Correction: single-drug therapy for hypertension in men.
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Antihypertensive Agents↗
Biomedical subjects
B J Materson
Publications and source records attributed to B J Materson.
Angiotensin-converting enzyme inhibitors in hypertension. A dozen years of experience.
Introduction of the first angiotensin-converting enzyme (ACE) inhibitor, captopril, in 1981 marked a major advance in the treatment of essential hypertension. This article reviews the 12 years of clinical experience during which it and other ACE inhibitors have become recognized as first-line agents for treating hypertension. The benefits of ACE inhibition in diabetic patients are being defined. In recent years, beneficial effects on glucose handling, left-ventricular mass, quality of life, renal function, and myocardial protection have become recognized. For these reasons, and because of their excellent safety profile, ACE inhibitors are now widely used for the treatment of hypertensive patients.
Angiotensin-Converting Enzyme Inhibitors↗
Modern strategies to prevent coronary sequelae and stroke in hypertensive patients differ from the JNC V Consensus Guidelines.
In recent years, government agencies of many countries have established consensus guidelines for the evaluation and treatment of hypertension. Once published, guidelines tend to be perceived as directives by a variety of health care providers. Unfortunately, these guidelines often do not reflect the practices of most hypertension experts. This report summarizes the opinions of seven hypertension experts concerning the impact of "official" guidelines on clinical practice. In addition, the individual therapeutic recommendations of these panel members are summarized. Their different treatment strategies reflect the diversity of first rate treatment plans that aim to reduce the cardiovascular sequelae in individual patients with essential hypertension. Most importantly, not one of these seven treatment strategies followed the "preferred" treatment of the U.S. guidelines, which recommend diuretics and beta-blockers as first-line therapy. The present authors approach the treatment of hypertension as a means to reduce cardiovascular events. Thus, reduction of blood pressure is not the most important therapeutic endpoint. The panel believes that whereas many different drugs can produce effective blood pressure reduction, the modern primary goal of antihypertensive drug therapy is to select a regimen most likely to prolong the quality and duration of life. In real terms, this means that the primary goal of treatment is the prevention of the major vascular sequelae of hypertension (heart attack, ventricular remodeling, hypertrophy, heart failure, and stroke) that shorten useful life. There are a number of effective hypertensive treatments, which can be selected based on individual patient requirements. However, many consensus guidelines do not allow the flexibility required to optimize individual patient treatment. As a result, health care providers should not feel compelled to regard the preferences of "official" guidelines as the best, modern, state-of-the-art therapy for an individual patient. All seven experts who are deeply involved in the daily care of patients preferred drugs other than beta-blockers and diuretics (the Joint National Committee [JNC] choices) for first-line therapy of hypertension.
Cardiovascular Diseases↗
Fluid and electrolyte disorders in congestive heart failure.
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Acid-Base Imbalance↗
Single-drug therapy for hypertension in men. A comparison of six antihypertensive agents with placebo. The Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents.
BACKGROUND: Characteristics such as age and race are often cited as determinants of the response of blood pressure to specific antihypertensive agents, but this clinically important issue has not been examined in sufficiently large trials, involving all standard treatments, to determine the effect of such factors. METHODS: In a randomized, double-blind study at 15 clinics, we assigned 1292 men with diastolic blood pressures of 95 to 109 mm Hg, after a placebo washout period, to receive placebo or one of six drugs: hydrochlorothiazide (12.5 to 50 mg per day), atenolol (25 to 100 mg per day), captopril (25 to 100 mg per day), clonidine (0.2 to 0.6 mg per day), a sustained-release preparation of diltiazem (120 to 360 mg per day), or prazosin (4 to 20 mg per day). The drug doses were titrated to a goal of less than 90 mm Hg for maximal diastolic pressure, and the patients continued to receive therapy for at least one year. RESULTS: The mean (+/- SD) age of the randomized patients was 59 +/- 10 years, and 48 percent were black. The average blood pressure at base line was 152 +/- 14/99 +/- 3 mm Hg. Diltiazem therapy had the highest rate of success: 59 percent of the treated patients had reached the blood-pressure goal at the end of the titration phase and had a diastolic blood pressure of less than 95 mm Hg at one year. Atenolol was successful by this definition in 51 percent of the patients, clonidine in 50 percent, hydrochlorothiazide in 46 percent, captopril in 42 percent, and prazosin in 42 percent; all these agents were superior to placebo (success rate, 25 percent). Diltiazem ranked first for younger blacks (< 60 years) and older blacks (> or = 60 years), among whom the success rate was 64 percent, captopril for younger whites (success rate, 55 percent), and atenolol for older whites (68 percent). Drug intolerance was more frequent with clonidine (14 percent) and prazosin (12 percent) than with the other drugs. CONCLUSIONS: Among men, race and age have an important effect on the response to single-drug therapy for hypertension. In addition to cost and quality of life, these factors should be considered in the initial choice of a drug.
Age Factors↗
Alterations in heart rate variability and its circadian rhythm in hypertensive patients with left ventricular hypertrophy free of coronary artery disease.
Heart rate variability (HRV) and its circadian rhythm were evaluated in 22 patients with treated hypertension and left ventricular hypertrophy in whom coronary artery disease was excluded by stress thallium or angiography. By using 24-hour Holter monitoring, HRV and its spectral components were measured. Findings were compared with 11 age-matched normal controls. The difference between mean R-R intervals during sleep (11 PM to 7 AM) and while awake (9 AM to 9 PM) (73 +/- 33 vs 263 +/- 63 msec, p < 0.0001) and the mean 24-hour SD of the R-R intervals (55 +/- 6.3 vs 93 +/- 11, p < 0.0001) were lower among the hypertensive patients compared with controls. The percentage of difference between successive R-R intervals that exceeded 50 msec, a measure of parasympathetic tone, was also lower among the hypertensive patients (6.8 +/- 7.1 vs 13.6 +/- 8.9, p < 0.002); it increased at night and decreased during the day among the controls, and this circadian rhythm was blunted among the patients. Spectral analysis showed that power in the high-frequency range (0.15 to 0.40 Hz) was lower among the hypertensive patients during 21 of 24 hours but that the difference was statistically significant only during 9 hours (p ranging from < 0.05 to 0.009). Power in the low-frequency range (0.04 to 015 Hz) was lower at night, increased in the morning, and higher during the day among controls; this circadian rhythm was absent among hypertensive patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
Adverse effects of angiotensin-converting enzyme inhibitors in antihypertensive therapy with focus on quinapril.
Angiotensin-converting enzyme (ACE) inhibitors are useful first-line drugs in the therapy of mild and moderate hypertension. Adverse reactions to this drug class are rarely serious. Hypotension, cough, rash, and taste disturbance are uncommon; reduced glomerular filtration and hyperkalemia occur infrequently; angioedema is rare and neutropenia is extremely rare. Quinapril is a new ACE inhibitor that is converted to biologically active quinaprilat in the liver. This ACE inhibitor has a rapid onset of action and inhibits local tissue converting enzyme systems in kidney, heart, and brain, as well as in the circulating renin-angiotensin system. Clinically significant adverse effects of quinapril occur at low rates. In 1,771 patients receiving quinapril, the reported incidence of the first occurrence of orthostatic hypotension was comparable to that seen in patients receiving placebo. In other studies, headache was reported by up to 4.7% of patients receiving quinapril, which is comparable to reported incidences of headache in patients receiving other ACE inhibitors. Other adverse events reported at rates greater than 1% include cough with associated rhinitis and bronchitis, dizziness, and somnolence. Such adverse events have only rarely led to the withdrawal of patients from clinical studies of quinapril.
Angiotensin-Converting Enzyme Inhibitors↗
Antihypertensive drug therapy does not perturb the circadian blood pressure pattern.
The literature was reviewed to determine whether failure of older antihypertensive drugs to suppress the early morning increase of blood pressure was responsible, in part, for the less than satisfactory rate of reduction in cardiovascular mortality rates in the United States. The authors found that neither the old nor the new antihypertensive drugs altered the 24-hour blood pressure curve pattern, although long-acting drugs did show continued effect at the end of the 24-hour period when compared with placebo. The efficacy of these drugs most likely lies with their blood pressure lowering and other ancillary effects and not with pattern changes. More importantly, examination of new data (1989) shows that the rate of decline in death due to diseases of the heart has exceeded that for cerebrovascular diseases. Our overall health care effort may be more successful than we thought.
Antihypertensive Agents↗
Renal and electrolyte complications of congestive heart failure and effects of therapy with angiotensin-converting enzyme inhibitors.
Blood pressure declines in virtually all patients with severe congestive heart failure given an angiotensin-converting enzyme (ACE) inhibitor, but hypotension is of concern only if symptomatic. Acute renal insufficiency induced by an ACE inhibitor is due to reduced renal perfusion pressure together with blockade of angiotensin II-induced constriction of the efferent arteriole. Risk factors (or markers) for renal failure include hyponatremia, hypotension, volume contraction. Hyponatremia is an index of increased hemodynamic impairment, marked activation of the renin-angiotensin-aldosterone axis, and poor prognosis. Preventive measures for both ACE inhibitor-associated hypotension and renal insufficiency include withholding diuretics for a few days, initiating therapy with very small doses of ACE inhibitors, and cautious dose titration. Therapy for both hypotension and renal insufficiency involves increasing dietary sodium intake and reducing the dosage of, or temporarily discontinuing, the diuretic. The ACE inhibitor may have to be given at reduced dosage or discontinued for a time. If discontinuation is deemed necessary, administration of these survival-prolonging medications should be reinitiated after a brief respite whenever possible.
Acute Kidney Injury↗
Abnormal left ventricular diastolic filling in eccentric left ventricular hypertrophy of obesity.
Left ventricular (LV) diastolic filling pattern of obese subjects with eccentric LV hypertrophy was studied. Findings were compared with those of normal control subjects and hypertensive patients with concentric LV hypertrophy. M-mode, 2-dimensional and Doppler echocardiograms were recorded in 11 obese (body mass index greater than 30 kg/m2) normotensive patients with eccentric LV hypertrophy, 10 normal control subjects, and 18 nonobese, hypertensive patients with concentric LV hypertrophy whose antihypertensive medications were discontinued 2 weeks before study. LV hypertrophy was defined as LV mass/height greater than 143 g/m. Hypertrophy in the obese patients was eccentric: Their LV internal dimension (61 +/- 3 mm) was greater than that of hypertensive patients (55 +/- 5 mm, p less than 0.001) and normal control subjects (55 +/- 2 mm, p less than 0.01); their septal (10.7 +/- 0.7 mm) and posterior (10.9 +/- 0.6 mm) wall thicknesses were smaller than those of the hypertensive patients (12.2 +/- 1.7 mm, p less than 0.05 and 11.7 +/- 1.2 mm, respectively, difference not significant). Pulsed-wave Doppler echocardiographic filling indexes were used to evaluate LV diastolic filling. Obese patients had a higher peak velocity of atrial filling (69 +/- 14 vs 54 +/- 15 cm/s, p less than 0.05), lower early/atrial filling velocity ratio (1.0 +/- 0.26 vs 1.32 +/- 0.21, p less than 0.05), prolonged deceleration half-time (108 +/- 9 vs 86 +/- 15 ms, p less than 0.01) and lower peak filling rate corrected to stroke volume (4.08 +/- 0.68 vs 4.96 +/- 0.88 stroke volume/s, p less than 0.05) than normal control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
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↗
Isolated systolic hypertension: new answers, more questions.
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Aged↗
Classic therapeutic trials in hypertension. Were patients vulnerable to unsuppressed peak morning blood pressure?
A metaanalysis of the major clinical trials on the benefits of antihypertensive therapy revealed that there is an overall reduction of coronary events by treatment, but that it is only about one-half of the reduction predicted. The reduction in stroke achieved the predicted number. This "failure" has been attributed to study design, patient age at entry, preexisting disease, high-lipid diets, drug-associated cardiac dysrhythmias, and the "J-curve" effect. It is also possible that the drugs used in these trials did not suppress the morning acceleration of blood pressure during which most coronary and cerebrovascular events occur. Ambulatory blood pressure monitoring studies suggest that antihypertensive drugs reduce overall blood pressure throughout the 24-h period, but do not change the circadian curve. The beneficial effect of antihypertensive therapy probably rests with the magnitude of blood pressure reduction. It is unlikely that lack of suppression of morning acceleration alone accounted for the failure of "older" drugs to prevent as much cardiac mortality as expected.
Aged↗
Right ventricular diastolic function in systemic hypertension.
Right (RV) and left ventricular (LV) diastolic function was evaluated in 50 patients with mild, uncomplicated essential hypertension using pulsed-wave Doppler echocardiography. Patients with pulmonary, valvular or coronary artery disease were excluded and antihypertensive drugs were discontinued for the 2 weeks preceding the study. Ten normotensive patients without heart disease acted as control subjects. In the hypertensive patients, RV peak velocity of atrial filling was higher (42 +/- 10 vs 31 +/- 7 cm/s, p less than 0.01) and deceleration half-time was prolonged (96 +/- 20 vs 83 +/- 10 ms, difference not significant); ratio of early/atrial filling velocity (1.1 +/- 0.3 vs 1.7 +/- 0.4, p less than 0.001) and peak filling rate corrected to stroke volume (3.6 +/- 0.7 vs 5.3 +/- 0.9 SV/s, p less than 0.001) were lower. LV filling parameters showed similar changes. RV filling parameters did not correlate with age, LV mass or septal thickness but correlated weakly with LV radius/thickness ratio. There was good correlation between RV and the following corresponding LV filling parameters: peak filling rate, r = 0.68, p less than 0.001; ratio of early/atrial filling, r = 0.88, p less than 0.0001; and deceleration half-time, r = 0.62, p less than 0.001. Data indicate that RV diastolic function is abnormal in essential hypertension and these abnormalities are closely related to those of LV diastolic function.
Adult↗
Renal biopsy in patients 65 years of age or older. An analysis of the results of 334 biopsies.
We studied the clinical and pathological data for 334 patients age 65 or more who underwent renal biopsy for acute renal failure (ARF, n = 55), subacute renal failure (SRF, n = 72), chronic renal failure (CRF, n = 57), proteinuria (n = 137), and hematuria (n = 13). Tissue diagnoses were glomerulopathy (n = 252, 75.4%), acute tubular lesions (n = 18), interstitial nephritis (n = 23), vascular diseases (n = 36, including 14 with cholesterol emboli), and five miscellaneous diagnoses. Of the 55 patients with ARF, 23 had a glomerular lesion, 15 had acute tubular necrosis, and 8 had acute interstitial nephritis. Of 72 patients with SRF, 49 had a glomerulopathy, 12 had a vascular disorder, and six had acute interstitial nephritis. Hence, patients with ARF or SRF exhibited a high potential for reversible lesions. Only 11.3% of patients with CRF had potentially reversible causes. The most common causes of proteinuria were membranous glomerulopathy (34.3%), minimal change disease (14.6%), focal segmental sclerosis (11.7%), and amyloidosis (8.8%). Of the 25 patients with advanced nephrosclerosis, 24 had renal failure, 20 were hypertensive, and 13 had cholesterol emboli. Of 33 patients with diabetes mellitus, 66.7% were found to have lesions not related to diabetes. We conclude that renal biopsy is most useful in older patients with ARF or SRF because of potentially reversible renal disease. Old age alone is not a contraindication to performing a renal biopsy.
Acute Kidney Injury↗
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↗
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↗
Influence of beta 2 agonism and beta 1 and beta 2 antagonism on adverse effects and plasma lipoproteins: results of a multicenter comparison of dilevalol and metoprolol.
Dilevalol combines vasodilation due to selective beta 2 agonism and nonselective beta antagonism. We studied 311 patients randomized to dilevalol and 138 to metoprolol in a multicenter trial. After a 4-week placebo washout, dilevalol was titrated from 200 to 1,600 mg once daily and metoprolol from 100 to 400 mg to a goal supine diastolic blood pressure less than 90 and greater than or equal to 10 mm Hg decrease from baseline. Responders were followed for 1 year. The average age of patients was 51 years; 72% were men and 54% were white. Both drugs reduced blood pressure effectively to a similar level. Fewer patients discontinued dilevalol than did those taking metoprolol (9 vs 16%; p less than 0.03). More metoprolol-treated patients withdrew because of depression (6 vs less than 1%; p = 0.03) and impotence (5 vs less than 1%; p = 0.03). Lipoprotein levels before and after treatment were measured in 99 patients treated for 53.5 weeks with dilevalol (mean dose 438 mg). Dilevalol increased high-density lipoprotein (HDL) cholesterol by 2.5 mg/dl to 47.2 (p = 0.05), reduced low-density lipoprotein (LDL) cholesterol by 2.5 mg/dl, increased HDL/LDL by 0.03, and decreased total cholesterol/HDL cholesterol by 0.18. Triglycerides increased by 21 mg/dl (p = 0.06). In patients with an initial HDL cholesterol less than 35 mg/dl, dilevalol increased it by 9 mg/dl. In patients treated with metoprolol, the only significant change (p = 0.02) was a 41.9-mg/dl increase in triglyceride levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenergic beta-Agonists↗