Which antihypertensive drugs first--and why!
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Adrenergic beta-Antagonists↗
Biomedical subjects
M H Alderman
Publications and source records attributed to M H Alderman.
Parallel cardiac and vascular adaptation in hypertension.
BACKGROUND: Although vascular damage in the noncoronary circulation is a major cause of complications in hypertension, relatively little is known of the in vivo geometry and function of the arterial circulation in patients with uncomplicated hypertension or of their relation to left ventricular hypertrophy, a marker of enhanced risk of cardiovascular complications. METHODS AND RESULTS: Wall thickness and internal diameter of the common carotid artery and the presence of atherosclerosis within the extracranial carotid arteries were determined by ultrasound in 43 asymptomatic hypertensive patients and 43 normotensive subjects matched for sex, age, and body size. Vascular stiffness was estimated from simultaneous superimposed carotid pressure waveforms obtained with an external solid-state transducer. Left ventricular size and function were determined echocardiographically. Compared with normal subjects, hypertensive patients had greater left ventricular absolute and relative wall thicknesses, left ventricular mass, and carotid absolute and relative wall thicknesses (p < 0.005). Carotid intimal-medial thickness exceeded the 95th percentile of normal values in 28% of hypertensive patients (p < 0.01). Carotid atherosclerosis was equally prevalent within the two blood pressure groups and was associated with older age, larger left ventricular and carotid wall thicknesses, and carotid diameter. Despite similar carotid pulse pressures, vascular stiffness was significantly increased in the hypertensive patients. Among the population as a whole, significant relations existed between cardiac and vascular wall thicknesses and internal dimensions. In multivariate analyses, these relations were statistically independent of age and blood pressure. CONCLUSIONS: The present study documents the presence of geometric and functional changes within the common carotid artery in uncomplicated hypertension that parallel findings within the left ventricle. The potential contribution of these changes to the cardiovascular complications of hypertension, particularly in the setting of left ventricular hypertrophy, is unknown.
Adaptation, Physiological↗
Differences in urinary albumin excretion rate between normotensive and hypertensive, white and nonwhite subjects.
Eighty-one normotensive and 61 hypertensive white and nonwhite subjects were studied cross-sectionally to determine the prevalence and determinants of elevated urinary albumin levels. Twenty-four-hour urinary albumin excretion was determined by radioimmunoassay. The prevalence of elevated urinary albumin level (greater than or equal to 15 mg/24 h) was significantly greater in hypertensive than in normotensive subjects (31.1% and 8.6%). Among hypertensive subjects, a much greater proportion of whites than nonwhites had urinary albumin levels of 15 mg/24 h or greater (39.5% and 17.4%). The independent association of blood pressure with urinary albumin level was affirmed by logistic regression analyses for white normotensive and hypertensive subjects combined, and for hypertensive subjects alone. Furthermore, among hypertensive subjects, whites were five times as likely as nonwhites to have elevated urinary albumin levels. Thus, blood pressure and ethnicity were the important determinants of urinary albumin excretion among hypertensive subjects.
Adolescent↗
Gender differences in left ventricular anatomy, blood viscosity and volume regulatory hormones in normal adults.
Gender differences in left ventricular (LV) anatomy, whole blood and plasma viscosity, and blood volume regulatory hormones were studied in 110 normotensive employed adults (28 black and 34 white men [mean age 51 +/- 12 years], 20 black and 28 white women [mean age 53 +/- 12 years]). LV mass and wall thicknesses were positively related to whole blood viscosity, primarily because of higher values of both variables in men. LV chamber size was inversely related to hematocrit and to blood viscosity (p less than 0.002) in women but not in men. Whole blood viscosity increased with age in men (p less than 0.01), but tended to decrease in women; older women also had better LV function, larger LV chambers, and a trend toward increasing LV mass. Atrial natriuretic factor increased with age in women but not in men (r = 0.60, p less than 0.001), and plasma renin activity decreased (r = -0.35, p less than 0.02). Thus, in women, increase in LV chamber size with age and associated changes in LV systolic function, atrial natriuretic factor levels and plasma renin activity suggest plasma volume expansion related to the aging process. These findings also suggest that an increase in LV volume load with age may contribute to previously reported increases in LV mass in older women.
Adolescent↗
Association of the renin-sodium profile with the risk of myocardial infarction in patients with hypertension.
BACKGROUND: To test the prognostic value of plasma renin activity prospectively, we determined the pretreatment renin-sodium profile of 1717 subjects with mild-to-moderate hypertension (mean age, 53 years; 36 percent white; 67 percent men) in a systematic work-site treatment program. METHODS: Renin profiles, obtained by plotting plasma renin activity against the urinary excretion of sodium, were classified as high (12 percent of the subjects), normal (56 percent), and low (32 percent), and there were expected variations according to age, sex, and race. Modified stepped-care treatment for hypertension, prescribed without reference to the renin profile, was similar in the three renin groups. RESULTS: Mean (+/- SD) blood pressure at entry was 151 +/- 19/100 +/- 10 mm Hg in the subjects with a high renin profile, 151 +/- 19/97 +/- 10 mm Hg in those with a normal profile, and 151 +/- 20/96 +/- 11 mm Hg in those with a low profile. During 8.3 years of follow-up, there were 27 myocardial infarctions. As adjusted for age, sex, and race, the incidence of myocardial infarction per 1000 person-years was 14.7 among the subjects with a high renin profile, 5.6 among those with a normal profile, and 2.8 among those with a low profile (rate ratio for high vs. low, 5.3; 95 percent confidence interval, 3.4 to 8.3). The rate of mortality from all causes was 9.3 in the high-profile group, 5.3 in the normal-profile group, and 3.9 in the low-profile group. The independent association of a high renin profile with myocardial infarction (but not with stroke or noncardiovascular events) was affirmed by Cox analyses (rate ratio for high vs. normal plus low, 3.2; 95 percent confidence interval, 1.2 to 8.4) after adjustment for race, sex, age at entry, serum cholesterol level, smoking status, electrocardiographic evidence of left ventricular hypertrophy, blood glucose level, body-mass index, history of cardiovascular disease or treatment, blood pressure, and use of beta-blockers. CONCLUSIONS: In the study population, whose blood pressure before and during treatment was in a narrow range, and after other cardiovascular risk factors had been considered, the renin profile before treatment remained independently associated with the subsequent risk of myocardial infarction.
Blood Pressure↗
Echocardiographic left ventricular mass and electrolyte intake predict arterial hypertension.
OBJECTIVE: To identify predictors of arterial hypertension. PATIENTS: One hundred thirty-two normotensive adults from a large employed population. METHODS: Echocardiography, standard blood tests, and 24-hour urine collection, at baseline and after an interval of 3 to 6 years (mean, 4.7 +/- 0.8 years). RESULTS: At follow-up, 15 subjects (11%; 7 men, 8 women) had a systolic blood pressure greater than 140 mm Hg or a diastolic blood pressure greater than 90 mm Hg or both (mean, 143 +/- 7 and 87 +/- 6 mm Hg, respectively). At baseline, subjects who developed hypertension had a greater left ventricular mass index than those who did not (92 +/- 25 compared with 77 +/- 19 g/m2 body surface area; P less than 0.005) and higher 24-hour urinary sodium/potassium excretion ratio (3.6 +/- 1.7 compared with 2.6 +/- 1.4; P less than 0.04); there were no differences in race, initial age, systolic or diastolic blood pressure, coronary risk factors, or plasma renin activity. The likelihood of developing hypertension rose from 3% in the lowest quartile of sex-adjusted left ventricular mass index to 24% in the highest quartile (P less than 0.005); a parallel trend was less regular for quartiles of the sodium/potassium excretion ratio (P less than 0.04). In multivariate analyses, follow-up systolic pressures in all subjects and in the 117 who remained normotensive were predicted by initial age, systolic blood pressure, black race, and sex-adjusted left ventricular mass index; final diastolic blood pressure was predicted by its initial value, plasma triglyceride levels, urinary sodium/potassium ratio, low renin activity, black race, and plasma glucose level. CONCLUSIONS: Echocardiographic left ventricular mass in normotensive adults is directly related to the risk for developing subsequent hypertension. Left ventricular mass improves prediction of future systolic pressure, whereas diastolic pressure is more related to initial metabolic status. Black race is also an independent determinant of higher subsequent blood pressure.
Adolescent↗
Cellular ions in hypertension, diabetes, and obesity. A nuclear magnetic resonance spectroscopic study.
To investigate the cellular basis linking hypertension, non-insulin-dependent diabetes mellitus (NIDDM), and obesity, we used 31P and 19F nuclear magnetic resonance spectroscopy to measure intracellular pH (pHi), free magnesium (Mgi), and cytosolic free calcium (Cai) in erythrocytes of obese and NIDDM subjects with and without hypertension. Compared with normotensive, nondiabetic controls (Cai, 25.2 +/- 1.4 nM; Mgi, 232 +/- 8 microM), Cai was elevated in both normotensive (36.8 +/- 2.7 nM, sig = 0.005) and hypertensive (43.4 +/- 2.9 nM, sig = 0.001) NIDDM subjects, and Mgi was concomitantly suppressed (normotensive: 206 +/- 11 microM, sig = 0.05; hypertensive: 196 +/- 8 microM, sig = 0.001). Similar but less striking changes were noted in obese subjects. Values of pHi were significantly lower (sig = 0.05) in all hypertensive groups compared with their normotensive controls. Continuous relations were observed for all subjects between Cai and diastolic blood pressure (r = 0.649, p less than 0.001) and body mass index (r = 0.565, p less than 0.001), between Mgi and diastolic blood pressure (r = -0.563, p less than 0.001) and fasting blood glucose (r = -0.580, p less than 0.001), and in diabetics, between pHi and diastolic blood pressure (r = -0.680, p less than 0.001). Thus, the constellation of elevated Cai and suppressed Mgi and pHi levels is characteristic of the hypertensive state. These abnormalities of cellular ion handling in whole or in part common to hypertension, diabetes, and obesity may contribute to the pathophysiology of these syndromes and may help to explain their frequent clinical coexistence.
Calcium↗
Heterogeneity among hypertensive subjects: a tool for clinical decision-making.
Current antihypertensive treatment strategy tends to approach all patients similarly, with decision to treat, the goal of treatment, and medication use based largely on blood pressure measurement. Clearly, it would make far more sense if a management strategy could be developed that was not solely dependent on measurement of blood pressure, but rather reflected a clearer understanding of individual likelihood of adverse outcome, the nature of blood pressure control, and the importance of associated clinical and biological characteristics. New tools make it possible to accurately assess the status of the heart, kidney, and blood vessels, both as a guide to the need for therapy and as a measure of treatment progress when the treatment is used. New understanding of the vasoconstrictor and volume contributions to blood pressure control coupled with a rich armamentarium of therapeutic agents make it possible to tailor therapy more appropriately. Finally, growing awareness of the contribution of concomitant risk factors has made it clear that overall success depends on attention to the whole patient.
Antihypertensive Agents↗
Antihypertensive efficacy of guanfacine and prazosin in patients with mild to moderate essential hypertension.
Guanfacine, an alpha 2 adrenoceptor agonist, was compared with prazosin hydrochloride for the treatment of patients with mild to moderate essential hypertension in an 8-week, double-blind, randomized, parallel evaluation to determine efficacy and safety. The study consisted of a 2-week screening/weaning period (phase I), a 3-week treatment period with chlorthalidone 25 mg every morning (phase II), and an 8-week double-blind treatment period with diuretic plus prazosin or guanfacine (phase III). Those who had an average seated diastolic blood pressure (BP) of 95 to 114 mm Hg at the end of the phase II period were eligible to enter the phase III period and were randomly assigned to chlorthalidone plus either guanfacine, 1 mg every night, or prazosin, 1 mg three times a day. Of the 102 patients who were randomly assigned to guanfacine or prazosin, 80% completed the entire study. Guanfacine and prazosin appeared to be equally effective and reduced seated as well as standing diastolic and systolic BP. The mean seated systolic and diastolic BP were reduced 11/9 mm Hg by guanfacine and 11/10 mm Hg by prazosin. The mean reduction in seated pulse was 3 beats/minute for guanfacine and no change with prazosin. Similar changes occurred in the standing position. Very few adverse effects were reported during the study. Adverse effects with an incidence of 5% or greater for either drug group were dizziness (6% guanfacine, 8% prazosin), xerostomia (6% guanfacine, 2% prazosin), and somnolence (0% guanfacine, 6% prazosin). Three patients (6%) in the prazosin group experienced symptoms of orthostasis requiring premature discontinuation of the drug and termination from the study.
Adult↗
Blood pressure reactivity predicts myocardial infarction among treated hypertensive patients.
High blood pressure (BP) defines a prognostically heterogeneous group. Because BP varies according to time, setting and means of observation, it has been postulated that BP reactivity might better predict cardiovascular disease (CVD) than does unidimensional measurements. To assess BP reactivity, the difference between pretreatment nurse (RN) and physician (MD) diastolic BP (DBP)--systematically recorded in that order--or MD-RN DBP, was obtained in 1737 previously untreated patients with sustained, RN BP greater than or equal to 160 and/or 95 mmHg. Patients stratified by tertiles of MD-RN DBP [(I) less than or equal to - 3, (II) -2 to 3 and (III) greater than or equal to 4 mmHg] were similar by sex, race, age, body mass index, cholesterol, electrocardiography, prior CVD, smoking and pretreatment or attained in-treatment BPs. During 14 years of followup, myocardial infarction (MI) incidence per 1000/year were, tertile I (3.2), II (3.7), III (7.6) (relative risk = 2.4, III vs I + II, p less than 0.05), whereas stroke incidence and non-CVD mortality were evenly distributed. By Cox survival analysis, controlling for other entry characteristics only age, sex and DBP reactivity remained predictive (p less than or equal to 0.03) of MI or total CVD. Thus, BP reactivity, probably a centrally-mediated phenomenon, identifies a subgroup of hypertensives with an increased propensity for MI despite successful BP control.
Adult↗
Labelling of hypertensives: a review of the data.
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Antihypertensive Agents↗
Hypertension and peripheral insulin resistance. Possible mediating role of intracellular free magnesium.
To investigate the association of hypertension and insulin resistance, we utilized 31P-NMR spectroscopy to noninvasively assess intracellular free magnesium levels (Mgif) in erythrocytes of normotensive (n = 20) and essential hypertensive (n = 20) subjects given an oral 100 g glucose load. In hypertensive compared with normotensive subjects, fasting glucose and insulin levels were similar, but the integrated insulinemic responses to glucose were 45% greater (312 +/- 13.4 v 215 +/- 7.5 microU/mL, P less than .001). In hypertension, Mgif levels were significantly reduced (183 +/- 9 v 251 +/- 9 mumol/L, P less than .001), and for all subjects were closely and inversely related to systolic (r = -0.77, P less than .001) and diastolic (r = -0.81, P less than .001) blood pressures, and to the integrated insulin response (r = -0.72, P less than .001). Furthermore, while insulin responses were also related to the underlying systolic (r = 0.69, P less than .001) and diastolic (r = .73, P less than .001) pressures, these relations were no longer significant when adjusted for Mgif levels. We hypothesize that hypertension and peripheral insulin resistance may be different clinical expressions of a common abnormal intracellular ionic environment, characterized at least in part by suppressed levels of intracellular free magnesium.
Erythrocytes↗
Moderate sodium restriction. Do the benefits justify the hazards?
Moderate sodium restriction (70 to 100 mEq/day) leads to a fall in blood pressure for only a minority (approximately 25%) of patients with mild hypertension. At the same time, it may also be hazardous by 1) increasing blood pressure in some patients (perhaps 15%); 2) disturbing sleep; 3) reducing intake of other valuable nutrients; and 4) decreasing host resistance to such stressful events as diarrhea, hyperthermia, and bleeding. In view of the limited positive effect demonstrated in short term studies, the absence of proven reduction in cardiovascular disease occurrence, as well as both documented and theoretical hazards, a blanket recommendation that all hypertensives restrict sodium intake is unwarranted. Moderate sodium restriction is, like other strategies, one therapeutic modality that may be applied, with caution, in individual cases.
Blood Pressure↗
Relation of blood viscosity to demographic and physiologic variables and to cardiovascular risk factors in apparently normal adults.
Although increased blood viscosity occurs in several cardiovascular diseases, little is known of factors influencing blood rheology in normal adults. Accordingly, we examined the relations of whole blood viscosity (WBV) to its rheologic determinants (hematocrit level, plasma viscosity, protein concentration, and red cell aggregability and rigidity), to demographic and laboratory variables, and to cardiovascular risk factors in 128 normotensive employed adults. Hematocrit levels accounted for 67-84% of variability of WBV at shear rates from 208 to 0.1 sec-1 with lesser contributions from plasma viscosity, red cell aggregability, and rigidity (multiple r = 0.95-0.97); WBV was predicted accurately from standard measurements of hematocrit and total plasma protein levels (multiple r = 0.78-0.92 in "learning" and "test" analysis). Male sex, obesity, dietary Na+ intake, and increasing age had additive effects on WBV (multiple r greater than or equal to 0.59, p less than 0.00001); the last three of these factors and black race independently predicted plasma viscosity (multiple r = 0.36, p less than 0.001). Among regulators of plasma volume, plasma renin activity and urinary Na+ excretion bore independent positive relations to WBV. Diastolic and mean blood pressures were independent predictors of WBV and hematocrit levels (all p less than 0.05). Conventional risk factors (e.g., triglycerides, obesity, and cholesterol levels) were positively related to WBV or plasma viscosity. Thus, in apparently normal adults, 1) WBV or plasma viscosity are increased by male sex, obesity, high sodium intake, aging, and black race, 2) WBV is positively related to plasma renin activity, 3) WBV or plasma viscosity are related to diastolic and mean blood pressures, triglycerides and cholesterol concentrations, and 4) WBV can be predicted from simple measurements of hematocrit and total plasma protein levels.
Adult↗
Clinical diagnosis of congestive heart failure in patients with acute dyspnea.
The validity and utility of physical examination maneuvers were determined in diagnosing congestive heart failure (CHF) in patients with acute dyspnea. Fifty one patients presented to the emergency room with the chief complaint of shortness of breath. History and physical examination were obtained independently, and the physical examination included hepatojugular reflux and the Valsalva maneuver. The diagnosis of CHF was made by predetermined criteria, and was compared with the diagnosis of the emergency room (ER) physician and with the response to bedside maneuvers. The hepatojugular reflux and Valsalva maneuvers were valid in the diagnosis of congestive heart failure in acutely dyspneic patients. Although these maneuvers rarely added to the routine assessment of patients in this study, they may provide a useful, noninvasive adjunct to clinical diagnosis in problematic cases.
Acute Disease↗
Treatment-induced blood pressure reduction and the risk of myocardial infarction.
To examine the relationship between degree of treatment-induced blood pressure (BP) reduction and myocardial infarction, the experience of 1765 previously untreated, mild to moderate hypertensives (initial BP greater than or equal to 160 and/or greater than or equal to 95 mm Hg) in a systematic treatment program was reviewed. Over an average of 4.2 years, there were 39 morbid or fatal myocardial infarctions. Three types of fall in diastolic BP (final minus pretreatment) were defined: small (less than or equal to 6 mm Hg), moderate (7 to 17 mm Hg), and large (greater than or equal to 18 mm Hg). By Cox regression, an association was observed between myocardial infarctions and both a large and a small fall, relative to a moderate decline. Age and sex were independent risk factors. Body mass index, cholesterol level, electrocardiogram, race, prior cardiovascular disease, smoking status, initial and final revisit BP, total intreatment BP, and systolic BP were not. Since both a large and small reduction in diastolic BP were associated with a higher incidence of myocardial infarction (relative to a moderate fall), perhaps a moderate reduction in diastolic BP should be the goal of treatment for mild and moderate hypertensives.
Blood Pressure↗
Evaluation of the efficacy of prazosin versus propranolol as initial antihypertensive therapy.
The long-term effects of prazosin and propranolol therapy were compared over the course of one year in 93 patients with mild-to-moderate hypertension. Thirty-four of the 44 patients randomly assigned to receive prazosin therapy and 38 of the 49 patients assigned to propranolol therapy received monotherapy for one year, whereas the remaining patients received concomitant hydrochlorothiazide therapy. Blood pressure was significantly decreased (p less than 0.01) in all treatment groups throughout the study compared with baseline measurements. The blood pressure responses to treatment were not shown to differ among patients with low, normal, or high renin levels on entry. No significant differences from baseline were noted among treatment groups with regard to lipid profiles. In summary, prazosin and propranolol were shown to have comparable long-term blood pressure-lowering effects when given as monotherapy in patients with mild-to-moderate hypertension.
Adult↗
Assessment of the effects of alpha- and beta-blockade in hypertensive patients who smoke cigarettes.
A 24-week, crossover, comparison study was conducted to observe the effects of alpha-blockade with prazosin and beta-blockade with propranolol on blood pressure and plasma lipoprotein levels in 15 hypertensive cigarette smokers. Before treatment, mean sitting blood pressure was 140/100 mm Hg and rose to 147/105 mm Hg after the patients smoked two cigarettes. Treatment with prazosin and propranolol lowered sitting blood pressure to 127/89 mm Hg and 129/91 mm Hg, respectively (not significant), and did not alter the pressor response to smoking. The total cholesterol level at baseline was 207.3 +/- 11.0 mg/dl. This increased to 210.5 +/- 10.2 mg/dl with propranolol treatment and decreased to 201.0 +/- 11.1 mg/dl with prazosin treatment. The low-density lipoprotein cholesterol level was 132.5 +/- 8.1 mg/dl at baseline, 136.9 +/- 8.3 mg/dl with propranolol treatment, and 129.4 +/- 9.0 mg/dl with prazosin treatment (0.05 less than p less than 0.10 between-group comparison). The data indicated that whereas prazosin and propranolol are equally effective in controlling blood pressure in hypertensive cigarette smokers, effects on plasma lipoproteins also may need to be considered when selecting a first-step antihypertensive agent in this coronary-prone population.
Adult↗