Prevalence and correlates of lower extremity arterial disease in elderly women.

Although lower extremity arterial disease occurs in 15-20% of the population over the age of 75 years, little is known about the etiology of the disease in women. In this cross-sectional study involving 1,601 healthy elderly women (mean age, 71 years; range, 65-93 years), the occurrence of lower extremity arterial disease was assessed noninvasively by measuring brachial and ankle pressures bilaterally. Disease prevalence ranged from 2.9% in those aged 65-69 years to 15.5% in those aged 80 years or older. Approximately 20% of those with disease had symptoms of claudication. Age, systolic blood pressure, and current smoking status were strong independent risk factors for arterial disease; a history of arthritis, use of nonthiazide diuretics, current coffee drinking, and upper body obesity were also independent correlates. The number of pack-years in current and former smokers and the number of cigarettes per day used by current smokers showed a dose-response relation with disease. The population attributable risk for current smoking was 26%. The major correlates for symptomatic arterial disease were current smoking and systolic blood pressure. It is concluded that the major risk factors for lower extremity arterial disease in elderly women are similar to those in men. Preventive efforts should focus on smoking cessation and management of hypertension.

Diuretics, serum and intracellular electrolyte levels, and ventricular arrhythmias in hypertensive men.

OBJECTIVE: To investigate the patterns of electrolyte abnormalities resulting from thiazide administration and whether they cause ventricular arrhythmias, and to help resolve the controversy over whether clinicians should routinely prescribe potassium-conserving therapy to all patients treated with thiazides. DESIGN: Double-blind, randomized controlled trial. PARTICIPANTS: A total of 233 hypertensive men aged 35 to 70 years. INTERVENTIONS: Participants were withdrawn from prior diuretic treatment and were replenished with oral potassium chloride and magnesium oxide. They were then randomized to 2 months of treatment with (1) hydrochlorothiazide; (2) hydrochlorothiazide with oral potassium; (3) hydrochlorothiazide with oral potassium and magnesium; (4) hydrochlorothiazide and triamterene; (5) chlorthalidone; or (6) placebo. MAIN OUTCOME MEASURES: Ventricular arrhythmias on 24-hour Holter monitoring and serum and intracellular potassium and magnesium levels. RESULTS: Of the 233 participants, 212 (91%) completed the study. Serum potassium levels were 0.4 mmol/L lower in the hydrochlorothiazide group than in the placebo group (P less than 0.01), and this mean difference was not affected by supplementation with potassium, with potassium and magnesium, or with triamterene. However, the supplements did prevent the occasional occurrence of marked hypokalemia; all 12 of the men who developed serum potassium levels of 3.0 mmol/L or less were among the 90 who received diuretics without supplementation (P less than 0.01). Similarly, the overall proportion of men with ventricular arrhythmias was not affected by randomized treatment, but there was a twofold increase in the proportion with arrhythmias among the 12 men with serum potassium levels of 3.0 mmol/L or less (P = .02). Serum magnesium and intracellular potassium and magnesium levels were not reduced by hydrochlorothiazide, nor were they related to ventricular arrhythmias. CONCLUSIONS: In the majority of hypertensive patients, treatment with 50 mg/d of hydrochlorothiazide does not cause marked hypokalemia or ventricular arrhythmias. However, because some individuals will develop hypokalemia after starting diuretic therapy, serum potassium levels should be monitored and potassium-sparing strategies should be used when indicated.

Beneficial effects from systematic dosage reduction of the diuretic, chlorthalidone: a randomized study within a clinical trial.

The purpose of this study was to determine the effects on blood pressure and selected biochemical measures of reducing the dosage of chlorthalidone from 100 mg to 50 mg. Within the larger study (Multiple Risk Factor Intervention Trial), 140 Special Intervention hypertensive men, taking 100 mg of chlorthalidone daily, were randomly assigned to either a continuation of 100 mg or a dosage reduction to 50 mg daily. Men were followed monthly for 4 months. Measures were made of blood pressure, serum potassium, serum uric acid, serum glucose, serum cholesterol, and triglycerides. Blood pressure change from baseline to 4 months revealed a significantly higher diastolic blood pressure in the group continued on the 100 mg dose compared to the dose reduction group. However, analysis of covariance, which took into account baseline differences in blood pressure, resulted in a nonsignificant difference in follow-up blood pressure (systolic and diastolic) between groups. Serum potassium increased significantly in the dose reduction group, especially in those participants taking supplemental potassium chloride. The results of this study demonstrate that a reduced dose of 50 mg chlorthalidone over the 4-month period was as effective as the 100 mg dose in long-term, well-controlled hypertensive men. Careful study of other antihypertensive agents is warranted to determine the drug dose that is maximally effective for blood pressure lowering and that also minimized toxic and adverse effects.

Effect of the diphosphonate EHDP on bone mineral metabolism during prolonged bed rest.

The effect of disodium ethane-1-hydroxy-1, 1-diphosphonate (EHDPTM) on bone mineral metabolism was tested in 4 healthy young men during 20 weeks of continuous bed rest. Two subjects received an oral dose of 5 mg/kg/day and the other 2 20 mg/kg/day. The low dose had two minor effects: the increase in bone accretion rate which usually occurs during bed rest was prevented, and there was an accentuation of the bed rest induced increase in hydroxyproline excretion. Skeletal mineral loss, assessed by calcium balance measurements and gamma ray absorptiometry of the calcaneus, occurred at the rate previously noted in untreated control subjects. Two types of drug effect were apparent at the higher dosage: one was immediate and sustained--a rise in serum phosphorus concentration and a fall in serum alkaline phosphatase activity. The other was delayed and progressive--a decline in urinary hydroxyproline excretion and in the rates of bone accretion and resorption. Skeletal mineral loss may have been affected; the usual negative mineral balance developed during the first half of the study, then disappeared during the last few weeks. However, gamma ray absorptiometry revealed no attenuation of the calcaneal mineral losses.

The effect of supplemental oral phosphate on the bone mineral changes during prolonged bed rest.

Five healthy young men were studied during 24-30 wk of continuous bed rest. During the first 12 wk of bed rest, untreated subjects increased calcium excretion in the urine by 109 mg/day and in the feces by 147 mg/day. The rate of total body calcium loss was 0.5-0.7% per month. Losses of central calcaneus mineral, assessed by gamma ray transmission scanning, occurred at a tenfold higher rate, whereas the mineral content of the radius did not change. Changes in phosphorus balance resembled the calcium pattern, and increased excretion of nitrogen and hydroxyproline also occurred during bed rest. Upon reambulation, the subjects' calcium balance became positive in 1 month and recovery of their calcaneus mineral was complete within 10-20 wk. Treatment with potassium phosphate supplements (1327 mg P/day) entirely prevented the hypercalciuria of bed rest, but fecal calcium tended to increase. During the first 12 wk, calcium balance was slightly less negative (mean - 193 mg/day) than during bed rest without added phosphate (mean - 267 mg/day). This effect was not seen during the second 12 wk of bed rest. The patterns of magnesium excretion were similar to those of calcium. Fecal and urinary phosphorus excretions were doubled, and phosphorus balance became positive (+ 113 mg/day). Mineral loss from the central calcaneus was similar to that of untreated subjects. It is concluded that this form of phosphate supplementation reduces urinary calcium excretion but does not prevent bone loss during bed rest.