                Lowering of salt intake with 100 mmol/day induces clinically relevant ABP reductions. Renin and Nt-proANP, measured with individuals on their habitual diet, could be useful biomarkers to identify individuals with the greatest blood pressure-lowering benefit from reduced salt intake. A reduction in salt intake lowers blood pressure. However, most previous trials were in whites with few in blacks and Asians. Salt reduction may also reduce other cardiovascular risk factors (eg, urinary albumin excretion, arterial stiffness). However, few well-controlled trials have studied these effects. We carried out a randomized double-blind crossover trial of salt restriction with slow sodium or placebo, each for 6 weeks, in 71 whites, 69 blacks, and 29 Asians with untreated mildly raised blood pressure. From slow sodium to placebo, urinary sodium was reduced from 165+/-58 (+/-SD) to 110+/-49 mmol/24 hours (9.7 to 6.5 g/d salt). With this reduction in salt intake, there was a significant decrease in blood pressure from 146+/-13/91+/-8 to 141+/-12/88+/-9 mm Hg (P<0.001), urinary albumin from 10.2 (IQR: 6.8 to 18.9) to 9.1 (6.6 to 14.0) mg/24 hours (P<0.001), albumin/creatinine ratio from 0.81 (0.47 to 1.43) to 0.66 (0.44 to 1.22) mg/mmol (P<0.001), and carotid-femoral pulse wave velocity from 11.5+/-2.3 to 11.1+/-1.9 m/s (P<0.01). Subgroup analysis showed that the reductions in blood pressure and urinary albumin/creatinine ratio were significant in all groups, and the decrease in pulse wave velocity was significant in blacks only. These results demonstrate that a modest reduction in salt intake, approximately the amount of the current public health recommendations, causes significant falls in blood pressure in all 3 ethnic groups. Furthermore, it reduces urinary albumin and improves large artery compliance. Although both could be attributable to the falls in blood pressure, they may carry additional benefits on reducing cardiovascular disease above that obtained from the blood pressure falls alone. A controlled prospective study compared two groups of obese hypertensive subjects during 12 weeks of a hypocaloric protein-supplemented fast containing 40 mEq of sodium daily. One group received additional sodium chloride sufficient to maintain baseline sodium intake measured prior to the fast (210 m/Eq/day). Sodium restriction resulted in greater weight loss and slightly greater BP reduction only during the initial week of fasting. Thereafter, despite sodium equilibrium, further substantial weight loss and BP reduction were identical in both groups, the decrement in weight being linear (1.89 kg/wk) and the BP reduction asymptotic. Although the initial reduction in BP during the first week of supplemented fast may be attributable to negative salt and water balance, the further reduction in BP during a period of constant sodium balance must be caused by weight loss per se or by the triggering of other antihypertensive mechanisms associated with weight reduction. Previous studies, mainly evaluating short-term very low salt diets, suggest that salt restriction may influence glucose and insulin metabolism, catecholamines, renin, aldosterone, and lipid levels adversely. The authors wanted to explore whether sodium restriction for eight weeks influenced insulin secretion unfavourably, and evaluate the efficacy and safety of such treatment also in terms of other parameters important in the management of hypertensive patients.
                A double-blind randomized controlled parallel group designed trial. All participants received dietary advice aimed at a moderate salt-restricted diet. Half of the participants received salt capsules, the others received identical placebo capsules.
                General practice.
                Forty-six hypertensive patients inadequately controlled by drug treatment.
                Fasting serum insulin C-peptide and glucose and levels of these measures after oral glucose, blood pressure, serum aldosterone and lipids, peripheral resistance, and skin conductance.
                Salt restriction did not influence glucose and insulin metabolism, aldosterone, or lipid levels adversely. We observed better blood pressure regulation in the low salt group than in the high salt group, with a systolic and diastolic blood pressure difference of 5/5 mmHg after eight weeks. The difference was only statistically significant for diastolic blood pressure, p 0.02.
                This study revealed a modest diastolic blood pressure reducing effect of moderate sodium restriction. This reduction was obtained without any apparent unfavourable side effects such as increased insulin secretion, impaired glucose tolerance or dyslipidaemia. Index subjects were selected from the population of Milton studied in the May 1981 survey. Index subjects aged 64 or less with a systolic blood pressure 138-179 mmHg (18.35/23.8 kPa), including those on antihypertensive treatment, were invited to participate with their families. Index subjects were divided into two matched groups. One group was randomly assigned to be the control group and the other to be the salt-restriction group. Age, weight, height and 24-hour urinary excretion of sodium, potassium and creatinine at the start of the study in August 1981 were similar for the control and salt-restriction groups. When tested in November 1981, the salt-restriction group had achieved a reduction in 24-hour sodium excretion to a mean of 84 mmol for men and 70 mmol for women; corresponding values for the control groups were 150 and 120 mmol. A further test in March 1982 showed little further change. Potassium output changed very little. Attitudes to the low-salt diet varied, but 87 percent found it tolerable or actually preferable. There is no doubt that major reductions in sodium intake are feasible. However, if these are to be achieved on a large scale, food, manufacturers will need to offer a variety of low-sodium foods. The aim of this study was to determine whether moderate restriction of dietary salt intake leads to an additional fall in blood pressure in treated hypertensive men who are asked to simultaneously reduce their usual alcohol intake. Sixty-three subjects entered an initial 2-week familiarization period during which they continued their usual alcohol intake and commenced a "low sodium" diet (less than 60 mmol/day) supplemented with 100 mmol sodium chloride per day as enteric-coated tablets. Subjects were then randomly assigned to either drink a low alcohol beer alone for a 4-week period (reducing their self-reported alcohol consumption from 537 to 57 ml/week) or to continue their usual alcohol intake (543 versus 557 ml/week). Within the low and normal alcohol intake groups, subjects were assigned to either a low or normal sodium intake. The low sodium groups continued the sodium-restricted diet but were switched to placebo sodium chloride tablets for the 4 weeks. This resulted in a fall in the 24-hour urinary sodium excretion from 144 to 69 mmol/day. The normal sodium groups continued the low sodium diet but kept taking 100 mmol/day of the sodium chloride tablets, and their urinary sodium excretion remained unchanged (125 versus 142 mmol/day). Regular antihypertensive therapy was continued throughout. Fifty-nine subjects completed the trial. In those who reduced their alcohol intake there was a fall in both systolic blood pressure (-5.4 mm Hg supine, p less than 0.01) and diastolic blood pressure (-3.2 mm Hg supine, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) Nine white and 13 black hypertensive patients with normal serum creatinine were randomized to receive either 2 weeks of a low-salt (40 mEq Na+/d) or high-salt (200 mEq Na+/d) diet followed by 2 weeks of the other diet separated by a 1-week washout on their regular diet. The entire study was conducted in an outpatient setting with intensive dietary instruction and monitoring of blood pressure and 24-hour collections of urine for analysis. Urine electrolyte measurement showed that the patients were able to achieve only a modestly reduced (100 +/- 14 mEq Na+/24 h [mean +/- SEM]) low-salt diet as outpatients, while the higher-salt diet (236 +/- 22 mEq Na+/24 h) was more easily achieved. Eleven patients (8 black, 3 white) were classified as modestly salt sensitive on the basis of an increase or decrease in mean arterial pressure of > or = 3 mm Hg going from lower- to high- or high- to lower-salt diets, respectively. In the salt-sensitive patients, the increase in dietary salt intake increased glomerular filtration rate by 29% (71.2 +/- 6.6 to 85.8 +/- 7.3 mL.min-1.1.73 m2, P = .05), with no significant change in renal plasma flow (412.7 +/- 36.4 to 399.6 +/- 27.8 mL.min-1.1.73 m2). There were no changes in these parameters in the salt-resistant patients.(ABSTRACT TRUNCATED AT 250 WORDS) Stroke is directly related to blood pressure and treatment trials in older hypertensive individuals show a reduction in strokes. However, the majority of strokes occur in normotensive individuals in whom no attempt is made to lower blood pressure. We compared the effects of modest salt restriction on blood pressure in older hypertensive and normotensive people.
                47 untreated elderly people (24 men, age range 60-78 years; blood-pressure range 123-205 mm Hg systolic and 64-112 mm Hg diastolic) completed a 2-month double-blind randomised placebo-controlled crossover study of modest salt restriction with slow sodium and placebo to give a salt intake of either 10 g (equivalent to the normal amount for the UK population) or 5 g.
                On the normal salt intake for the UK population, supine blood pressure was 163/90 (SD 21/10) mm Hg with urinary sodium excretion of 177 (49) mmol/day. With modest sodium restriction, blood pressure fell to 156/87 (22/9) mm Hg (p < 0.001/0.004) with a urinary sodium excretion of 94 (50) mmol/day. A reduction in sodium intake of 83 mmol/day was associated with a reduction of 7.2/3.2 mm Hg. There was no significant difference in the blood-pressure fall between 18 normotensive and 29 hypertensive participants (8.2/3.9 vs 6.6/2.7 mm Hg).
                A modest reduction in salt intake leads to a fall in blood pressure in both normotensive and hypertensive older people similar to that in outcome trials of thiazide-based treatment. Since the majority of strokes in older people occur below the current definition of hypertension, our results have important implications for the prevention of stroke. To provide a firmer basis for preventing high blood pressure (BP), we tested interventions to promote weight loss, dietary sodium reduction, and their combination for lowering diastolic BP, systolic BP, and the incidence of hypertension during a 3- to 4-year period.
                We conducted a randomized, 2 x 2 factorial, clinical trial, with BP levels measured by blinded observers. Nine academic medical centers recruited 2382 men and women (age range, 30-54 years) not taking antihypertensive drugs, with a diastolic BP of 83 to 89 mm Hg, a systolic BP lower than 140 mm Hg, and a body mass index (the weight in kilograms divided by the square of the height in meters) representing 110% to 165% of desirable body weight. Counseling aimed at helping participants achieve their desirable weight or a 4.5-kg or more weight reduction (in the weight loss and combined groups) and/or sodium intake of 80 mmol/d (in the sodium reduction and combined groups) was provided.
                From baseline, participants' weight decreased by 4.3 to 4.5 kg at 6 months and by approximately 2 kg at 36 months in the weight loss and combined groups compared with weight changes in the usual care group (all groups, P < .001). Sodium excretion decreased 50 and 40 mmol/d at 6 and 36 months, respectively, in the sodium reduction group and about 15 mmol/d less at each time point in the combined group compared with the usual care group (all groups, P < .01). Compared with the usual care group, BP decreased 3.7/2.7 mm Hg in the weight loss group, 2.9/1.6 mm Hg in the sodium reduction group, and 4.0/2.8 mm Hg in the combined group at 6 months (all groups, P < .001). At 36 months, BP decreases remained greater in the active intervention groups than in the usual care group (weight loss group, 1.3/0.9 mm Hg; sodium reduction group, 1.2/0.7 mm Hg; combined group, 1.1/0.6 mm Hg). Differences were statistically significant for systolic and diastolic BP in the weight loss group and for systolic BP in the sodium reduction group. Through 48 months, the incidence of hypertension (BP > or = 140 mm Hg systolic or > or = 90 mm Hg diastolic or the use of antihypertensive drugs) was significantly less in each active intervention group than the usual care group (average relative risks, 0.78-0.82).
                In overweight adults with high-normal BP, weight loss and reduction in sodium intake, individually and in combination, were effective in lowering systolic and diastolic BP, especially in the short-term (6 months). Although the effects on average BP declined over time, reductions in hypertension incidence were achieved. We examined the reproducibility of dietary salt-sensitivity testing by studying the effects on blood pressure (BP) of low sodium intake (20 mmol/day) and high sodium intake (220 mmol/day) in 10 men with borderline hypertension on two separate occasions. A difference in mean arterial pressure of 8 mm Hg between the high salt and the low salt regimen was arbitrarily chosen to define salt sensitivity. In addition, the reproducibility of changes in renal haemodynamics and in humoral factors, such as plasma renin activity, plasma aldosterone, atrial natriuretic peptide and urinary dopa and dopamine excretion, on the alteration in sodium intake were studied. As far as changes in BP are concerned, there was perfect agreement between the two tests, because in the second investigation, all subjects were classified in the same category as before. The salt-induced changes in plasma atrial natriuretic peptide and in renal excretion of dopa (dihydroxyphenylalanine) and dopamine were repeatedly and consistently different between the salt-sensitive and the salt-resistant group. The study revealed no support for a role of renal haemodynamics or the renin-angiotensin-aldosterone system in the pathophysiology of salt-induced elevations of BP in salt-sensitive subjects. Observational studies indicate a significant relation between dietary sodium and level of blood pressure. However, the role of salt sensitivity in the development of resistant hypertension is unknown. The present study examined the effects of dietary salt restriction on office and 24-hour ambulatory blood pressure in subjects with resistant hypertension. Twelve subjects with resistant hypertension entered into a randomized crossover evaluation of low (50 mmol/24 hours x 7 days) and high sodium diets (250 mmol/24 hours x 7 days) separated by a 2-week washout period. Brain natriuretic peptide; plasma renin activity; 24-hour urinary aldosterone, sodium, and potassium; 24-hour ambulatory blood pressure monitoring; aortic pulse wave velocity; and augmentation index were compared between dietary treatment periods. At baseline, subjects were on an average of 3.4+/-0.5 antihypertensive medications with a mean office BP of 145.8+/-10.8/83.9+/-11.2 mm Hg. Mean urinary sodium excretion was 46.1+/-26.8 versus 252.2+/-64.6 mmol/24 hours during low- versus high-salt intake. Low- compared to high-salt diet decreased office systolic and diastolic blood pressure by 22.7 and 9.1 mm Hg, respectively. Plasma renin activity increased whereas brain natriuretic peptide and creatinine clearance decreased during low-salt intake, indicative of intravascular volume reduction. These results indicate that excessive dietary sodium ingestion contributes importantly to resistance to antihypertensive treatment. Strategies to substantially reduce dietary salt intake should be part of the overall treatment of resistant hypertension. Some observations suggest that a strict low-salt diet may induce unfavourable metabolic side-effects. The main aim of this study was to analyse the possible consequences of severe salt restriction in mildly hypertensive patients.
                The study was carried out through a randomized double-blind protocol.
                Forty-seven ambulatory patients proceeding from the hypertension unit were initially admitted: 17 were lost, and 30 non-diabetic mildly hypertensives (DBP 90-104 mmHg) with normal renal function completed the protocol.
                After a wash-out period, patients were maintained on a low-salt intake (2.8 +/- 1.0 g day-1 of NaCl) and placebo for 2 weeks, and the same diet and salt supplements (11.7 +/- 2.5 g day-1 of NaCl) for another 2 weeks, separated by a second wash-out period.
                At the end of each dietary period, blood pressure (BP) and body weight were measured, and a blood sample was taken for determination of routine serum chemistries, plasma lipid and apolipoprotein concentrations, immunoreactive insulin (IRI), and plasma renin activity (PRA). Urinary 24 h excretion of sodium and potassium were measured.
                During the salt restriction period BP did not change, weight lowered, and PRA raised. There was a significant increase in serum level of creatinine, uric acid, IRI, total cholesterol and apo B, and a decrease in HDL cholesterol and apo A-I.
                As previously suggested, these observations seem to indicate that strict salt restriction may cause, at least in the short-term, adverse metabolic changes in hypertensive patients. Few trials have evaluated the effects of reduced sodium intake in older individuals, and no trial has examined the effects in relevant subgroups such as African Americans.
                The effects of sodium reduction on blood pressure (BP) and hypertension control were evaluated in 681 patients with hypertension, aged 60 to 80 years, randomly assigned to a reduced sodium intervention or control group. Participants (47% women, 23% African Americans) had systolic BP less than 145 mm Hg and diastolic BP less than 85 mm Hg while taking 1 antihypertensive medication. Three months after the start of intervention, medication was withdrawn. The primary end point was occurrence of an average systolic BP of 150 mm Hg or more, an average diastolic BP of 90 mm Hg or more, the resumption of medication, or a cardiovascular event during follow-up (mean, 27.8 months).
                Compared with control, mean urinary sodium excretion was 40 mmol/d less in the reduced sodium intervention group (P<.001); significant reductions in sodium excretion occurred in subgroups defined by sex, race, age, and obesity. Prior to medication withdrawal, mean reductions in systolic and diastolic BPs from the reduced sodium intervention, net of control, were 4.3 mm Hg (P<.001) and 2.0 mm Hg (P =.001). During follow-up, an end point occurred in 59% of reduced sodium and 73% of control group participants (relative hazard ratio = 0.68, P<.001). In African Americans, the corresponding relative hazard ratio was 0.56 (P =.005); results were similar in other subgroups. In dose-response analyses, end points were progressively less frequent with greater sodium reduction (P for trend =.002).
                A reduced sodium intake is a broadly effective, nonpharmacologic therapy that can lower BP and control hypertension in older individuals. The objectives of the study were to assess the effects of moderate sodium restriction on blood pressure in insulin-dependent diabetic (IDDM) patients with nephropathy and high normal or mildly hypertensive blood pressure (primary objective), and to document possible associated changes of exchangeable body sodium, body volumes, components of the renin-angiotensin-aldosterone system, atrial natriuretic peptide, and catecholamines (secondary objective). Sixteen patients with untreated systolic blood pressure > or = 140 < 160 mmHg and/or diastolic blood pressure > or = 85 < 100 mmHg were included in a double-blind, randomized, placebo-controlled trial. After a 4-week run-in period on their usual diet and a 2-week dietary training period to reduce sodium intake to about 90 mmol/day, eight patients received 100 mmol/day sodium supplement (group 2) and eight patients a matching placebo (group 1) for 4 weeks while continuing on the reduced-sodium diet. Patients were examined at weekly intervals. Main response variables were mean values of supine and sitting systolic and diastolic blood pressure as measured in the clinic and by the patients at home. The differences in blood pressure between the beginning and the end of the blinded 4-week study period were calculated and the differences in changes between the two patient groups were regarded as the main outcome parameters. During the blinded 4-week study period, average urinary sodium excretion was 92 +/- 33 (mean +/- SD) mmol/day in group 1 and 199 +/- 52 mmol/day in group 2 (p = 0.0002). The differences in blood pressure changes between the two patient groups were 3.9(-1.2 to 9) mmHg [mean (95% confidence intervals)] for systolic home blood pressure, 0.9(-3.7 to 5.5) mmHg for diastolic home blood pressure, 4.9(-3.3 to 13.1) mmHg for clinic systolic blood pressure and 5.3(1 to 9.7 mmHg, p = 0.02) for clinic diastolic blood pressure. Combining all patients, there were relevant associations between changes of urinary sodium excretion and blood volume (Spearman correlation coefficient r = 0.57), blood pressure and angiotensin II (diastolic: r = -0.7; systolic: r = -0.48), and exchangeable body sodium and renin activity (r = -0.5). In conclusion, in this study of IDDM patients with nephropathy and high normal or mildly hypertensive blood pressure, a difference in sodium intake of about 100 mmol/day for a period of 4 weeks led to a slight reduction of clinic diastolic blood pressure. Studies including larger numbers of patients with various stages of nephropathy and hypertension are needed to definitely clarify the effects of sodium restriction in IDDM. Weight loss, sodium reduction, increased physical activity, and limited alcohol intake are established recommendations that reduce blood pressure (BP). The Dietary Approaches to Stop Hypertension (DASH) diet also lowers BP. To date, no trial has evaluated the effects of simultaneously implementing these lifestyle recommendations.
                To determine the effect on BP of 2 multicomponent, behavioral interventions.
                Randomized trial with enrollment at 4 clinical centers (January 2000-June 2001) among 810 adults (mean [SD] age, 50 [8.9] years; 62% women; 34% African American) with above-optimal BP, including stage 1 hypertension (120-159 mm Hg systolic and 80-95 mm Hg diastolic), and who were not taking antihypertensive medications.
                Participants were randomized to one of 3 intervention groups: (1) "established," a behavioral intervention that implemented established recommendations (n = 268); (2) "established plus DASH,"which also implemented the DASH diet (n = 269); and (3) an "advice only" comparison group (n = 273).
                Blood pressure measurement and hypertension status at 6 months.
                Both behavioral interventions significantly reduced weight, improved fitness, and lowered sodium intake. The established plus DASH intervention also increased fruit, vegetable, and dairy intake. Across the groups, gradients in BP and hypertensive status were evident. After subtracting change in advice only, the mean net reduction in systolic BP was 3.7 mm Hg (P<.001) in the established group and 4.3 mm Hg (P<.001) in the established plus DASH group; the systolic BP difference between the established and established plus DASH groups was 0.6 mm Hg (P =.43). Compared with the baseline hypertension prevalence of 38%, the prevalence at 6 months was 26% in the advice only group, 17% in the established group (P =.01 compared with the advice only group), and 12% in the established plus DASH group (P<.001 compared with the advice only group; P =.12 compared with the established group). The prevalence of optimal BP (<120 mm Hg systolic and <80 mm Hg diastolic) was 19% in the advice only group, 30% in the established group (P =.005 compared with the advice only group), and 35% in the established plus DASH group (P<.001 compared with the advice only group; P =.24 compared with the established group).
                Individuals with above-optimal BP, including stage 1 hypertension, can make multiple lifestyle changes that lower BP and reduce their cardiovascular disease risk. In order to explore the hypothesis of an atrial natriuretic factor (ANF) deficiency in prehypertension, we compared the response to sodium loading on ANF and renal function in subjects with positive and negative histories of hypertension.
                Twenty-two offspring of hypertensive parents (OH) and 20 offspring of normotensive parents (ON) were studied after 4 days of low (50 mmol/day) or high (300 mmol/day) dietary sodium intake. The diets were allocated randomly. Blood pressure (BP), renal function, plasma concentration of ANF, cyclic guanosine monophosphate (cGMP), renin, angiotensin I and II, aldosterone, endothelin and catecholamines were determined during a clearance period of 90 min on both diets. Neurohormones were measured by radioimmunoassays. Renal function was determined by simultaneous measurements of 51Cr-ethylenediaminetetraacetate (a marker of glomerular filtration rate), lithium and sodium clearances.
                Supine systolic and diastolic BPs were significantly elevated in OH, with both low and high dietary sodium intake. There was no difference in ANF and cGMP concentrations on the low sodium diet. Increasing sodium intake caused a similar increase in ANF in OH and ON but cGMP did not change significantly. As expected the activity of the renin-angiotensin-aldosterone system was decreased by enhancing sodium intake but with both low and high sodium intake plasma renin concentration was significantly higher in OH than in ON. Activation of the sympathetic nervous system with low sodium intake was indicated by a moderate increase in plasma concentrations of epinephrine and norepinephrine in both groups. The renal effects were characterized by significant increases in GFR, lithium and sodium clearances with increasing sodium intake. There were no differences between OH and ON. Estimated values of fractional proximal and distal tubular sodium reabsorption decreased significantly and in a similar way in both OH and ON.
                These results indicate that the renal and neuroendocrine responses to dietary sodium loading are similar in both OH and ON. The only difference was a higher BP and an elevated plasma renin concentration on both dietary regimens in OH compared with ON. In particular, in OH and ON an identical increase in plasma ANF concentration in response to sodium loading was found. Thus, this study cannot support the hypothesis of a dysregulation of ANF in hypertension-prone humans. In order to determine factors contributing to sodium induced changes of blood pressure, 20 patients with essential hypertension were studied when on their regular sodium intake and after two weeks of a low sodium diet (50 mmol daily) and two weeks of a high sodium diet (300 mmol daily). There were two periods of regular sodium intake, one of four weeks at the beginning and one of two weeks at the end of the study. The change in mean arterial pressure between the high and low salt diets (delta MAP) was regarded as a measure of sodium sensitivity, and was directly correlated with age and initial blood pressure. Compared with non-responders, responders (delta MAP 10 mmHg or more) showed a lesser activation of the renin-angiotensin-aldosterone system during the low salt period. The response to the administration of intravenous frusemide was not helpful in predicting sodium sensitivity. A significant but relatively small (4.2 mmHg) reduction in MAP was obtained during low salt period compared with the first period of regular sodium intake. The data suggest that moderate dietary sodium restriction can help to reduce the blood pressure of the relatively older patient with hypertension. The overall prevalence of salt sensitivity was studied in 75 men stratified by diagnosis (hypertensive v normotensive) and race (black v white). All were studied in a crossover design employing a 200 mEq and 10 mEq Na/day. High salt led to a decrease in diastolic pressure for all groups (P less than .002). For systolic pressure, there was no salt effect on blood pressure across the whole group; however amongst the hypertensives, particularly the black hypertensives, high salt led to increases in systolic pressure (P less than .022). Obese patients were more likely to increase their systolic pressure in response to salt loading (P less than .05). The patients whose pressure increased on high salt were those who manifested less of a decrease in plasma levels of norepinephrine and renin in response to salt loading (both P less than .05). Systolic salt sensitivity was predicted with high statistical power (R = 0.689, P less than .00001) by a multiple regression equation employing: race; diagnosis; the change in renin and norepinephrine levels with diet; and the change in BP sensitivity to infused norepinephrine across the two diets. In view of the findings of increased norepinephrine, renin and diastolic pressure on low salt and in view of the particular physiological and epidemiological setting associated with systolic salt sensitivity, one wonders about the advisability of across-the-board recommendations of low salt diets for all hypertensive patients. The effect of dietary salt restriction on blood pressure was measured in patients with moderate hypertension receiving antihypertensive medication. Patients were studied during a randomly allocated 6 week period of moderate dietary salt restriction and during a 6 week period of normal diet. Twenty-four of twenty-eight patients achieved a reduction of salt excretion exceeding 20%. In these patients mean urinary sodium excretion fell from 169 (s.e.m. = 13) mmol/24 h to 92 (s.e.m. = 7) mmol/24 h. Potassium excretion and body weight did not change, and with the exception of the erect systolic pressure, there was no overall change in blood pressure. When the data were grouped according to the patient medication, mean supine systolic pressure fell from 148.9 (s.e.m. = 4.4) to 140.3 (s.e.m. = 5.0) mmHg (n = 14, P greater than 0.05) and mean supine diastolic pressure fell from 100.8 (s.e.m. = 2.9) to 97.0 (s.e.m. = 2.8) mmHg (n = 14, P greater than 0.05) in patients taking diuretics. Blood pressure did not change in patients whose medication did not include diuretics. Moderate dietary salt restriction may be therapeutically useful in patients with moderate hypertension treated with diuretics but is of little value in those not receiving diuretics.
A modest reduction in salt intake for 4 or more weeks causes significant and, from a population viewpoint, important falls in BP in both hypertensive and normotensive individuals, irrespective of sex and ethnic group. With salt reduction, there is a small physiological increase in plasma renin activity, aldosterone and noradrenaline. There is no significant change in lipid levels. These results provide further strong support for a reduction in population salt intake. This will likely lower population BP and, thereby, reduce cardiovascular disease. Additionally, our analysis demonstrates a significant association between the reduction in 24-h urinary sodium and the fall in systolic BP, indicating the greater the reduction in salt intake, the greater the fall in systolic BP. The current recommendations to reduce salt intake from 9-12 to 5-6 g/d will have a major effect on BP, but are not ideal. A further reduction to 3 g/d will have a greater effect and should become the long term target for population salt intake.