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Showing papers by "Suzanne Oparil published in 1998"


Journal ArticleDOI
TL;DR: The Losartan Intervention For Endpoint (LIFE) Reduction in Hypertension Study as discussed by the authors is a double-blind, prospective, parallel group study designed to compare the effects of losartan with those of the beta-blocker atenolol on the reduction of cardiovascular morbidity and mortality.
Abstract: -Losartan was the first available orally administered selective antagonist of the angiotensin II type 1 receptor developed for the treatment of hypertension. The Losartan Intervention For Endpoint (LIFE) Reduction in Hypertension Study is a double-blind, prospective, parallel group study designed to compare the effects of losartan with those of the beta-blocker atenolol on the reduction of cardiovascular morbidity and mortality. Patients with essential hypertension, aged between 55 and 80 years, and ECG-documented left ventricular hypertrophy (LVH) were included. Altogether, 9223 patients in Scandinavia, the United Kingdom, and the United States were randomized from June 1995 through April 1997, and 9194 remain after exclusion of a study center at which irregularities were discovered. This population of hypertensives (mean systolic/diastolic blood pressure, 174.4/97.8 mm Hg) with LVH comprises women (54.1%) and men, mostly retired from active work (mean age, 66.9 years), with a high prevalence of overweight (mean body mass index, 28.0 kg/m2), diabetes mellitus (12.3%), lipid disorders (18.0%), and symptoms or signs of coronary heart disease (15.1%). There were fewer current smokers (<17%) than in the general population, and approximately 7% were nonwhite. Almost 30% of participants had been untreated for at least 6 months when screened for the study. Only 1557 persons who entered the placebo run-in period of 14 days were excluded, predominantly because of sitting blood pressures above or below the predetermined range of 160-200/95-115 mm Hg and ECG-LVH criteria not met. By application of simple 12-lead ECG criteria for LVH (Cornell voltage QRS duration product formula plus Sokolow-Lyon voltage read by a core laboratory), hypertensive patients with LVH with an average 5-year coronary heart disease risk of 22.3% according to the Framingham score were identified. This population is now being treated (goal, <140/90 mm Hg) in adherence with the protocol for at least 4 years after final enrollment (ie, through April 2001) and until at least 1040 patients suffer myocardial infarction, stroke, or cardiovascular death.

305 citations


Journal ArticleDOI
TL;DR: This multicenter, randomized, double-masked, elective-titration study was designed to compare the effectiveness, safety, and tolerability of irbesartan and losartan, two angiotensin II subtype AT1-receptor blockers, in the treatment of patients with mild-to-moderate hypertension.

90 citations


Journal ArticleDOI
TL;DR: It is documented that garlic blocks hypoxic pulmonary hypertension in vivo and a combination of endothelium-dependent and -independent mechanisms for the effect in pulmonary arterial rings are demonstrated.
Abstract: Hypoxic pulmonary vasoconstriction underlies the development of high-altitude pulmonary edema. Anecdotal observations suggest a beneficial effect of garlic in preventing high-altitude symptoms. To ...

70 citations


Journal ArticleDOI
TL;DR: In conclusion, candesartan cilexetil 8 to 16 mg once daily was an effective and well-tolerated therapy for lowering BP when added to HCTZ 12.5 mg in a diverse population of patients with severe systemic hypertension in the United States.
Abstract: The efficacy, tolerability, and safety of the potent angiotensin II receptor blocker candesartan cilexetil were evaluated in 217 adult patients (68% men, 41% black) with severe systemic hypertension on background therapy with hydrochlorothiazide (HCTZ) in a 4-week, multicenter, randomized, double-blind, placebo-controlled study. Patients with sitting diastolic blood pressure (BP) ≥110 mm Hg during the placebo run-in received HCTZ 12.5 mg once daily for 1 week. Those with sitting diastolic BP >95 mm Hg after the HCTZ run-in were randomized (2:1) to receive candesartan cilexetil 8 mg once daily (n = 141) or placebo (n = 76), plus HCTZ 12.5 mg. After 1 week of double-blind treatment, patients with sitting diastolic BP ≥90 mm Hg were uptitrated to candesartan cilexetil 16 mg once daily or matching placebo, plus HCTZ 12.5 mg; 84% required uptitration. Primary efficacy measurement was a change in trough (24 ± 3 hours after treatment) sitting diastolic BP from the end of the HCTZ run-in to double-blind week 4. Mean changes in systolic and diastolic BP were significantly greater with candesartan cilexetil than with placebo, −11.3/−9.1 mm Hg versus −4.1/−3.1 mm Hg, p

66 citations


Journal Article
TL;DR: Most patients with hypertension in the United States have their blood pressure under control, mainly because of inadequate or inappropriate therapy and noncompliance, but major causes of unresponsiveness to antihypertensive therapy include "white coat" hypertension, pseudohypertension, obesity, volume overload, excess alcohol intake and sleep apnea.
Abstract: Less than 25 percent of patients with hypertension in the United States have their blood pressure under control, mainly because of inadequate or inappropriate therapy and noncompliance. Approximately one half of these treatment failures are related to factors such as cost and adverse effects of medication, complex drug regimens, failure of clinicians to fully realize the benefits of antihypertensive therapy and lack of patient education. Other major causes of unresponsiveness to antihypertensive therapy include "white coat" hypertension, pseudohypertension, obesity, volume overload, excess alcohol intake and sleep apnea, as well as inappropriate antihypertensive drugs and drug combinations, and unfavorable interactions with prescription and other drugs. In many patients, these factors must be dealt with before blood pressure can be controlled.

54 citations


Journal ArticleDOI
TL;DR: In this paper, the efficacy, tolerability, and safety of the potent angiotensin II receptor blocker candesartan cilexetil were evaluated in 217 adult patients with severe systemic hypertension on background therapy with hydrochlorothiazide (HCTZ) in a 4-week, multicenter, randomized, double-blind, placebo-controlled study.
Abstract: The efficacy, tolerability, and safety of the potent angiotensin II receptor blocker candesartan cilexetil were evaluated in 217 adult patients (68% men, 41% black) with severe systemic hypertension on background therapy with hydrochlorothiazide (HCTZ) in a 4-week, multicenter, randomized, double-blind, placebo-controlled study. Patients with sitting diastolic blood pressure (BP) > or =110 mm Hg during the placebo run-in received HCTZ 12.5 mg once daily for 1 week. Those with sitting diastolic BP >95 mm Hg after the HCTZ run-in were randomized (2:1) to receive candesartan cilexetil 8 mg once daily (n = 141) or placebo (n = 76), plus HCTZ 12.5 mg. After 1 week of double-blind treatment, patients with sitting diastolic BP > or =90 mm Hg were uptitrated to candesartan cilexetil 16 mg once daily or matching placebo, plus HCTZ 12.5 mg; 84% required uptitration. Primary efficacy measurement was a change in trough (24+/-3 hours after treatment) sitting diastolic BP from the end of the HCTZ run-in to double-blind week 4. Mean changes in systolic and diastolic BP were significantly greater with candesartan cilexetil than with placebo, -11.3/-9.1 mm Hg versus -4.1/-3.1 mm Hg, p or =10 mm Hg decrease) and 32% were controlled (diastolic BP <90 mm Hg). Tolerability and safety profiles were similar in the candesartan and placebo groups. In conclusion, candesartan cilexetil 8 to 16 mg once daily was an effective and well-tolerated therapy for lowering BP when added to HCTZ 12.5 mg in a diverse population of patients with severe systemic hypertension in the United States.

49 citations


Journal ArticleDOI
TL;DR: The data demonstrate that valsartan provides dose-responsive antihypertensive efficacy across the therapeutic dose range, with clinically relevant blood-pressure lowering at doses > or = 80 mg once daily.

42 citations


Journal ArticleDOI
TL;DR: Special considerations that can dictate antihypertensive treatment choices for women include increased vulnerability to the adverse effects of some drugs, including angiotensin-converting enzyme inhibitor-induced cough, calcium channel blocker-induced edema, and minoxidil-induced hirsutism.
Abstract: There is a sexual dimorphism in blood pressure: men tend to have higher blood pressures than women with functional ovaries, whereas ovariectomy or menopause tends to abolish the sexual dimorphism and cause women to develop a "male" pattern of blood pressure. Synthetic estrogens and progestins, found in oral contraceptives, tend to elevate blood pressure, whereas naturally occurring estrogens, used in postmenopausal hormone replacement therapy, lower it or have no effect. Women are more likely than men to be aware of their hypertension, to be treated with antihypertensive drugs, and to have their blood pressure controlled. Antihypertensive therapy induces similar blood pressure reductions in men and women. However, men experience larger reductions in total cardiovascular risk with successful treatment of high blood pressure, because their absolute risk of coronary events at baseline is so much higher. Special considerations that can dictate antihypertensive treatment choices for women include increased vulnerability to the adverse effects of some drugs, including angiotensin-converting enzyme inhibitor-induced cough, calcium channel blocker-induced edema, and minoxidil-induced hirsutism. Beta-adrenergic blockers tend to be less effective in women than in men, and diuretics are particularly useful in women because they protect against hip fracture. Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers are contraindicated during pregnancy or if pregnancy is planned because of the risk of fetal developmental abnormalities.

27 citations


Journal ArticleDOI
TL;DR: Cardiac pathology in 51 female victims of sudden death identified at the Office of the Chief Medical Examiner of the State of Maryland are related to antecedent symptoms and cardiac risk factors and compare these to findings in 15Female victims of fatal trauma as control subjects.
Abstract: Despite major progress in detection, prevention, and treatment, coronary artery disease remains the leading cause of death in the world. More than half of all coronary deaths are sudden and unexpected, occurring within 6 hours of the onset of symptoms and usually outside the hospital.1 Coronary artery disease is by far the most common pathology underlying the 300 000 cases of sudden cardiac death occurring in the United States each year.2 The insidious nature of sudden cardiac death and the finality of the outcome represent major barriers to development of effective preventative and therapeutic strategies. This is a particular problem in women, in whom the risk of coronary artery disease and of sudden death is lower than in men and in whom the index of suspicion of serious cardiovascular pathology remains low. Data from carefully conducted postmortem studies of victims of sudden cardiac death provide important insights into the pathogenesis of sudden cardiac death and the risk factors that predispose to it. In a study reported in the current issue of Circulation , Burke et al relate cardiac pathology in 51 female victims of sudden death identified at the Office of the Chief Medical Examiner of the State of Maryland to antecedent symptoms and cardiac risk factors and compare these to findings in 15 female victims of fatal trauma as control subjects.3 Several striking findings emerge from the study: (1) Of the 36 deaths that were witnessed, only 8 (22%) were preceded by chest pain; 12 (33%) were preceded by other, nonspecific symptoms, including back pain, dizziness, nausea and vomiting, shortness of breath, malaise, fatigue, fever and chills, stomach distension, and tingling of the left shoulder; and 16 (45%) were preceded by no symptoms whatsoever. (2) Only one patient was receiving hormone replacement therapy. (3) Coronary anatomy …

17 citations


Journal ArticleDOI
TL;DR: It is demonstrated that improving the total diet to include the full array of recommended dietary guidelines, rather than focusing on single nutrients, has significant benefits for the cardiovascular risk profile of hypertensive persons beyond BP control.

12 citations


Book ChapterDOI
01 Jan 1998
TL;DR: Emerging evidence suggests that estrogen may be cardioprotective through a combination of mechanisms in the prevention of cardiovascular morbidity and mortality.
Abstract: There is a sexual dimorphism in the development of atherosclerotic cardiovascular disease in humans (1). The incidence of cardiovascular disease is much lower in premenopausal women than in age matched men, but rises steadily in women after the menopause (2). Epidemiologic and observational clinical studies have shown that postmenopausal women on estrogen replacement therapy have less severe coronary artery disease and a lower risk of cardiovascular mortality than women without hormone treatment (3). Thus, ovarian hormones, principally estrogens, appear to inhibit the development of atherosclerotic cardiovascular disease in women (4). Large-scale clinical studies, including the Women’s Health Initiative (WHI) and the Heart Estrogen-Progestin Replacement Study (HERS), are currently evaluating the role of estrogen in the prevention of cardiovascular morbidity and mortality. Emerging evidence from these and other studies suggests that estrogen may be cardioprotective through a combination of mechanisms. For example, estrogen replacement therapy results in decreased plasma low-density lipoprotein (LDL) and increased high-density lipoprotein (HDL) concentrations (5-7). Other benefits of estrogen replacement therapy, including the improvement of systemic hemodynamic parameters, appear to be unrelated to changes in plasma lipoprotein profiles (8). It has been clearly shown that endothelial cells and vascular smooth muscle cells (VSMCs) possess estrogen receptors (ER) and are thus physiological targets for estrogen action (9,10).

Journal ArticleDOI
TL;DR: Mibefradil, at the recommended doses of 50 to 100 mg/day, is safe and effective for the treatment of mild-to-moderate hypertension and was better tolerated than the comparison drugs.