Effect of atorvastatin on energy expenditure and skeletal muscle oxidative metabolism at rest and during exercise.

Statins are associated with adverse effects in skeletal muscle. This study tested the hypothesis that atorvastatin would increase the respiratory exchange ratio (RER) at rest and during exercise. Twenty-eight healthy subjects (mean age 52 years) were enrolled in a double-blind, placebo-controlled, randomized study of the effects of atorvastatin (40 mg/day) on whole body energetics over 8 weeks.

Inferring the location of tumor suppressor genes by modeling frequency of allelic loss.

Allelic loss is often part of a multistep process leading to tumorigenesis. Analysis of genomic markers highlights regions of elevated allelic loss, which in turn suggests a nearby tumor suppressor. Furthermore, pooling published analyses to combine evidence can increase the power to detect a tumor suppressor gene.

Acceptability of a bilingual interactive computerized educational module in a poor, medically underserved patient population.

We evaluated the acceptability and impact of an audiovisual, bilingual, interactive computer module relating to appropriate antibiotic use. In winter 2001, adults seeking urgent care for acute respiratory infections at an inner-city urgent care clinic were invited to complete the computer module and survey (N = 296). After responding to questions about their symptoms, patients were provided information about their illness and appropriate antibiotic use, and then asked several questions about the acceptability of the module.

Adjunctive parenteral therapy with lipo-ecraprost, a prostaglandin E1 analog, in patients with critical limb ischemia undergoing distal revascularization does not improve 6-month outcomes.

Purpose: In patients with critical limb ischemia (CLI), distal revascularization remains the procedure of choice for preventing limb loss, but long-term outcomes for pain relief, wound healing, and prevention of amputation remain suboptimal. Prostaglandin drug therapy as an adjuvant to revascularization may improve these outcomes. The current trial was designed to test the hypothesis that the use of lipo-ecraprost, a lipid encapsulated prostaglandin E(1) prodrug, as an adjunctive therapy after distal revascularization would improve amputation-free survival in patients with CLI.

The US experience with cilostazol in treating intermittent claudication.

The management of peripheral arterial disease (PAD) patients with intermittent claudication (IC) requires both aggressive risk management and targeted symptomatic therapies. The phosphodiesterase inhibitor cilostazol is the only US Food and Drug Administration (FDA) approved medication to demonstrate consistent benefits on both objective measures of exercise capacity and subjective measures of everyday functioning and quality of life. Pentoxifylline is also approved by the FDA for the treatment of claudication, but with less clinical benefit than cilostazol.

Quality of the assessment of primary and secondary endpoints in claudication and critical leg ischemia trials.

Clinical trials in peripheral arterial disease (PAD) require an accurate definition of the disease for inclusion; they typically use treadmill testing, questionnaires and hemodynamic measures as primary and secondary endpoints. Trials of new pharmacologic therapies for PAD often employ multiple clinical sites with presumed expertise in the diagnosis and management of PAD as well as in clinical trials. However, considerable variability has been observed in the assessment of endpoints used in PAD trials, as well as a marked placebo response with treadmill testing.

Carnitine and peripheral arterial disease.

Patients with peripheral arterial disease (PAD) who become symptomatic with claudication (approximately one-third of the population) have a marked impairment in exercise performance and overall functional capacity. Patients with claudication have a peak oxygen consumption measured during graded treadmill exercise testing that is 50% of that in age-matched normal subjects, and also report great difficulty in walking relatively short distances, even at a slow walking speed. The reduced walking capacity is associated with impairment in activities of daily living and quality of life.

Treatment of disability in peripheral arterial disease: new drugs.

Peripheral arterial disease is a major manifestation of systemic atherothrombosis that affects a large segment of the adult population. The major treatment goals for this population are to address the marked increase risk in cardiovascular events and then secondarily to treat the disability and reduced exercise tolerance. The primary goals for treating the limb symptoms of PAD are to improve functional capacity, exercise performance and qualify of life.

Randomized trial of AT-1015 for treatment of intermittent claudication. A novel 5-hydroxytryptamine antagonist with no evidence of efficacy.

AT-1015 is a novel selective 5-HT2A serotonin receptor antagonist that is known to impair platelet aggregation and vasoconstriction. Serotonin has been hypothesized to contribute to claudication symptoms in individuals with peripheral arterial disease (PAD) via microvascular vasoconstrictor and thrombotic effects. AT-1015 was thus evaluated in 439 patients with claudication who were randomized in a double-blind, placebo-controlled trial comparing 10 mg, 20 mg, and 40 mg BID versus placebo for 24 weeks.

Pharmacologic therapy for peripheral arterial disease and claudication.

Peripheral arterial disease (PAD) is a common manifestation of systemic atherosclerosis that is associated with a high risk of cardiovascular mortality and significant limitation in function because of limb ischemia. Patients with PAD should be considered to have significant coronary and cerebral arterial disease that requires aggressive risk factor management, including the prescription of antiplatelet drugs, to lower the subsequent risk of myocardial infarction, stroke, and death. In the population with PAD, level 1 and level 2 evidence supports the use of statin drugs for lipid management, angiotensin-converting enzyme-1 inhibitors for blood pressure control, and aspirin or clopidogrel as antiplatelet agents.

Treatment of high-risk diabetic patients with angiotensin II receptor blockers.

In the United States, approximately 16 million people have diabetes; 90-95% have type 2 diabetes. They are at increased risk of developing hypertension and cardiovascular disease (CVD). The benefits of treating hypertension in diabetic patients and the potential to delay complications and reduce mortality have been demonstrated in clinical trials.

Preventing atherothrombotic events in peripheral arterial disease: the use of antiplatelet therapy.

Patients with peripheral arterial disease (PAD) are at increased risk of generalized atherothrombotic events. Epidemiologic data shows a high rate of co-prevalence of PAD and atherosclerosis in other vascular beds. Aggressive risk-factor modification and antiplatelet therapy has become the cornerstone of treatment to prevent ischaemic events associated with PAD.

Effect of blood pressure control on diabetic microvascular complications in patients with hypertension and type 2 diabetes.

Objective: The Appropriate Blood Pressure Control in Diabetes (ABCD) Trial is a prospective randomized blinded clinical trial that compares the effects of intensive versus moderate blood pressure control on the incidence and progression of type 2 diabetic complications. The current article discusses the results of 5.3 years of follow-up of 470 patients with hypertension and evaluates the effects of intensive and moderate blood pressure therapy using nisoldipine versus enalapril as the initial antihypertensive medication for nephropathy, retinopathy, and neuropathy.

Antihypertensive therapy in type 2 diabetes: implications of the appropriate blood pressure control in diabetes (ABCD) trial.

As the population ages, the incidence of type 2 diabetes will increase as will the incidence of concomitant vascular complications. Hypertension substantially increases the risk of cardiovascular disease in patients with diabetes. Results from the recent Appropriate Blood Pressure Control in Diabetes (ABCD) trial demonstrated an advantage of an angiotensin-converting enzyme (ACE) inhibitor (enalapril) over a long-acting calcium antagonist (nisoldipine) with regard to the incidence of cardiovascular events over a 5-year follow-up period in hypertensive persons with type 2 diabetes.

The effect of nisoldipine as compared with enalapril on cardiovascular outcomes in patients with non-insulin-dependent diabetes and hypertension.

Background: It has recently been reported that the use of calcium-channel blockers for hypertension may be associated with an increased risk of cardiovascular complications. Because this issue remains controversial, we studied the incidence of such complications in patients with non-insulin-dependent diabetes mellitus and hypertension who were randomly assigned to treatment with either the calcium-channel blocker nisoldipine or the angiotensin-converting-enzyme inhibitor enalapril as part of a larger study.

Methods: The Appropriate Blood Pressure Control in Diabetes (ABCD) Trial is a prospective, randomized, blinded trial comparing the effects of moderate control of blood pressure (target diastolic pressure, 80 to 89 mm Hg) with those of intensive control of blood pressure (diastolic pressure, 75 mm Hg) on the incidence and progression of complications of diabetes.