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Biomedical subjects

S Oparil

Publications and source records attributed to S Oparil.

At least 73 records · Page 4Linked to original sources
PubMed1999

Treating multiple-risk hypertensive populations.

The majority of patients with hypertension have one or more additional risk factors for cardiovascular disease. In planning an appropriate treatment program, it is useful to identify and stratify hypertensive patients according to their risk of developing cardiovascular, cerebrovascular, or renal disease. At particular risk are the elderly, patients with diabetes, and those with target-organ damage manifested by impaired renal function. Evidence supports increased risk in these patients, and clinical trial results demonstrate the considerable benefits realized through aggressive blood pressure (BP) control. The number of elderly individuals continues to increase in the United States and other industrialized countries. The prevalence of isolated systolic hypertension (ISH) is higher in the elderly than in younger individuals. ISH is associated with significant morbidity and mortality and should not be considered a physiologic manifestation of the normal aging process. Type 2 diabetes is also increasing in prevalence. Patients with diabetes are at increased risk for coronary heart disease, stroke, renal failure, and other cardiovascular complications. Aggressive treatment of elevated BP can produce dramatic decreases in the cardiovascular complications of diabetes. The incidence of end-stage renal disease has increased 2.5-fold in the past two decades, and poorly controlled BP is a major contributor to the increase. Lowering BP to levels well below the traditional goal of 140/90 mm Hg is needed to slow the progression of renal dysfunction and prevent renal failure in hypertensive patients with renal disease, whether related to diabetes or to another etiology. Aggressive treatment of hypertension in multiple-risk populations (to the goals of JNC VI and the recent WHO-ISH Guidelines for the Management of Hypertension) can be expected to produce significant reductions in the incidence and prevalence of stroke, heart failure, coronary heart disease, chronic renal failure, and total cardiovascular mortality.

Antihypertensive Agents↗
PubMed1999

Co-administration of an ACE-inhibitor (moexipril) and hormonal replacement therapy in postmenopausal women.

Co-administration of antihypertensive drug therapy and hormonal replacement therapy (HRT) is frequent in postmenopausal women but it is not known whether HRT interacts with concomitant antihypertensive therapy. The present study was designed to investigate efficacy and safety of the ACE inhibitor moexipril in comparison to placebo in hypertensive, postmenopausal women on HRT. After a 4-week placebo run-in phase, 95 postmenopausal women (35-74 years of age) who had a sitting diastolic blood pressure (BP) of 95-114 mm Hg and were treated with HRT were randomised to a 12-week treatment with moexipril 15 mg or placebo. Efficacy and safety were assessed by measuring changes in sitting BP and metabolic parameters associated with cardiovascular disease including triglycerides, total cholesterol, HDL, LDL, total cholesterol/HDL ratio and glucose. Adverse events were recorded continuously. After 12 weeks of treatment, moexipril 15 mg was significantly more effective in reducing sitting systolic and diastolic BP from baseline than placebo (-12.2/-9.9 mm Hg vs -1.6/-4.3 mm Hg, P < 0.001). Metabolic parameters were not affected by treatment with moexipril: mean levels of triglycerides, total cholesterol, HDL, LDL, total cholesterol/HDL ratio and glucose remained unchanged throughout the study. Fibrinogen, an independent cardiovascular risk factor, increased after placebo (+35.0 mg/dl) and decreased after treatment with moexipril (-33.6 mg/dl), the difference, however, was not statistically significant. Moexipril was well-tolerated by postmenopausal women using HRT. The most frequent adverse events included headache (21.3%), cough (12.8%) and rhinitis (10.6%) and there were no significant differences in the number and severity of adverse events between the moexipril and placebo groups. This study indicates that moexipril is effective and well tolerated in the treatment of hypertensive, postmenopausal women and can safely be co-administered to HRT.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1999

Increased dietary micronutrients decrease serum homocysteine concentrations in patients at high risk of cardiovascular disease.

BACKGROUND: Elevated blood homocysteine is a risk factor for cardiovascular disease. A 5-micromol/L increase is associated with an approximately 70% increase in relative risk of cardiovascular disease in adults. For patients with established risk factors, this risk is likely even greater. OBJECTIVE: Effects of increased dietary folate and recommended intakes of vitamins B-12 and B-6 on serum total homocysteine (tHcy) were assessed in individuals at high risk of cardiovascular disease. DESIGN: This trial was conducted at 10 medical research centers in the United States and Canada and included 491 adults with hypertension, dyslipidemia, type 2 diabetes, or a combination thereof. Participants were randomly assigned to follow a prepared meal plan (PMP; n = 244) or a self-selected diet (SSD; n = 247) for 10 wk, which were matched for macronutrient content. The PMP was fortified to provide >/=100% of the recommended dietary allowances for 23 micronutrients, including folate. RESULTS: Mean folate intakes at 10 wk were 601 +/- 143 microgram/d with the PMP and 270 +/- 107 microgram/d with the SSD. With the PMP, serum tHcy concentrations fell from 10.8 +/- 5.8 to 9.3 +/- 4.9 micromol/L (P < 0.0001) between weeks 0 and 10 and the change was associated with increased intakes of folate, vitamin B-12, and vitamin B-6 and with increased serum and red blood cell folate and serum vitamin B-12 concentrations. tHcy concentrations did not change significantly with the SSD. CONCLUSIONS: The PMP resulted in increased intakes and serum concentrations of folate and vitamin B-12. These changes were associated with reduced serum tHcy concentrations in persons at high risk of cardiovascular disease.

Adult↗
PubMed1999

Nontraditional cardiovascular risk factors.

A number of newer, "nontraditional" cardiovascular risk factors have been identified based on recent studies of the pathogenesis of atherosclerosis and atherothrombotic cardiovascular events. These include chronic inflammation and its markers, such as C-reactive protein; homocysteine; oxidative stress or endothelial dysfunction; lipoprotein Lp (a); psychosocial factors, such as environmental stress and responsiveness to stress; plasma insulin levels and markers of insulin resistance; and activation of the renin-angiotensin system, which is in part a function of polymorphisms in genes for components of the system, such as angiotensinogen and the angiotensin II type 1 receptor. The strength of the associations of the newer risk factors with cardiovascular therapy are currently being tested. This review will briefly discuss evidence that these risk factors are related to cardiovascular disease.

Blood Coagulation Factors↗
PubMed1999

Long-term morbidity and mortality trials with amlodipine.

Prospective controlled clinical trials with cardiovascular events and mortality as end points are needed to provide clinicians with a fully informed choice of optimal hypertensive therapy. Seven trials (six of them still ongoing) have provided insight into the effects of the third-generation calcium antagonist, amlodipine, on mortality and end-organ damage in patients with hypertension or other forms of cardiovascular disease. The completed PRAISE study has addressed the safety of amlodipine in patients with advanced heart failure (CHF). The trial showed that amlodipine does not increase mortality or morbidity in CHF patients and significantly reduces the risk for these end points in patients whose CHF has a nonischemic etiology. The PRAISE-2 study is now under way to further evaluate the benefits of amlodipine in nonischemic CHF patients. The ALLHAT trial compares the effects of standard diuretic treatment with three alternative treatments (amlodipine, lisinopril, and doxazosin) on the incidence of fatal coronary artery disease (CAD) and nonfatal myocardial infarction (MI) in 40,000 hypertensive patients. The ASCOT trial compares the effects of amlodipine +/- perindopril with atenolol +/- bendrofluazide on fatal CAD and nonfatal MI in 18,000 high-risk patients. The PREVENT trial tests a similar hypothesis, looking at the effects of amlodipine on arterial atherosclerotic lesions, and the AASK trial is evaluating the effects of amlodipine on renal disease. The PRAISE trial has provided valuable information on the safety and efficacy of amlodipine in preventing death and disability in patients with CHF. The six ongoing trials will provide important additional information on the effect of amlodipine in patients with heart disease of other etiologies.

Amlodipine↗
PubMed1999

Clinical experience with transdermal clonidine in African-American and Hispanic-American patients with hypertension: evaluation from a 12-week prospective, open-label clinical trial in community-based clinics.

The objective of this study was to assess the efficacy and tolerability of transdermal clonidine in inner-city African-American and Hispanic-American patients with essential hypertension. A multiclinic open-label, prospective trial for 12 weeks was used. Dose titration was based on office blood pressure (BP) measurements of > 140/90 mm Hg. Clinical sites were community-based primary care centers. Untreated and treated hypertensive patients whose diastolic BP exceeded 90 mm Hg were administered transdermal clonidine at 0.1 mg or 0.2 mg delivery daily. The drug was titrated after 1 month if diastolic BP was greater than 90 mm Hg. At 12 weeks of treatment, change in blood pressure from baseline as well as adverse effects and patient satisfaction were assessed. A total of 357 patients entered the treatment phase of the study, and 315 patients (244 African-Americans, 67 Hispanic-Americans) had evaluable data. Transdermal clonidine significantly (P <.001) lowered BP in all patients by 15.7/12.8 +/- 18.1/9.6 mm Hg, and heart rate was reduced by 3 +/- 9 beats/min (P <.001). There were no differences in BP reduction according to race and ethnicity, gender, or age. The most common adverse effects were pruritus or discomfort at the patch site, dizziness, dry mouth, and fatigue. Eleven percent of the patients discontinued treatment because of one of these adverse effects. A large proportion of patients (67%) reported that transdermal clonidine was more convenient to use than oral therapy. Transdermal clonidine, alone or in combination with other antihypertensive therapies, significantly lowered BP and heart rate in inner-city hypertensive patients. The drug was generally well tolerated, with 89% of the patients remaining in the trial. Patient acceptability was high with the once-weekly treatment, which is an important feature for this particular hypertensive population.

Administration, Cutaneous↗
PubMed1999

Comparison of telmisartan with lisinopril in patients with mild-to-moderate hypertension.

In this study, telmisartan, a new angiotensin AT ( 1 ) receptor antagonist given as monotherapy and in combination with hydrochlorothiazide (HCTZ), was compared with lisinopril as monotherapy and in combination with HCTZ. This 52-week, randomized, multicenter, double-blind, double-dummy, parallel-group, dose-titration study of 578 patients with mild-to-moderate essential hypertension (mean diastolic blood pressure [DBP], >/=95 mm Hg), compared the efficacy and safety of telmisartan (n = 385) with lisinopril (n = 193). Dosage could be increased for both telmisartan (40 --> 80 --> 160 mg) and lisinopril (10 --> 20 --> 40 mg) at each of the first 2 monthly visits if DBP control (<90 mm Hg) had not been established. Once DBP control was established, patients entered the 48-week maintenance period. During this period, the dose of the study drug was fixed, although open-label HCTZ at 12.5 mg or 25 mg was added, when needed, to regain DBP control. At the end of the titration period, DBP control was achieved on monotherapy by 67% and 63% of the telmisartan and lisinopril patients, respectively. At the end of the maintenance period, supine DBP was controlled in 83% and 87% of the telmisartan and lisinopril patients, respectively, with systolic blood pressure over DBP reductions of 23.8/16.6 mm Hg for telmisartan and 19.9/15.6 mm Hg for lisinopril. Treatment-related side effects occurred in fewer telmisartan-treated patients (28%) than in lisinopril-treated patients (40%; P =.001). Significantly fewer patients (P =.018) receiving telmisartan experienced treatment-related cough (3% v 7%), and cough led to discontinuation significantly less often (P =.007) with telmisartan treatment than with lisinopril treatment (0.3% v 3.1%). In addition, two cases of angioedema were observed, both in the lisinopril group. The selective AT (1) receptor antagonist, telmisartan, is extremely effective in the treatment of mild-to-moderate hypertension both as monotherapy and in combination with HCTZ and is at least comparable in efficacy to lisinopril, with a tolerability profile that may offer advantages in terms of a reduced incidence of adverse events.

Angioedema↗
PubMed1999

Arthur C. Corcoran Memorial Lecture. Hormones and vasoprotection.

There is a strong link between menopause and increased cardiovascular disease incidence in women, and observational studies suggest that postmenopausal hormone replacement therapy reduces cardiovascular disease risk by about half. Observational studies suffer from important limitations, however, and the only published prospective controlled trial of the effects of hormone replacement therapy on cardiovascular outcomes, the Heart Estrogen-Progestin Replacement Study (HERS), showed no net benefit of continuous estrogen plus synthetic progestin treatment in women with established coronary disease. Fundamental mechanistic studies of the cellular and molecular events by which hormones protect (or fail to protect) blood vessels from damage are needed to define the role of postmenopausal hormone replacement therapy in cardiovascular disease prevention. Most studies suggest that estrogen inhibits the neointimal response to acute injury in normal blood vessels, but this vasoprotective effect was not seen in vessels with preexisting atherosclerosis. Studies from our laboratory in the rat carotid injury model have shown that estrogen inhibits neointima formation via effects on all 3 layers of the vascular wall, including inhibition of medial smooth muscle cell migration and proliferation, stimulation of regrowth of endothelium, and inhibition of adventitial cell migration into neointima. Our laboratory is currently using transduced (lacZ) syngeneic fibroblasts as 'reporter' cells to delineate the factors that stimulate migration of adventitial cells into neointima after vascular injury and their modulation by estrogen and the other sex hormones. These fundamental studies will establish more rational strategies for therapeutic intervention in vascular diseases, including the basis for future gene therapy.

Animals↗
PubMed1999

Hypertension in women.

Hypertension is an important risk factor for cardiovascular disease in women. Although younger, premenopausal women have lower blood pressures than age-matched men, population blood pressure rises with age, and the prevalence of hypertension is higher in older women. Oral contraceptive use increases the risk of hypertension in women, and women using this therapy should have blood pressure monitored twice yearly. The risk of hypertension is low in normotensive women receiving HRT. Few studies of HRT in hypertensive women have been performed, and more information is needed to assess the risk of worsening hypertension in hypertensive postmenopausal receiving this therapy. Investigations of gender differences in pathophysiology and response to treatment of essential hypertension have not been extensive, and current evidence does not support gender-specific treatment of hypertension at the present time.

Antihypertensive Agents↗
PubMed1999

Multicenter randomized trial of a comprehensive prepared meal program in type 2 diabetes.

OBJECTIVE: To evaluate the clinical effects of a comprehensive prepackaged meal plan, incorporating the overall dietary guidelines of the American Diabetes Association and other national health organizations, relative to those of a self-selected diet based on exchange lists in free-living individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 202 women and men (BMI < or = 42 kg/m2) whose diabetes was treated with diet alone or an oral hypoglycemic agent were enrolled at 10 medical centers. After a 4-week baseline period, participants were randomized to a nutrient-fortified prepared meal plan or a self-selected exchange-list diet for 10 weeks. On a caloric basis, both interventions were designed to provide 55-60% carbohydrate, 20-30% fat, and 15-20% protein. At intervals, 3-day food records were completed, and body weight, glycemic control, plasma lipids, and blood pressure were assessed. RESULTS: Food records showed that multiple nutritional improvements were achieved with both diet plans. There were significant overall reductions in body weight and BMI, fasting plasma glucose and serum insulin, fructosamine, HbA1c, total and LDL cholesterol, and blood pressure (P < 0.001 or better for all). In general, differences in major end points between the diet plans were not statistically significant. CONCLUSIONS: Glycemic control and cardiovascular risk factors improve in individuals with type 2 diabetes who consume diets in accordance with the American Diabetes Association guidelines. The prepared meal program was as clinically effective as the exchange-list diet. The prepared meal plan has the additional advantages of being easily prescribed and eliminating the complexities of meeting the multiple dietary recommendations for type 2 diabetes management.

Adult↗
PubMed1998

Effects of candesartan cilexetil in patients with systemic hypertension. Candesartan Cilexetil Study Investigators.

The objectives of this double-blind, multicenter, randomized, parallel-arm, placebo-controlled study were to evaluate the dose-related efficacy, tolerability, and safety of candesartan cilexetil, a potent, AT1 selective, long-acting angiotensin II receptor blocker, in 365 adult patients with systemic hypertension and mean sitting diastolic blood pressure (BP) of 95 to 114 mm Hg. Patients received either placebo or candesartan cilexetil 2, 4, 8, 16, or 32 mg once daily for 8 weeks. All doses of candesartan cilexetil reduced trough (24 hours after treatment) sitting diastolic and systolic BP significantly compared with placebo (p < 0.005). A significant (p < or = 0.0001) dose response was evident, with greater decreases in BP at higher doses. Mean changes in BP were -10.7/-7.8 mm Hg and -12.6/-10.2 mm Hg in the 16- and 32-mg groups, respectively, versus -0.3/-2.6 mm Hg in the placebo group. The 16- and 32-mg doses were consistently significantly superior to placebo in antihypertensive effect with regard to all BP measurements, including peak (6 hours after treatment), trough, sitting, and standing measurements of diastolic and systolic BP. Responder rates (trough sitting diastolic BP < 90 or > or = 10 mm Hg BP decrease) were 54% and 64% for the 16- and 32-mg groups, respectively. Tolerability and safety profiles were similar to placebo at all doses. In conclusion, candesartan cilexetil administered once daily effectively reduces BP in a dose-related manner while maintaining safety and tolerability; doses of 16 and 32 mg are most effective for treatment of hypertension.

Adult↗
PubMed1998

Managing the patient with hard-to-control hypertension.

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.

Antihypertensive Agents↗
PubMed1998

Comprehensive nutrition plan improves cardiovascular risk factors in essential hypertension.

Increased arterial pressure is known to be influenced by a variety of nutrients. Compliance with dietary recommendations for risk reduction is often limited by the complexity of their implementation. In addition, how improvements in total diet, rather than single nutrients, influence concomitant cardiovascular risk factors has not been thoroughly explored. We assessed the effects of a nutritionally complete prepared meal program, the Campbell's Center for Nutrition and Wellness plan (CCNW), compared with dietary therapy in which participants received a structured nutritional assessment and prescription and selected their own foods, in 101 women and men with mild-to-moderate hypertension. Outcome measures included blood pressure (BP), lipids and lipoproteins, glucose, glycosylated hemoglobin (HbA1c), insulin, homocysteine, nutrient intake, compliance, and quality of life. Both dietary interventions significantly lowered BP (P < .0001), while simultaneously improving the overall cardiovascular risk profile. Significantly greater benefits were observed with the CCNW plan as compared with the participant selected diet in cholesterol and LDL levels (both P < .0001), LDL:HDL (P < .001), HbA1c (P < .05), homocysteine (P < .001), total nutrient intake (P < .0001), compliance (P < .0001), and quality of life (P < .001). This study demonstrates 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. Compared with typical dietary therapy, the comprehensive CCNW meal plan has significantly greater effects on multiple cardiovascular risk factors while yielding greater compliance and improved quality of life.

Adult↗
PubMed1998

Mibefradil, a T-channel-selective calcium antagonist: clinical trials in hypertension.

Mibefradil, a tetralol derivative, is the first representative of a new class of calcium antagonists. It selectively blocks entry of calcium into cells through T-type channels. The efficacy and tolerability of mibefradil in the treatment of mild-to-moderate essential hypertension were evaluated in four placebo-controlled, double-blind, dose-finding studies involving over 1000 patients. Two trials involved patients from the general population, one examined a subpopulation of elderly patients, and one evaluated patients receiving chronic hydrochlorothiazide (HCTZ) treatment. Based on these studies, the recommended doses of mibefradil are 50 mg and 100 mg. Doses >100 mg/day were associated with small gains in efficacy and an increased incidence of adverse effects. Response (sitting diastolic blood pressure normalization to < or =90 mm Hg or reduction by > or =10 mm Hg) rates to mibefradil ranged from 46.0% to 68.6% with 50 mg, and from 60.0% to 93.2% with 100 mg. Normalization rates paralleled the response rates, ranging from 34.0% to 62.9% with 50 mg, and from 42.5% to 81.8% with 100 mg. The effects on sitting systolic blood pressure were similar. Treatment was associated with a slight, potentially beneficial reduction in heart rate. Results were similar across all populations, indicating that no dose adjustment is required for elderly and for HCTZ-treated patients. The frequency of adverse events was similar to that reported for placebo groups, with headache being the most common complaint. In comparative trials, mibefradil was more effective than nifedipine SR and diltiazem CD, and at least as effective as amlodipine and nifedipine GITS. Overall, mibefradil was better tolerated than the comparison drugs. Mibefradil, at the recommended doses of 50 to 100 mg/day, is safe and effective for the treatment of mild-to-moderate hypertension.

Benzimidazoles↗
PubMed1998

The Sexual Dimorphism of High Blood Pressure.

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.

Journal Article↗
PubMed1998

Garlic prevents hypoxic pulmonary hypertension in rats.

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 determine whether garlic influences pulmonary vasoconstriction, we assessed the effect of garlic on pulmonary pressures in rats subjected to alveolar hypoxia and on vasoconstriction in isolated pulmonary arterial rings. Garlic gavage (100 mg/kg body wt) for 5 days resulted in complete inhibition of acute hypoxic pulmonary vasoconstriction compared with the control group. No difference in mean arterial pressure or heart rate response to hypoxia was seen between the groups. Garlic solution resulted in a significant dose-dependent vasorelaxation in both endothelium-intact and mechanically endothelium-disrupted pulmonary arterial rings. The administration of NG-nitro-L-arginine methyl ester (a nitric oxide synthase inhibitor) inhibited the vasodilatory effect of garlic by 80%. These studies document that garlic blocks hypoxic pulmonary hypertension in vivo and demonstrate a combination of endothelium-dependent and -independent mechanisms for the effect in pulmonary arterial rings.

Acetylcholine↗