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Biomedical subjects

E D Freis

Publications and source records attributed to E D Freis.

At least 19 recordsLinked to original sources
PubMed1992

The role of salt in hypertension.

There is considerable evidence that salt is an important cause of hypertension. Primitive societies who ingest little or no salt have no hypertension. Also when diets very low in salt such as the rice and fruit diet are given to hypertensive patients, the blood pressure often falls toward normal. Unfortunately, when diets only moderately low in sodium have been given only minor reductions in blood pressure occur. Salt-induced hypertension has been produced in both man and experimental animals. The basic cause of the hypertension is an inability of the kidney to excrete the increased salt. Hemodynamic changes then occur which raise the blood pressure and so excrete the excess salt by pressure diuresis. The ability to excrete salt at normal levels of blood pressure varies from one individual to another. Those who require a higher than normal blood pressure are said to be "salt-sensitive". Those who can excrete excess salt at normal levels of blood pressure are called "salt resistant". The difference may be due to an inherited defect in the kidney to excrete salt. In any event, salt sensitive hypertension is effectively controlled with the administration of diuretics.

Humans↗
PubMed1991

Treatment of hypertension in the elderly. III. Response of isolated systolic hypertension to various doses of hydrochlorothiazide: results of a Department of Veterans Affairs cooperative study. Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents.

In a double-blind randomized study, we evaluated the effects of 25 mg vs 50 mg of hydrochlorothiazide in 51 elderly patients (aged 68.9 +/- 7.0 years) with isolated systolic hypertension (blood pressure, 160 to 239 mm Hg systolic and less than 90 mm Hg diastolic). Dose levels could be increased to twice daily to control blood pressure. The reductions in blood pressure (25.4/6.8 mm Hg and 28.9/7.4 mm Hg) and proportion of patients in whom blood pressure was controlled (78% and 89%) were similar in the lower- and higher-dose groups during the titration phase. However, serum potassium level was reduced more in the higher-dosage (0.57 mmol/L) than the lower-dosage (0.17 mmol/L) group. There were no significant changes in blood pressure during a 24-week maintenance phase. No patient required withdrawal from the study because of adverse effects, and cognitive-behavioral function was well preserved. We conclude that hydrochlorothiazide is effective and well tolerated in older patients with isolated systolic hypertension, many of whom may be effectively treated with 25 mg of hydrochlorothiazide once daily.

Aged↗
PubMed1991

Veterans Administration Cooperative Study Group on Hypertensive Agents: effects of age on treatment results.

In three double-blind studies of 1,396 hypertensive patients, the age-related effects of hydrochlorothiazide or bendroflumethazide were compared with those of propranolol, nadolol, or captopril, given singly or in combination with a thiazide. Patients in each treatment group were divided into those aged 55 to 69 years and those aged under 55. Whereas no age-related differences were apparent with propranolol, nadolol alone, or captopril alone, in all three studies the blood pressure-reducing effect was found to be greater in the older group of thiazide-treated patients than in the younger thiazide-treated group. The antihypertensive drugs studied are at least as effective in older as in younger hypertensive patients and the antihypertensive response with diuretics is greater in older patients than in younger patients.

Adult↗
PubMed1990

The cardiotoxicity of thiazide diuretics: review of the evidence.

Careful consideration of all relevant scientific evidence and a critical assessment of data quality show that thiazide diuretics are not cardiotoxic. Of 12 reported trials only two recorded more coronary heart disease events in thiazide-treated patients than in controls. One of these two was a subgroup of a larger study (Heart Attack Prevention in Primary Hypertension, HAPPHY) which found no difference between thiazide-treated and beta-blocker-treated patients. The other, the Oslo study, was too small to allow valid conclusions. Results from a subgroup in the Multiple Risk Factor Intervention Trial (MRFIT) that appeared to supply evidence for thiazide-related cardiotoxicity are suspect when examined critically. Further evidence from 24- to 28-h ECG monitoring does not support the hypothesis that thiazide diuretics, either in the presence or absence of hypokalemia, increase the frequency or severity of ventricular arrhythmias. Reports of a thiazide-induced intracellular magnesium deficiency as a cause of ventricular arrhythmias have also not been confirmed; the development of arrhythmias in acute myocardial infarction appears to be due to an increase in catecholamine levels rather than hypokalemia. There appears to be little evidence to support the assumption that long-term use of thiazide diuretics aggravates or accelerates atherosclerosis of the coronary arteries; any fall in serum cholesterol appears to be transient. For the great majority of patients with uncomplicated hypertension, without a previous myocardial infarction, congestive heart failure, diabetes mellitus or gout, thiazide diuretics appear to be both safe and effective antihypertensive agents.

Arrhythmias, Cardiac↗
PubMed1990

Treatment of hypertension in the elderly: I. Blood pressure and clinical changes. Results of a Department of Veterans Affairs Cooperative Study.

We compared the efficacy and adverse effects of antihypertensive drug regimens in 690 men past age 60 with diastolic blood pressure 90-114 mm Hg and systolic blood pressure less than 240 mm Hg. They received either a low (25-50 mg) or high (50-100 mg) dose of hydrochlorothiazide daily. Of 644 patients who completed the hydrochlorothiazide titration, 375 (58.2%) were responders (diastolic blood pressure less than 90 and less than or equal to 5 mm Hg below baseline) and 92.8% of these completed a 6-month maintenance period. Blood pressure was reduced from 157.6/98.5 mm Hg by 18.3/9.5 mm Hg with low dose hydrochlorothiazide and by 20.4/9.6 mm Hg with high dose hydrochlorothiazide; more patients achieved goal blood pressure with the high dose. Whites and blacks responded equally. Serum potassium less than 3.5 mmol/l occurred in 104 of 321 (32.3%) of the high dose versus 62 of 333 (18.6%) of the low dose hydrochlorothiazide patients. The 269 nonresponders to hydrochlorothiazide were randomly assigned in a double-blind study to receive hydralazine, methyldopa, metoprolol, or reserpine in addition to hydrochlorothiazide; 79.2% responded to the addition of the second drug and 87.3% of these completed a 6-month maintenance phase. Overall, there were no significant efficacy differences among the step 2 regimens. We conclude that the lower dose of hydrochlorothiazide was nearly as effective as the higher dose, and the addition of a second drug was effective and generally well tolerated in elderly patients.

Aged↗
PubMed1990

Treatment of hypertension in the elderly: II. Cognitive and behavioral function. Results of a Department of Veterans Affairs Cooperative Study.

This study was designed to determine whether blood pressure reduction, per se, causes adverse effects on cognitive and behavioral function in elderly hypertensive patients. Men with mild-to-moderate diastolic hypertension who had passed their 60th birthday were entered into the trial. After a placebo washout period, they were assigned in a randomized, double-blind manner to one of two groups receiving hydrochlorothiazide (either 25 mg once or twice daily or 50 mg once or twice daily). Responders entered a 1-year maintenance period. Nonresponders were randomly assigned to double-blind treatment with hydralazine, methyldopa, metoprolol, or reserpine added to the diuretic therapy. During the placebo and treatment periods, patients underwent a battery of psychometric tests designed to assess cognitive function, motor skills, memory, and affect. A separate questionnaire assessed the patient's ability to perform activities of daily living. A subset of patients blindly being treated with placebo received the same battery of tests as a control for practice effect. The results showed that there was similar improvement on the psychometric tests between those patients whose blood pressure was successfully reduced and the placebo-treated control group. Therefore, the practice effect did not obscure a true deterioration in function. There were no substantive differences between the lower and higher doses of diuretic or among the four drugs added to the diuretic, although there were qualitative differences in side effects. We conclude that blood pressure reduction, per se, does not adversely affect cognitive and behavioral function in elderly hypertensive patients and that antihypertensive treatment is safe and effective in these patients.

Activities of Daily Living↗
PubMed1989

Effects of diuretic therapy and exercise-related arrhythmias in systemic hypertension.

The effect of aerobic exercise on cardiac arrhythmias, plasma catecholamines, potassium and magnesium in patients with systemic hypertension was assessed. Twenty patients (age 54 +/- 8 years) with uncomplicated hypertension underwent exercise treadmill testing twice while receiving placebo and twice while receiving hydrochlorothiazide 100 mg daily. Blood samples for electrolytes and catecholamines were obtained at rest, at peak exercise and 10 minutes after exercise. There were no substantial differences comparing the first to the second placebo phase or the first to the second treatment period. As expected, hydrochlorothiazide treatment caused a significant decrease in serum potassium (4.00 +/- 0.44 to 3.32 +/- 0.49 mEq/liter, p less than 0.001). Serum magnesium did not change with treatment. Serum potassium, serum magnesium and plasma catecholamines increased significantly with exercise. No rebound hypokalemia occurred during recovery. Occasional ventricular premature contractions were noted at rest during all phases of the study, with only a slight increase in frequency during exercise. Couplets were noted only rarely. No difference in the frequency or complexity of arrhythmias was noted between placebo and treatment periods. Diuretic therapy or diuretic-induced hypokalemia has no profound effect on cardiac arrhythmias during or after exercise in patients with uncomplicated systemic hypertension.

Blood Pressure↗
PubMed1989

Effects of reduction in drugs or dosage after long-term control of systemic hypertension.

The possibility of discontinuing--compared to reducing--antihypertensive drug treatment was investigated in 606 male hypertensive patients with entry diastolic blood pressure (BP) in the range of 90 to 114 mm Hg. Diastolic BP was controlled at less than 90 mm Hg with 1 of 4 regimens: low dose hydrochlorothiazide (HCTZ), 25 mg twice daily; high dose HCTZ, 50 mg twice daily; or high dose HCTZ plus a low or high dose of a step II drug (propranolol, clonidine or reserpine). After 6 months of treatment that controlled BP, dosages were reduced in two-thirds of the patients. In those patients receiving low dose HCTZ and randomized to dose reduction, antihypertensive drugs were completely discontinued. Although approximately half of these patients remained normotensive for the first 6 months, a significantly greater proportion had elevation of BP compared to the control group, which continued to receive treatment (p less than 0.0001). In the high dose HCTZ drug group, the proportion of patients remaining normotensive did not differ among those stepped down to low dose HCTZ and the fully treated control group. While not achieving significance the trend was similar with the step II regimens. Although some patients remained normotensive after discontinuation of step II drugs, a greater proportion returned to elevated BP than when step II dosage was unchanged. Therefore, while stopping therapy may be effective in some patients, a decreased dosage is significantly more effective as a method for maintaining an antihypertensive effect. Decreasing drug dosages offers the dual benefit of minimizing side effects and reducing drug costs.

Antihypertensive Agents↗
PubMed1989

Exercise blood pressure response and left ventricular hypertrophy.

Although hypertension is the major cause of left ventricular hypertrophy (LVH), numerous studies failed to demonstrate a close correlation between resting blood pressure (BP) and degree of LVH. Some authors have shown better correlation between BP at work and left ventricular mass (LV mass), whereas other studies supported an association between catecholamines or angiotensin II and LV mass. In this study we investigated the relationship of resting and exercise BP and catecholamines to the degree of LVH. Nineteen patients with established mild to moderate hypertension were studied. Blood pressure was measured following a ten-minute rest and every three minutes during exercise using a Bruce protocol. Electrolytes, epinephrine (EP), and norepinephrine (NE) were measured at rest, at peak exercise, and at ten-minutes postexercise. Resting BP averaged 154 +/- 24/99 +/- 9 mm Hg and at three minutes of exercise 195 +/- 30/101 +/- 6 (P less than .001). Resting EP was 51 +/- 20 pg/mL, NE 314 +/- 187, and at peak exercise EP was 107 +/- 61 (P less than .001) and NE 1016 +/- 566 (P less than .001). The average LV mass was 277 +/- 85 g. A significant correlation was found only between systolic BP at three minutes of exercise and LV mass (r = .479, P less than .04). No other variable correlated significantly with LV mass. These data suggest that systolic BP achieved at low level of exercise (5 mets), corresponding to usual daily activities, may be the most important determinant of LVH in patients with hypertension.

Blood Pressure↗
PubMed1989

Humoral Na+-K+ pump inhibitory activity in essential hypertension and in normotensive subjects after acute volume expansion.

Plasma from black male patients with essential hypertension was bioassayed for vascular Na+-K+ pump inhibitory activity. Halves of the same rat tail artery were incubated for two hours in boiled plasma supernates from a hypertensive patient and a paired age-, sex-, and race-matched normotensive subject and then ouabain-sensitive 86Rb uptake was measured. Ouabain-sensitive 86Rb uptake by their leukocytes was also measured. Eighteen pairs of subjects were studied. The uptakes were not significantly different in the hypertensive patients and control subjects. However, when we selected from the eighteen hypertensive patients, nine with low plasma renin activity on the day of the study, uptakes were reduced in the hypertensive patients relative to the paired control subjects. We also assayed plasma supernates from normotensive black and white male subjects before and after acute volume expansion (2.5 L saline IV + 1.5 L distilled water orally over a three-hour period) and from paired normotensive subjects before and after sham volume expansion and obtained a positive bioassay in the expanded subjects both on intraindividual and interindividual comparisons. These studies demonstrate increased vascular Na+-K+ pump inhibitory activity in the plasma of black male patients with low renin essential hypertension and in the plasma of normotensive subjects after acute volume expansion. The findings suggest that the inhibitory activity in the hypertensive subjects' plasma is related to volume expansion, relative or absolute.

Adult↗
PubMed1989

Diuretic therapy and exercise in patients with systemic hypertension.

Twenty patients with uncomplicated systemic hypertension underwent treadmill testing twice during placebo treatment and twice during hydrochlorothiazide treatment. Data were collected at rest, at peak exercise and 10 min after exercise. Serum potassium, magnesium and plasma catecholamines increased significantly with exercise. There was no rebound hypokalaemia during the recovery period. Occasional ventricular premature complexes were recorded in all phases of the study. However, there was no difference in the frequency or complexity of arrhythmias between the placebo and the treatment periods.

Arrhythmias, Cardiac↗
PubMed1989

Potassium restoration in hypertensive patients made hypokalemic by hydrochlorothiazide.

Among 447 hypertensive patients, most with a history of diuretic-induced hypokalemia, 252 developed diuretic-induced hypokalemia while receiving hydrochlorothiazide, 50 mg/d. In a randomized study we evaluated the efficacy of three drug regimens in restoring potassium levels while maintaining blood pressure control: hydrochlorothiazide (50 mg/d) plus potassium supplement (20 mmol/d); hydrochlorothiazide (50 mg/d) plus potassium supplement (40 mmol/d); or hydrochlorothiazide (50 mg/d) with triamterene (75 mg/d) in one combination tablet. In all groups, mean serum levels of potassium rose within 1 week and showed no further change thereafter. However, the hydrochlorothiazide/triamterene and hydrochlorothiazide plus 40 mmol of potassium regimens were significantly more effective in restoring serum potassium levels than was the hydrochlorothiazide plus 20 mmol of potassium regimen. A significant increase in magnesium levels was observed only in the group treated with the hydrochlorothiazide/triamterene combination. Each regimen provided continued control of mild to moderate hypertension.

Adult↗