Left ventricular hypertrophy: unresolved issues.
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Antihypertensive Agents↗
Biomedical subjects
J A Schoenberger
Publications and source records attributed to J A Schoenberger.
Alpha-blockade and thiazide treatment of hypertension. A double-blind randomized trail comparing doxazosin and hydrochlorothiazide.
This trial involved 107 patients in a two-group, parallel, double-blind, randomized study comparing the diuretic, hydrochlorothiazide (HCTZ) (dose 25 to 50 mg) and the alpha 1 antagonist, doxazosin (dose 2 to 16 mg). All randomized participants were followed for at least 1 year. Participants were recruited from the community. The study was carried out in four phases: Phase I-Baseline; Phase II-Monotherapy Titration; Phase III-Combination Therapy Titration; and Phase IV-Maintenance. The following measures were carried out: blood pressure, biochemistries, lipids/lipoproteins, quality of life, ambulatory electrocardiograms, echocardiograms, adverse experiences, and drug adherence. Both drugs were well tolerated, with only 4% taken off doxazosin and 7% off HCTZ. Adverse experiences were uncommon and mostly mild. Both drugs were effective in managing hypertension over 1 year of therapy. There was no difference noted in terms of efficacy of blood pressure lowering between the two study drugs, nor was there any evidence of tolerance developing or of any serious adverse effects. Average final doses for drugs were 7.8 mg for doxazosin and 36 mg for HCTZ. The results show that, over the course of 1 year, both drugs significantly lowered systolic and diastolic pressures compared to baseline; doxazosin (-19 and -16 mm Hg); HCTZ (-22 and 15 mm Hg). Blood pressure lowering was not significantly different between drugs. Sitting heart rate was not affected by drugs. Changes in quality of life measures were similar between groups. Echocardiographic measures at 1 year showed significant between-drug differences in change in left internal end systolic and diastolic dimensions and end systolic stress. Both doxazosin and HCTZ were effective drugs over 1 year for treating hypertension.
Adrenergic alpha-Antagonists↗
Once-daily monotherapy with trandolapril in the treatment of hypertension.
Once-daily antihypertensive drugs that control blood pressure (BP) for the full 24-h dosing period, enhance patient compliance and may reduce the cardiovascular complications of hypertension which occur with increased frequency in the early morning. Since some once-daily agents are more effective than others in maintaining antihypertensive effects toward the end of the 24-h dosing interval this study was designed to evaluate the duration of antihypertensive action of trandolapril using 48 h ambulatory blood pressure monitoring (ABPM) in 41 patients with mild-to-moderate essential hypertension. Twenty-four hour ABPM was performed on two consecutive days (48 h) after a 4 week single blind placebo run-in period and repeated after an 8 week double-blind period during which 20 patients were randomized to treatment with trandolapril (2-4 mg once-daily) and 21 patients to matching placebo. During the second 48 h monitoring period, placebo rather than active medication was taken by both of the groups at the beginning of the second 24 h segment. Trandolapril reduced ambulatory systolic and diastolic BP by 9.4 and 6.2 mm Hg respectively (P < or = 0.01) during the first 24 h of the post treatment monitoring period while placebo increased the systolic and diastolic BPs in the same period by 3.8 and 2.6 mm Hg (P < 0.05). During the second monitoring period (hours 25-48), trandolapril reduced systolic and diastolic BP by 5.6 and 3.9 mm Hg while placebo increased BP by 2.3 and 1.6 mm Hg (P < 0.03). When compared to placebo by 2 h time blocks, throughout the 2 days of monitoring, trandolapril produced clinically significant decreases in systolic and diastolic BP for 30 and 28 h following dosing. This indicates that trandolapril can be considered a true once-daily antihypertensive agent.
Adult↗
Urinary albumin and N-acetyl-beta-D-glucosaminidase excretions in mild hypertension.
Renal effects of mild hypertension and therapy have not been established. Since urinary albumin and N-acetyl-beta-D-glucosaminidase excretions reflect renal effects of hypertension, they were related to blood pressure, other cardiovascular risk factors, cardiac target organ effects, and response to therapy in mild hypertension (diastolic blood pressure 85-99 mm Hg). Participants were from two clinics of the Treatment of Mild Hypertension Study (TOMHS), a multicenter randomized, double-blind, controlled trial. Participants received nutritional-hygienic therapy and one of five active drugs or placebo. Urinary albumin and N-acetyl-beta-D-glucosaminidase excretions were assessed prospectively using office "spot" collections from one clinic (n = 213) and retrospectively using overnight collections from the other clinic (n = 210). Relationships were determined between protein excretions and blood pressure, age, gender, race, blood glucose, cholesterol concentrations, and indices of body mass and left ventricular mass and function at baseline. Treatment effects were assessed after 3 to 12 months. Spot and overnight albumin excretions related positively to baseline systolic blood pressure by univariate analyses. Spot albumin excretion related positively to systolic blood pressure, age, creatinine clearance, and left ventricular function while overnight albumin excretion related positively to left ventricular mass and female gender by multiple regression analyses. Spot, but not overnight, albumin excretion declined significantly with active drug therapy. N-acetyl-beta-D-glucosaminidase excretion did not relate to blood pressure or decline with therapy. The combined results suggest albumin excretion correlates with blood pressure, decreases with antihypertensive drug therapy, and is associated with greater left ventricular function and mass, as well as glomerular filtration rate, even at mild levels of hypertension.
Acetylglucosaminidase↗
Treatment of Mild Hypertension Study. Final results. Treatment of Mild Hypertension Study Research Group.
OBJECTIVE: To compare six antihypertensive interventions for the treatment of mild hypertension. DESIGN: Randomized, double-blind, placebo-controlled clinical trial. SETTING: Four hypertension screening and treatment centers in the United States. PARTICIPANTS: Hypertensive men and women, aged 45 to 69 years, with diastolic blood pressure less than 100 mm Hg. INTERVENTION: Sustained nutritional-hygienic advice to all participants to reduce weight, dietary sodium intake, and alcohol intake, and increase physical activity. Participants were randomly allocated to take (1) placebo (n = 234); (2) chlorthalidone (n = 136); (3) acebutolol (n = 132); (4) doxazosin mesylate (n = 134); (5) amlodipine maleate (n = 131); or (6) enalapril maleate (n = 135). MAIN OUTCOME MEASURES: Blood pressure, quality of life, side effects, blood lipid levels and analysis of other serum components, echocardiographic and electrocardiographic changes, and incidence of cardiovascular events over an average of 4.4 years of follow-up. RESULTS: Blood pressure reductions were sizable in all six groups, and were significantly greater for participants assigned to drug treatment than placebo (-15.9 vs -9.1 mm Hg for systolic blood pressure and -12.3 vs -8.6 mm Hg for diastolic blood pressure; P < .0001). After 4 years, 59% of participants assigned to placebo and 72% of participants given drug treatment continued on their initial medication as monotherapy. A smaller percentage of participants assigned to the drug-treatment groups died or experienced a major nonfatal cardiovascular event than those assigned to the placebo group (5.1% vs 7.3%; P = .21). After including other clinical events, the percentage of participants affected was 11.1% for those in the drug-treatment groups and 16.2% for those in the placebo group (P = .03). Incidence rates of most resting electrocardiographic abnormalities were lower and quality of life was improved more for those assigned to drug-treatment groups rather than the placebo group. Differences among the five drug treatments did not consistently favor one group in terms of regression of left ventricular mass, blood lipid levels, and other outcome measures. CONCLUSIONS: As an initial regimen, drug treatment in combination with nutritional-hygienic intervention was more effective in preventing cardiovascular and other clinical events than was nutritional-hygienic treatment alone. Drug-treatment group differences were minimal. Pending results from large-scale clinical trials to evaluate drug treatments for their effect on cardiovascular clinical events, these findings support the recommendations of the new fifth Joint National Committee report regarding treatment choices for people with stage 1 ("mild") hypertension.
Acebutolol↗
Psychosocial predictors of mortality in the Cardiac Arrhythmia Suppression Trial-1 (CAST-1).
Psychosocial variables predict the recurrence of clinical events in symptomatic patients, controlling for measures of disease severity. The Cardiac Arrhythmia Suppression Trial-1, a pharmacologic test of the arrhythmia suppression and mortality hypothesis among postmyocardial infarction patients, allowed a prospective test of the relationship of distress, perceived support, social interaction, life stress, and other variables, to mortality, adjusting statistically for ejection fraction, arrhythmia rates, and other known risk factors for coronary heart disease. Results indicated that the treatment medications, encainide and flecainide, were powerful predictors of mortality. Although the psychosocial variables were significant as univariate predictors, these variables were not significant as predictors in a multivariate model that included drug treatment. When the data analysis was restricted to patients randomized to placebo, thereby eliminating the antiarrhythmic drug effect, the level of perceived social support was a significant multivariate predictor of mortality, adjusting for measures of disease severity. The adjusted hazards ratio for a 1-point decrease in the perceived support score is equal to 1.46, based on the multivariate model.
Arrhythmias, Cardiac↗
Antihypertensive drug therapy and coronary heart disease risk.
Coronary heart disease (CHD) is the major cause of death in the United States. Major modifiable risk factors for CHD are hypertension, hypercholesterolemia, and cigarette smoking, with concomitant risk factors, especially left ventricular hypertrophy, that act synergistically to significantly increase overall risk. Antihypertensive therapy, while reducing the incidence of stroke, has not consistently reduced the incidence of CHD. This may be a result, in part, of adverse effects on the metabolic profile, especially on blood lipids, which are induced by diuretics and certain beta-blockers. Other antihypertensive agents appear to be either lipid neutral, such as calcium channel blockers and angiotensin-converting enzyme inhibitors, or lipid positive, such as selective alpha 1-blockers. The choice of initial antihypertensive therapy should be made with all of a patient's risk factors in mind. In addition to the drugs recommended in the 1988 Guidelines of the Joint National Committee on Detection, Evaluation and Treatment of High Blood Pressure, selective alpha 1-blockers should also be considered since they improve the lipid profile as well as reduce blood pressure.
Antihypertensive Agents↗
Effects of antihypertensive agents on coronary artery disease risk factors.
The adverse effects of certain antihypertensive medications, most notably diuretics and beta blockers, on serum lipids, glucose, and potassium may explain why control of hypertension has not been accompanied by declines in coronary artery disease. Evidence indicates that angiotensin-converting enzyme (ACE) inhibitors, including quinapril, the newest member of this class of drugs, have no deleterious effects on these coronary risk factors. In addition to differences in chemical structure, the unique activity of quinapril at the local tissue level might to some degree explain its comparatively favorable clinical profile. Consequently, ACE inhibiting agents may be better choices for the management of patients with mild-to-moderately elevated blood pressure. However, controlled clinical trials with these drugs are needed to determine their impact on events related to coronary artery disease.
Angiotensin-Converting Enzyme Inhibitors↗
Epidemiology and evaluation: steps toward hypertension treatment in the 1990s.
The percentage of persons in the United States over age 65--especially over 85--is increasing more rapidly than other age groups. Two thirds of people over age 65 have blood pressure higher than 140 mm Hg systolic or 90 mm Hg diastolic. Isolated systolic hypertension (systolic blood pressure greater than 160 mm Hg with diastolic blood pressure less than 90 mm Hg) is also highly prevalent. In a number of clinical trials, treatment of diastolic hypertension in the elderly has been shown to be beneficial, although the value of treatment of isolated systolic hypertension is not yet established. The benefit of antihypertensive therapy on the incidence of stroke and heart failure has been clearly established, but prevention of the atherosclerotic complications of high blood pressure (sudden death or myocardial infarction, for example) has not been convincingly demonstrated. Since clinical trials designed to investigate this atherosclerotic complication of hypertension have relied on stepped-care regimens (diuretics and beta blockers), the question arises whether the use of different drugs might have a better effect on prevention of myocardial infarction. The basis for this supposition includes the known adverse effects of diuretics and beta blockers on electrolytes, lipid metabolism, glucose metabolism, insulin resistance, and quality of life. Hypertension treatment in the 1990s will focus on the mechanisms by which blood pressure is lowered by various antihypertensive agents, as well as individualization of drug therapy based on coexisting diseases and conditions. Emphasis will be placed on use of monotherapy whenever possible; diuretics in low doses will probably be used more frequently for second-line therapy. In recognition of their lack of adverse lipid effects and their tolerability, first-line therapy with alpha blockers, angiotensin-converting enzyme inhibitors, and calcium antagonists will become increasingly common. The goal of antihypertensive therapy will be to extend the life expectancy of hypertensive patients to that of subjects without high blood pressure; hopefully, these new treatment approaches will bring us closer to that goal.
Aged↗
Self-reported side effects from antihypertensive drugs. A clinical trial. Quality of Life Research Group.
We report on the distress associated with physical symptoms in 761 male hypertensive patients enrolled in a clinical trial of the effects of captopril, methyldopa or propranolol on quality of life. Educational level at entry into the trial showed a negative association with a series of physical symptom distress items among patients not previously treated with antihypertensive medications but no association with symptoms among the previously treated. Over the 24 weeks of therapy captopril as monotherapy was associated with no change from baseline in distress in all symptoms examined. In contrast, distress increased in the methyldopa treated patients for dry mouth and blurred vision. Propranolol treated patients had increased "trouble getting breath," bradycardia, shortness of breath or wheezing, and blurred vision. Between group comparisons revealed significant differences favorably comparing captopril to both methyldopa and propranolol in regard to fatigue, and blurred vision, as well as to methyldopa alone for dry mouth and "feeling worn out." There were significant differences as well between captopril and propranolol with patients on propranolol worsening in bradycardia. Other comparisons of patients on propranolol and methyldopa monotherapy showed propranolol patients worsening in bradycardia and loss of taste, but methyldopa patients reported more dry mouth and feeling worn out than those on propranolol. The addition of hydrochlorothiazide to therapy worsened total physical symptom distress scores for methyldopa and propranolol patients. This study confirms the value of methods which assess the degree of distress associated with symptoms commonly reported by hypertensive patients receiving antihypertensive medications. This approach can be useful in establishing a treatment regimen least likely to cause distress and can be of value in preserving quality of life, preventing noncompliance, and withdrawal from treatment.
Adult↗
Post-load plasma glucose and cancer mortality in middle-aged men and women. 12-year follow-up findings of the Chicago Heart Association Detection Project in Industry.
The relation of post-load plasma glucose to 12-year cancer mortality was studied in 11,521 white men and 8,591 white women aged 35-64 years at entry in the Chicago Heart Association Detection Project in Industry. There were 298 deaths in which cancer was the underlying cause in men and 186 such deaths in women. Plasma glucose levels at baseline measured one hour after a 50 g oral glucose load were positively related to cancer mortality in men but not in women. This increased mortality in men persisted after controlling for age, body mass index, smoking, serum cholesterol, systolic blood pressure, education, and anti-hypertensive treatment. A site-specific analysis of the male cancer deaths demonstrated higher mean plasma glucose levels for decedents for nearly all sites except oral cancers, liver cancer, and other respiratory cancers. For women, elevations existed for those who died of colon, lung, and hematologic/lymphatic tumors, but not for most other sites. The associations between baseline post-load plasma glucose levels and cancer mortality were similar for earlier and later cancer deaths, which indicates that incipient or occult neoplasm at baseline was not responsible for elevated glucose levels in men who subsequently died of cancer. Cancer mortality rates were also higher for those with a clinical diagnosis of diabetes than for those without, but the numbers of persons with diabetes were small as were the numbers of cancer deaths (19 in the men and 10 in the women).
Administration, Oral↗
Controversies in the use of combination therapy in the older patient.
Monotherapy of hypertension should be the goal of treatment. Even in the elderly hypertensive patient there is a good response to monotherapy with angiotensin-converting enzyme inhibitors as well as to diuretics and calcium channel blockers, despite the low plasma renin activity seen in the elderly. Adverse effects on metabolism and quality of life should be avoided in elderly patients as well as in younger hypertensive patients. Combinations of 2 drugs will not necessarily eliminate these undesirable effects, but drug combinations will be required in half of the hypertensive population. It is reasonable, when a second drug is added, to use one with a different mode of action. The role of diuretics, which have been the mainstay of antihypertensive therapy for a long time, may ultimately become that of a second drug in combination treatment.
Age Factors↗
Cardiovascular risk factors: multiple interventions in man.
Cardiovascular disease, especially coronary heart disease, is multifactoral. Therefore, it is reasonable to use multiple interventions to try to obtain the greatest reduction in risk. This has been attempted in several controlled clinical trials and in two community educational trials. The results have been variable, showing either benefit or a favorable trend with no statistically significance change. Although the benefit of multiple intervention has not been conclusively demonstrated, there has been a downward trend in cardiovascular mortality in many countries which parallels a downward trend in the level of cardiovascular risk, supporting the concept of benefit from multiple intervention.
Cardiovascular Diseases↗
Efficacy, safety, and quality-of-life assessment of captopril antihypertensive therapy in clinical practice.
Successful long-term treatment of hypertension must include consideration of individual patients' life-style interfaced with the potential for adverse drug events. In a postmarketing surveillance study, 30,515 patients received captopril monotherapy and were evaluated by 7792 physicians. Mean systolic and diastolic blood pressures were reduced 17 and 11 mm Hg, respectively. Mean diastolic blood pressure was reduced 10% for patients with mild hypertension; larger mean reductions were noted for patients with moderate (16.5%) and severe (21.5%) hypertension. Captopril therapy was equally effective in all races (white, Hispanic, and black patients), age groups, and in isolated instances of systolic hypertension. Only 4.9% of patients reporting an adverse event required discontinuation of therapy. Headache (1.8%) and dizziness (1.6%) were the most frequently reported adverse events. Quality-of-life measures improved.
Adult↗
Dilevalol compared with propranolol and placebo for systemic hypertension.
Dilevalol is a new antihypertensive agent that is both a vasodilator, through its beta 2-agonist action, and a nonselective beta antagonist. Two multicenter, double-blind studies were performed: study 1 compared dilevalol administered once-daily with either dilevalol or propranolol every 12 hours; study 2 compared dilevalol administered once daily with placebo. Both studies had a placebo run-in period to establish that the baseline supine diastolic blood pressures were consistent in the mild to moderate severity range (95 to 115 mm Hg) at 2 consecutive visits for study 1 and in the mild severity range (95 to 105 mm Hg) in study 2. Patients then were randomized to the double-blind titration phase, during which doses were titrated over a 9-week period to achieve a supine diastolic blood pressure of less than 90 mm Hg and a decrease from baseline of greater than or equal to 10 mm Hg. Patients were then maintained on a fixed dose for 2 months (study 1) or for 1 month (study 2). Dilevalol given once daily was as effective in reducing supine diastolic blood pressure as dilevalol every 12 hours and propranolol every 12 hours (study 1) and was superior to placebo (p less than 0.001) (study 2). In both studies, dilevalol given once daily was effective and well tolerated. The side-effect profile of dilevalol was similar to that of placebo and different from that of propranolol. Treatment with dilevalol resulted in significantly less fatigue (p less than 0.05), bradycardia (less than 50 beats/minute) and mental depression than with propranolol, but significantly (p less than 0.05) more diarrhea/loose stools.(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
Effects of dilevalol, metoprolol and atenolol on left ventricular mass and function in nonelderly and elderly hypertensive patients.
Using serial M-mode echocardiographic determinations of left ventricular (LV) mass and function, the effects of dilevalol, a selective beta 2 agonist with nonselective beta-antagonist properties, were compared with those of metoprolol in 2 centers in double-blind, randomized clinical trials using similar protocols in nonelderly hypertensive patients (aged less than 65 years) (study 1). In a separate bicenter study with a similar design, dilevalol was compared with atenolol in elderly hypertensive patients (aged greater than or equal to 65 years) (study 2). Patients in both studies received placebo for 2 to 4 weeks, and were then randomized to receive increasing doses of dilevalol (200, 400, 800, 1,600 mg) or metoprolol (100, 200, 300, 400 mg) in study 1, and dilevalol (100, 200, 400, 800 mg) or atenolol (50, 100 mg) in study 2, to achieve a supine diastolic blood pressure (BP) of less than 90 mm Hg. In both studies, LV function and mass (Penn convention) were determined by echocardiographic examinations performed before randomization and at the end of the active treatment phase. Dilevalol, metoprolol and atenolol significantly reduced BP compared with placebo. In the nonelderly patients, a modest reduction in LV mass was observed with dilevalol (p less than 0.03) but not with metoprolol. Indexes of LV function--as assessed by end-diastolic and end-systolic dimensions, LV ejection time and ejection fraction--were better preserved by dilevalol than by metoprolol. In the elderly, neither dilevalol nor atenolol affected LV mass; however, indexes of LV function were better preserved with dilevalol than with atenolol.(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenergic beta-Antagonists↗
Usefulness of penbutolol for systemic hypertension. Penbutolol Research Group.
Dose-response relations with penbutolol--a beta-adrenergic blocking agent--were evaluated in a double-blind multiclinic study conducted in 302 outpatients with mild to moderate hypertension (untreated supine diastolic blood pressure [BP] greater than or equal to 95 and less than or equal to 115 mm Hg). Penbutolol was administered once daily in 10, 20 or 40 mg doses for 6 weeks and compared with placebo. Mean declines from baseline in supine diastolic BP were comparable in the 3 penbutolol treatment groups and significantly superior to placebo (p less than 0.05). A significant difference between penbutolol dosage groups was observed only for supine systolic BP; the mean decline at 20 mg/day was significantly larger than that at 10 mg/day (p less than 0.05). Maximum BP response developed in approximately 4 weeks at 10 mg/day and in 2 weeks at the higher dosages. Decline in mean heart rate after 6 weeks of penbutolol therapy significantly exceeded placebo only at 40 mg/day (7.2 vs 2.5 beats/min, p less than 0.05). Treatment was well-tolerated and discontinued because of adverse effects in only 7 patients receiving penbutolol and 3 receiving placebo. The lack of significant bradycardia and the low incidence of other troublesome adverse effects are potential advantages during antihypertensive therapy with penbutolol. With rapid onset of effect and good efficacy and tolerability, the 20 mg once-daily dose appears to be optimum for therapy with this new agent.
Blood Pressure↗
Serum uric acid and 11.5-year mortality of middle-aged women: findings of the Chicago Heart Association Detection Project in Industry.
The relationships of serum uric acid to mortality from all causes, the cardiovascular diseases, and cancer were evaluated in 6797 white women age 35-64 years followed for an average of 11.5 years in the Chicago Heart Association Detection Project in Industry (CHA). Serum uric acid levels at baseline were strongly and significantly associated with all causes mortality in this cohort, with control for multiple risk factors and with exclusion of hypertensives on treatment. When the analysis was performed on age-specific groups 35-44, 45-54, and 55-64 years of age, the association was observed primarily in women in the oldest age group. All cardiovascular deaths, deaths due to coronary heart disease, and all cancer deaths were also associated with serum uric acid levels in the 55-64 year old group. The relationships persisted with control for multiple risk factors and with exclusion of treated hypertensives. A site-specific analysis of cancer deaths demonstrated elevations in mean serum uric acid levels for nearly all sites. Differences in mean serum uric acid levels between decedents and survivors tended to be largest in the first 5 years of follow-up for the cardiovascular deaths, but for cancer decedents they tended to be larger for subsequent years of follow-up. As an initial report on the association of serum uric acid and cancer in women in this age group, the results of this study require confirmation. Although hormonal influences may play a role, pathophysiologic mechanisms relating serum uric acid to mortality in white women aged 55-64 are currently unknown.
Adult↗