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Background- Hypoxia-inducible factor-1[alpha] (HIF-1[alpha]) is a transcriptional regulatory factor that orchestrates cellular responses to hypoxia. It increases collateral vessel growth and blood flow in models of hind-limb ischemia. This study tested whether intramuscular administration of Ad2/HIF-1[alpha]/VP16, an engineered recombinant type 2 adenovirus vector encoding constitutively active HIF-1[alpha], improves walking time in patients with peripheral artery disease and intermittent claudication. Methods and Results- Two hundred eighty-nine patients with claudication were randomized in a double-blind manner to 1 of 3 doses of Ad2/HIF-1[alpha]/VP16 (2x10(9), 2x10(10), or 2x10(11) viral particles) or placebo, administered by 20 intramuscular injections to each leg. Graded treadmill tests were performed at baseline and then 3, 6, and 12 months after treatment. The primary end point was the change in peak walking time from baseline to 6 months. The secondary end point was change in claudication onset time, and tertiary end points included changes in ankle-brachial index and quality-of-life assessments. Median peak walking time increased by 0.82 minutes (interquartile range, -0.05-1.93 minutes) in the placebo group and by 0.82 minutes (interquartile range, -0.07-2.12 minutes), 0.28 minutes (interquartile range, -0.37-1.70 minutes), and 0.78 minutes (interquartile range, -0.02-2.10 minutes) in the HIF-1[alpha] 2x10(9), 2x10(10), and 2x10(11) viral particle groups, respectively (P=NS between placebo and each HIF-1[alpha] treatment group). There were no significant differences in claudication onset time, ankle-brachial index, or quality-of-life measurements between the placebo and each HIF-1[alpha] group. Conclusions- Gene therapy with intramuscular administration of Ad2/HIF-1[alpha]/VP16 is not an effective treatment for patients with intermittent claudication. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00117650. [ABSTRACT FROM AUTHOR]

Background: Smoking has a well-documented detrimental effect on risk for myocardial infarction and stroke, but less information is available regarding peripheral artery disease (PAD), particularly among women.Objective: To prospectively assess the association of current smoking status, cumulative smoking exposure, and smoking cessation with incident symptomatic PAD in women.Design: Prospective cohort study.Setting: U.S. female health care professionals in the Women's Health Study.Participants: 39,825 women with no cardiovascular disease who were prospectively followed for a median of 12.7 years.Measurements: Incidence of symptomatic PAD. Cox proportional hazards models were used to compare PAD risk across smoking categories.Results: 178 confirmed PAD events occurred. Across the 4 smoking categories (never, former, <15 cigarettes/d, and ≥15 cigarettes/d), age-adjusted incidence rates were 0.12, 0.34, 0.95, and 1.63 per 1000 person-years of follow-up, respectively. Multivariate adjustment had little effect on this relationship (adjusted hazard ratios [HRs], 3.14 [95% CI, 2.01 to 4.90], 8.93 [CI, 5.02 to 15.89], and 16.95 [CI, 10.77 to 26.67], respectively, vs. women who never smoked). Additional adjustment for high-sensitivity C-reactive protein and soluble intercellular adhesion molecule-1 levels among women with available blood samples (28,314 participants, 117 events) attenuated risk estimates (HR, 5.58 [CI, 2.61 to 11.93] for smoking <15 cigarettes/d and 9.52 [CI, 5.17 to 17.53] for smoking ≥15 cigarettes/d). Lifetime exposure showed a strong dose-response relationship; fully adjusted HRs for smoking abstinence of fewer than 10, 10 to 29, and 30 or more pack-years were 2.52 (CI, 1.49 to 4.25), 6.75 (CI, 4.33 to 10.52), and 11.09 (CI, 6.94 to 17.72), respectively. Compared with current smokers, the adjusted HRs for fewer than 10 years, 10 to 20 years, more than 20 years, or lifelong abstinence were 0.39 (CI, 0.24 to 0.66), 0.28 (CI, 0.17 to 0.46), 0.16 (CI, 0.10 to 0.26), and 0.08 (CI, 0.05 to 0.12), respectively.Limitation: The use of symptomatic PAD as the a priori primary end point excludes asymptomatic disease.Conclusion: Among initially healthy women, smoking is a potent risk factor for symptomatic PAD and was associated with subclinical inflammation. Smoking cessation substantially reduces risk for PAD, but an increased occurrence of PAD persists even among former smokers who maintain abstinence.Primary Funding Source: The National Heart, Lung, and Blood Institute and National Cancer Institute. [ABSTRACT FROM AUTHOR]

The purpose of this study is to primarily evaluate the lumen area and secondarily evaluate wall area measurements of in vivo lower extremity peripheral vein bypass grafts patients using high spatial resolution, limited field of view, cardiac gated, black blood inner volume three-dimensional fast spin echo MRI. Fifteen LE-PVBG patients prospectively underwent ultrasound followed by T1-weighted and T2-weighted magnetic resonance (MR) imaging. Lumen and vessel wall areas were measured by direct planimetry. For graft lumen areas, T1- and T2-weighted measurements were compared with ultrasound. For vessel wall areas, differences between T1- and T2-weighted measurements were evaluated. There was no significant difference between ultrasound and MR lumen measurements, reflecting minimal MR blood suppression artifact. Graft wall area measured from T1-weighted images was significantly larger than that measured from T2-weighted images (P < 0.001). The mean of the ratio of T1- versus T2-weighted vessel wall areas was 1.59 (95% CI: 1.48-1.69). The larger wall area measured on T1-weighted images was due to a significantly larger outer vessel wall boundary. Very high spatial resolution LE-PVBG vessel wall MR imaging can be performed in vivo, enabling accurate measurements of lumen and vessel wall areas and discerning differences in those measures between different tissue contrast weightings. Vessel wall area differences suggest that LE-PVBG vessel wall tissues produce distinct signal characteristics under T1 and T2 MR contrast weightings. [ABSTRACT FROM AUTHOR]

Objective: To demonstrate lower extremity peripheral vein bypass graft wall thickness changes over time in a patient using very high spatial resolution cardiac gated, black blood inner volume three-dimensional (3D) fast spin echo (FSE) magnetic resonance imaging (MRI).Case Report: A 52-year-old diabetic man with a history of hyperlipidemia underwent uncomplicated bypass grafting for an asymptomatic 5.2 cm popliteal artery aneurysm using reversed great saphenous vein. A segment of the bypass graft was studied at 1 and 6 months after surgery with cardiac gated inner volume 3D-FSE imaging with non-interpolated 0.195 mm(3) voxel volumes (0.3125 x 0.3125 x 2 mm). T1- and T2-weighted images were acquired in 10 min per contrast weighting. Graft imaging at one month after implantation illustrates expansion of the outer wall of the graft that partially resolves 5 months later.Conclusion: In this patient, expansion of the lower extremity peripheral bypass graft wall can be characterized in clinical scan times with a 3D-FSE MRI protocol using highly selective inner volume excitation followed by non-selective refocusing pulses. The resulting 3D images can potentially be used to study the biology of the vessel wall. [ABSTRACT FROM AUTHOR]

BACKGROUND: There has been increasing recognition of the detrimental effect of peripheral arterial disease (PAD) on the health of Americans, and yet there is no common national program of public PAD education designed to diminish this effect. FORMAT: To heighten awareness of this problem, a 2-day PAD Public Education Strategy Meeting was recently attended by representatives of 17 professional societies and public health associations whose missions support the prevention, diagnosis, treatment, and rehabilitation of vascular diseases. This Public Education Strategy Meeting was intended to provide the rationale and structure to create a national PAD public awareness campaign to diminish the health effect of PAD and to improve cardiovascular outcomes in the United States. This document (1) provides the rationale for creation of a national PAD public education program; (2) reviews the development and success of national hypertension, hypercholesterolemia, and Women's Heart Health public education programs as models of educational efficacy; (3) elucidates how the work of many vascular professionals has led to a national consensus for creation of a national PAD public educational program; (4) provides an overview of the National Heart, Lung, and Blood Institute PAD education meeting; and (5) outlines the 'next steps' required to accomplish these goals. OUTCOME: This meeting achieved consensus that we share responsibility for developing accurate, unified messages to promote PAD awareness and improved care. Participants agreed that the creation of such messages should be linked to plans to disseminate them to all Americans at risk. A consensus was reached that such messages, when commonly created and offered to the public, are most likely to achieve the rewards in better health that all Americans deserve. The Vascular Disease Foundation, a not-for-profit foundation whose mission includes public education about the prevention, diagnosis, treatment, and rehabilitation of PAD, will devote its resources to guide a new coalition in this process and to create a national PAD awareness campaign. During 2003 and 2004, the coalition will create the organizational underpinnings and time line for what will undoubtedly be a multiyear effort. CONCLUSION: Participants of the Public Education Strategy Meeting agreed to create a broad coalition to develop a National PAD Public Awareness Program, with the objectives to develop and disseminate public education messages on PAD. A successful national PAD education program will contribute to creation of a broader mandate to improve global cardiovascular health in the United States. [ABSTRACT FROM AUTHOR]

1 To determine the distribution of flow, the regional haemodynamic response to 100 mg of captopril was determined in 36 patients with refractory cardiac heart failure. Measurements included forearm blood flow by venous occlusion plethysmography (eight patients), splanchnic blood flow by indocyanine green clearance (10 patients), and coronary blood flow by thermodilution (12 patients). 2 Cardiac index significantly rose in one hour (1.9 +/- 0.1 to 2.2 +/- 0.1 1/m/m2, p less than 0.01) while forearm blood flow rose slightly (2.9 +/- 0.8 to 3.2 +/- 0.3 ml/100 ml/min). Renal blood flow rose significantly by 30% (344 +/- 48 to 533 +/- 82 ml/min, p less than 0.02). Despite a fall in rate pressure product (8.8 +/- 0.7 to 7.1 +/- 0.5 mm Hg bt x 10(3), p less than 0.02), coronary blood flow did not significantly change (160 +/- 20 to 133 +/- 12 ml/min), indicating an improved supply-demand relationship. 3 External myocardial efficiency improved (19 +/- 3 to 26 +/- 6%, p less than 0.05). Coronary blood flow is unaffected and converting-enzyme inhibitor improves myocardial efficiency. This strategic reduction in vascular impedence distinguishes converting- enzyme inhibitors as a unique class of vasodilators in the treatment of coronary heart failure. [ABSTRACT FROM AUTHOR]

Background: Dual antiplatelet therapy with clopidogrel plus low-dose aspirin has not been studied in a broad population of patients at high risk for atherothrombotic events.Methods: We randomly assigned 15,603 patients with either clinically evident cardiovascular disease or multiple risk factors to receive clopidogrel (75 mg per day) plus low-dose aspirin (75 to 162 mg per day) or placebo plus low-dose aspirin and followed them for a median of 28 months. The primary efficacy end point was a composite of myocardial infarction, stroke, or death from cardiovascular causes.Results: The rate of the primary efficacy end point was 6.8 percent with clopidogrel plus aspirin and 7.3 percent with placebo plus aspirin (relative risk, 0.93; 95 percent confidence interval, 0.83 to 1.05; P=0.22). The respective rate of the principal secondary efficacy end point, which included hospitalizations for ischemic events, was 16.7 percent and 17.9 percent (relative risk, 0.92; 95 percent confidence interval, 0.86 to 0.995; P=0.04), and the rate of severe bleeding was 1.7 percent and 1.3 percent (relative risk, 1.25; 95 percent confidence interval, 0.97 to 1.61 percent; P=0.09). The rate of the primary end point among patients with multiple risk factors was 6.6 percent with clopidogrel and 5.5 percent with placebo (relative risk, 1.2; 95 percent confidence interval, 0.91 to 1.59; P=0.20) and the rate of death from cardiovascular causes also was higher with clopidogrel (3.9 percent vs. 2.2 percent, P=0.01). In the subgroup with clinically evident atherothrombosis, the rate was 6.9 percent with clopidogrel and 7.9 percent with placebo (relative risk, 0.88; 95 percent confidence interval, 0.77 to 0.998; P=0.046).Conclusions: In this trial, there was a suggestion of benefit with clopidogrel treatment in patients with symptomatic atherothrombosis and a suggestion of harm in patients with multiple risk factors. Overall, clopidogrel plus aspirin was not significantly more effective than aspirin alone in reducing the rate of myocardial infarction, stroke, or death from cardiovascular causes. (ClinicalTrials.gov number, NCT00050817.). [ABSTRACT FROM AUTHOR]

Endothelial function is thought to be an important factor in the pathogenesis of atherosclerosis, hypertension and heart failure. In the 1990s, high-frequency ultrasonographic imaging of the brachial artery to assess endothelium-dependent flow-mediated vasodilation (FMD) was developed. The technique provokes the release of nitric oxide, resulting in vasodilation that can be quantitated as an index of vasomotor function. The noninvasive nature of the technique allows repeated measurements over time to study the effectiveness of various interventions that may affect vascular health. However, despite its widespread use, there are technical and interpretive limitations of this technique. State-of-the-art information is presented and insights are provided into the strengths and limitations of high-resolution ultrasonography of the brachial artery to evaluate vasomotor function, with guidelines for its research application in the study of endothelial physiology. [ABSTRACT FROM AUTHOR]

Objectives: Smoking is an established risk factor in many pathologies of the cardiovascular system. The Best Endovascular versus Best Surgical Therapy in Patients with Critical Limb Ischemia (BEST-CLI) trial affords an in-depth evaluation into the effect of smoking on patients with chronic limb threatening ischemia (CLTI). BEST-CLI's prospective, randomized design evaluated outcomes in patients suitable for both open or endovascular intervention and randomized patients between endovascular intervention (ENDO) versus open surgical bypass (OPEN). The outcomes are reported stratified by smoking status., Methods: In the BEST-CLI trial, patients were stratified by current smokers (CS) and non-smokers (NS), which included both previous smokers or never smokers. Endpoints at 4 years include the primary trial outcomes (major adverse limb events [MALE] or all-cause death), as well as above ankle amputation, all cause death, major or minor reintervention, major adverse cardiac events (MACE), MALE, and MALE or peri-operative death (MALE-POD). Multivariable Cox regression models were created with NS serving as the reference group., Results: Patients received bypass using single segment saphenous vein (SSGSV) (n=621), bypass using alternative conduits (n=236) or endovascular procedures (n=923). There were 641 current smokers and 1,137 nonsmokers. In the combined cohort of patients receiving ENDO or OPEN, CS status was associated with a higher rate of MALE [HR 1.27 (1.05,1.55), p=0.02] but a lower rate of all-cause death [HR 0.80 (0.66,0.97), p=0.02] when compared to NS. In the OPEN group, CS had a lower rate of all-cause death [HR 0.74 (0.56,0.98), p=0.04] than NS and no significant difference in MALE [HR 1.18 (0.85,1.63), p=0.34]. In the ENDO group, CS had a higher rate of above ankle amputation [HR 1.51 (1.04,2.19), p=0.03] and MALE [HR 1.33 (1.04,1.69), p=0.02]. Additionally, on subset analysis of the entire cohort it was found that when comparing prior smokers to never smokers there was a 24% increase in reintervention (p=0.05) and when comparing current smokers to never smokers there was a 27% increase in reintervention (p=0.04)., Conclusion: Current smokers had worse limb outcomes in the BEST-CLI trial. Current smokers undergoing endovascular revascularization had higher rates of MALE and above ankle amputations following adjustment. Current smoking did not impact MALE in patients with CLTI undergoing open surgical bypass., (Copyright © 2025. Published by Elsevier Inc.)