Guidelines for the treatment of hypertension.
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Biomedical subjects
Publications and source records attributed to M H Alderman.
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To determine the effect of race on cardiovascular disease occurrence among treated hypertensive patients, the experience of 1,807 black and 2,962 white hypertensive patients who entered a union/management--sponsored, worksite-based treatment program (1973-1985), was evaluated. Participants had similar socioeconomic profiles, equal access to health benefits, and received standard treatment. Median duration of observation was 42 months. Blacks had 48, and whites 129, of the 177 morbid (strokes and heart attacks) or mortal cardiovascular disease outcomes. At baseline, blacks had more electrocardiographic abnormalities (32% vs. 19%, p less than 0.0001), lower mean cholesterol (218 vs. 230 mg%, p less than 0.001), smoked more (35% vs. 30%, p less than 0.001), and were less likely to be treated for hypertension before entering the program (53% vs. 58%, p less than 0.01) than whites. They were also more likely than whites to belong to unions employing less skilled workers (p less than 0.0001). Overall, all-cause mortality rates between the races were similar. However, total cardiovascular disease morbidity and mortality rates were 10.5 (whites) and 6.4 (blacks) per 1,000 person years (p less than 0.005); the difference was largely explained by higher myocardial infarction rates among older (55 years or older) white men (15.6 vs. 7.5, p less than 0.05). That advantage was not present amongst younger black persons. In fact, blacks lost more years of life before age 65 (102 vs. 64 years/1,000 persons, p less than 0.025).(ABSTRACT TRUNCATED AT 250 WORDS)
There are no uniform diagnostic criteria for congestive heart failure. To determine the pattern of diagnostic criteria used, reports of 51 randomized, double-blind, placebo-controlled, clinical drug trials published between 1977 and 1985 were reviewed. Only 23 (45%) of the trials specified objective diagnostic criteria beyond treatment history, clinical diagnosis, or functional class. Of these, there were two trials each for digoxin, hydralazine, amrinone, and metoprolol; for each pair, only one study showed therapy beneficial. Of the amrinone pair, the positive study required a lower ejection fraction (less than 30% compared with less than 45%) and selected patients with more clinical severity. Conversely, for metoprolol, the positive study specified a higher ejection fraction (less than 49% compared with less than 35%) and selected patients with clinically milder disease, suggesting that conflicting results may relate to differences in study population. Many studies of congestive heart failure are done without explicit diagnostic criteria. Criteria lack uniformity, and such discrepancies may explain conflicting results.
Left ventricular muscle mass is increased in the presence of large body size, high blood pressure and obesity, but the relative contributions to ventricular mass of these and other factors have not been elucidated. Accordingly, echocardiographic left ventricular mass in unmedicated employed adults (162 normotensive, 145 borderline hypertension and 317 with established essential hypertension) was related to height, weight, lean body mass, body mass index, systolic and diastolic blood pressure, age, gender, race and 24 h urinary sodium and potassium excretion. In the total population, body mass index, systolic blood pressure and height were the most significant (p less than 0.0001) independent correlates of left ventricular mass, whereas gender and age made smaller contributions. In each normotensive and hypertensive subgroup, body mass index and height remained highly significant independent predictors of left ventricular mass, systolic blood pressure became a weaker predictor (0.001 less than p less than 0.02) and only among patients with established hypertension was diastolic blood pressure a weak independent determinant (p less than 0.05) of ventricular mass. The increase in left ventricular mass attributable to obesity was due to eccentric hypertrophy because end-diastolic relative wall thickness was similar in obese and nonobese subjects in each blood pressure group. Thus obesity, as measured by body mass index, is as important a potential determinant of left ventricular muscle mass as is systolic blood pressure and it is of greater statistical significant in an adult employed population than is diastolic blood pressure, height, gender, age or dietary sodium intake.
A worksite-based program to detect and provide long-term treatment for working persons with high blood pressure was begun in 1973. In this setting, systematic categorical care, provided primarily by nurses under physician supervision, is effective, acceptable, and produces a reduction in cardiovascular morbidity and mortality when compared to conventional community-based care. The existence of a large, stable, treated group drawn from a defined working population has also provided an unusual opportunity to pursue clinical epidemiological research requiring prolonged prospective study. Issues of patient management, the course of clinical disease, and more fundamental biological research, have all been successfully addressed in this setting. The worksite may, therefore, present a useful opportunity for the investigation and treatment of other common chronic diseases.
Although patients with AIDS have been noted to be at risk for bacterial pneumonia as well as opportunistic infections, little is known about the risk of bacterial pneumonia in HIV-infected populations without AIDS. To determine the incidence of bacterial pneumonia in a well defined population of intravenous drug users (IVDUs), and to examine any association with HIV infection, we prospectively studied 433 IVDUs without AIDS, enrolled in a longitudinal study of HIV infection in an out-patient methadone maintenance program. At enrollment, 144 (33.3%) subjects were HIV-seropositive, 289 (66.7%) were seronegative. Over a 12-month period, 14 out of 144 (9.7%) seropositive subjects were hospitalized for community-acquired bacterial pneumonia, compared with six out of 289 (2.1%) seronegative subjects. The cumulative yearly incidence of bacterial pneumonia was 97 out of 1000 for seropositives and 21 out of 1000 for seronegatives (risk ratio = 4.7, P less than 0.001). Eleven out of 14 (78.6%) cases among the seropositive patients were due to either Streptococcus pneumoniae [5] or Hemophilus influenzae [6]. Two out of 14 (14.3%) cases among the seropositives were fatal. Stratifying by level of intravenous drug use indicated that even among subjects not reporting active intravenous drug use at study entry, eight out of 82 (9.8%) seropositives compared with three out of 211 (1.4%) seronegatives were hospitalized for bacterial pneumonia over the study period (risk ratio = 6.9, P less than 0.01). This study shows a markedly increased incidence of bacterial pneumonia associated with HIV infection in IVDUs without AIDS.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension patients (1781), drawn from seven large employee groups in and around New York City, were studied to determine the prevalence of resistant hypertension among them. The blood pressure criteria for resistance (potential resistance) were failure to reach and maintain a blood pressure less than 160/95 mm Hg on two separate occasions during at least 1 year of treatment. Confirmed resistance required that during the same period of follow-up, in which at least two antihypertensive agents had been prescribed simultaneously, blood pressure control had not been achieved. Potential resistance during 1 year of treatment was found in 75 patients (4.2%), and confirmed resistance for the same period was found in 52 patients (2.9%). Diastolic resistance was far more common than systolic; the systolic/diastolic resistance was the rarest of all. Of the 52 patients with confirmed resistance for the first year, 33 achieved control in subsequent years. In sum, true resistance as defined by rigorous criteria pertaining to the hypotensive effects of pharmacological intervention in the general population is exceedingly rare.
Heterogeneity of response to antihypertensive therapy is a well-recognized clinical phenomenon. An agent that is antihypertensive in one patient may increase blood pressure in another or have no effect in a third. We believe that this variety of individual response to drug treatment can provide a new framework for the study of hypertensive subjects. Different patterns of response elicited by sequential trials of individual drugs with different mechanisms of action (diuretics, calcium channel blockers, alpha-blockers, beta-blockers, and converting enzyme inhibitors) should provide another means to classify hypertensive patients into biologically relevant groups. The documentation and analysis of this therapeutic heterogeneity in relation to renin profiling and to other physiological and demographic parameters may add a new dimension to the investigation of the pathophysiology of hypertension; it may serve as a basis for more appropriate stratification of participants in clinical trials and may ultimately contribute to a more rational approach to patient management.
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In less than a decade since development of echocardiographic measurement of left ventricular muscle mass, studies using this technique have provided considerable information about the prevalence and pathophysiology of left ventricular hypertrophy in human hypertension. Increased left ventricular mass has been found in a significant minority of patients with systemic hypertension, with the exact prevalence dependent both on how a population is selected and on the sex, race, and possibly age composition of its members. All published studies have reported that left ventricular hypertrophy is more closely related to blood pressure recorded in the patient's natural setting during normal activity or exercise-whether measured by portable recorder or home manometer-than to blood pressure measured by the physician. In addition, studies indicate that the classic hypertensive abnormalities of concentric left ventricular hypertrophy and increased peripheral resistance are interrelated, while left ventricular hypertrophy is absent in a subgroup of patients with mild essential hypertension who exhibit high cardiac output and evidence of supernormal myocardial contractility. Conversely, the left ventricular functional response to exercise is inversely related to the degree of hypertrophy. High levels of blood viscosity, which would tend to blunt the reduction in peripheral resistance expected during sleep or exercise, have also been associated with left ventricular hypertrophy in patients with essential hypertension. Echocardiographic studies have provided evidence both for and against the hypothesis that activity of the sympathetic or reninangiotensin systems plays a direct role in causing hypertensive cardiac hypertrophy. These findings demonstrate the useful role that echocardiographic assessment of left ventricular structure and function may play in hypertension research.
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To evaluate the performance of M-mode echocardiography for detection of pressure-overload left ventricular hypertrophy (LVH), we tested the sensitivity of previously defined sex-specific upper limits of normal echo LV measurements in 31 patients with necropsy-proven pressure-overload LVH and determined the prevalence of LVH detected by each echo criterion in 316 employed patients with uncomplicated hypertension, 100 patients with hypertension evaluated in a referral center, and 38 hospital patients with moderate to severe (WHO class 2) hypertension. Echo measurements were LV mass (LVM), LVM index (LVMI), cross-sectional area (CSA), septal and posterior wall thickness (IVST and PWT), LV internal dimension (LVID), and relative wall thickness (RWT). Prevalences of echo LVH were as follows. (Table: see text). Thus, echo criteria based on LVM are more sensitive than other measurements for detection of necropsy-proven pressure-overload LVH and reveal the highest prevalence of LVH in clinical hypertension populations, and the prevalence of LVH in hypertension is highly dependent on the population studied.
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Guanfacine, an alpha-adrenoceptor agonist, may exhibit distinct dose-related curves for efficacy and adverse effects in the step-2 therapy of essential hypertension. To determine the lowest clinically effective safe dose, 462 newly or previously diagnosed subjects were admitted to a 5-week prerandomization phase at 8 centers. Patients were weaned from any current antihypertensive drugs and placed on 25-mg chlorthalidone, daily, in the morning. At the end of the 5-week weaning period, 362 patients with seated diastolic blood pressures (BPs) between 95 and 114 mm Hg qualified for the 12-week postrandomization phase. Subjects were randomized to receive either an indistinguishable placebo or 0.5, 1, 2 or 3 mg of guanfacine. Chlorthalidone was changed to bedtime administration and taken with the study medications. Guanfacine was started at the lowest dose in all subjects and increased (if scheduled, according to the randomization code) to the next higher dose at biweekly intervals. Of the 362 randomized patients, 278 completed the study. The 1-mg guanfacine dosage produced a 14/13 mm Hg decrease in BP (p less than 0.0125 compared with placebo). Doses of guanfacine at 2 and 3 mg/day were not more effective than the 1 mg/day dose; 0.5 mg/day was not better than placebo. There was an increase in the frequency of side effects possibly or probably associated with 2 and 3 mg/day guanfacine. Only 3.2% of the patients in the 1 mg/day group dropped out of the study because of side effects. We conclude that when added to a diuretic, 1 mg/day guanfacine at bedtime is the lowest safe and therapeutically effective dose.
Increasing awareness of the hazards of diuretic therapy has cast doubt on the appropriateness of its uniform use as initial treatment for hypertension. To establish the relative efficacy and acceptability of alternative forms of initial therapy, prazosin and hydrochlorothiazide were prospectively compared. In a one-year study, 62 patients with a diastolic blood pressure greater than or equal to 100 mm Hg were randomly allocated to receive one of the two agents. Twenty of 32 (63 percent) patients receiving prazosin and 17 of 30 (57 percent) receiving hydrochlorothiazide satisfied the year-long study requirements. For the most part, the dropout rate was not drug related. The percentages of subjects completing the study with the initial drug, without addition of a second drug, were identical in both groups (prazosin: 10 of 32 [31 percent] and hydrochlorothiazide: nine of 30 [30 percent]). In both treatment groups, blood pressure declined similarly and significantly (p less than 0.001) by the end of the study. The blood pressure of subjects receiving prazosin decreased from 150.3/105.8 mm Hg to 135.3/90.3 mm Hg, whereas the blood pressure of subjects receiving hydrochlorothiazide declined from 147.3/103.8 to 130.0/89.1 mm Hg. A reduction in diastolic blood pressure to less than 95 mm Hg was achieved in 80.0 percent of patients started with prazosin and in 78.6 percent of those started with hydrochlorothiazide. A further reduction to less than 90 mm Hg was achieved in 45.0 and 64.3 percent, respectively (not significant). Patients who completed the study with single-drug therapy in both treatment groups showed nonsignificant decreases in mean potassium levels from initial to final readings when compared with baseline readings (prazosin: 0.21 meq; hydrochlorothiazide: 0.41 meq). However, patients receiving prazosin had 11.5 percent of their readings less than or equal to 4.0 meq, whereas those receiving hydrochlorothiazide had 38.1 percent of their readings similarly distributed (p less than 0.05). Furthermore, four patients receiving hydrochlorothiazide had potassium levels less than or equal to 3.5 meq; none of those receiving prazosin had levels in that range. At baseline, no patient in the study had potassium levels of less than 4.0 meq. Prazosin-treated patients whose initial fasting blood glucose was less than 110 mg/dl had 3.7 percent (one of 27) of subsequent measurements greater than or equal to 110 mg/dl. These abnormal levels were found 18.2 percent (six of 33) (not significant) of the time in similar hydrochlorothiazide-treated subjects. Symptomatic side effects were primarily mild and transient in those receiving either drug alone.(ABSTRACT TRUNCATED AT 400 WORDS)
To determine the prevalence and correlates of echocardiographic left ventricular hypertrophy among subjects in a general population, we studied 621 employed subjects. Patients with uncomplicated essential hypertension in a worksite-based treatment program included 145 with borderline hypertension and 316 with sustained hypertension by World Health Organization criteria. Normotensive subjects were randomly selected from members of the same unions. M-mode echocardiographic left ventricular dimensions were used to calculate left ventricular mass and other indexes of left ventricular anatomy. The specificity of 13 echocardiographic criteria of left ventricular hypertrophy was determined in normotensive individuals, and the prevalence of left ventricular hypertrophy by each criterion was assessed in patients with borderline or sustained essential hypertension. The results suggest that the most suitable reference standard for detection of left ventricular hypertrophy in a heterogeneous urban population utilizes sex-specific cutoff values for left ventricular mass index of 110 g/m2 or greater for women and 134 g/m2 or greater for men. With 97% specificity, the prevalence of left ventricular hypertrophy by these criteria is approximately 12% among patients with borderline hypertension and 20% among patients with relatively mild, uncomplicated sustained essential hypertension. Wall thickness measurements performed slightly less well. At similar levels of blood pressure, black patients were more likely than white patients to exhibit concentric left ventricular hypertrophy, especially among borderline hypertensive patients. Left ventricular hypertrophy occurred in patients with sustained hypertension who also exhibited increased cardiac output, strongly associated with low plasma renin activity.
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