Lack of effectiveness of a low-sodium/high-potassium diet in reducing antihypertensive medication requirements in overweight persons with mild hypertension. TAIM Research Group. Trial of Antihypertensive Interventions and Management.

The Trial of Antihypertensive Interventions and Management (TAIM) was a multicenter randomized drug (double-blind, placebo-controlled)-diet trial. One objective of TAIM was to assess the long-term ability of a low-sodium/high-potassium (Na+ decreases/K+ increases) diet to maintain blood pressure control in persons at 110% to 160% ideal weight with diastolic blood pressure from 90 to 100 mm Hg who were on no drugs or on low-dose monotherapy. Participants, 56% men and 33% black, were randomized to usual diet (n = 296) or to Na+ decreases/K+ increases diet (n = 291) and within each diet group to placebo, 25 mg/day chlorthalidone, or 50 mg/day atenolol. Treatment failure was defined as lack of blood pressure control requiring additional drugs according to specified criteria. At baseline, the mean value for age was 48 years; blood pressure, 143/93 mm Hg; weight, 88 kg; and 24-h urinary sodium and potassium excretion rates, 133 and 57 mmol/day, respectively. At 3 years, the net difference in 24-h urinary sodium/potassium excretion rates between the Na+ decreases/K+ increases and the usual diet groups was -30 and +11 mmol/L/day. The relative risk of treatment failure for Na+ decreases/K+ increases compared to usual diet by proportional hazards regression was 0.95 (P = .71). This study provides no support for the sole use of a low-sodium/high-potassium diet as a practical therapeutic strategy in maintaining blood pressure control in the moderately obese.

Effect of withdrawal of antihypertensive drug on depressive mood.

To evaluate the effects on depressive mood of withdrawal of antihypertensive medication, we conducted a randomized, multi-center study with clinical centers at the Albert Einstein College of Medicine, Bronx, NY, University of Alabama School of Medicine, Birmingham, and the University of Mississippi School of Medicine in Jackson. Patients were formerly active participants in the Hypertension Detection and Follow-Up Program (HDFP) whose blood pressure was controlled with drugs for a period of 5 years. Of 496 patients, 431 had both baseline and "1-year" mood scores. Patients, stratified by obesity, were randomized to one of three groups: continue the HDFP medication; discontinue medication with no dietary intervention, or with sodium restriction and potassium increase; or, for those overweight, to a weight reduction intervention. Depression was assessed using the CES-D scale (Center for Epidemiological Studies--Depressed Mood), administered at baseline and again approximately 1 year after randomization. Of the seven treatment groups, only those who continued their HDFP medication showed significant improvement in mood from baseline. The overweight continue-medication group showed significantly greater improvement compared to the no-drugs, no-diet intervention groups, and to the overweight sodium-restriction group. Patients who had their blood pressure successfully controlled with weight reduction had a significant improvement in mood from 11.0 scale points to 8.0, P = .006. Comparisons between those withdrawn from diuretic alone and those withdrawn from both diuretic plus reserpine were inconclusive. Dietary Intervention Study of Hypertension (DISH) shows no evidence that continued use of chlorthalidone has a negative impact on quality of life, while our results concerning reserpine were inconclusive.(ABSTRACT TRUNCATED AT 250 WORDS)

Reduction in long-term antihypertensive medication requirements. Effects of weight reduction by dietary intervention in overweight persons with mild hypertension.

BACKGROUND: Increasing concern over long-term drug treatment of mild hypertension has stimulated several studies of weight reduction. Phase I of the Trial of Antihypertensive Interventions and Management demonstrated a short-term effect of weight loss on blood pressure control in overweight persons with mild hypertension, who were either taking placebo or taking low-dose monotherapy. Phase II investigates the long-term benefit of weight loss on the ability to maintain blood pressure control. METHODS: From 10148 community-based screenees, 587 persons (5.8%), aged 21 to 65 years, entered a multicenter, randomized drug (double-blind, placebo-controlled) and diet trial. Participants had a diastolic blood pressure between 90 and 100 mm Hg and were at 110% to 160% of their ideal weight. They were randomized to a usual diet (n = 296) or to a weight loss diet (n = 291) and within each diet group to placebo, chlorthalidone, 25 mg/d, or atenolol, 50 mg/d. Treatment failure was defined as using additional antihypertensive medications if diastolic blood pressure rose above 90 mm Hg according to protocol-specified criteria. RESULTS: At baseline, mean diastolic blood pressure was 93 mm Hg; systolic blood pressure, 143 mm Hg; weight, 88 kg; percent ideal weight, 137%; age, 48 years; 56% were men; and 33% were black. Mean follow-up was 4.5 years. There was a net loss of 2 to 3 kg with weight loss diet compared with usual diet over most of the follow-up period. The 5-year incidence of treatment failure was 56.7 per 100 participants with usual diet and 49.8 per 100 with weight loss. Long-term weight loss decreased failure of blood pressure control for those receiving placebo or low-dose diuretic or beta-blocker by 23%. The results were similar in direction in each drug group. CONCLUSIONS: The Trial of Antihypertensive Interventions and Management demonstrated that weight reduction is an effective long-term therapy for maintaining blood pressure in the normal range when used as monotherapy or in combination with either thiazide diuretics or beta-blockers. Consequently, weight loss should be recommended for the management of obese individuals with mild hypertension.

Trial of antihypertensive intervention and management: greater efficacy with weight reduction than with a sodium-potassium intervention.

The Trial of Antihypertensive Intervention and Management evaluated nine diet-drug combinations in 878 mildly hypertensive, moderately obese participants using a 3 x 3 factorial design. Drugs evaluated were placebo, diuretic (chlorthalidone), and beta-blocker (atenolol); diets were usual (no intervention), weight reduction, and low sodium/high potassium (Na/K). This article reports 6-month dietary changes and the effect of dietary change on blood pressure. Six-month mean weight change was -4.7 kg in the weight reduction group, -0.3 kg in the Na/K group, and -0.5 kg in the usual-diet group. At 6 months, daily electrolyte excretion had changed in the Na/K intervention group. Daily sodium excretion decreased from 138.0 to 112.0 mmol in the Na/K group and increased from 134.1 to 138.4 mmol in the weight reduction group and from 129.1 to 137.0 mmol in the usual-diet group. Daily potassium output increased from 58.7 to 71.4 mmol in the Na/K group, from 57.0 to 60.5 mmol in the weight reduction group, and from 55.3 to 59.1 mmol in the usual diet group. Analysis of 3-day food records indicated that sodium intake decreased from 141.1 to 85.8 mmol and potassium intake increased from 76.4 to 90.5 mmol. Our results indicate that the goal for weight reduction was more easily achieved than the goal for electrolyte modification.

Case report: autonomic postganglionic denervation--sural nerve and saphenous vein biopsy.

The authors describe a 31-year-old woman of British Isle ancestry who developed a syndrome resembling familial dysautonomia in her early teenage years. Predominant manifestations included achalasia, severe orthostatic hypotension, and abnormal sweating. The study included resting and stimulated fractional catecholamines, which were almost nonexistent in both situations, and urinary catecholamines, demonstrating an increase in dopamine degradation products. Immunohistochemistry of saphenous vein was negative for dopamine beta-hydroxylase (DBH), serotonin (5-HT) and several vasoactive neuropeptides. The only neuropeptide detected at levels thought to be physiologically relevant was calcitonin gene-related peptide (CGRP), a vasodilator. This was in contrast to control veins, all of which had DBH and neuropeptide Y immunoreactive fibers but few CGRP fibers. Also in contrast to controls, electron microscopy of the saphenous vein indicated a close to total absence of terminals with norepinephrine containing vesicles. Sural nerve biopsy showed, on electron microscopy, a considerable reduction in the number of myelinated fibers, while unmyelinated fibers appeared to be in the normal range. The authors suggest, from the above findings, that the autonomic fibers were undergoing some form of distal axonal degeneration. Their findings differ from most biopsies performed in dysautonomic children, and they believe their patient has a different neurologic entity.

Effect of antihypertensive therapy on weight loss. The Trial of Antihypertensive Interventions and Management Research Group.

We report the effect of weight changes of the type of antihypertensive medication prescribed in a trial of the relative efficacy of drug and dietary measures in mild hypertension. The Trial of Antihypertensive Interventions and Management studied 878 mildly hypertensive individuals randomly assigned, in a 3 x 3 design, to no diet change, weight loss, or a low sodium-high potassium diet and to placebo, 25 mg chlorthalidone, or 50 mg atenolol. The type of drug prescribed affected weight change with all diets. The drug effect on weight change, present in all groups at 6 months, was most pronounced in those randomly assigned to the weight loss diet, where the placebo group lost 4.4 kg, the atenolol group lost 3.0 kg, and the chlorthalidone group lost 6.9 kg. The group differences were attenuated but persisted at 24 months. We suggest that the antihypertensive drug prescribed affects the success of a conjoint weight loss program and speculate that the difference between the drugs may be due to their intrinsic effects on the sympathetic nervous system and related metabolic changes.

The Trial of Antihypertensive Interventions and Management (TAIM) study. Adequate weight loss, alone and combined with drug therapy in the treatment of mild hypertension.

This report examines the effect of weight loss, alone and in combination with drugs, on diastolic blood pressure change in the Trial of Antihypertensive Interventions and Management (TAIM), which is a randomized, multicenter, placebo-controlled clinical trial of drug and diet combinations in the treatment of mild hypertension among 787 patients. Diastolic blood pressure drop (11.6 mm Hg) at 6 months among those patients who were randomized to weight reduction and placebo drug treatment was greater among those who lost 4.5 kg or more, than the 7-mm Hg drop for those who lost less than 2.25 kg or for the placebo-treated control group, and it was statistically equivalent to the reduction achieved by 25 mg of chlorthalidone or 50 mg of atenolol (11.1- and 12.4-mm Hg drop, respectively). Weight loss potentiated effects of drugs, with reductions of 18.4 mm Hg, for those patients who were taking atenolol and had a 4.5-kg or more weight loss, and of 15.4 mm Hg, for those patients who were taking chlorthalidone and had at least a 2.25-kg weight loss. We concluded that effective weight loss (greater than or equal to 4.5 kg) lowers blood pressure similarly to low-dose drug therapy and potentiates drug effects, with the apparent 4.5-kg threshold being lowered to 2.25 kg for those patients who receive chlorthalidone.

Effect of thiazide-based therapy on serum alkaline phosphatase. Hypertension Detection and Follow-up Group.

This study reports a correlation of alkaline phosphatase (AP) with diastolic blood pressure (DBP), and a reduction of alkaline phosphatase after chlorthalidone therapy that reached a nadir at three years of therapy, then gradually returned toward, but not reaching, baseline values. The data is from the baseline examination and follow-up of 3928 initially untreated stepped-care patients in the Hypertension Detection and Follow-up Program. In multiple regression analysis, both age and DBP were significantly correlated with increased AP in males and females. After initiation of therapy with chlorthalidone, AP levels fell progressively until the third year, when they were reduced by 11 +/- 15 IU in the males and 14 +/- 15 IU in the females. The data are compatible with the interpretation that thiazide-induced reduction in urinary calcium excretion has led to a more positive calcium balance and reduction of bone turnover, and suggests that a beneficial effect of thiazide-based antihypertensive therapy could be decreased osteoporosis.

Trials of hypertension prevention. Phase I design.

Phase I of the Trials of Hypertension Prevention (TOHP) was a National Heart, Lung, and Blood Institute-sponsored, 3-year, national, multicenter, randomized, controlled trial designed to test the feasibility and efficacy of three life-style (weight loss, sodium restriction, and stress management) and four nutrition supplement (calcium, magnesium, fish oil, and potassium) interventions aimed at lowering diastolic blood pressure in those whose blood pressure was initially in the high normal range (80 to 89 mm Hg). A total of 2182 volunteers were recruited and allocated to the various treatment arms, such that each hypothesis was tested with a power of 85% or higher to detect a diastolic blood pressure treatment effect of 2 mm Hg. The four nutrition supplement interventions were delivered in a double-blinded fashion and the three life-style interventions, single (observed) -blinded. Phase I was designed to provide a rigorous test of short-term lowering of blood pressure for each of the seven treatments chosen and provides the basis for planning of a subsequent long-term trial of hypertension prevention.

Chronic effect of KCl on black-white differences in plasma renin activity, aldosterone, and urinary electrolytes.

In a 10-week trial of the effect of 80 mEq KCl/day on blood pressure, the following biochemical changes were noted: plasma renin activity (PRA), originally significantly lower in blacks than whites, increased to the same level as whites after K supplementation. A similar trend was noted with aldosterone. KCl increased creatinine excretion in blacks and whites, and lowered Ca excretion in blacks. These results suggest that the low PRA found in blacks is due, at least in part, to low K intake, and not to genetic causes.

Effect of antihypertensives on sexual function and quality of life: the TAIM Study.

OBJECTIVE: To evaluate treatment of mild hypertension using combinations of diet and low-dose pharmacologic therapies. DESIGN: Multicenter, randomized, placebo-controlled clinical trial. SETTING: Three university-based tertiary care centers. PATIENTS: Patients (697) 21 to 65 years of age with diastolic blood pressure between 90 and 100 mm Hg as well as weight between 110% and 160% of ideal weight. INTERVENTION: Patients were stratified by clinical center and race and were randomly assigned to one of three diets (usual, low-sodium and high-potassium, weight loss) and one of three agents (placebo, chlorthalidone, and atenolol). MEASUREMENTS: Changes in measures of sexual problems, distress, and well-being after 6 months of therapy were analyzed. MAIN RESULTS: Low-dose chlorthalidone and atenolol produced few side effects, except in men. Erection-related problems worsened in 28% (95% CI, 15% to 41%) of men receiving chlorthalidone and usual diet compared with 3% (CI, 0% to 9%) of those receiving placebo and usual diet (P = 0.009) and 11% (CI, 2% to 20%) of those receiving atenolol and usual diet (P greater than 0.05). The weight loss diet ameliorated this effect. The low-sodium diet with placebo was associated with greater fatigue (34%; CI, 23% to 45%) than was either usual diet (18%; CI, 10% to 27%; P = 0.04) or weight reduction (15%; CI, 7% to 23%; P = 0.009). The low-sodium diet with chlorthalidone increased problems with sleep (32%; CI, 22% to 42%) compared with chlorthalidone and usual diet (16%; CI, 8% to 24%; P = 0.04). The weight loss diet benefited quality of life most, reducing total physical complaints (P less than 0.001) and increasing satisfaction with health (P less than 0.001). Total physical complaints decreased in 57% to 76% of patients depending on drug and diet group, and were markedly decreased by weight loss. CONCLUSION: In general, low-dose antihypertensive drug therapy (with chlorthalidone or atenolol) improves rather than impairs the quality of life; however, chlorthalidone with usual diet increases sexual problems in men.

Effect of drug and diet treatment of mild hypertension on diastolic blood pressure. The TAIM Research Group.

The Trial of Antihypertensive Interventions and Management is a multicenter randomized trial designed to examine the diastolic blood pressure response of various combinations of pharmacological and dietary interventions in the treatment of mild hypertension (diastolic blood pressure 90-100 mm Hg). Eight hundred and seventy-eight participants at 110-160% of ideal weight were randomly allocated to nine drug/diet treatment groups receiving either a placebo, chlorthalidone (25 mg), or atenolol (50 mg), combined with a usual, a weight loss, or a low sodium/high potassium diet. The primary outcome was diastolic blood pressure change from baseline to 6 months. Seven hundred and eighty-seven participants had follow-up data. The mean baseline diastolic blood pressure was 93.8 mm Hg; 55.9% of the participants were male, and the weight loss diet group lost an average of 4.7 kg. Multiple comparisons were accounted for in the analysis. A significantly greater lowering of diastolic blood pressure (12.4 mm Hg) was achieved in the atenolol group compared with either the low sodium/high potassium diet group (7.9 mm Hg, p = 0.001) or weight loss group (8.8 mm Hg, p = 0.006). Adding weight loss to chlorthalidone significantly enhanced blood pressure lowering (15.1 mm Hg) when compared with the diuretic alone (10.8 mm Hg, p = 0.002), but adding a low sodium/high potassium diet (12.2 mm Hg, p = 0.029) did not. In the short-term treatment of mild hypertension where diastolic blood pressure is the sole consideration, drugs outperform diet, and weight loss is beneficial, especially with diuretics.

Judging the effectiveness of antihypertensive therapy in an individual patient.

The physician's decision as to whether a hypertensive drug has produced satisfactory blood pressure lowering is more difficult than it is usually perceived to be. Variability of blood pressure, regression to the mean and habituation to the taking of blood pressure all conspire to blur the significance of the observed drop. We present algorithms outlining the number of visits before and after the initiation of therapy and the mmHg drop required for determination with acceptable certainty that any response to the hypotensive drug has occurred. Our conclusion is that the variability of blood pressure limits the clinician's ability to confidently conclude that antihypertensive therapy is effective unless the change in blood pressure exceeds a relatively high threshold and/or the number of visits both before and after the initiation of antihypertensive therapy is large. Because regression to the mean will be minimized, fewer visits and/or a lesser blood pressure fall in the treated patient changing or adding medications will be necessary to determine that a real decline has occurred.

Sodium-potassium interaction in hypertension and hypertensive cardiovascular disease.

Epidemiological evidence suggests that low potassium intake is associated with the probability of occurrence of hypertension and stroke. The short-term response to increased potassium intake is increased sodium excretion as well as increased potassium excretion; the short-term response to increased sodium intake is increased potassium excretion as well as increased sodium excretion. In some experimental studies, increased amounts of potassium have been able to block the noxious influences of sodium. Sodium and potassium must be concomitantly considered in the investigation of the association of either of these cations with hypertension and cardiovascular disease. The chloride ion is also important for sodium's effects; its importance in potassium's effects has not been extensively explored.

The effect of thiazide therapy on glucose, insulin and cholesterol metabolism and of glucose on potassium: results of a cross-sectional study in patients from the Hypertension Detection and Follow-up Program.

Fasting and one hour post-glucose load blood samples were obtained from 497 participants in the Hypertension Detection and Follow-up Program (HDFP), 79.8% of whom were on antihypertensive therapy at the time of their five-year examination. Major findings include a positive correlation between glucose/insulin ratio and serum potassium (P = 0.0014) and a weaker negative correlation between fasting insulin and serum potassium (P = 0.004). These data are compatible with a primary effect of hypokalaemia producing insulin 'resistance'. In addition, the glucose load was followed by a mean reduction in serum potassium of 0.135 +/- 0.525 meq/l (P less than 0.001). Twenty percent of participants experienced a drop of more than 0.5 meq/l. Cholesterol was associated with the fasting glucose/insulin ratio (P less than 0.032). The results are compatible with the hypothesis that prevention of hypokalaemia may prevent certain metabolic effects attributed to thiazide.

Potassium and calcium intake, excretion, and homeostasis in blacks, and their relation to blood pressure.

Blacks in the United States have higher blood pressures than whites. They ingest and excrete less calcium and potassium. There is some evidence that blacks have a difference in vitamin D metabolism that might increase any problem caused by low calcium intake. Some studies can be interpreted to suggest that calcium or potassium therapy has greater hypotensive effects in blacks than in whites. Decreased intake of calcium and potassium may be major causes of the greater prevalence of hypertension in blacks than in whites.

Estimation of protein intake: comparison of dietary assessment and urinary excretion.

Estimates of dietary intake of nutrients have many problems, and confirmation of these estimates by chemical measurements of excretory products helps to establish their validity. The correlation between urinary amino acid excretion and dietary history of protein intake are reported herein. Diet diaries were kept by and 24-h urine collected from participants in the Trial of Antihypertensive Therapy and Management, a multicenter cooperative trial comparing the effects of drugs and diet on blood pressure control, side effects, and quality of life. The nutritional information was coded and the data stored by the nutritional analyses facility at Albert Einstein College of Medicine. The chemical determinations were done in the laboratories of the Department of Pathology, Izumo, Japan. The correlation between total protein and 3-methylhistidine was r = 0.42 (n = 96). The correlation was similar for animal protein (r = 0.4). These correlations are of the same order of magnitude as those between dietary sodium and urine sodium, and dietary potassium and urine potassium. We conclude that measurement of urinary protein excretion products may be a useful way to estimate dietary protein intake.

Pharmacologic and nutritional treatment of mild hypertension: changes in cardiovascular risk status.

OBJECTIVE: To evaluate the 6-month change in cardiovascular (coronary heart disease) risk as a function of diet and drug therapy for mild hypertension. DESIGN: Collaborative randomized, controlled clinical trial to assess the efficacy of alternative regimens in treating mild hypertension. SETTING: Three university-based tertiary care centers-the Trial of Antihypertensive Interventions and Management (TAIM). PATIENTS: Six hundred and ninety-two men and women ages 21 to 65 years with diastolic blood pressure between 90 and 100 mm Hg and weight between 110% and 160% of ideal weight. MEASUREMENTS AND MAIN RESULTS: Patients stratified by clinical center and race were randomized into diet (usual, low sodium-high potassium, weight loss) and drug (placebo, chlorthalidone, and atenolol) groups resulting in nine diet plus drug combinations. The cardiovascular risk at 6-month follow-up was estimated relative to baseline in 692 participants using the Framingham Study model. Due to the blood pressure reduction, cardiovascular risk declined from baseline for all treatment groups (except the usual diet plus chlorthalidone group because of increased cholesterol levels). The relative cardiovascular risk at 6 months compared to baseline ranged from 0.83 in the weight loss plus atenolol subgroup to 1.03 in the usual diet plus chlorthalidone subgroup. The active drug plus weight loss groups showed the lowest relative cardiovascular risk at 6 months. CONCLUSIONS: Mild hypertension was generally reduced to desirable levels within 6 months by monotherapy. Evaluating blood pressure changes together with the risk factors indicated a differential effect on overall cardiovascular risk depending on the diet and drug used. Dietary therapy, particularly weight reduction, was important adjunctive treatment in reducing overall cardiovascular risk.

Effect of weight loss on thiazide produced erectile problems in men.

Thiazide-type diuretics frequently produce erectile dysfunction in men on a regular diet. However, men on a weight-loss diet have much less erectile dysfunction. Thiazide-type diuretics also produce erectile dysfunction in rats and interfere with normal copulation. The mechanism of the dysfunction and the favorable response to weight loss is unknown.