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Biomedical subjects

William H Frishman

Publications and source records attributed to William H Frishman.

At least 19 recordsLinked to original sources
PubMed2007

Use of diuretics in the treatment of heart failure in the elderly.

Diuretics are tools of considerable therapeutic importance. First, they effectively reduce blood pressure, while at the same time decreasing the morbidity and mortality associated with hypertension. Diuretics are currently recommended as first-line therapy for the treatment of hypertension. In addition, they remain an important component of heart failure therapy, in that they improve the symptoms of congestion, which typify the more advanced stages of heart failure. This article reviews the mode of action of the various diuretic classes and the physiologic adaptations that follow; sets up the basis for their use in the treatment of volume-retaining states, particularly as applies to the elderly; and reviews diuretic-related side effects that are normally encountered.

Aged↗
PubMed2006

Pathophysiology and medical management of systemic hypertension in preeclampsia.

Hypertension that complicates preeclampsia in pregnancy is a disorder that requires special consideration in both prevention and pharmacologic treatment. In recent years, few advances have been made regarding the pathophysiology and prevention of preeclampsia; however, there have been some promising results from studies on possible modes of screening women for preeclampsia before clinical signs and symptoms are apparent. The recommendations for first-line drug therapy for the hypertensive complications of preeclampsia have changed little, primarily because first-line medications have had the advantage of extensive research experience. Recent clinical trials have demonstrated the efficacy and safety of various second-line drugs for the hypertensive complications of preeclampsia; whether these therapies can eventually replace the standard recommended first-line medications will require more extensive long-term investigation.

Adrenergic beta-Antagonists↗
PubMed2006

A factorial study of combination hypertension treatment with metoprolol succinate extended release and felodipine extended release results of the Metoprolol Succinate-Felodipine Antihypertension Combination Trial (M-FACT).

BACKGROUND: Many hypertensive patients require combination therapy to achieve target blood pressure (BP). beta-Blockers and dihydropyridine calcium channel blockers are effective as monotherapy in hypertensive patients and have complementary mechanisms for lowering BP. METHODS: This multicenter, randomized, placebo-controlled, unbalanced factorial study included a 4- to 5-week single-blind placebo, 9-week, double-blind treatment as well as a 2-week double-blind, down-titration period. Patients (N = 1092) were randomized to one of 16 treatment groups: extended-release (ER) metoprolol succinate (25, 100, or 400 mg), ER felodipine (2.5, 10, or 20 mg), ER felodipine/ER metoprolol succinate (2.5/25, 2.5/100, 2.5/400, 10/25, 10/100, 10/400, 20/25, 20/100, or 20/400 mg), or placebo. RESULTS: At baseline, treatment groups were well balanced; mean sitting BP was 152.6/99.9 mm Hg. Monotherapy with ER metoprolol succinate induced dose-related reductions in sitting systolic/diastolic BP (DBP) (mean 8.1/7.7 to 9.7/11.1 mm Hg) as did ER felodipine (mean 7.7/7.7 to 14.0/11.8) and the combinations reflected additive effects (mean 13.8/11.0 to 19.8/15.2). The decline in the placebo group was 2.1/4.0 mm Hg. All combinations were more effective than their components (P < .05 for all but ER metoprolol succinate 25/ER felodipine 20). When compared with the highest doses of the individual agents (ER metoprolol succinate 400 mg; ER felodipine 20 mg), the low-dose combination ER metoprolol succinate 25/ER felodipine 2.5 was approximately as effective (differences in DBP <1 mm Hg). The most common adverse events leading to discontinuation were peripheral edema (4%), headache (2%), and fatigue (1%). Higher rates of peripheral edema and flushing were associated with high-dose ER felodipine, either alone or in combination. CONCLUSIONS: The antihypertensive effects of ER metoprolol succinate and ER felodipine are dose-related, and when given in combination, their BP-lowering effects are additive over a wide dose range. Low-dose combination therapy is comparable in effectiveness to high-dose monotherapy but is better tolerated.

Administration, Oral↗
PubMed2005

Left ventricular ejection fraction and prevalence of new left ventricular wall motion abnormality at long-term follow-up in patients with automatic implantable cardioverter-defibrillators treated with dual-chamber rate-responsive pacing at a rate of 70/minute versus backup ventricular pacing at a rate of 40/minute.

Baseline and long-term follow-up 2-dimensional echocardiograms were obtained in 160 patients with automatic implantable cardioverter-defibrillators without indications for antibradycardia pacing, who had backup ventricular pacing at a rate of 40/minute (VVI-40) or dual-chamber rate-responsive pacing at a rate of 70/minute (DDDR-70). At 37 months of follow-up for 80 patients treated with VVI-40 and 23 months of follow-up for 80 patients treated with DDDR-70, the mean left ventricular ejection fraction was 36 +/- 8% at baseline and 36 +/- 8% at follow-up and 36 +/- 7% at baseline and 30 +/- 7% at follow-up (p <0.01), respectively. At follow-up, the left ventricular ejection fraction was decreased >7% in 25 of 80 patients (31%)treated with DDDR-70 and in 9 of 80 patients (11%) treated with VVI-40 (p <0.01). A new left ventricular wall motion abnormality developed in 23 of 80 patients (29%) treated with DDDR-70 and in 11 of 80 patients (14%) treated with VVI-40 (p <0.025).

Aged↗
PubMed2005

Association of ankle-brachial index with severity of angiographic coronary artery disease in patients with peripheral arterial disease and coronary artery disease.

The ankle-brachial index (ABI) was correlated with the severity of coronary artery disease (CAD) in 273 patients, mean age 71 years, with peripheral arterial disease and angiographically obstructive CAD (> 50% occlusion). Of 155 patients with an ABI < 0.40, 130 (84%) had 3- or 4-vessel CAD, 17 (11%) had 2-vessel CAD and 8 (5%) had 1-vessel CAD. Of 80 patients with an ABI of 0.40-0.69, 37 (46%) had 3- or 4-vessel CAD, 33 (41%) had 2-vessel CAD and 10 (13%) had 1-vessel CAD. Of 38 patients with an ABI of 0.70-0.89, 10 (26%) had 3- or 4-vessel CAD, 16 (42%) had 2-vessel CAD and 12 (32%) had 1-vessel CAD. The lower the ABI, the higher the prevalence of 3- or 4-vessel CAD and the lower the prevalence of 1-vessel CAD.

Adult↗
PubMed2004

Comparison of self-report, hospital discharge codes, and adjudication of cardiovascular events in the Women's Health Initiative.

Limited information is available from large clinical investigations about the agreement among sources of diagnoses for endpoints. The authors used data from the Women's Health Initiative clinical trials and observational study from January 1994 to November 2000 to evaluate the agreement among self-report, hospital discharge codes, and two different levels of physician review of medical records for cardiovascular endpoints. For myocardial infarction, stroke, pulmonary embolism, and venous thrombosis, the agreement of hospital discharge codes or self-report with review by study physicians at clinical centers was substantial (kappa = 0.64-0.84). For coronary revascularization, agreement among these sources of information was substantial to almost perfect (kappa = 0.79-0.92), but for angina, congestive heart failure, and peripheral vascular disease, concordance was only fair to moderate (kappa = 0.37-0.56), indicating that these endpoints remain difficult to classify reliably. Agreement between physician adjudicators at clinical centers and central physician adjudicators was substantial to almost perfect (kappa = 0.67-0.94). The findings also suggest that, for the endpoint of myocardial infarction, physician review of events with hospital discharge codes for angina and congestive heart failure is an important source of validated events, and for stroke, review of all events with cerebrovascular codes is important.

Aged↗
PubMed2004

Treatment of hypertension and prevention of ischemic stroke.

Data clearly indicate that treatment with antihypertensive drugs reduces the incidence of all strokes in men (by 34%), women (by 38%), elderly persons (by 36%), including those older than 80 years (by 34%), younger persons, those with systolic and diastolic hypertension, persons with isolated systolic hypertension, and in those with a history of stroke or transient ischemic attack (by 28%). Blood pressure should be reduced to less than 140/90 mm Hg. The overall data also suggest that reduction of stroke in persons with hypertension is related more to a reduction in blood pressure than to the type of antihypertensive drugs used.

Algorithms↗
PubMed2004

Aldosterone and aldosterone antagonism in systemic hypertension.

Aldosterone mediates both water and electrolyte balance by acting on the renal mineralocorticoid receptors. Recent experimental studies have also documented the presence of these receptors in other body organs, including the brain, blood vessels, and heart, suggesting that aldosterone plays a larger role in normal physiologic function and in cardiovascular diseases such as systemic hypertension and congestive heart failure (CHF). The nonspecific aldosterone inhibitor spironolactone, and the selective aldosterone inhibitor eplerenone, are both approved for clinical use in treating patients with hypertension and/or symptomatic CHF. Studies have shown that spironolactone lowers blood pressure, improves endothelial function, reduces myocardial hypertrophy and fibrosis, and lowers the incidence of fatal arrhythmias. Eplerenone, which is more specific for the mineralocorticoid receptor, appears to provide all the beneficial effects of spironolactone in hypertensive patients, with the potential to modify many of the side effects related to nonspecific steroid-receptor blockade. Hyperkalemia remains a potential problem with all aldosterone antagonists.

Aldosterone↗
PubMed2004

Estrogen and progestin use and the QT interval in postmenopausal women.

OBJECTIVE: To determine whether menopausal hormone therapy alters the QT interval in primarily healthy postmenopausal women. BACKGROUND: Despite well-known gender differences in myocardial repolarization that include a longer heart-rate-corrected QT interval (QT(C)) in women compared to men, the effects of menopausal hormone therapy on myocardial repolarization in women have not been well characterized. METHODS: We studied 34,378 postmenopausal women participating in the dietary intervention component of the Women's Health Initiative. Cross-sectional associations were examined to assess possible effects of estrogen + progesterone on myocardial repolarization. Women who reported that they were never treated with menopausal hormone therapy (n = 12,451) were compared to women with a past use of menopausal hormone therapy (n = 3891), currently taking unopposed estrogen therapy (n = 9987), or combined current estrogen and progesterone therapy (n = 8049). RESULTS: Using analysis of covariance, the mean (+/-SEM) QT(C) interval was 423.1 +/- 0.2 milliseconds (ms) in those never treated with menopausal hormone therapy, 423.9 +/- 0.3 ms in past menopausal hormone therapy users, 425.6 +/- 0.2 ms in those currently on estrogen alone, and 424.0 +/- 0.2 ms in women currently on combined estrogen-progesterone therapy. Differences in mean QT(C) between those on estrogen alone and the other three groups were statistically significant. Comparisons of JT intervals, QT intervals, and linear corrected QT intervals among the groups yielded similar results. CONCLUSION: These results suggest that unopposed estrogen in menopausal women mildly prolongs myocardial repolarization, and the effect is reversed by progesterone. Whether these findings have clinical significance requires further study.

Analysis of Variance↗
PubMed2004

Amlodipine/atorvastatin: the first cross risk factor polypill for the prevention and treatment of cardiovascular disease.

In 2002, the World Health Organization estimated that over 58% of cardiovascular disease in North America is due to 'both blood pressure and cholesterol higher than optimal'. Unfortunately, less than a third of patients with both conditions are identified, and fewer than one in ten reach the treatment goals for both factors. Adherence to treatment is notably improved when therapy is initiated simultaneously. Combination therapy of amlodipine besylate (Norvasc, Pfizer Ltd) with atorvastatin calcium (Lipitor, Pfizer Ltd), marketed as Caduet (Pfizer Ltd) is the first dual-therapy compound designed to treat hypertension and/or angina and dyslipidemia concurrently with a single daily pill in the full range of dosing combinations. Amlodipine/atorvastatin retains the safety and efficacy of its parent compounds whilst simplifying the management of these comorbid conditions, in what may be considered the first version of a polypill.

Amlodipine↗
PubMed2002

Compliance with National Cholesterol Education Program dietary and lifestyle guidelines among older women with self-reported hypercholesterolemia. The Women's Health Initiative.

PURPOSE: Dietary therapy remains the first line of treatment for patients with high blood cholesterol levels. Among free-living persons, compliance with National Cholesterol Education Program (NCEP) dietary recommendations is uncertain. SUBJECTS AND METHODS: We performed a cross-sectional, baseline analysis of 91,627 postmenopausal women enrolled in the Women's Health Initiative Observational Study. Among women with self-reported hypercholesterolemia, we ascertained factors associated with compliance with National Cholesterol Education Program dietary recommendations, defined for the Step II diet as <or=30% of total calories from fat, <7% of calories from saturated fat, and daily dietary cholesterol <200 mg. RESULTS: Of the 13,777 participants who reported having high cholesterol levels requiring drug therapy, only 20% reported total fat, saturated fat, and dietary cholesterol consumption consistent with Step II dietary goals. Factors associated with Step II dietary compliance included having a college degree (odds ratio [OR] = 1.26; 95% confidence interval [CI]: 1.14 to 1.40), a prior cardiovascular event (OR = 1.48; 95% CI: 1.28 to 1.70), and consumption of five or more daily servings of fruits or vegetables (OR = 3.0; 95% CI: 2.7 to 3.3). Being married, smoking, a sedentary lifestyle, and a higher body mass index were all associated with reduced compliance (all P <0.0001). In the subsample in which plasma lipid levels were measured, dietary compliance was associated with higher levels of low-density lipoprotein cholesterol (P = 0.02). CONCLUSION: Since the inception of the NCEP in 1985, health care providers, public health programs, and patients have not successfully implemented the dietary recommendations.

Age Factors↗
PubMed2002

Effects of nonsteroidal anti-inflammatory drug therapy on blood pressure and peripheral edema.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used drugs with potential effects on systemic blood pressure. NSAIDs act by inhibiting synthesis of prostaglandins (PGs) from arachidonic acid via cyclooxygenase (COX)-1 and COX-2, the 2 isoforms of COX. NSAIDs may affect blood pressure via the renin-angiotensin pathway, alterations in sodium and water retention in the kidneys, inhibition of vasodilating PGs, and production of various vasoconstricting factors, including endothelin-1 and P450-mediated metabolites of arachidonic acid. In 2 meta-analyses, it was found that NSAIDs have small but significant effects on blood pressure, most notably in hypertensive patients on antihypertensive medication. NSAIDs cause small (<5 mm Hg) elevations in systolic blood pressure, and little or no change in diastolic blood pressure. The incidence rates of hypertension and peripheral edema were low, ranging from <1% to >9% of patients. The incidence and levels of hypertension associated with COX-2 inhibitors are within the range of those observed with nonspecific NSAIDs. Apparent differences between the COX-2 inhibitors celecoxib and rofecoxib may be functions of differences in study population susceptibilities to NSAID-mediated hypertensive effects. Patients at risk for hypertension should be monitored for changes in blood pressure during NSAID treatment.

Aged↗
PubMed2002

Beta-adrenergic blockers in systemic hypertension: pharmacokinetic considerations related to the current guidelines.

Beta-adrenergic blockade has provided one of the major pharmacotherapeutic advances of the 20th century. Beta-blockers are first-line drugs for the management of systemic hypertension, used alone and in combination with other antihypertensive agents. Drugs in the beta-blocking class have the common property of blocking the binding of catecholamines to beta-adrenergic receptor sites; however, there are significant pharmacodynamic and pharmacokinetic differences between the individual agents that are of clinical importance. Among these differences are the completeness of gastrointestinal absorption, the degree of hepatic first-pass metabolism, lipid solubility, protein binding, brain penetration, concentration within the cardiac tissue, rate of hepatic biotransformation, and renal clearance of drug and/or metabolites. Long-acting formulations of existing beta-blockers are currently in use, and ultra-short-acting agents are also available. Age, race, cigarette smoking and concomitant drug therapy can also influence the pharmacokinetics of beta-blocking drugs. The wide interpatient variability in plasma drug concentrations observed with beta-blockers makes this parameter unreliable in routine patient management. Despite the pharmacokinetic differences among beta-blockers, these drugs should always be titrated to achieve the desired individual patient response.

Adrenergic beta-Antagonists↗