Validation of improved vessel-specific leads (VSLs) for detecting acute myocardial ischemia.

Background: Existing criteria recommended by ACC/ESC for identifying patients with ST elevation myocardial infarction (STEMI) from the 12-lead ECG perform with high specificity (SP), but low sensitivity (SE). In our previous studies, we found that the SE of ischemia detection can be markedly improved without any loss of SP by calculating, from the 12-lead ECG, ST deviation in 3 "optimal" vessel-specific leads (VSLs). Our original VSLs, based on ΔST body-surface potential maps (BSPMs), have been modified by using the more appropriate J-point BSPMs at peak ischemia (without subtraction of pre-occlusion distributions).

The relationship between anthropometric indexes of adiposity and vascular function in the FATE cohort.

Objective: Numerous indexes of adiposity have been proposed and are currently in use in clinical practice and research. However, the correlation of these indexes with measures of vascular health remain poorly defined. This study investigated which measure of adiposity is most strongly associated with endothelial function.

Microvascular function predicts cardiovascular events in primary prevention: long-term results from the Firefighters and Their Endothelium (FATE) study.

Background: Biomarkers of atherosclerosis may refine clinical decision making in individuals at risk of cardiovascular disease. The purpose of the study was to determine the prognostic significance of endothelial function and other vascular markers in apparently healthy men.

Methods And Results: The cohort consisted of 1574 men (age, 49.

Cardiometabolic effects of rosiglitazone in patients with type 2 diabetes and coronary artery bypass grafts: A randomized placebo-controlled clinical trial.

Objectives: To assess the efficacy and safety of rosiglitazone on saphenous vein graft (SVG) atherosclerosis prevention and on modification of the global cardiometabolic risk profile.

Methods And Results: This was a double-blind, randomized, placebo-controlled, multicenter trial which enrolled 193 post-CABG patients with type 2 diabetes. Atherosclerosis changes in one SVG were assessed with intravascular ultrasound at baseline and at 12 months.

Intensive multifactorial intervention for stable coronary artery disease: optimal medical therapy in the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial.

Objectives: This paper describes the medical therapy used in the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial and its effect on risk factors.

Background: Most cardiovascular clinical trials test a single intervention. The COURAGE trial tested multiple lifestyle and pharmacologic interventions (optimal medical therapy) with or without percutaneous coronary intervention in patients with stable coronary disease.

Comparison of new measures of vascular function to flow mediated dilatation as a measure of cardiovascular risk factors.

Although flow-mediated dilatation (FMD) is widely used, the ideal vascular parameter for the measurement of cardiovascular risk is not clear. Recently, it has been proposed that shear stress and blood velocity during hyperemia (VRH) may provide stronger correlations with cardiovascular risk factors than FMD. The aim of this study was to evaluate the relations of VRH and shear stress during reactive hyperemia (SSRH) to FMD and the association of these measures to cardiovascular risk factors in 1,477 men without cardiovascular disease.

Relationship between brachial artery flow-mediated dilatation, hyperemic shear stress, and the metabolic syndrome.

Metabolic syndrome (MetSyn) may predispose to cardiovascular disease (CVD) by causing vascular dysfunction. This study aimed to determine the association of MetSyn with vascular function, as assessed by brachial artery flow-mediated dilatation (FMD) and hyperemic shear stress (HSS). A total of 1,417 male firefighters without established diabetes and CVD were classified for MetSyn, according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP) definition.

Optimal medical therapy with or without PCI for stable coronary disease.

Background: In patients with stable coronary artery disease, it remains unclear whether an initial management strategy of percutaneous coronary intervention (PCI) with intensive pharmacologic therapy and lifestyle intervention (optimal medical therapy) is superior to optimal medical therapy alone in reducing the risk of cardiovascular events.

Methods: We conducted a randomized trial involving 2287 patients who had objective evidence of myocardial ischemia and significant coronary artery disease at 50 U.S.

Effects of the antioxidant succinobucol (AGI-1067) on human atherosclerosis in a randomized clinical trial.

Background: The antioxidant AGI-1067 was shown to reduce experimental atherosclerosis. The present study originally intended to study restenosis as a primary endpoint but was subsequently modified to primarily investigate the effects of AGI-1067 on coronary atherosclerosis.

Methods And Results: This placebo-controlled randomized trial assessed the effects of AGI-1067 280 mg qd started before percutaneous coronary intervention (PCI) and administered for 12 months after PCI on atherosclerosis progression as assessed by coronary intravascular ultrasound (IVUS).

Folic acid improves endothelial dysfunction in type 2 diabetes--an effect independent of homocysteine-lowering.

Diabetes is associated with endothelial dysfunction, which in part may be related to uncoupling of the endothelial nitric oxide (NO) synthase enzyme, thus reducing the availability of NO. As folates may potentially reverse the uncoupling of NO synthase, we wanted to determine whether folic acid supplementation could modulate endothelial function and markers of inflammation in patients with type 2 diabetes without vascular disease. Nineteen patients with type 2 diabetes were treated with folic acid (10mg/day for 2 weeks) versus placebo in a randomized, placebo-controlled, cross-over study with an 8-week washout period between treatments.

The effect of iron status on vascular health.

The effect of increased iron stores on the progression of atherosclerosis and endothelial health remains inconclusive. This study was designed to evaluate the relationship between hemochromatosis genotypes, serum ferritin levels and presymptomatic vascular abnormalities in a cohort of healthy subjects. Carotid intima-media thickness (CIMT) and brachial flow-mediated vasodilation (FMD) were assessed by high-resolution ultrasound in 907 male (47 +/- 10 years) participants enrolled in the Firefighters and their Endothelium (FATE) study.

Improved prediction of early-onset coronary artery disease using APOE epsilon4, BChE-K, PPARgamma2 Pro12 and ENOS T-786C in a polygenic model.

Objectives: Coronary artery disease (CAD) is often polygenic due to multiple mutations that contribute small effects to susceptibility. Since most prior studies only evaluated the contribution of single candidate genes, we therefore looked at a combination of genes in predicting early-onset CAD [apolipoprotein E (APOE) epsilon4, butyrylcholinesterase (BChE) K, peroxisome proliferator-activated receptor gamma2 (PPARgamma2) Pro12Ala and endothelial nitric oxide synthase (ENOS) T-786C].

Design And Methods: We examined the frequencies, individually and in combination, of all four alleles among patients with early-onset CAD (n = 150; <50 years), late-onset CAD (n = 150; >65 years) and healthy controls (n = 150, age range 47-93 years).

Intensity of lipid lowering with statins and brachial artery vascular endothelium reactivity after acute coronary syndromes (from the BRAVER trial).

The time course and differential effects of statin regimens on endothelial function after acute coronary syndromes (ACSs) are unknown and could contribute to the superiority of a more intense strategy. A subset of subjects who were enrolled in the PROVE IT-TIMI 22 trial (n = 50) underwent evaluation of vascular reactivity by high-resolution brachial ultrasound. Endothelium-dependent flow-mediated dilation (FMD) and endothelium-independent sublingual nitroglycerin-mediated dilation (NMD) were measured at baseline and at 48 hours, 1 month, and 4 months after the initiation of 40 mg of pravastatin (n = 26) or 80 mg of atorvastatin (n = 24).

The relationship between soluble CD40 ligand levels and Framingham coronary heart disease risk score in healthy volunteers.

Elevated soluble CD40 ligand (sCD40L) levels are associated with an increased risk of cardiovascular events in patients with acute coronary syndromes and in middle-aged healthy women. However, the relationship between sCD40L and global risk assessment remains unclear. The present study was designed to examine the relationship between sCD40L and Framingham Coronary Heart Disease Risk Scores (FCRS) in healthy middle-aged men.

Effects of the acyl coenzyme A:cholesterol acyltransferase inhibitor avasimibe on human atherosclerotic lesions.

Background: Inhibition of the acyl coenzyme A:cholesterol acyltransferase (ACAT) enzyme may prevent excess accumulation of cholesteryl esters in macrophages. The ACAT inhibitor avasimibe was shown to reduce experimental atherosclerosis. This study was designed to investigate the effects of avasimibe on human coronary atherosclerosis.

Cross-sectional evaluation of brachial artery flow-mediated vasodilation and C-reactive protein in healthy individuals.

Aims: The present study was designed to (a) examine the interrelationship between endothelial function and CRP in healthy individuals and (b) evaluate the relationship of each biomarker towards global Framingham risk scores.

Methods And Results: Brachial artery flow-mediated vasodilatation (FMD), CRP, and traditional cardiovascular risk factors were measured in the Firefighters and Their Endothelium (FATE) study, which recruited 1154 male participants (mean age 47.4+/-9.

The Canadian study of the sirolimus-eluting stent in the treatment of patients with long de novo lesions in small native coronary arteries (C-SIRIUS).

Objectives: We assessed the safety and effectiveness of the sirolimus-eluting stent (SES) in treating single de novo long lesions in small native coronary arteries compared to an identical bare metal stent (BMS).

Background: The SES was previously demonstrated to reduce restenosis significantly. However, patients with long lesions in small vessels have not been well studied and may define a group at very high risk.

Quantitative assessment of myocardial ischemia by electrocardiographic and scintigraphic imaging.

We calculated distributions of epicardial potentials from body-surface electrocardiograms (ECGs) recorded during controlled myocardial ischemia and compared them with scintigraphic estimates of ischemia's extent/severity. The study population consisted of patients suffering from single-vessel coronary artery disease, referred for elective percutaneous transluminal coronary angioplasty of either the left anterior descending (n=7), the right coronary (n=9), or the left circumflex (n=2) artery. After the target vessel had been dilated, a 1960s "study" inflation was performed with a non-perfusion-type balloon catheter; at its commencement, technetium-99m sestamibi was injected via a femoral-vein catheter, and ECGs were recorded throughout the inflation from 120 leads.

Effect of cyclooxygenase-2 inhibition with rofecoxib on endothelial dysfunction and inflammatory markers in patients with coronary artery disease.

Objectives: The aim of this study was to determine whether selective cyclooxygenase-2 (COX-2) inhibition with rofecoxib can modulate endothelial dysfunction and levels of circulating inflammatory markers in patients with established coronary artery disease (CAD).

Background: Expression of COX-2 is upregulated in atherosclerosis. Thus, it has been hypothesized that COX-2 may contribute to atherogenesis by producing eicosanoids, which mediate vascular inflammation and endothelial dysfunction.

Relation between butyrylcholinesterase K variant, paraoxonase 1 (PON1) Q and R and apolipoprotein E epsilon 4 genes in early-onset coronary artery disease.

Objectives: The common K variant of butyrylcholinesterase (BChE-K), an enzyme which metabolizes acetylcholine and organophosphates, has been associated with Alzheimer's disease, especially in the presence of the apolipoprotein E epsilon 4 allele (APOE-epsilon 4). Although APOE-epsilon 4 has been associated with the development of coronary artery disease (CAD), an association between the BChE-K variant and CAD has not been explored. Paraoxonase 1 (PON1), located within HDL, is an enzyme which also metabolizes organophosphates and may be antiatherogenic.