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Biomedical subjects

J M Neutel

Publications and source records attributed to J M Neutel.

At least 55 records · Page 3Linked to original sources

Combination therapy with diuretics: an evolution of understanding.

One of the current recommendations for the treatment of hypertension is a stepped-care approach in which a second drug is added to a first-line agent when adequate blood pressure control has not been achieved. It has been well demonstrated in multiple studies that the response rate to any single class of antihypertensive agent, given as monotherapy, is approximately 45-55%. Thus, in approximately half of the hypertensive population, a second drug will be required. This is not surprising, since it is now well recognized that hypertension is a multifaceted disease process. The use of combination therapy with low-dose diuretics (< 25mg hydrochlorothiazide [HCTZ] or its equivalent) has become a very attractive alternative choice to first-line therapy. The data from clinical trials clearly demonstrate that 6.25 mg or 12.5 mg HCTZ has an additive or synergistic effect on blood-pressure reduction when used in combination with most drugs. At low doses, the side-effect profile with diuretics is similar to placebo. Furthermore, metabolic side effects are significantly reduced when diuretics are used in low doses. The use of low-dose diuretics in combination with other first-line agents significantly enhances blood-pressure control and reduces the likelihood of adverse events and alteration in carbohydrate, lipid, and electrolyte metabolism. Thus, combination therapy with low-dose diuretics provides an attractive alternative approach to first-line treatment of essential hypertension.

Blood Pressure↗

Metabolic manifestations of low-dose diuretics.

Hypertension has been defined and treated as a disease of abnormal systolic and diastolic blood pressure. Recent data have, however, demonstrated that effective blood-pressure control has not resulted in the expected decrease in coronary artery disease. These findings are probably a result of hypertension being a complex inherited syndrome of cardiovascular risk factors, all of which are genetically linked and all of which contribute to the development of cardiovascular disease in these patients. Included in the hypertension syndrome are abnormalities of lipid profile, insulin resistance, changes in renal function, left ventricular hypertrophy and reduced arterial compliance. In many patients, high blood pressure is a late manifestation of this disease process. Since all cardiovascular risk factors contribute to heart disease in these patients, they should all be considered in the management of this disease process. Diuretics and beta blockers, when used at high doses, negatively impact lipid metabolism and insulin sensitivity, while angiotensin converting enzyme (ACE) inhibitors and calcium antagonists tend to have a neutral effect on these metabolic risk factors. These findings have resulted in decreased use of diuretics and beta blockers in favor of newer agents such as ACE inhibitors and calcium antagonists. However, recent data have demonstrated that when used at low doses (6.25 or 12.5 mg of hydrochlorothiazide), diuretics lack significant metabolic side effects while bringing about significant reductions in blood pressure. Thus, at these doses, hydrochlorothiazide is a useful drug in the treatment of hypertension, both as monotherapy and in combination therapy.

Antihypertensive Agents↗

Novel delivery system for verapamil designed to achieve maximal blood pressure control during the early morning.

Because the risk of cardiovascular events appears to be greatest in the early morning, this period is a time during which adequate blood pressure (BP) control appears to be most desirable. In this study, a controlled-onset extended-release system (COER-24) that delivers verapamil in a manner designed to achieve maximal levels of drug during the early morning surge in BP was compared with placebo. Ninety-five patients with mild to moderate hypertension were studied. Of this group, 49 patients (mean age 57.6 +/- 1.4 years; 35 men and 14 women) were randomized to take verapamil COER-24 240 mg at 10 PM, and 46 subjects (mean age 55.8 +/- 1.5 years; 29 men and 17 women) were randomized to take placebo. Ambulatory BP monitoring was performed after a 4-week initial placebo period and was repeated after 4 weeks of treatment with verapamil or placebo. Verapamil COER-24 resulted in significant (p < 0.001) decreases in mean whole-day systolic and diastolic BP (-8.2/-6.3 mm Hg; baseline 152/93.0 mm Hg) when compared with placebo (+0.3/-0.9 mm Hg; baseline 150.3/93.2 mm Hg). From 6 AM to noon, verapamil COER-24 resulted in a change in systolic and diastolic BP of -11.6/-9.0 mm Hg, which was significantly (p < 0.001) greater than the change that occurred with placebo (-0.5/-1.0 mm Hg) during the same period. In the last 4 hours of the dosing interval (6 PM to 10 PM), verapamil COER-24 caused significantly greater (p < 0.001) decreases in BP (-7.4/-4.8 mm Hg) than did placebo (+2.7/+1.0 mm Hg). These data demonstrate that the COER-24 system, when administered in the late evening, achieves maximal BP reduction during the early morning hours. Moreover, BP reductions were sustained throughout the 24-hour period.

Blood Pressure↗

Role of whole-day ambulatory blood pressure monitoring in the management of hypertension.

As we learn more about hypertension, it is becoming increasingly apparent that conventional blood pressure measurements are fraught with potential error. Noninvasive ambulatory blood pressure monitoring is proving to be extremely valuable in both diagnosis and treatment. Advancing medical technology has provided small, noninvasive, reliable systems what are well tolerated by patients. The commercial availability of these systems facilitates their use in both clinical practice and in research. There have been legitimate concerns that continuous blood pressure monitoring may add considerably to the costs of diagnosing and treating hypertension. These worries, however, may be misplaced. If there are indeed as many patients being treated unnecessarily as has been suggested by many studies, then the money saved on drugs may well cover the costs of prolonged blood pressure monitoring. Moreover, many subjects can be spared unnecessary therapy. Although much work needs to be done with larger groups of patients followed over longer periods of time, the early experiences with 24-h ambulatory blood pressure monitoring have been extremely encouraging. These procedures have added to our understanding of hypertension and of the agents used in its treatment and are rapidly assuming an increasing importance in overall management.

Antihypertensive Agents↗

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↗

Bioelectrical impedance analysis as an assessment of diuresis in congestive heart failure.

OBJECTIVE: To compare changes in bioimpedance parameters and calculated total body water (TBW) with conventional measurements used to assess the efficacy of diuretic therapy in the treatment of heart failure. SETTING: A Veterans Affairs tertiary care, teaching hospital. SUBJECTS: Twelve patients with New York Heart Association (NYHA) class III congestive heart failure (CHF). DESIGN: Prospective, consecutive sample, cohort, open label. INTERVENTIONS: Parenterally administered furosemide; clinically dictated, outcome-oriented, adjunctive therapy of CHF. OUTCOMES: Bioelectrical impedance analysis (BIA) parameters, measured volume of diuresis and changes in body weight, defined clinical endpoints (NYHA criteria). RESULTS: Three days of diuretic therapy with furosemide (oral and/or intravenous) for CHF was associated with a measured weight loss of 4.1 +/- 0.6 kg and statistically significant increases in resistance and reactance of 20.8% +/- 2.7% and 22.7% +/- 6.1%, respectively (p < 0.005). Calculated TBW using BIA parameters and standard equations decreased on average by 6.1 +/- 0.6 L or 11.2% +/- 1.1% (p < 0.001). A significant inverse correlation was observed between change in measured body weight and total body reactance (p = 0.02). CONCLUSIONS: Single-frequency BIA appears to have limited clinical usefulness as a method of assessing diuretic therapy in the management of CHF. Its greatest usefulness appears to lie in the assessment of serial changes in individual patients and patient populations that are physiologically or metabolically homogeneous. Further studies are needed to establish the validity of BIA in patients with decompensated CHF.

Administration, Oral↗

Relationship of left ventricular structure to maximal heart rate during exercise.

Previous investigators using clinical, hemodynamic, or exercise parameters to predict maximal exercise heart rate (HRmax) have demonstrated age to be the major determinant. Regression coefficients have ranged from -0.3 to -0.6, leaving approximately two thirds of the variance in HRmax unexplained. Because cardiac size and function are directly related to stroke volume and should influence HRmax, we studied 114 male subjects (aged 19 to 73 years) with two-dimensional and M-mode echocardiography who underwent maximal treadmill testing with respiratory gas analysis. Seventy-three were normotensive (diastolic BP < 95 mm Hg) and 41 were hypertensive. As in previous studies, HRmax was inversely related to age (HRmax = 199-0.63[age], r = -0.47, p < 0.001). M-mode left ventricular (LV) diastolic dimension (LVD) added significantly to the explanation of the variance in HRmax (r = -0.57, p < 0.001) (HRmax = 236 - 0.72 [age]-6.8 [LVD]). Thus, the larger the heart, the lower the HRmax. No other echocardiographic measurement or derived parameter added significantly to the explanation of the variance in HRmax. To evaluate the effects of hypertension on HRmax, we studied hypertensives and normotensives separately. Only age was significantly related to HRmax in the normotensives (r = -0.50, p < 0.001). In the hypertensive subjects, however, both age and relative wall thickness (RWT) (which describes LV wall thickness in relation to LV chamber size) were significantly related to HRmax. Age explained 45% of the observed variance in HRmax (r = 0.67, p < 0.001) and RWT added modestly (9%) but significantly to the relationship (HRmax = 173-0.96[age]+94 [RWT], p < 0.001), together explaining 54% of the variance observed in HRmax. Thus, HRmax is inversely related to LVD and patients with larger ventricles achieve lower HRmax. In hypertensives, the amount of LV muscle mass in relation to chamber size is an additional predictor of HRmax. However, despite controlling for age, sex, and cardiovascular disease, and the inclusion of echocardiographic indices of cardiac size and function, a large portion of the variance in HRmax could not be explained. The unexplained variance in HRmax is most likely due to intersubject variability in resting cardiac size, volume, function, and other as yet undefined factors.

Adult↗

Hypertension in the elderly: 24 h ambulatory blood pressure results from a placebo-controlled trial.

Calcium channel blockers are increasingly used to treat hypertension in elderly patients. To assess the effects of low-dose, long-acting verapamil on blood pressure (BP) and quality of life (QOL) in elderly patients, verapamil 120-240 mg of placebo was given once daily for 8 weeks to 76 patients aged > or = 60 years. After a 4-week placebo wash-out period, patients with a sitting DBP of 95-110 mm Hg and a mean daytime (6 am to 6 pm) ambulatory DBP > or = 90 mm Hg were entered into the study. Twenty four-hour BP monitoring as well as QOL self-assessment and digit span testing of cognitive function were performed at the end of the placebo wash-out and double-blind treatment periods. Patients treated with verapamil showed a significant decrease in mean whole-day BP, while those treated with placebo showed a small increase in BP. Treatment differences between the two groups in SBP and DBP were each statistically significant (P < 0.01). Significant differences were also seen when the 24 h period was divided into daytime and night-time readings. Both QOL and digit span testing scores were unchanged from baseline for verapamil-treated patients and were not different from the placebo-treated group. The results of this study demonstrate consistent and significant decreases in BP throughout the 24 h period with no adverse effects on QOL or cognitive function this this formulation of verapamil in elderly hypertensive patients.

Aged↗

Metabolic and cardiovascular characteristics of hypertension. Familial aspects.

There are many convincing data showing that hypertension is an inherited syndrome of cardiovascular risk factors that clinically manifest at different times and occur independently of one another. These risk factors independently increase the potential for a patient to develop coronary heart disease, but when occurring together they appear to be synergistic in their ability to cause heart disease. It appears that in many patients high blood pressure may be a late manifestation of the disease process and may be indicative of a fairly advanced stage of disease. Moreover, it is possible that patients with the hypertension syndrome will develop coronary artery disease prior to the development of high blood pressure. We have recently demonstrated that when comparing cardiovascular risk factors in normotensive patients with a family history of hypertension to hypertensive patients with and without a family history of hypertension, there were no differences among the groups (Fig. 5). All three groups, however, were significantly worse off than normotensive subjects without a family history of hypertension. Thus, in terms of cardiovascular risk, these "normotensive hypertensive" patients were at a risk of developing heart disease equal to that of the hypertensive patients, the only difference being that there were not as many of such patients. The existence of the hypertension syndrome has some important diagnostic and therapeutic consequences. Because of our dependence on high blood pressure to isolate patients with the hypertension syndrome, it is unlikely that these patients will be treated. With an increased awareness of the presence of the hypertension syndrome and better screening techniques, it is likely that in the future we will be diagnosing and treating normotensive hypertension. We have demonstrated that when comparing normotensive hypertensive patients with truly hypertensive patients there are no differences in cardiovascular risk factors. The only difference between the groups is that the normotensive hypertensive patients do not have the high numbers (which may not be particularly important). It is thus likely that normotensive hypertensive patients have a risk of developing heart disease similar to that of truly hypertensive patients. For this reason, it is possible that normotensive patients with the hypertension syndrome will benefit from either conservative or pharmacologic therapy that reverses underlying cardiovascular risk factors without lowering the blood pressure. In treating high blood pressure in patients with the hypertension syndrome, it becomes important to select drugs that will reduce blood pressure while having a beneficial or at least a neutral effect on all of the other risk factors. Although the reduction in strokes and overall mortality in treated hypertensive patients warrants our continued enthusiasm for treating high blood pressure, an improved performance in reducing other cardiovascular risk factors adds to the benefits of antihypertensive therapy. Perhaps treating this disease as a syndrome rather than a number will result in a reduction in the incidence of coronary heart disease, as has been seen in the incidence of stroke.

Coronary Disease↗

Controlling blood pressure throughout the day: issues in testing a new anti-hypertensive agent.

Lessons learned from ambulatory blood pressure (BP) monitoring strongly influence the development of new anti-hypertensive drugs. Efficacy should be demonstrated not only in the conventional clinical setting, but also throughout the full 24 h day, including the important early morning hours near the end of dosing intervals. Preservation of the circadian pattern, including appropriate day/night BP differences, may be a further important goal of therapy. The reproducibility of ambulatory monitoring measurements, together with the absence of placebo effects with this technique, adds greatly to its power and efficiency. Moreover, the use of ambulatory monitoring to accurately diagnose hypertension and exclude non-confirmed or white coat hypertensives from clinical trials adds further sensitivity to quantifying drug action. This technique was recently applied to the evaluation of the new angiotensin II receptor antagonist losartan. Hypertensive patients diagnosed by ambulatory monitoring were divided into four groups: placebo, losartan 50 mg once daily, 100 mg once daily or 50 mg twice daily. Compared with placebo, which had no effect, all three losartan regimens decreased SBP and DBP significantly. There was no difference in efficacy between the two once daily regimens, although 50 mg twice daily was slightly more effective than 50 mg once daily but not statistically significantly different from 100 mg once daily. However, all losartan groups exhibited sustained BP reductions throughout the 24 h dosing interval and preserved the circadian BP patterns. Ambulatory monitoring was thus able to accurately quantity the efficacy and the key chronobiological aspects of anti-hypertensive therapy with losartan in an efficient and cost-effective manner.

Adult↗

A comparison of intravenous nicardipine and sodium nitroprusside in the immediate treatment of severe hypertension.

The primary objective of this study was to compare the antihypertensive efficacy and safety of intravenously administered nicardipine with that of intravenous nitroprusside (SNP) in patients with severe hypertension. The study was conducted in 121 patients with severe hypertension (diastolic blood pressure [BP] > 120 mm Hg, or systolic BP > 200 mm Hg). Patients were randomized to receive intravenous nicardipine or SNP. Drugs were administered according to a predetermined dosing schedule for a 10 to 12 h period. Sixty-one patients were randomized to intravenous nicardipine and 60 to SNP. Pretreatment BP values for the nicardipine and SNP groups were 217/128 mm Hg and 219/128 mm Hg, respectively. Therapeutic response (diastolic BP < 100 mm Hg, or a decrease of > 15 mm Hg; systolic BP < 180 mm Hg, or a decrease of > 20 mm Hg) was achieved in 98% (60/61) of patients treated with nicardipine and 93% (56/60) of patients treated with SNP. The mean decreases in systolic and diastolic BP were 61 mm Hg and 40 mm Hg after 4 h of nicardipine, and 59 mm Hg and 38 mm Hg after 4 h of SNP. The mean increases in heart rate also were similar in both groups (nicardipine, 12 beats/min; SNP 10 beats/min). The mean numbers of dose adjustments per hour required to maintain the BP reductions were lower (P < .01) in the nicardipine-treated patients (0.5 +/- 0.1 times per hour) than in the SNP-treated patients (1.5 +/- 0.2 times per hour).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Diagnosis of mild hypertension by ambulatory blood pressure monitoring.

BACKGROUND: Between 20% and 30% of patients with clinically diagnosed hypertension have normal blood pressure (BP) values during automated ambulatory 24-hour BP monitoring. It has not been clear, however, whether these patients can be regarded as normotensive or whether they should be treated in the same way as confirmed hypertensive patients. METHODS AND RESULTS: Ambulatory BP monitoring was performed in 88 normal control subjects and 171 hypertensive patients (office diastolic BP > or = 90 mm Hg on three visits; never treated or off treatment for more than 6 months). Hypertensive patients were classified as nonconfirmed or white coat (n = 58) if their 24-hour diastolic averages were < 85 mm Hg and at least 15 mm Hg lower than their office values. For comparisons, white coat patients were pair-matched with normal subjects by 24-hour diastolic averages and sex, and by similar age and weight; there were 40 such pairs. White coat patients were likewise pair-matched with confirmed hypertensive patients by identical office BPs (51 pairs). Participants were studied by individualized treadmill testing, Doppler echocardiography, and assays of resting plasma catecholamines, upright plasma renin and aldosterone, and lipid, glucose, and insulin concentrations. Because of the matching, compared with normal subjects, patients with white coat hypertension and normal subjects had identical 24-hour BP averages. The white coat patients exhibited slightly greater variability among individual readings (obtained each 15 minutes) throughout the day [P < .05]), but there were no differences in hemodynamic responses to exercise. Plasma norepinephrine (P < .05), renin and aldosterone (P < .01 for each), and insulin and low-density lipoprotein cholesterol levels (P < .01 for each) were higher in the white coat group, as were left ventricular septal wall (P < .05) and muscle mass (P = .07) echocardiographic measurements. When compared with the confirmed hypertensive patients, the white coat patients had higher renin (P < .01) but were otherwise similar. Within the white coat group, plasma norepinephrine correlated with total cholesterol and triglycerides (P < .05 for each), and aldosterone correlated with left ventricular mass (P < .01); there were no significant correlations within the normal control subject or confirmed hypertension groups. CONCLUSIONS: Patients with white coat hypertension differ in metabolic, neuroendocrine, and cardiac findings from normal control subjects and have greater BP variability. These changes appear to be mediated by heightened activity of the sympathetic and renin-angiotensin systems. Although these characteristics could reflect an alerting reaction in the clinic due to awareness of their diagnosis, the white coat hypertensive patients also have evidence for additional, more-sustained differences from normal subjects. Thus, this condition appears to be a true variant of hypertension.

Adult↗

A repressive coping style protecting from emotional distress in low-renin essential hypertensives.

OBJECTIVE: To investigate the relationship between the behavioural characteristics and specified subgroups of patients with essential hypertension. DESIGN AND METHODS: Fifty-four patients were classified into groups with a high (n = 9), normal (n = 35) or low plasma renin activity (n = 10), and were compared with 20 normotensive subjects by psychological tests. Standardized tests were used to measure anger expression, defensiveness and the subjects' psychological status (e.g. anxiety, depression). RESULTS: A repressive coping style, defined by a high defensiveness and low anxiety levels, was found significantly more often in patients with low than in patients with high plasma renin activity and normotensive subjects. The patients with high plasma renin activity scored significantly higher on suppressed anger, anxiety and interpersonal sensitivity than did those with low plasma renin activity. The scores of the normal plasma renin activity group were similar to those of the normotensive group. CONCLUSIONS: The results underline that there is not one hypertensive 'personality'. Whereas the patients with a high plasma renin activity appear to be more susceptible to emotional conflicts, the patients with low plasma renin activity report low emotional distress and maintain an apparently well-adjusted facade.

Adaptation, Psychological↗

Comparison of bisoprolol with atenolol for systemic hypertension in four population groups (young, old, black and nonblack) using ambulatory blood pressure monitoring. Bisoprolol Investigators Group.

The antihypertensive effects of drugs are partly determined by characteristics of the patients treated. A randomized, double-blind study used 24-hour ambulatory blood pressure (BP) monitoring to compare the effects of 2 beta blockers, bisoprolol (10 to 20 mg; n = 107) and atenolol (50 to 100 mg; n = 96), administered once daily in 4 population groups. After a 4-week placebo period, patients with an office diastolic BP between 95 and 114 mm Hg were stratified according to race and age, and were randomly assigned to treatment with bisoprolol or atenolol for 8 weeks. BP averages measured by automated monitoring for the 24-hour periods were compared between groups. In elderly patients, the reductions in both average 24-hour systolic and diastolic BP were greater with bisoprolol than with atenolol (13 +/- 3/13 +/- 1 mm Hg [n = 23] vs 4 +/- 2/6 +/- 1 mm Hg [n = 30]; p < 0.01). Similarly, bisoprolol produced greater reductions in average 24-hour diastolic BP than did atenolol in nonblack patients (16 +/- 2/12 +/- 1 mm Hg [n = 85] vs 12 +/- 2/9 +/- 1 mm Hg [n = 83]; p = 0.02). Bisoprolol and atenolol were similar in the black (10 +/- 5/9 +/- 3 mm Hg [n = 22] and 10 +/- 6/6 +/- 3 mm Hg [n = 13], respectively) and young (15 +/- 1/11 +/- 1 mm Hg [n = 84] and 16 +/- 2/10 +/- 1 mm Hg [n = 66], respectively) groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Metabolic characteristics of hypertension: importance of positive family history.

This study was performed to compare metabolic and endocrine characteristics of untreated hypertensive patients and normal controls. Measurements were made in age-matched, body mass index (BMI) matched, normotensive patients with (n = 40; age = 53; BMI = 28) and without (n = 39; age = 54; BMI = 27) a family history of hypertension and hypertensive patients with (n = 38; age = 53; BMI = 28) and without (n = 25; age = 54; BMI = 29) a family history of hypertension. Norepinephrine, renin activity, and total cholesterol blood concentrations were similar in normotensive patients with a positive family history of hypertension and in hypertensive patients with or without a family history. Similarly, there were no differences in plasma insulin concentrations or insulin/glucose ratios between the normotensive patients with a family history of hypertension and hypertensive patients with or without a family history. But in all three groups the values were significantly greater (at least p < 0.05 for each) than in the normotensive patients without a family history. Increases in systolic blood pressure during treadmill testing were 51 +/- 4 mm Hg in the normotensive patients with a family history, 50 +/- 3 mm Hg in hypertensives with a family history, and 45 +/- 5 mm Hg in hypertensives without a family history; these changes were all less (p < 0.05 for each) than in normotensives without a family history (65 +/- 3 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Application of ambulatory blood pressure monitoring in differentiating between antihypertensive agents.

PURPOSE: This multicenter, double-blind, parallel group study assessed the usefulness of the ambulatory blood pressure monitoring (ABPM) technique in differentiating between the once-daily administration of the beta blockers bisoprolol (10 to 20 mg) and atenolol (50 to 100 mg) in terms of efficacy and duration of action. PATIENTS AND METHODS: The study population consisted of 659 patients with essential hypertension and an average office diastolic blood pressure (BP) between 95 and 115 mm Hg after 4 weeks of placebo treatment. Office BPs were recorded at the end of the 24-hour dosing interval (trough). ABPM was performed in 11 of the 28 institutions participating in this study in a total of 203 patients. These procedures were performed at the end of the placebo phase and again after 8 weeks of active treatment. RESULTS: With the use of conventionally measured office BPs, the two drugs significantly (p < 0.001) decreased trough systolic and diastolic BPs to a similar extent. By 24-hour monitoring, bisoprolol demonstrated a 33% greater reduction in whole-day average diastolic BP than did atenolol (11.6 +/- 0.7 mm Hg versus 8.7 +/- 0.8 mm Hg, p < 0.01). Significant treatment differences in systolic (p < 0.05) and diastolic (p < 0.01) BPs were also noted for bisoprolol compared with atenolol during the final 4 hours of the dosing interval (-13.2 +/- 1.5/-10.9 +/- 1.0 mm Hg versus -8.9 +/- 1.6/-7.3 +/- 1.1 mm Hg, respectively), and over the time period 6:00 AM to noon (-14.2 +/- 1.3/-11.5 +/- 0.9 mm Hg versus -9.9 +/- 1.4/-7.7 +/- 0.9 mm Hg). CONCLUSIONS: Whereas conventional BP measurements did not detect differences in the antihypertensive effects of the beta blockers bisoprolol and atenolol, ABPM revealed significant treatment differences in both the efficacy and duration of action of these two agents. These findings indicate the power of this technique to discriminate potentially important differences between apparently similar antihypertensive drugs.

Adult↗

The relationship of arterial compliance with endothelial-derived proteins of the hemostatic system.

Cardiovascular risk factors associated with hypertension include alterations in arterial compliance and an increased tendency to thrombosis. In this study we examined the relationship between arterial compliance and endothelial derived components of the hemostatic system: von Willebrand factor (vWF) and tissue plasminogen activator (t-PA). Ten males (4 normal and 6 untreated hypertensives, 41 +/- 12 years) were studied. Compliance of proximal (large vessel) and distal (small vessel) arteries was measured by intraarterial pulse wave analysis; left ventricular wall thickness by echocardiography; and vWF and t-PA by immunoassay of plasma obtained before and immediately after maximum treadmill exercise. Baseline t-PA and vWF correlated inversely with distal compliance (r = -0.74, p = 0.01; r = -0.56, p = 0.09). Exercise strengthened the relationship between vWF and both distal compliance (r = -0.56 to r = -0.86) and proximal compliance (r = -0.44 to r = -0.70). Moreover, post-exercise levels of vWF and t-PA were each significantly related to left ventricular posterior wall and septal thickness. Of note, these protein concentrations correlated more strongly with arterial compliance and left ventricular wall thickness than with blood pressure. Thus, arterial compliance and left ventricular wall thickness appear to be more powerful than blood pressure as predictors of the endothelial release of vWF and t-PA in response to exercise. These findings indicate that some of the key cardiac and arterial characteristics of hypertension might be linked to increased endothelial reactivity to hemodynamic stress.

Adult↗