Showing papers by "Suzanne Oparil published in 2001"

Comparative efficacy of olmesartan, losartan, valsartan, and irbesartan in the control of essential hypertension.

Abstract: In a multicenter, randomized, double-blind trial, the authors compared the antihypertensive efficacy of once-daily treatment with the new angiotensin II type 1 receptor blocker (ARB) olmesartan (20 mg) with recommended starting doses of losartan (50 mg), valsartan (80 mg), and irbesartan (150 mg) in 588 patients with a cuff diastolic blood pressure (DBP) of greater than or equal to 100 and less than or equal to 115 mm Hg and a mean daytime DBP of greater than or equal to 90 mm Hg and less than 120 mm Hg, as measured by ambulatory blood pressure monitoring Cuff and ambulatory blood pressures were monitored at baseline and after 8 weeks of treatment All groups were predominantly white and approximately 62% male, and their mean age was approximately 52 years In all groups, mean baseline DBP and systolic blood pressure (SBP) were approximately 104 and 157 mm Hg, respectively The reduction of sitting cuff DBP with olmesartan (115 mm Hg), the primary efficacy variable of this study, was significantly greater than with losartan, valsartan, and irbesartan (82, 79, and 99 mm Hg, respectively) Reductions of cuff SBP with the four ARBs ranged from 84-113 mm Hg and were not significantly different The reduction in mean 24-hour DBP with olmesartan (85 mm Hg) was significantly greater than reductions with losartan and valsartan (62 and 56 mm Hg, respectively) and showed a trend toward significance when compared to the reduction in DBP with irbesartan (74 mm Hg; p=0087) The reduction in mean 24-hour SBP with olmesartan (125 mm Hg) was significantly greater than the reductions with losartan and valsartan (90 and 81 mm Hg, respectively) and equivalent to the reduction with irbesartan (113 mm Hg) All drugs were well tolerated The authors conclude that olmesartan, at its starting dose, is more effective than the starting doses of the other ARBs tested in reducing cuff DBP in patients with essential hypertension

Estrogen depletion induces NaCl-sensitive hypertension in female spontaneously hypertensive rats

Abstract: In women, arterial pressure generally increases after menopause, but several studies suggest that women who eat large amounts of plant estrogens (phytoestrogens) experience a slower rise in the inc...

Estrogen-induced vasoprotection is independent of inducible nitric oxide synthase expression: evidence from the mouse carotid artery ligation model.

Abstract: Background Estrogen is vasoprotective in animal models of vascular injury, yet the mechanisms involved are incompletely understood. The role of inducible nitric oxide synthase (iNOS) in vascular repair is controversial, but many lines of evidence indicate that it plays a role in neointima formation after arterial injury and that 17β-estradiol (E2) modulates iNOS expression. This study tested the hypothesis that E2 reduces neointima formation after vascular injury via a mechanism that is dependent on modulation of iNOS expression. Methods and Results Male and female wild-type (iNOS+/+) mice and mice with homozygous deletion of the iNOS gene (iNOS−/−) were studied intact (INT) or after ovariectomy (OVX) and implantation of E2 or vehicle (V) pellets. Mice were randomized to 8 groups based on sex, iNOS status, OVX, and treatment with E2 or V. Twenty-eight days after carotid artery ligation, mice were euthanized, and occluded vessels were evaluated for neointima formation by morphometric analysis. There was a marked sexual dimorphism in neointima formation in both the iNOS+/+ mice and the iNOS−/− mice. iNOS+/+ INT females had a >90% reduction in neointima formation compared with iNOS+/+ males, and iNOS−/− INT females had a 65% reduction in neointima formation compared with iNOS−/− males. The sexually dimorphic response was attenuated by OVX and restored by E2 replacement in both iNOS+/+ and iNOS−/− mice. Conclusions These results demonstrate that the vasoprotective effects of E2 after ligation vascular injury are, at least in part, independent of iNOS expression. Received July 18, 2001; revision received September 7, 2001; accepted September 12, 2001.

Once-daily treatment of patients with hypertension: a placebo-controlled study of amlodipine and benazepril vs amlodipine or benazepril alone.

Abstract: Objective: To compare the efficacy, tolerability, and safety of once-daily therapy with amlodipine 5 mg/benazepril 10 mg vs amlodipine 5 mg, benazepril 10 mg, and placebo. Design: Randomised, double-blind, placebo-controlled, parallel-group, multicentre trial. Setting: Twenty-two clinical centres, including private practice groups and academic research clinics. Patients: A total of 530 patients between 21 and 80 years of age with essential hypertension were screened for the study, and 454 were randomised to treatment with amlodipine 5 mg/benazepril 10 mg, amlodipine 5 mg, benazepril 10 mg, or placebo for 8 weeks. Results: Amlodipine 5 mg/benazepril 10 mg produced greater reductions from baseline in sitting diastolic blood pressure than amlodipine 5 mg (P < 0.03), benazepril 10 mg (P < 0.001), and placebo (P < 0.001). The response rate in the amlodipine 5-mg/benazepril 10-mg treatment group (66.4%) was better than that observed in the amlodipine 5-mg (50.0% P < 0.02), benazepril 10-mg (38.3% P < 0.001), and placebo (24.4% P < 0.001) groups. There was no significant difference in heart rate among the four groups. The incidence of oedema in the amlodipine 5-mg/benazepril 10-mg (1.7%) group was somewhat less than that in the amlodipine 5-mg (4.5%) group. Conclusions: Therapy with amlodipine 5 mg/benazepril 10 mg was well tolerated and was superior to amlodipine 5 mg, benazepril 10 mg, and placebo in reducing sitting diastolic blood pressure in patients with essential hypertension.

Genetic Variation in Angiotensin-Converting Enzyme Does Not Prevent Development of Cardiac Hypertrophy or Upregulation of Angiotensin II in Response to Aortocaval Fistula

Abstract: Background —Experimental and clinical evidence suggests that angiotensin II may be an important mediator of cardiac hypertrophy in response to hemodynamic stress. We investigated the effect of genetic variation in angiotensin-converting enzyme (ACE) on the development of cardiac hypertrophy and left ventricular (LV) dysfunction in response to volume overload. Methods and Results —Male heterozygous ACE knockout (1/0) and wild-type (1/1) mice were studied 4 weeks after the creation of an aortocaval fistula (ACF). The LV weight/body weight ratio increased 74% in ACF versus sham-operated control mice but did not differ between genotypes. Echocardiographic circumferential stress versus rate-corrected velocity of circumferential shortening curves demonstrated depressed LV function in ACF versus sham-operated mice but no difference between genotypes. LV ACE activity was higher in 1/1 versus 1/0 mice and in ACF versus sham-operated mice, and it increased significantly more in the 1/1 versus the 1/0 mice after ACF ( P <0.001 for effect of genotype, ACF/sham operation, and interaction term). LV angiotensin II was higher in ACF versus sham-operated mice but did not differ between genotypes, despite 3-fold higher LV ACE activity in ACF 1/1 versus ACF 1/0 mice. Conclusions —ACE underexpression does not prevent cardiac hypertrophy or LV dysfunction in response to volume overload. LV angiotensin II is unaffected by ACE genotype, both at baseline and after volume overload, indicating that the heart can maintain angiotensin II levels across a broad range of genetic ACE variation under both physiological and pathophysiological conditions.

Tyrosine kinase receptor activation inhibits NPR-C in lung arterial smooth muscle cells.

Abstract: We have previously demonstrated that expression of the atrial natriuretic peptide (ANP) clearance receptor (NPR-C) is reduced selectively in the lung of rats and mice exposed to hypoxia but not in ...

Efficacy and safety of losartan/hydrochlorothiazide in patients with severe hypertension

Abstract: This 12-week, open-label, multicenter study assessed the efficacy and safety of losartan/hydrochlorothiazide (HCTZ), alone or in combination with other antihypertensive agents, in the treatment of patients with severe systemic hypertension. Treatment began with once-daily losartan/HCTZ 50/12.5 mg. The dose was increased to 100/25 mg, if required, to achieve blood pressure (BP) control (sitting diastolic BP <95 mm Hg); felodipine (extended release) and/or atenolol could be added if target sitting diastolic BP was not achieved with losartan/HCTZ alone. Mean sitting systolic BP of the 131 patients enrolled was 165.3 mm Hg at baseline and 139.8 mm Hg at final visit (reduction -25.4 mm Hg; p < or =0.01). Mean sitting diastolic BP was 111.9 mm Hg at baseline and 93.6 mm Hg at final visit (reduction -18.4 mm Hg; p < or =0.01). After 2 weeks of treatment, 63.8% of patients (83 of 130) were taking losartan/HCTZ 50/12.5 mg alone. By the final visit, one third of patients (35.1%; 46/131) were still only taking losartan/HCTZ. Most patients (48.1%; 63 of 131) were taking losartan/HCTZ 100/25 mg plus felodipine (extended release) at the final visit. Losartan/HCTZ was well tolerated. Drug-related adverse experiences occurred in 30 patients (22.9%). Only 2 patients (1.5%) had a serious adverse experience; 6 patients (4.6%) discontinued the drug because of an adverse experience. In conclusion, losartan/ HCTZ, alone or as part of a regimen with other standard antihypertensive agents, is effective and well tolerated in the treatment of patients with severe hypertension.

Primary aldosteronism: a practical approach to diagnosis and treatment.

Abstract: Primary aldosteronism (PA) may account for as many as 10%–14% of hypertension cases. The plasma aldosterone concentration/plasma renin activity ratio is a simple screening test for PA that should be performed in all patients with refractory/severe hypertension, spontaneous or provoked (by diuretics) hypokalemia, or a requirement for excessive potassium supplementation to maintain normokalemia. PA can be confirmed by a fludrocortisone suppression test or 24-hour urine collection for aldosterone. Confirmatory testing should be followed by high-resolution computerized tomography of the adrenal glands to distinguish bilateral hyperplasia or an adenoma. A solitary tumor greater than 1 cm in size in a younger patient is an indication for surgery; all other (nondiagnostic) findings should be followed by bilateral adrenal venous sampling (if available) to identify a unilateral cause of PA. Treatment for a later alizing positive study is surgical; spironolactone or another mineralocorticoid receptor antagonist is the treatment of choice for a nonlateralizing study. If adrenal venous sampling is not readily available, patients may be successfully treated pharmacologically.

Hormone replacement therapy and stroke: are the results surprising?

Abstract: Despite major progress in treatment and prevention, stroke remains the leading cause of disability and the third leading cause of death, surpassed only by heart disease and cancer, in the United States.1 An estimated 500 000 to 600 000 first and 100 000 recurrent strokes occur each year, and ≈160 000 of these are fatal.2 Among stroke survivors, the burden of long-term disability is great. In the Framingham Heart Study, 71% had impairments that affected their ability to work in their previous capacity and 31% needed help in caring for themselves.3 Stroke rates in women increase sharply with age, doubling in each successive decade after the age of 55 years. Stroke incidence is substantially lower in younger women than in age-matched men, but it tends to equalize in the two sexes in the postmenopausal years.1 Thus, stroke is a major health problem for postmenopausal women and one that merits aggressive preventive strategies. A number of preventive strategies have been proven effective in reducing the risk of stroke. A review of 14 prospective, randomized, controlled trials demonstrated a 42% risk reduction for stroke when the diastolic blood pressure was reduced by 5 to 6 mm Hg,4 and the Systolic Hypertension in the Elderly Program (SHEP) study showed that treating isolated systolic hypertension in the elderly reduced stroke by 36%.5 Similarly, pharmacological intervention with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statin agents), aspirin, and warfarin in patients with decreased left ventricular function or evidence of left ventricular thrombi after myocardial infarction has proven effective in stroke prevention. Oral anticoagulation and antiplatelet therapy also reduce the risk of stroke in patients with atrial fibrillation, and carotid endarterectomy is effective in preventing stroke in persons with asymptomatic carotid stenosis with 60% to 99% occlusion. Lifestyle modifications, including smoking cessation, …

Efficacy of perindopril in the treatment of systemic hypertension

Abstract: The angiotensin-converting enzyme inhibitor, perindopril erbumine, has been approved for use in the United States only recently but has been studied extensively worldwide over the last decade Placebo-controlled trials in a wide range of patients with hypertension, including the elderly, those with isolated systolic hypertension, and those with concomitant diseases such as hyperlipidemia, diabetes, cardiac arrhythmia, peripheral arterial occlusive disease, nephropathy with proteinuria, and chronic obstructive pulmonary disease, have shown that perindopril is highly effective in lowering both systolic and diastolic blood pressure (BP) Studies in which BP has been monitored for 24-hour intervals show that perindopril (1) has a gradual onset of action, (2) provides smooth BP control over its once-daily dosing interval, (3) has a trough-peak ratio of about 1, and (4) maintains its antihypertensive efficacy despite missed doses Perindopril increases arterial compliance and reverses left ventricular hypertrophy in hypertensive patients Both of these effects are at least partly independent of its ability to lower BP Perindopril is safe and well tolerated in patients with hypertension Rates of adverse events and discontinuation because of such events are low