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Biomedical subjects

V DeQuattro

Publications and source records attributed to V DeQuattro.

At least 37 records · Page 2Linked to original sources

Individualization of therapy for hypertension in the 1990's: the role of calcium antagonists.

The Joint National Committee Reports IV (1988) and V (1992) have emphasized individualization of drug therapy for patients with hypertension-a departure from the "stepped" care approach of initiating therapy with diuretics as advocated by the JNC I-III in the 1970's and 1980's. This review highlights individualization or "patient profiling" using calcium channel blockers as first-line treatment strategy for patients with primary hypertension--especially in the patient who has attendant risk factors and sequelae. The calcium channel antagonists, especially effective in elderly and Black patients, have proven efficacy in reducing left ventricular hypertrophy and improving diastolic function in patients with hypertensive heart disease. The heart rate limiting calcium antagonist, verapamil, has been found effective in outcome trials of reducing death and reinfarction rates post myocardial infarction and is an alternative therapy for the beta blocker intolerant hypertensive post myocardial infarction. More vascular specific dihydropyridines (felodipine, isradipine, and amlodipine) may be preferable to rate limiting agents in hypertensives with sinus node or AV conduction disorders and in those with impaired left ventricular systolic function. Verapamil and diltiazem have been effective in preliminary trials in reducing proteinuria and preserving renal function in both diabetic and non diabetic hypertensives. Calcium channel antagonists appear to prevent the progress of atherosclerosis independent of their antihypertensive properties. Further, they have theoretic value in improving endothelial mediated vasodilation.

Arteriosclerosis↗

Silent myocardial ischemia in patients with essential hypertension.

The aim of this study was to determine the significance of the "coronary factor" in patients with essential hypertension (EH). Electrocardiogram Holter monitoring was performed in 61 patients with EH stage II (according to the World Health Organization criteria). Silent, ie, painless ST-segment depression, was found in 34 patients on whom echocardiography, a treadmill test, and transesophageal pacing were performed. In 21 patients with EH and silent ischemia, the examination included 201Tl stress scintigraphy, coronary angiography, and a platelet aggregation test. In 15 patients, catecholamines and beta-endorphins were obtained in blood samples during silent ischemia. 201Tl scintigraphy showed transient defects of perfusion without clearance abnormalities (group I) and with clearance abnormalities (group II). The patients in group I had more severe left ventricular hypertrophy (LVH) and a significantly higher platelet aggregation response to 0.5 mumol/L adenosine diphosphate; one patient in this group had coronary atherosclerosis. LVH and the platelet aggregation response was less pronounced in the patients in group II, but atherosclerotic lesions of a coronary artery were observed in four patients. In both groups, norepinephrine and beta-endorphin levels were increased during silent episodes of ischemia. The results suggest that there are different pathogenetic mechanisms of coronary insufficiency in patients with EH, a hypertensive heart, and silent ischemia.

Adult↗

The perioperative management of pheochromocytoma in children.

The perioperative experiences of 15 children and adolescents who underwent a total of 18 surgical procedures for resection of a pheochromocytoma were analyzed to determine clinical or hemodynamic events associated with intraoperative or postoperative complications. Of the pre- and intraoperative factors assessed, only preoperative resolution of symptoms and normalization of blood pressure were predictive of uncomplicated outcome. No intraoperative factors were statistically associated with outcome, but the four patients with complicated outcomes had had aggressively administered intraoperative fluids. Noninvasive measures of cardiac function did not help predict outcome; however, echocardiography results were available only for six patients. Two of the patients with complicated outcomes had cardiac dysfunction, suggesting undiagnosed catecholamine-induced cardiomyopathy in the other two with complicated outcomes. Intraoperative fluids should be given based on intraoperative blood pressures, the presence or absence of prior adrenergic blockade, and assessment of preoperative myocardial function. If preoperative myocardial dysfunction is revealed, intraoperative measurement of right atrial and pulmonary capillary wedge pressures may be indicated.

Adolescent↗

Efficacy and safety of felodipine, a new dihydropyridine calcium channel blocker, in elderly hypertensive patients.

Felodipine is a new dihydropyridine calcium channel blocker with a number of properties that enhance its suitability as a first-line antihypertensive drug for the elderly. Felodipine has a 100-fold selectivity for inhibiting the contribution of vascular smooth muscle compared with cardiac muscle. Negative inotropic action appears minimal while selectivity appears to increase with age. Felodipine has a minimal effect on smooth muscle of venous capacitance vessels, thereby greatly reducing the likelihood of orthostatic hypotension. Renal effects are favorable; the glomerular filtration rate is increased in some patients. The extended-release formulation of felodipine produces a smooth 24-hour plasma concentration curve and is effective when prescribed once daily. Felodipine appears to lower blood pressure effectively in the elderly patient with few, generally mild, adverse effects.

Aging↗

Comparison of benazepril and other antihypertensive agents alone and in combination with the diuretic hydrochlorothiazide.

The safety and efficacy of benazepril, as monotherapy or as part of combination therapy with the diuretic hydrochlorothiazide, have been assessed in a number of studies, including comparative trials with the antihypertensive agents propranolol and nifedipine. These studies have included over 1300 patients with mild-to-moderate hypertension. Comparisons of the efficacy of benazepril and hydrochlorothiazide alone and in combination have shown that benazepril 20 mg once daily is as effective as or more effective in lowering diastolic blood pressure than hydrochlorothiazide 25 mg once daily and that the combination of benazepril 20 mg and hydrochlorothiazide 25 mg has a possibly synergistic effect on diastolic blood pressure. The results of comparative trials of benazepril with propranolol and nifedipine suggest that benazepril, administered alone or with the diuretic hydrochlorothiazide, is as effective as the other antihypertensive agents alone or in combination with hydrochlorothiazide. An additional study demonstrated that the combination of benazepril and nifedipine further lowered diastolic blood pressure in patients not responding to monotherapy with these agents. The safety of monotherapy with benazepril was found to be similar to that of the other antihypertensive agents. Safety of the combination of benazepril and hydrochlorothiazide was shown to be better than that of the combination of propranolol and hydrochlorothiazide. An attenuation of adverse experiences observed during nifedipine monotherapy was obtained when benazepril was added to the nifedipine regimen.

Angiotensin-Converting Enzyme Inhibitors↗

Effect of beta-blockade on low heart rate-related ischemia during mental stress.

To explore the effect of beta-adrenergic blockade on low heart rate-related (mental stress) ischemia, 19 patients with coronary artery disease were randomized into a double-blind crossover trial of metoprolol, 100 mg twice daily, and underwent serial mental stress/bicycle exercise studies. Mental stress-induced wall motion abnormalities occurred at a lower heart rate than exercise-induced wall motion abnormalities during placebo administration (81 +/- 16 vs. 123 +/- 20 beats/min, p less than 0.05). Metoprolol reduced the mean magnitude of exercise-induced wall motion abnormalities (2.8 +/- 2.0 vs. 1.6 +/- 2.4, p = 0.003); improvement was related to the magnitude of hemodynamic beta-blockade effect. Metoprolol did not significantly reduce the mean magnitude of mental stress-induced wall motion abnormalities (3.0 +/- 2.2 vs. 2.6 +/- 2.2), although individual responses predominantly either improved (50%) or worsened (29%). Unlike exercise, the magnitude of hemodynamic beta-blockade did not predict mental stress response and metoprolol did not block mental stress-induced blood pressure elevations. Patients with abolition of exercise-induced ischemia were more likely to have reduction of mental stress-induced ischemia. Patients whose ischemia worsened with metoprolol during mental stress had more easily inducible ischemia, as assessed by exercise-induced placebo wall motion abnormality, chest pain and prior myocardial infarction. Beta-blockade was associated with a lowering of ischemia-related hemodynamic thresholds compared with placebo. These results suggest that beta-blockade has a variable effect on low heart rate-related ischemia that may be due to a lack of effect on mental stress-induced blood pressure elevation in patients with easily induced ischemia or to effects on coronary vasomotor tone, or both.

Adrenergic beta-Antagonists↗

Blood pressure reactivity and sympathetic hyperactivity. Predictors of hypertension.

Raised sympathetic nerve activity appears to be a predictor and factor in primary hypertension. Sympathetic activation alone does not appear to be a sufficient cause of sustained hypertension, however. Over the past two decades we have studied several populations of primary hypertensive patients and found neural hyperactivity in 25 to 30% of them. Metaanalyses of other studies have supported these findings.

Blood Pressure↗

Comparison of labetalol versus enalapril as monotherapy in elderly patients with hypertension: results of 24-hour ambulatory blood pressure monitoring.

PURPOSE: This study compared the safety and efficacy of labetalol and enalapril as antihypertensive therapy for elderly patients. PATIENTS AND METHODS: A randomized, open-label, parallel controlled trial was conducted. After completing a 4-week placebo phase, 79 elderly (65 years or older) patients with an average standing diastolic blood pressure (BP) 95 mm Hg or above and 114 mm Hg or less were randomized to receive a 12-week course of either labetalol or enalapril in an open-label design. The patients' BP and heart rate were evaluated biweekly by trained observers unaware of the treatment status, and drug dosage was titrated (up to 400 mg twice a day of labetalol or 40 mg daily of enalapril) to achieve a standing diastolic BP of less than 90 mm Hg and a decrease of 10 mm Hg from baseline. Patients underwent 24-hour ambulatory BP monitoring (ABPM) at the end of the placebo phase and again after 8 weeks of active treatment. RESULTS: The treatment groups were comparable in their reduction of supine diastolic BP, with no significant differences between the two treatments. Labetalol demonstrated a significantly greater reduction (p less than 0.05) in standing diastolic BP at the end of the titration period compared to enalapril, but this difference was not significant by the end of the study period. Based on 24-hour ABPM readings, labetalol reduced mean 24-hour diastolic BP (p less than 0.05) and mean heart rate (p less than 0.05) more than enalapril. The labetalol-treated patients were significantly less often above their diastolic BP goal throughout the 24-hour ABPM period (p less than 0.01). The two treatments were equally well tolerated. CONCLUSIONS: The results indicate that labetalol and enalapril are equally effective in lowering supine diastolic BP in the elderly, but labetalol is more effective in lowering ambulatory BP and heart rate throughout the day.

Aged↗

Evaluation of the clinical pharmacology of nilvadipine in patients with mild to moderate essential hypertension.

Eighty-four patients with diastolic blood pressure ranging from 100-115 mm Hg were randomized into a multicenter, parallel, double-blind, placebo-controlled, dose response study with nilvadipine (6 mg, 8 mg, 10 mg tid for 28 days). The hypotensive response pattern to nilvadipine was similar with all three doses although duration of response was dose dependent. Maximal decreases in diastolic blood pressure occurred at 1 hour when assessed on days 1 and 15 (16.0, 17.4, and 15.8 mm Hg, vs 17.2, 18.7, and 17.5 mm Hg, respectively). The hypotensive effect remained significant compared to placebo for at least 4 hours after dosing. The increase in heart rate associated with the maximal hypotensive response was minimal and not clinically significant (day 1: 7.6, 5.2, and 4.0 beats/min with 6, 8, and 10 mg; day 15: 4.0, 5.1, 2.6 beats/min with 6, 8, 9, and 10 mg, respectively). Finally, a correlation between plasma drug concentrations and nilvadipine-induced hypotensive response was observed (r = 0.48). Black and white hypertensive patients had similar hypotensive responses. Plasma nilvadipine concentrations on day 15 were similar to those on day 1 suggesting no accumulation of drug with a tid regimen. The most common drug related side effect was headache; less frequently seen were dizziness, edema, palpitations, and abdominal pain. Nilvadipine was well tolerated (only three patients were discontinued due to side effects). The efficacy, lack of tachycardia, and side effect profile observed in this study suggest that nilvadipine may be an important addition to the treatment of hypertension.

Blood Pressure↗

Hypertensive heart disease: relationship of silent ischemia to coronary artery disease and left ventricular hypertrophy.

ECG evidence of silent ischemia occurs commonly in patients with systemic hypertension, but its relationship to left ventricular hypertrophy (LVH), large-vessel coronary artery disease (CAD), and neurohumoral factors remains unclear. Accordingly we validated the results of the echocardiographic method used to measure left ventricular (LV) mass in the Soviet Union by comparison with necropsy measurements in 30 patients, and we examined the relationships in 46 men with essential hypertension among ST segment depression during ambulatory monitoring, exercise stress and transesophageal pacing (n = 38), and LV mass, catheterization evidence of CAD (n = 25), and neurohumoral factors (plasma catecholamines and platelet aggregability). Echocardiographic measurements of LV mass by both the Soviet and Penn methods were closely correlated with necropsy values (r = 0.78 and 90, respectively; both p less than 0.001). During ambulatory monitoring from 1 to 17 episodes of greater than or equal to 1 mm ST depression occurred in 26 of 46 (65%) patients with hypertension; ischemia was also provoked by exercise or pacing stress in most but not all of these patients (65% and 80%, respectively). Neither ST depression nor the occurrence of additional episodes of symptomatic angina was related to the presence of coronary obstruction at catheterization; patients with and without ST depression did not differ in age, blood pressure, or LV mass.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Generalized anxiety disorder: some biochemical aspects.

Fifty-one patients who met DSM-III criteria for generalized anxiety disorder, and who were recruited to participate in a drug outcome study, filled out a variety of rating scales and had blood samples drawn for plasma norepinephrine, epinephrine, and free 3-methoxy-4-hydroxyphenylglycol (MHPG) after a 20-min rest period. This group was compared to 15 normal controls who also had their blood drawn after a 20-min rest period. While the two groups were initially found to have significantly different levels of plasma free MHPG through the use of t tests, this finding was not confirmed by subsequent discriminant analysis.

Adolescent↗

JNC-IV and the evolution of stepped care to individualized treatment of hypertension.

There have been many changes in the treatment of hypertension over the past few decades. The Joint National Committee on the Detection, Evaluation, and Treatment of High Blood Pressure (JNC) has published four reports since 1977. The first three highlighted diuretic therapy as the main ingredient of stepped care for hypertensive patients. In the fourth report, this position has been revised to a patient-oriented, or individualized, approach. The shift reflects the results of many studies on hypertensive patients treated with a variety of approaches and drugs, including diuretics, beta-blockers, angiotensin converting enzyme (ACE) inhibitors, sympatholytics, and calcium channel blockers. After analyzing the patient's history, physical, and laboratory findings, the report recommends making choices from the various agents, based on patient demographics, sequelae, concomitant diseases, and other risk factors such as cholesterol levels.

Angiotensin-Converting Enzyme Inhibitors↗

Noradrenergic activity and silent ischaemia in hypertensive patients with stable angina: effect of metoprolol.

30 patients (10 normotensive, 20 hypertensive) with stable angina and positive treadmill exercise tests entered a double-blind, placebo-controlled crossover trial of metoprolol, 100 mg twice daily. At the end of each treatment phase, blood pressure was monitored for 24 h and Holter and real-time electrocardiographic (ECG) monitoring were carried out and an activity diary kept for 48 h. Blood samples for catecholamine measurement were taken after 30 min supine, 60 min standing, and at the first silent ischaemic event, triggered by the real-time ECG monitor, by means of an ambulatory blood withdrawal pump. Metoprolol lowered blood pressure and heart rate in both normotensive and hypertensive subjects, and reduced the frequency and duration of silent ischaemic episodes in hypertensive subjects. Plasma noradrenaline measured during silent ischaemia while the patients were resting was significantly higher than the control supine level without ischaemia. These findings suggest that noradrenergic hyperactivity may have a role in coronary vasoconstriction and that treatment which neutralizes sympathetic tone may be especially beneficial in treatment of silent ischaemia in hypertensive patients.

Angina Pectoris↗

Plasma norepinephrine in Chagas' cardioneuromyopathy: a marker of progressive dysautonomia.

Chronic Chagas' disease produces pathologic changes of the cardiovascular, digestive, and autonomic nervous systems. In an attempt to elucidate the nature of the dysautonomia in patients with Chagas' disease, we measured plasma norepinephrine levels, blood pressure, and heart rate, both supine and standing in 26 patients, and compared these values of patients classified according to three clinical subsets of cardiovascular manifestations with the values of nine normal volunteers and 16 patients with nonchagasic heart failure. Results suggested (1) progressive blockade of the alpha receptor in patients with Chagas' disease who have minimal clinical symptoms (group I) and in those who have ECG alterations without congestive symptoms (group II), as reflected by normal or raised plasma norepinephrine levels without change of diastolic blood pressure during standing, which indicates absent postural reflexes; and (2) blockade associated with partial denervation in patients with Chagas' disease who have class III or IV heart failure (group III), as suggested by a lower supine plasma norepinephrine level and a fall in diastolic blood pressure in the upright position. The findings of reduced plasma norepinephrine levels are in contrast to the elevated plasma norepinephrine levels in patients without Chagas' disease with class III and IV heart failure who have sympathetic hyperactivity.

Adult↗

Primary hypertension, neural tone, and behavior. Role in pressor responses to stress.

Patients with primary hypertension follow a hierarchical pattern of hemodynamic and neurohumoral responses to laboratory and environmental mental and physical stress. The stressor responses are regulated by the central and peripheral autonomic nervous system. The psychological and behavioral characteristics of these persons--for example, whether they conform to the Type A pattern of behavior, including hostility and anxiety--alter the magnitude and duration of their stress responses. For some patients, the magnitude of the neurohumoral activation can predict the effectiveness of therapy with sympatholytic and other types of drugs used to treat hypertension.

Animals↗

Relaxation therapy lowers blood pressure more effectively in hypertensives with raised plasma norepinephrine and blunts pressor response to anger.

The effects of relaxation therapy on blood pressure and neural responses to "social stress"-anger instigation were determined in 30 male patients with mild primary hypertension. "Social stress"-anger induced increases in systolic and diastolic blood pressures (both p less than 0.01) and plasma norepinephrine (p less than 0.05) before therapy. Diastolic blood pressure before and during anger challenge were related to simultaneous plasma norepinephrine (r = 0.56, p less than 0.01 and r = 0.39, p less than 0.05). Relaxation reduced resting diastolic blood pressure (p less than 0.01), the reduction of blood pressure was related to baseline plasma norepinephrine (p less than 0.05). The pressor response of systolic blood pressure to anger challenge (p less than 0.02) was blunted by relaxation therapy. These findings suggested that noradrenergic control of blood pressure was amplified during stress and relaxation therapy was effective in lowering blood pressure and neutralizing the response to "social stress" anger instigation.

Adult↗

Effects of celiprolol on plasma renin, aldosterone, norepinephrine and epinephrine in primary hypertension.

Celiprolol is a newly developed cardioselective beta-blocking agent with mild beta 2-agonist and weak alpha 2-antagonist properties. To evaluate the acute (2.5 hours) and chronic (2 weeks) effects of celiprolol (400 mg once a day) on plasma renin, aldosterone, norepinephrine and epinephrine, 20 patients with mild to moderate primary hypertension were studied in a double-blind placebo-controlled crossover trial. Two and one-half hours after the first dose of both placebo and celiprolol, supine and standing measurements of blood pressure showed a significant reduction, whereas plasma norepinephrine increases were comparable with baseline values. Placebo and celiprolol produced similar changes on supine blood pressure and plasma norepinephrine. In 9 patients celiprolol decreased plasma renin (from a mean +/- standard deviation of 1.09 +/- 0.35 to 0.77 +/- 0.52 ng/ml/hr, p less than 0.05) and aldosterone (from 9.2 +/- 3.7 to 6.7 +/- 3.9 ng/dl, p less than 0.05) acutely both supine and standing, but placebo did not change these parameters. Celiprolol increased pulse rate supine (but not standing) as compared with baseline values. After 2 weeks of celiprolol therapy, blood pressure was decreased both supine and standing compared with placebo in 18 patients (140 +/- 18/88 +/- 8 vs 149 +/- 18/94 +/- 7, 136 +/- 18/91 +/- 6 vs 142 +/- 20/97 +/- 9 mm Hg, respectively, each p less than 0.05), without a change of pulse rate when supine and with a reduction when standing. There were no significant changes of plasma renin, aldosterone, norepinephrine and epinephrine levels during chronic therapy compared with placebo.

Adult↗

Behavioral vs beta-blocker therapy in patients with primary hypertension: effects on blood pressure, left ventricular function and mass, and the pressor surge of social stress anger.

We compared the relative effects of relaxation therapy, conventional hygienic techniques, and a beta-receptor blocker, atenolol, on control of arterial pressure, left ventricular mass, and diastolic function in patients with mild primary hypertension. Furthermore, we related these effects to baseline neural tone and its changes and assessed the efficacy of relaxation or the pressor surge of "social stress" anger. In group I left ventricular mass index was related to both systolic and diastolic blood pressure (r = 0.46; p less than 0.05). Plasma norepinephrine was related to age (r = 0.33; p less than 0.01). Slope was inversely related to both plasma norepinephrine (r = -0.29; p less than 0.05) and age (r = -0.31; p less than 0.05). Relaxation therapy reduced both supine systolic and diastolic blood pressures, 4.5% and 7.6%, respectively, but did not affect plasma norepinephrine. Hygienic informational therapy reduced plasma norepinephrine by 18%, (p less than 0.05) and did not change blood pressure. Blood pressure responders to nondrug therapy (i.e., diastolic blood pressure reduction of 7% or more) had a 7% reduction of left ventricular mass index (p less than 0.02). On the other hand, atenolol reduced systolic and diastolic blood pressure by 10% and 15%, respectively, (p less than 0.01) and improved left ventricular function by 17% (p less than 0.05) without a significant change in left ventricular mass index. Finally, relaxation therapy but not hygienic therapy reduced systolic blood pressures 4% and 6%, respectively (p less than 0.01), both before and during social stress anger.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗