Mark A Creager

CONTEXT: Peripheral arterial disease (PAD) is a manifestation of systemic atherosclerosis that is common and is associated with an increased risk of death and ischemic events, yet may be underdiagnosed in primary care practice.

OBJECTIVE: To assess the feasibility of detecting PAD in primary care clinics, patient and physician awareness of PAD, and intensity of risk factor treatment and use of antiplatelet therapies in primary care clinics.

DESIGN AND SETTING: The PAD Awareness, Risk, ...

BACKGROUND: Vorapaxar is a novel antagonist of protease-activated receptor-1, the primary receptor for thrombin on human platelets that is also present on vascular endothelium and smooth muscle. Patients with peripheral artery disease are at risk of systemic atherothrombotic events, as well as acute and chronic limb ischemia and the need for peripheral revascularization.

METHODS AND RESULTS: The Trial to Assess the Effects of SCH 530348 in Preventing Heart Attack and Stroke in Patients ...

BACKGROUND: The endothelium synthesizes and releases a relaxing factor with the physiochemical properties of nitric oxide (NO). However, the role of endothelium-derived NO in the basal regulation of systemic and pulmonary vascular resistance in humans is not known. Our primary objectives were to determine the effects of inhibiting NO synthesis on blood pressure and systemic vascular resistance and to establish the role of endothelium-derived NO in the regulation of normoxic pulmonary ...

OBJECTIVES: The aim of this study was to assess the efficacy of flosequinan in chronic heart failure.

BACKGROUND: Flosequinan is a new vasodilator drug that acts by interfering with the inositol-triphosphate/protein kinase C pathway, an important mechanism of vasoconstriction. The drug dilates both peripheral arteries and veins, is orally active and has a long duration of action that permits once-daily dosing. Previous studies have shown that flosequinan produces sustained hemodynamic ...

In addition to inhibiting cholesterol biosynthesis, statins also inhibit the formation of isoprenoid intermediates, which are required for the activation of the Rho/Rho kinase (ROCK) pathway. Increased ROCK activity has been implicated in causing endothelial dysfunction and atherosclerosis. However, it is not known whether statins, at doses used to lower cholesterol levels, inhibit ROCK activity in humans with atherosclerosis. Furthermore, it is not known whether lipophilic and ...

Enalapril is a recently developed angiotensin-converting enzyme inhibitor that improves cardiac function at rest in patients with congestive heart failure. This study investigated the acute effects of enalapril on the cardiovascular response to exercise, and then evaluated the long-term effects of enalapril on exercise capacity and functional status during a 12 week placebo-controlled trial in patients with heart failure. Ten patients underwent hemodynamic monitoring while at rest and ...

BACKGROUND: The endogenous nucleoside adenosine plays an important role in the regulation of vascular tone, especially during ischemia. Experimental data derived from animal models suggest that nitric oxide (NO) contributes to the vasodilator effect of adenosine. The primary purpose of this investigation was to determine whether the endothelial release of NO contributes to adenosine-induced vasodilation in humans.

METHODS AND RESULTS: Venous occlusion plethysmography was used to assess ...

BACKGROUND: Patients with peripheral artery disease (PAD) are at heightened risk of acute limb ischemia (ALI), a morbid event that may result in limb loss. We investigated the causes, sequelae, and predictors of ALI in a contemporary population with symptomatic PAD and whether protease-activated receptor 1 antagonism with vorapaxar reduced ALI overall and by type.

METHODS AND RESULTS: The Trial to Assess the Effects of Vorapaxar in Preventing Heart Attack and Stroke in Patients With ...

OBJECTIVES: The relation between endothelium-dependent vasodilator function in the brachial and coronary arteries was determined in the same subjects.

BACKGROUND: Coronary artery endothelial dysfunction precedes the development of overt atherosclerosis and is important in its pathogenesis. A noninvasive assessment of endothelial function in a peripheral conduit vessel, the brachial artery, was recently described, but the relation between brachial artery function and coronary artery ...

Endothelium-dependent vasodilation is impaired in humans with diabetes mellitus. Inactivation of endothelium-derived nitric oxide by oxygen-derived free radicals contributes to abnormal vascular reactivity in experimental models of diabetes. To determine whether this observation is relevant to humans, we tested the hypothesis that the antioxidant, vitamin C, could improve endothelium-dependent vasodilation in forearm resistance vessels of patients with non-insulin-dependent diabetes ...

Intensive antithrombotic therapy reduces major adverse cardiovascular events (MACE) and major adverse limb events (MALE) in patients with peripheral artery disease (PAD). Recent studies have suggested heterogeneity in risk and benefit in those with and without concomitant coronary artery disease (CAD) and peripheral revascularization. We evaluated the risk of MACE and MALE in patients with PAD stratified by history of concomitant CAD and prior peripheral revascularization and whether the ...

Importance: Clinical practice guidelines support home-based exercise for patients with peripheral artery disease (PAD), but no randomized trials have tested whether an exercise intervention without periodic medical center visits improves walking performance.

Objective: To determine whether a home-based exercise intervention consisting of a wearable activity monitor and telephone coaching improves walking ability over 9 months in patients with PAD.

Design, Setting, and Participants: ...

BACKGROUND: Nitric oxide (NO) attenuates the contractile response to beta-adrenergic stimulation in cultured cardiac myocytes in vitro and in myocardium in vivo. We tested the hypothesis that NO synthesized in the heart inhibits the positive inotropic response to beta-adrenergic stimulation in humans with left ventricular (LV) dysfunction.

METHODS AND RESULTS: Patients with various degrees of LV dysfunction and free from epicardial coronary artery disease were instrumented with an ...

CONTEXT: Complications of atherosclerosis cause most morbidity and mortality in patients with diabetes mellitus. Despite the frequency and severity of disease, proven medical therapy remains incompletely understood and underused.

OBJECTIVE: To review the epidemiology, pathophysiology, and medical and invasive treatment of atherosclerosis in patients with diabetes mellitus.

DATA SOURCES: Using the index terms diabetes mellitus, myocardial infarction, peripheral vascular diseases, ...

The objective of this study was to determine whether abnormal flow-induced endothelium-dependent vasodilation in the brachial artery identifies young patients with coronary artery disease (CAD). High-resolution ultrasonography was used to measure vascular reactivity in a peripheral conduit vessel, the brachial artery, in 14 young men with CAD and in 11 age-matched, healthy, male volunteers. Endothelium-dependent vasodilation was determined by measuring the change in brachial artery ...