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Tirasemtiv (CK-2017357), a novel small-molecule activator of the fast skeletal muscle troponin complex, slows the rate of calcium release from troponin, thus sensitizing fast skeletal muscle fibers to calcium. In preclinical studies, tirasemtiv increased muscle force and delayed the onset and reduced the extent of muscle fatigue during hypoxia in vitro and muscle ischemia in situ. This study evaluated the effect of single doses of tirasemtiv on measures of skeletal muscle function and fatigability in patients with stable calf claudication due to peripheral artery disease (PAD). Sixty-one patients with an ankle–brachial index ≤0.90 in the leg with claudication received single double-blind doses of tirasemtiv 375 mg and 750 mg and matching placebo in random order about 1 week apart. After 33 patients were treated, the 750 mg dose was decreased to 500 mg due to adverse events and these dose groups were combined for analysis. On each study day, bilateral heel-raise testing was performed before and at 3 and 6 hours after dosing; a 6-minute walk test was performed at 4 hours after dosing. Claudicating calf muscle performance was increased at the highest dose and plasma concentration of tirasemtiv; however, the 6-minute walk distance decreased with both the dose and plasma concentration of tirasemtiv, possibly due to dose-related adverse events, particularly dizziness, that could impede walking ability. In conclusion, the mechanism of fast skeletal muscle troponin activation improved muscle function but not 6-minute walking distance in patients with claudication due to PAD. ClinicalTrials.gov Identifier: NCT01131013 [ABSTRACT FROM AUTHOR]

Detection of peripheral artery disease (PAD) typically entails collection of medical history, physical examination, and noninvasive imaging, but whether a risk factor-based model has clinical utility in population screening is unclear. Our objective was to derive and validate a new score for estimating PAD probability in individuals or populations. PAD presence was determined by a history of previous or current intermittent claudication associated with an ankle–brachial index (ABI) of < 0.9 or previous lower extremity arterial intervention. Multivariable stepwise logistic regression identified cross-sectional correlates of PAD from demographic, clinical, and laboratory variables. Analyses were derived from 18,049 US REACH (REduction of Atherothrombosis for Continued Health) Registry outpatients with a complete baseline risk factor profile (enrolled from December 2003 to June 2004). Model performance was assessed internally using 10-fold cross validation, and effect estimates were used to generate the score. The model was externally validated using the Framingham Offspring Study. Age, sex, smoking, diabetes mellitus, body mass index, hypertension stage, and history of heart failure, coronary artery disease, and cerebrovascular disease were predictive of PAD prevalence. The model had reasonable discrimination on derivation and internal validation (c-statistic = 0.61 and 0.60, respectively) and external validation (c-statistic = 0.63 [ABI < 0.9] or 0.64 [clinical PAD]). The model-estimated PAD prevalence varied more than threefold from lowest to highest decile (range, 4.5–16.7) and corresponded closely with actual PAD prevalence in each population. In conclusion, this new tool uses clinical variables to estimate PAD prevalence. While predictive power may be limited, it may improve PAD detection in vulnerable, at-risk populations. [ABSTRACT FROM AUTHOR]

The article presents the nature and scope of the clinical performance measures for adults with peripheral artery disease(PAD) which was developed by the Peripheral Artery Disease Performance Measures Writing Committee in the U.S. It says that the performance measures deal with lower extremity and aortic disease, as covered by the ACC/AHA 2005 guidelines for the patients with PAD. Mandatory sequential steps in the development of performance systems, PAD guidelines, and outcome measures are cited.

Peripheral arterial disease (PAD) is common in patients with severe coronary artery disease (CAD) and is considered a relative contraindication to external enhanced counterpulsation (EECP), but there are no data that define the efficacy and safety of EECP in patients with PAD. The International EECP Patient Registry (IEPR) was used to compare initial posttherapy and 2-year follow-up clinical outcomes and adverse event rates in patients with and without PAD. From January 2002 to October 2004, 2126 patients were enrolled in the IEPR, of whom 493 (23%) had a history of PAD. Immediately following EECP, the reduction in angina (≥ 1 Canadian Cardiovascular Society class) was similar in patients with and without PAD (76.6% vs 79.0%, p = 0.27) as was improvement in the Duke Activity Score Index (DASI) score (+4.7% vs +6.1%, p < 0.001). Both angina reduction and DASI score improvement were sustained at 2 years. PAD patients discontinued EECP more frequently (12.0% vs 8.5%, p < 0.05), but lower extremity ulceration did not occur more frequently in patients with PAD (3.7% vs 2.7%, p = 0.26). Rates of death (17.1% vs 8.6%, p < 0.001) and myocardial infarction (9.5% vs 5.0%, p < 0.001) were, as expected, higher in patients with PAD compared to patients without PAD at 2 years. In conclusion, while PAD patients constitute a high-risk cohort with known higher adverse event rates, EECP led to similar short- and longterm improvements in angina and quality of life for individuals with PAD compared to those without PAD. [ABSTRACT FROM AUTHOR]

This study tested the hypothesis that patients with PAD have impaired health-related quality of life (HRQoL) to a degree similar to that of patients with other types of cardiovascular disease (other-CVD), and also evaluated the clinical features of PAD associated with impaired HRQoL. This was a cross-sectional study in 350 primary care practice sites nationwide with 6,499 participants. The reference group had no clinical or hemodynamic evidence of PAD or other-CVD; the PAD group had an ankle-brachial index < 0.90 or a prior history of PAD; the other-CVD group had a clinical history of cardiac or cerebral vascular disease (but no PAD), and the combined PAD-other-CVD group included both diagnoses. Individuals were assessed using four HRQoL questionnaires including the Walking Impairment Questionnaire (WIQ), Medical Outcomes Study SF-36 (SF-36), Cantril Ladder of Life and the PAD Quality of Life questionnaire. PAD patients had lower WIQ distance scores than the other-CVD group. Both the PAD and other-CVD groups had significantly lower SF-36 Physical Function scores compared with the reference group. The WIQ revealed that PAD patients were more limited by calf pain, whereas other-CVD patients were more limited by chest pain, shortness of breath and palpitations. In conclusion, in this nationwide study, one of the first to directly compare the HRQoL burden of CVD with that of PAD, the evaluation of PAD in office practice revealed a HRQoL burden as great in magnitude as in patients with other forms of CVD. [ABSTRACT FROM AUTHOR]

There is mounting evidence to suggest that psychosocial factors, including anger proneness, depression and social isolation, are risk factors for cardiovascular disease. Nevertheless, evidence relating these factors to peripheral arterial disease (PAD) and intermittent claudication remains sparse. Using data from the Atherosclerosis Risk in Communities Study, we analyzed the relationship of psychosocial variables (Spielberger anger score, depression score from the Maastricht questionnaire, and a perceived social support scale) at study visit 2 with incident PAD (ankle-brachial index ≤0.9; a hospital discharge diagnosis of PAD, leg amputation, or leg revascularization procedures; or intermittent claudication). In 12 965 middle-aged adults with no prior history of PAD, 854 developed PAD over a mean follow-up time of 9.7 years, yielding an incidence rate of 6.8 per 1000 person years. A modest, monotonic dose–response, positive association between anger proneness and incident PAD was observed in a multivariable model: relative risk (RR) = 1.15 (95% confidence interval (CI) 0.99–1.38) in the moderate anger group and RR = 1.38 (95% CI 1.08–1.76) in the high anger group, compared with the low anger group. When compared with a low level of depressive symptoms, moderate and high levels of depressive symptoms were also associated with greater incident PAD, with multivariable RRs of 1.20 (95% CI 0.99–1.45) and 1.44 (95% CI 1.19–1.74) respectively. There was no association of perceived level of social support with the occurrence of PAD. Anger proneness and depressive symptoms may be associated with the occurrence of PAD, as for other atherosclerotic syndromes. These findings may warrant confirmation in further studies and, if causal, could serve as a unique target for a PAD prevention trial. [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]

There has been increasing recognition of the detrimental impact 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 impact. 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 impact of PAD, and to improve cardiovascular outcomes in the USA. This paper: (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. 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 regarding 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 timeline for what will undoubtedly be a multi-year effort. In 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 the creation of a broader mandate to improve global cardiovascular health in the USA. [ABSTRACT FROM AUTHOR]

Examines the occurrence of basic fibroblast growth factor (bFGF)-related proteinuria for intermittent claudication in patients with peripheral arterial disease. Intravenous administration of bFGF; Association of limb blood flow with exercise; Ways of improving claudication symptoms.