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Gregory J. Dehmer, MD, MACC, MSCAI, FAHA, Co-Chair [∗∗][1] John U. Doherty, MD, FACC, Co-Chair [∗∗][1] Steven R. Bailey, MD, FACC, MSCAI, FAHA[††][2] Nicole M. Bhave, MD, FACC[∗∗][1] Alan S. Brown, MD, FACC, FSCAI, FAHA[††][2] Stacie L. Daugherty, MD, FACC[∗∗][1] Larry

BACKGROUND AND AIMS: Traditional glycemic markers, fasting glucose and hemoglobin A1c (HbA1c), predict incident peripheral artery disease (PAD). However, it is unknown whether nontraditional glycemic markers, fructosamine, glycated albumin, and 1,5-anhydroglucitol, are associated with PAD and whether these glycemic markers demonstrate particularly strong associations with severe PAD, critical limb ischemia (CLI). METHODS: We quantified the associations of these five glycemic markers with incident PAD (hospitalizations with PAD diagnosis or leg revascularization) in 11,634 ARIC participants using Cox regression models. Participants were categorized according to diabetes diagnosis and clinical cut-points of glycemic markers (nontraditional glycemic markers were categorized according to percentiles corresponding to the HbA1c cut-points). RESULTS: Over a median follow-up of 20.7 years, there were 392 cases of PAD (133 were CLI with tissue loss). HbA1c was more strongly associated with incident PAD than fasting glucose, with adjusted hazard ratios (HR) 6.00 (95% CI, 3.73–9.66) for diagnosed diabetes with HbA1c ≥ 7% and 3.53 (2.39–5.22) for no diagnosed diabetes with HbA1c ≥ 6.5% compared to no diagnosed diabetes with HbA1c

Background Patients with lymphedema suffer lifelong swelling and recurrent cellulitis despite use of complete decongestive therapy. Pneumatic compression devices (PCDs), including non-programmable and programmable devices that meet individual patient needs, support long term self-care in the home. Yet, to date, no direct comparison of their relative benefits has been available. Objective Patients who acquired either a non-programmable device (NP-PCD) or a dynamic pressure programmable device (P-PCD; Flexitouch®) were evaluated to compare associated clinical and health utilization outcomes pre/post-device acquisition. Methods Retrospective analysis of de-identified administrative claims from 2007 through 2013 of a large United States insurer. The study populations were defined pre hoc as distinct cancer- and non-cancer-related lymphedema cohorts. Outcome variables included rates of lymphedema-related cellulitis, manual therapy use, outpatient services, and inpatient hospitalizations. Multivariate regression analysis was performed to: (1) compare outcomes for the 12 months pre- and post-device acquisition and (2) compare these two device types for their treatment-associated benefits. Results The sample consisted of 1,013 NP-PCD and 718 P-PCD recipients. Compared with the NP-PCD group, P-PCD patients’ baseline cellulitis rate was higher, while their post-device cellulitis rate was lower. In the cancer cohort, the NP-PCD group had a 53% reduction in episodes of cellulitis (from 17.9% to 8.5%), compared to a greater 79% reduction in the P-PCD group (from 23.7% to 5.0%) (p

Low 25-hydroxyvitamin D [25(OH)D] concentrations have been associated with peripheral artery disease (PAD). Prevalence of low 25(OH)D and PAD differ between whites and blacks. However, these associations have not been studied prospectively or in a population based cohort. We tested the hypothesis that low 25(OH)D is associated with greater risk of incident PAD in white and black adults.25(OH)D was measured in serum collected at ARIC visit 2 (1990-1992). We followed 11,789 ARIC participants free of PAD at visit 2 through 2011 for incident PAD events. 25(OH)D (ng/mL) was categorized as deficient (20), insufficient (20 to30) or sufficient (≥30). PAD was defined by an ankle brachial index (ABI) of0.9 at ARIC visits 3 or 4 or a hospital diagnosis with an ICD-9 code indicating PAD during follow-up. Analysis used multivariable-adjusted Cox proportional hazards regressions.Over a mean follow-up of 17.1 years, 1250 incident PAD events were identified. 22% of whites and 61% of blacks were 25(OH)D deficient. After adjustment for demographic characteristics, the hazard ratio (95% CI) of PAD in participants with deficient versus sufficient 25(OH)D was 1.49 (1.26, 1.76). Inclusion of BMI, physical activity, and smoking status attenuated the association [1.25 (1.06, 1.48)]. The association between 25(OH)D and PAD was qualitatively stronger in blacks (p for interaction = 0.20).Deficient 25(OH)D was associated with increased risk of PAD in black and white participants. Whether treatment of low vitamin D through supplementation or modest sunlight exposure prevents PAD is unknown.

Nutritional and body weight recommendations for cardiovascular diseases are well established, yet there are no equivalent guidelines for peripheral arterial disease (PAD). This cross-sectional study measured the prevalence of cardiovascular-related nutritional and body composition risk factors in sixty PAD patients and their association with PAD severity. A diet that exceeds daily recommended intake of fat and that falls short of recommended intakes of fiber, folate, and vitamin D was associated with increased leg pain and walking difficulty. Increased body fat and waist circumference were associated with diminished walking ability and poorer psychosocial quality of life. Future prospective investigations are merited to inform both PAD clinical care and disease management guidelines.

Background Group-randomized trials of communities often rely on the convenience of pre-existing administrative divisions, such as school district boundaries or census entities, to divide the study area into intervention and control sites. However, these boundaries may include substantial heterogeneity between regions, introducing unmeasured confounding variables. This challenge can be addressed by the creation of exchangeable intervention and control territories that are equally weighted by pertinent socio-demographic characteristics. The present study used territory design software as a novel approach to partitioning study areas for The Minnesota Heart Health Program’s “Ask about Aspirin” Initiative. Methods Twenty-four territories were created to be similar in terms of age, sex, and educational attainment, as factors known to modify aspirin use. To promote ease of intervention administration, the shape and spread of the territories were controlled. Means of the variables used in balancing the territories were assessed as well as other factors that were not used in the balancing process. Results The analysis demonstrated that demographic characteristics did not differ significantly between the intervention and control territories created by the territory design software. Conclusions The creation of exchangeable territories diminishes geographically based impact on outcomes following community interventions in group-randomized trials. The method used to identify comparable geographical units may be applied to a wide range of population-based health intervention trials. Trial registration National Institutes of Health (Clinical Trials.gov), Identifier: NCT02607917. Registered on 16 November 2015.

BackgroundLiterature on health promotion evaluation and public understanding of health suggests the importance of investigating behaviour over time in conjunction with information environment trends as a way of understanding programme impact. We analysed population response to online promotion of an educational tool built by the Ask About Aspirin campaign in the USA to inform people about aspirin as a preventive aid.MethodsWe collected 156 weeks of time series data on audience behaviour, namely use of a self-assessment tool. We then used the Autoregressive Integrated Moving Average (ARIMA) modelling to predict that outcome as a function of paid search engine advertising, paid social media promotion and general search interest in aspirin.ResultsThrough ARIMA modelling of tool engagement data adjusted for outcome series autocorrelation, we found a significant effect of online promotional effort on audience behaviour. Total paid search advertising positively predicted weekly total of individuals who started using the self-assessment tool, coefficient=0.023, t=3.28, p=0.001. This effect did not appear to be an artefact of broader secular trends, as Google search data on the topic of aspirin use did not add explanatory power in the final model nor did controlling for general search interest eliminate the significant coefficient for paid search promotion.ConclusionResults hold implications both for educational tool development and for understanding health promotion campaign effects. We witnessed substantial but ephemeral effects on tool use as a function of paid search efforts, suggesting prioritisation of efforts to affect search engine results as a dissemination tactic.

Background: Health status outcomes, including symptoms, functional status, and quality of life, are critically important outcomes from patients’ perspectives. The PORTRAIT study (Patient-Centered Outcomes Related to Treatment Practices in Peripheral Arterial Disease: Investigating Trajectories) was designed to prospectively define health status outcomes and examine associations between patients’ characteristics and care to these outcomes among those presenting with new-onset or worsened claudication. Methods and Results: PORTRAIT screened 3637 patients with an abnormal ankle-brachial index and new, or worsened, claudication symptoms from 16 peripheral arterial disease (PAD) specialty clinics in the United States, the Netherlands, and Australia between June 2, 2011, and December 3, 2015. Of the 1608 eligible patients, 1275 (79%) were enrolled. Before treatment, patients were interviewed to obtain their demographics, PAD symptoms and health status, psychosocial characteristics, preferences for shared decision-making, socioeconomic, and cardiovascular risk factors. Patients’ medical history, comorbidities, and PAD diagnostic information were abstracted from patients’ medical records. Serial information about patients’ health status, psychosocial, and lifestyle factors was collected at 3, 6, and 12 months by a core laboratory. Follow-up rates ranged from 84.2% to 91%. Clinical follow-up for PAD-related hospitalizations and major cardiovascular events is ongoing. Conclusions: PORTRAIT systematically collected serial PAD-specific health status data as a foundation for risk stratification, comparative effectiveness studies, and clinicians’ adherence to quality-based performance measures. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01419080.

Despite the paucity of evidence, it is often presumed, and is physiologically plausible, that sudden, acute elevations in blood pressure may transiently increase the risk of recurrent aortic dissection (AD) or rupture in patients with a prior AD, because a post-dissection aorta is almost invariably dilated and may thus experience greater associated wall stress as compared with a nondilated aorta. Few data are available regarding the specific types and intensities of exercise that may be both safe and beneficial for this escalating patient population. The purpose of this editorial/commentary is to further explore this conundrum for clinicians caring for and counseling AD survivors. Moderate-intensity cardiovascular activity may be cardioprotective in this patient cohort. It is likely that severe physical activity restrictions may reduce functional capacity and quality of life in post-AD patients and thus be harmful, underscoring the importance of further exploring the role of physical activity and/or structured exercise in this at-risk patient population.

Background Tobacco use is an important preventable cause of peripheral artery disease (PAD) and a major determinant of adverse clinical outcomes. Objectives This study hypothesized that tobacco use by PAD patients would be associated with higher health care utilization and associated costs. Methods We conducted a retrospective, cross-sectional study using 2011 claims data from the largest Minnesota health plan. The total cohort included individuals with 12 months of continuous enrollment and ≥1 PAD-related claim. Tobacco cessation pharmacotherapy billing codes were queried in a subgroup with pharmacy benefits. Outcomes were total costs, annual proportion of members hospitalized, and primary discharge diagnoses. Results A PAD cohort of 22,203 was identified, comprising 1,995 (9.0%) tobacco users. A subgroup of 9,027 with pharmacy benefits included 1,158 (12.8%) tobacco users. The total cohort experienced 22,220 admissions. The pharmacy benefits subgroup experienced 8,152 admissions. Within 1 year, nearly one-half the PAD tobacco users were hospitalized, 35% higher than nonusers in the total cohort (p Conclusions Tobacco use in PAD is associated with substantial increases in PAD-related hospitalizations, coronary heart disease and PAD procedures, and significantly greater costs. The results suggest that immediate provision of tobacco cessation programs may be especially cost effective.

Background Treatment for claudication that is due to aortoiliac peripheral artery disease (PAD) often relies on stent revascularization (ST). However, supervised exercise (SE) is known to provide comparable short-term (6-month) improvements in functional status and quality of life. Longer-term outcomes are not known. Objectives The goal of this study was to report the longer-term (18-month) efficacy of SE compared with ST and optimal medical care (OMC). Methods Of 111 patients with aortoiliac PAD randomly assigned to receive OMC, OMC plus SE, or OMC plus ST, 79 completed the 18-month clinical and treadmill follow-up assessment. SE consisted of 6 months of SE and an additional year of telephone-based exercise counseling. Primary clinical outcomes included objective treadmill-based walking performance and subjective quality of life. Results Peak walking time improved from baseline to 18 months for both SE (5.0 ± 5.4 min) and ST (3.2 ± 4.7 min) significantly more than for OMC (0.2 ± 2.1 min; p Conclusions Both SE and ST had better 18-month outcomes than OMC. SE and ST provided comparable durable improvement in functional status and in quality of life up to 18 months. The durability of claudication exercise interventions merits its consideration as a primary PAD claudication treatment. (Claudication: Exercise Versus Endoluminal Revascularization [CLEVER]; NCT00132743 )

The Society for Vascular Medicine was founded in 1989. During the subsequent 25 years, the Society has grown to approximately 500 members and has achieved international recognition while making important contributions to vascular disease education, clinical vascular medicine and biology research, and patient care. In celebration of the Society’s 25th anniversary, its past and current presidents reflect on the Society’s history, challenges, and achievements, and emphasize the vital role of the SVM in the discipline of vascular medicine.

The purpose of this study was to implement and evaluate quality outcomes including referral, enrollment, and completion rates of a new peripheral artery disease (PAD)-specific supervised exercise therapy (SET) program within a preexisting clinical exercise wellness program and to evaluate the clinical effectiveness and patient-centered outcomes derived from 12 weeks of PAD-specific SET. Recruited participants completed an individualized, minimally supervised, PAD-specific SET program based on the AHA-ACC guidelines. Exercise workloads (metabolic equivalents of task [METs]) were tracked and evaluated throughout the program. Short Physical Performance Battery, 6-minute walk test (6MWT) Walking Impairment Questionnaire, Short-Form 36 (SF-36), and Peripheral Artery Disease Quality of Life Questionnaire (PADQOL) were assessed before and after the program. Paired t-tests were used to examine differences between baseline and follow-up outcome variables. On average, participants (n = 46) attended 23 (standard deviation [SD] 12.9) out of the possible 36 training sessions, for a 64% attendance rate. Among participants who used treadmill walking as the primary mode of exercise (n = 40), the overall mean MET level just prior to program completion was 3.79 (SD 1.49), which represented an increase of 0.92 (34%) METs compared to baseline (P .001). Total distance on the 6MWT increased 115 (11%) feet (P = .011), which is considered a clinically meaningful improvement. Significant improvements were noted in the PADQOL: symptoms and limitations in physical functioning (P = .007). This study demonstrates that a minimally staffed PAD-specific SET program can improve functional performance in patients with claudication due to PAD and serves as a foundation to help build a clinically effective, Centers for Medicare and Medicaid reimbursed PAD-specific rehabilitation program.

Background No previous study has evaluated the impact of past US Preventive Services Task Force statements on primary prevention ( PP ) aspirin use in a primary care setting. The aim of this study was to evaluate temporal changes in PP aspirin use in a primary care population, stratifying patients by their 10‐year global cardiovascular disease risk, in response to the 2009 statement. Methods and Results This study estimated biannual aspirin use prevalence using electronic health record data from primary care clinics within the Fairview Health System (Minnesota) from 2007 to 2015. A total of 94 270 patient encounters had complete data to estimate a 10‐year cardiovascular disease risk score using the 2013 American College of Cardiology/American Heart Association global risk estimator. Patients were stratified into low‐ (PP aspirin use averaged 43%. When stratified by low, intermediate and high risk, average PP aspirin use was 41%, 63%, and 73%, respectively. Average PP aspirin use decreased after the publication of the 2009 US Preventive Services Task Force recommendation statement: from 45% to 40% in the low‐risk group; from 66% to 62% in the intermediate‐risk group; and from 76% to 73% in the high‐risk group, before and after the guideline. Conclusions Publication of the 2009 US Preventive Services Task Force recommendation was not associated with an increase in aspirin use. High risk PP patients utilized aspirin at high rates. Patients at intermediate risk were less intensively treated, and patients at low risk used aspirin at relatively high rates. These data may inform future aspirin guideline dissemination.

Aims: Cardiac troponin T (cTnT) is suggested as a predictor of amputation in patients with peripheral artery disease (PAD). However, cTnT-PAD association has not been systematically studied in a large study. This study evaluated the association of high-sensitivity cTnT (hs-cTnT) with PAD incidence and also explored whether natriuretic peptide (NT-proBNP), another representative cardiac marker, predicts PAD risk. Methods and results: Among 12 288 middle-aged adults, the associations of hs-cTnT and NT-proBNP with incident PAD (hospitalizations with PAD diagnosis or leg revascularization [cases with rest pain or tissue loss considered as critical limb ischaemia (CLI)]) were quantified with multivariable Cox regression models. The risk discrimination was assessed by c-statistic. During a follow-up over 22 years, 454 participants developed PAD (164 CLI cases). In demographically adjusted models, the highest category of hs-cTnT (≥14 vs.

Introduction: Hemoglobin A1c (HbA1c) is a risk marker for incident peripheral artery disease (PAD). However, its relationship to critical limb ischemia (CLI), the most severe form of PAD, has not been fully characterized. Also, the prognostic value of non-traditional glycemic markers, glycated albumin, fructosamine, and 1,5-anhydroglucitol (1,5-AG) for PAD/CLI risk is unknown. Hypotheses: These glycemic markers will be particularly strongly associated with incident CLI, and non-traditional markers may provide additional information on PAD risk beyond HbA1c. Methods: We quantified the associations of four glycemic markers with PAD (hospitalizations with PAD diagnosis [ICD-9: 440.2-440.4] or leg revascularization [eg, 38.18]) in 11,797 ARIC participants free of a history of PAD at baseline (1990-92) using Cox models. Within these PAD cases, CLI was defined with an ICD code of ulcer, gangrene, or leg amputation. All markers were categorized into five groups according to diagnosed diabetes status and percentiles for clinical cut-points of HbA1c as in Table. Results: Over a median follow-up of 20.7 years, there were 397 cases of PAD (137 were CLI). Compared with the non-diabetic reference group, elevated glycemic marker levels (or reduced levels for 1-5AG) significantly contributed to increased risk of PAD (Table). The glycemic contribution was particularly strong for CLI events, with hazard ratios ranging 14-18 (vs. 6-8 for PAD, p for difference Conclusions: Glycemic markers were significantly associated with PAD, particularly with its severe form, CLI, supporting the importance of glucose metabolism in the progression of PAD. Non-traditional glycemic markers provide similar (but not much additional) predictive value as HbA1c for classifying PAD risk.

Background: Cardiovascular disease (CVD) is a leading cause of death that disproportionately impacts African Americans. Aspirin (ASA) is a simple, low-cost medication that lowers the risk of a first heart attack or stroke by 12-22%. This study investigates the prevalence of primary prevention ASA use among a metropolitan, predominantly African American population. It examines the association between primary prevention ASA use and measures of health beliefs, social norms, and perceptions of CVD risk hypothesized to influence ASA use. Methods: Between April and August 2015, trained community health workers administered 10 minute, in-person surveys to a convenience sample of adults ages 45-79 years within the Minneapolis-St. Paul metro area. The survey defined demographics, CVD history, atherosclerosis risk factors and ASA use. CVD risk perceptions and ASA-related health beliefs and social norms were evaluated using a 4 point Likert scale. Logistic regression with adjustment for age and number of risk factors was used to examine the association of demographics and health beliefs with ASA use. Results: Of the 797 survey participants, 590 had no CVD history. Of these, 460 (78%) were between the ages of 50-69, the range recently defined in the 2016 United States Preventive Services Task Force (USPSTF) recommendation. Overall primary prevention ASA use was 38% and increased as the number of CVD risk factors (RF) increased, from 21% (0 RF) to 62% (≥ 3 RF). After adjusting for age and risk factors, ASA use was associated with diabetes (OR 2.6, 95% CI: 1.6-4.2) and current smoking (OR 0.4, 95% CI: 0.2-0.6). If a participant discussed ASA use with a doctor, they were much more likely to use ASA (OR 5.5, 95% CI: 3.7-8.1). Participants who believed ASA could prevent a heart attack or stroke were also more likely to use it (OR 4.6, 95% CI: 1.9-11.4). ASA use was higher among participants who perceived that their peers were using ASA (OR 3.7, 95% CI: 2.0-6.6), and among participants who believed those close to them thought they should use ASA (OR 6.6, 95% CI: 4.1-10.5). Perceived safety and ease of use were also positively associated with ASA use, (OR 9.8, 95% CI: 5.0-19.3 and OR 23.2, 95% CI: 8.2-65.5 respectively). Conclusion: Increased primary prevention aspirin use was associated with positive beliefs regarding the expectations and behaviors of participants’ social network, and about perceived effectiveness, safety and convenience of the medication. Novel interventions to increase primary prevention ASA use could focus on promoting conversations with physicians about appropriate ASA use, and normalizing ASA for at-risk individuals within communities.

Background: The aging population along with the increased use of statins, anti-platelet agents, supervised exercise (SE) and smoking cessation (SC) may be altering the epidemiology of peripheral arterial disease (PAD) and may be delaying its onset. There are no insights into how older versus younger patients differ in terms of PAD severity, risk profiles, health status and treatment. We hypothesized that in the absence of any reliable age-related differences in treatment effectiveness, that risk reduction and revascularization would be used equally across PAD age cohorts. Aim: Assess age-specific differences in baseline characteristics, PAD-specific health status, and patterns of care in patients in the PORTRAIT registry. Methods: The PORTRAIT registry prospectively collected data from 1275 patients with new or worsening PAD symptoms who were treated in the US, the Netherlands or Australia between June 2011 and October 2015. Patients were grouped by age (< 60 years, 60 to ≤75 years, and > 75 years). We compared patient characteristics at the point of seeking specialty PAD care, including severity of PAD (Rutherford classification); health status assessed by the Peripheral Artery (PAQ) and EuroQol five dimensions (EQ5D) questionnaires; and subsequent clinical care offered for PAD, including statins, anti-platelet agents, SE, and SC. The use of revascularization (surgical or endovascular) was assessed at 3 months. Continuous variables were compared using the linear trend test. Categorical variables were compared using Mantel-Haenszel trend test. Results: There were 303 patients < 60 years (mean 55.0 ± 4.3), 675 patients 60 to ≤75 years (mean 67.8 ± 3.9), and 297 patients ≥ 75 years (mean 79.9 ± 4.1). There were no differences in baseline ABI (mean 0.66 ± 0.2, p=0.44) or Rutherford classification (p=0.47). PAQ summary, quality of life, social limitation, and symptom scores as well as EQ5D scores were significantly worse in patients < 60 years (p Conclusion: These data demonstrate that younger patients are characterized by worse PAD-specific health status at the time of entry into vascular specialty care and that there are age-related disparities in the prescription of PAD risk reduction and QOL improvement therapies. These data cannot document the reasons for these differences. Future quality improvement initiatives might focus on these disparities in presentation and care to improve outcomes in PAD.

Background: Atherosclerotic peripheral artery disease affects 8% to 12% of Americans >65 years of age and is associated with a major decline in functional status, increased myocardial infarction and stroke rates, and increased risk of ischemic amputation. Current treatment strategies for claudication have limitations. PACE (Patients With Intermittent Claudication Injected With ALDH Bright Cells) is a National Heart, Lung, and Blood Institute–sponsored, randomized, double-blind, placebo-controlled, phase 2 exploratory clinical trial designed to assess the safety and efficacy of autologous bone marrow–derived aldehyde dehydrogenase bright (ALDHbr) cells in patients with peripheral artery disease and to explore associated claudication physiological mechanisms. Methods: All participants, randomized 1:1 to receive ALDHbr cells or placebo, underwent bone marrow aspiration and isolation of ALDHbr cells, followed by 10 injections into the thigh and calf of the index leg. The coprimary end points were change from baseline to 6 months in peak walking time (PWT), collateral count, peak hyperemic popliteal flow, and capillary perfusion measured by magnetic resonance imaging, as well as safety. Results: A total of 82 patients with claudication and infrainguinal peripheral artery disease were randomized at 9 sites, of whom 78 had analyzable data (57 male, 21 female patients; mean age, 66±9 years). The mean±SEM differences in the change over 6 months between study groups for PWT (0.9±0.8 minutes; 95% confidence interval [CI] −0.6 to 2.5; P =0.238), collateral count (0.9±0.6 arteries; 95% CI, −0.2 to 2.1; P=0.116), peak hyperemic popliteal flow (0.0±0.4 mL/s; 95% CI, −0.8 to 0.8; P =0.978), and capillary perfusion (−0.2±0.6%; 95% CI, −1.3 to 0.9; P=0.752) were not significant. In addition, there were no significant differences for the secondary end points, including quality-of-life measures. There were no adverse safety outcomes. Correlative relationships between magnetic resonance imaging measures and PWT were not significant. A post hoc exploratory analysis suggested that ALDHbr cell administration might be associated with an increase in the number of collateral arteries (1.5±0.7; 95% CI, 0.1–2.9; P =0.047) in participants with completely occluded femoral arteries. Conclusions: ALDHbr cell administration did not improve PWT or magnetic resonance outcomes, and the changes in PWT were not associated with the anatomic or physiological magnetic resonance imaging end points. Future peripheral artery disease cell therapy investigational trial design may be informed by new anatomic and perfusion insights. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01774097.

Administrative data have been used to identify patients with various diseases, yet no prior study has determined the utility of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM)-based codes to identify CLI patients. CLI cases ( n=126), adjudicated by a vascular specialist, were carefully defined and enrolled in a hospital registry. Controls were frequency matched to cases on age, sex and admission date in a 2:1 ratio. ICD-9-CM codes for all patients were extracted. Algorithms were developed using frequency distributions of these codes, risk factors and procedures prevalent in CLI. The sensitivity for each algorithm was calculated and applied within the hospital system to identify CLI patients not included in the registry. Sensitivity ranged from 0.29 to 0.92. An algorithm based on diagnosis and procedure codes exhibited the best overall performance (sensitivity of 0.92). Each algorithm had differing CLI identification characteristics based on patient location. Administrative data can be used to identify CLI patients within a health system. The algorithms, developed from these data, can serve as a tool to facilitate clinical care, research, quality improvement, and population surveillance.

Aspirin (ASA) is recommended for the prevention of cardiovascular disease; however, the compliance is low. Reported use may not reflect actual use. Serum thromboxane B2 (STxB2) measurement was evaluated to validate reported ASA use. Males aged 45 to 79 years and females aged 55 to 79 years completed a survey and STxB2 measurement (Thromboxane B2 EIA Kit; Cayman Chemical, Ann Arbor, Michigan). The 107 patients were grouped by use of ASA (56 ASA+ and 51 ASA−) and possible interfering medications (INT) such as nonsteroidal anti-inflammatory drugs. The STxB2 levels (ng/mL) were significantly lower in ASA users: ASA+ INT− 3.0 (0.7, 8.4), ASA+ INT+ 2.0 (0.8, 4.9), ASA− INT+ 176 (75, 390), and ASA− INT− 271 (199, 366). The INT use did not cause a significant difference in STxB2 levels. A STxB2 cut point of 25 ng/mL had high sensitivity (94.1%) and specificity (91.1%) for ASA use. The STxB2 was a reliable marker of ASA use and could be used to confirm ASA exposure in population-based health studies.

From the Department of Radiology, Division of Vascular and Interventional Radiology (S.M.), Mayo Clinic, 200 First Street SW, Rochester, MN 55905; The Mount Sinai Hospital (R.L.), New York, New York; Cardiovascular Diseases Interventional Institute at Holy Name Hospital (J.R.), Teaneck, New Jersey; Vascular Medicine Program (A.T.H.), Lillehei Heart Institute, and Cardiovascular Division, University of Minnesota Medical School, Minneapolis, Minnesota; Division of Cardiology and CPC Clinical Research (W.R.H.), University of Colorado Denver School of Medicine, Aurora, Colorado; Vascular Medicine and Intervention Department (M.R.J., K.R.), Massachusetts General Hospital, Boston, Massachusetts; John Ochsner Heart & Vascular Institute (C.R.W.), Ochsner Medical Center, New Orleans, Louisiana; UCSF Heart and Vascular Center (M.C.), San Francisco, California; Washington University in St. Louis School of Medicine (P.G.), St. Louis, Missouri; Duke University Health System (M.P.), Durham, North Carolina. Received September 24, 2012; final revision received October 19, 2012; accepted October 22, 2012. Address correspondence to S.M.; E-mail: misra.sanjay@mayo.edu

Peripheral artery disease (PAD) is one of the most common cardiovascular diseases and is associated with high short-term morbidity and mortality.1,2 It is the primary cause of lower extremity amputation throughout the world and is a powerful marker of advanced systemic atherosclerosis. Chronic critical limb ischemia (CLI) represents the most advanced clinical manifestation of PAD and is defined by the presence of ischemic rest pain, nonhealing wounds, or tissue loss (gangrene). CLI does not represent a single pathophysiologic process (ie, progressive leg arterial atherosclerosis), but is caused by multiple pathogenetic mechanisms, including native artery atherosclerosis, cardioembolic events, inflammatory arteritides (eg, thromboangiitis obliterans), hypercoagulable states, or leg bypass graft failure. Article see p 68 CLI syndromes are currently classified by the clinical stages III and IV of the Fontaine classification, and this equates to the Rutherford categories 4, 5, and 6.1,2 Although there is no consensus regarding the precise level of objective malperfusion that should be required to define CLI, the Second European Consensus Document3 defined CLI by 2 criteria: persistent recurring ischemic rest pain requiring regular adequate analgesia for >2 weeks, with an ankle systolic pressure ≤50 mm Hg, or a toe systolic pressure of ≤30 mm Hg; or ulceration or gangrene of the foot or toes, with an ankle systolic pressure of ≤50 mm Hg, or a toe systolic pressure of ≤30 mm Hg. These definitions remain in widespread use in CLI clinical research. The current incidence and prevalence of CLI, and thus the public health impact of this syndrome, is incompletely defined. Population-based study of this syndrome is hampered by the inability of field surveys to measure incident cases, use of varying CLI definitions, and due to the lack of consistent coding in administrative billing databases. Yet, it has been estimated …

Background and aims Most prior studies investigating the association of lower extremity peripheral artery disease (PAD) with physical function were small or analyzed selected populations (e.g., patients at vascular clinics or persons with reduced function), leaving particular uncertainty regarding the association in the general community. Methods Among 5262 ARIC participants (age 71–90 years during 2011–2013), we assessed the cross-sectional association of ankle-brachial index (ABI) with the Short Physical Performance Battery (SPPB) score (0–12), its individual components (chair stands, standing balance, and gait speed) (0–4 points each), and grip strength after accounting for potential confounders, including a history of coronary disease, stroke, or heart failure. Results There were 411 participants (7.8%) with low ABI ≤0.90 and 469 (8.9%) participants with borderline low ABI 0.91–1.00. Both ABI ≤0.90 and 0.91–1.00 were independently associated with poor physical function (SPPB score ≤6) compared to ABI 1.11–1.20 (adjusted odds ratio 2.10 [95% CI 1.55–2.84] and 1.86 [1.38–2.51], respectively). The patterns were largely consistent across subgroups by clinical conditions (e.g., leg pain or other cardiovascular diseases), in every SPPB component, and for grip strength. ABI >1.3 (472 participants [9.0%]), indicative of non-compressible pedal arteries, was related to lower physical function as well but did not necessarily reach significance. Conclusions In community-dwelling older adults, low and borderline low ABI suggestive of PAD were independently associated with poorer systemic physical function compared to those with normal ABI. Clinical attention to PAD as a potential contributor to poor physical function is warranted in community-dwelling older adults.

Randomized clinical trials have not shown an additional clinical benefit of renal artery stent placement over optimal medical therapy alone. However, studies of renal artery stent placement have not examined the relationship of albuminuria and treatment group outcomes. The CORAL study (Cardiovascular Outcomes in Renal Atherosclerotic Lesions) is a prospective clinical trial of 947 participants with atherosclerotic renal artery stenosis randomized to optimal medical therapy with or without renal artery stent which showed no treatment differences (3(5.8% and 35.1% event rate at mean 43-month follow-up). In a post hoc analysis, the study population was stratified by the median baseline urine albumin/creatinine ratio (n=826) and analyzed for the 5-year incidence of the primary end point (myocardial infarction, hospitalization for congestive heart failure, stroke, renal replacement therapy, progressive renal insufficiency, or cardiovascular disease– or kidney disease–related death), for each component of the primary end point, and overall survival. When baseline urine albumin/creatinine ratio was ≤ median (22.5 mg/g, n=413), renal artery stenting was associated with significantly better event-free survival from the primary composite end point (73% versus 59% at 5 years; P =0.02), cardiovascular disease–related death (93% versus 85%; P ≤ 0.01), progressive renal insufficiency (91% versus 77%; P =0.03), and overall survival (89% versus 76%; P ≤0.01), but not when baseline urine albumin/creatinine ratio was greater than median (n=413). These data suggest that low albuminuria may indicate a potentially large subgroup of those with renal artery stenosis that could experience improved event-free and overall-survival after renal artery stent placement plus optimal medical therapy compared with optimal medical therapy alone. Further research is needed to confirm these preliminary observations. Clinical Trial Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT00081731.

Background Peripheral artery disease (PAD) is important to public health as a major contributor to cardiovascular morbidity and mortality. Recent developments in magnetic resonance imaging (MRI) techniques permit improved assessment of PAD anatomy and physiology, and may serve as surrogate end points after proangiogenic therapies. Methods The PACE study is a randomized, double-blind, placebo-controlled clinical trial designed to assess the physiologic impact and potential clinical efficacy of autologous bone marrow–derived ALDH br stem cells. The primary MRI end points of the study are as follows: (1) total collateral count, (2) calf muscle plasma volume (a measure of capillary perfusion) by dynamic contrast-enhanced MRI, and (3) peak hyperemic popliteal flow by phase-contrast MRI (PC-MRI). Results The interreader and intrareader and test-retest results demonstrated good-to-excellent reproducibility (interclass correlation coefficient range 0.61-0.98) for all magnetic resonance measures. The PAD participants (n=82) had lower capillary perfusion measured by calf muscle plasma volume (3.8% vs 5.6%) and peak hyperemic popliteal flow (4.1 vs 13.5mL/s) as compared with the healthy participants (n=16), with a significant level of collateralization. Conclusions Reproducibility of the MRI primary end points in PACE was very good to excellent. The PAD participants exhibited decreased calf muscle capillary perfusion as well as arterial flow reserve when compared with healthy participants. The MRI tools used in PACE may advance PAD science by enabling accurate measurement of PAD microvascular anatomy and perfusion before and after stem cell or other PAD therapies.

Background: Current national cardiovascular disease primary prevention (PP) guidelines recommend low dose aspirin (ASA) to prevent a first heart attack or stroke in appropriate candidates. The 2009 United States Preventive Services Task Force (USPSTF) ASA primary prevention recommendation was not widely implemented, and minimal data exist to define the efficacy of this “A” level recommendation. This study was designed to evaluate the impact of this recommendation on PP ASA use in primary care clinics in a large, regional health system over a 9 year period (2007-2015) stratifying patients by their 10 year global risk for a primary ischemic event. Methods: Bi-annual, cross-sectional electronic medical record (EMR) data were collected from 2007 to 2015 to evaluate documented ASA use for all office-based encounters involving a primary care provider within the Fairview Health System (Minnesota). PP candidates were defined as individuals within the USPSTF guideline target population (men ages 45-79 and women ages 55-79 years) with no documented history of an atherosclerotic syndrome. Appropriate ASA use candidates were defined as PP individuals with no ASA use contraindications (peptic ulcer disease, gastrointestinal bleeding or use of other antithrombotic medications). Ten year cardiovascular disease (CVD) risk was calculated using the ACC/AHA 2013 global risk calculator. ASA use was evaluated bi-annually in the total PP population and a stratified subset characterized by 20% ten year risk of an ischemic event. Secondary prevention (SP) ASA use was assessed as a reference standard for ideal penetration of guideline recommended ASA use. Results: Over 270,000 unique encounters were evaluated over the 9 year study period. Of those, 88,055 were PP ASA candidates with data for risk score calculation. Appropriate PP ASA use rates did not improve throughout the study period, with an average of 43% PP ASA use compared to 77% in the SP population. When stratified by 20% ten year CVD risk, average appropriate PP ASA use was 41%, 63% and 73% respectively, representing an absolute difference of 36%, 14% and 4% respectively compared to SP ASA use. Appropriate PP ASA use did not increase in any risk category following the publication of the 2009 USPSTF guidelines. Documented contraindications to ASA use were very low (6%) in the PP population. Conclusion: Appropriate PP ASA use in primary care settings increases as CVD risk increases. PP ASA use in the highest risk population is similar to the rate in the SP cohort. A large primary prevention aspirin treatment gap exists in the medium and low CVD risk categories. Publication of the 2009 USPSTF recommendation was not associated with improved aspirin use in any risk category. Public health interventions to safely and effectively disseminate this PP ASA recommendation, involving both the public and health care providers, are warranted.

The prevalence of peripheral arterial disease (PAD) is increasing as the population ages. Critical limb ischemia (CLI) represents the most advanced form of atherosclerotic lower extremity disease, with approximately 1.3% of the US population affected. Current management of CLI focuses on revascularization of the affected limb via peripheral endovascular or open surgical techniques. Medical management options are mandatory therapies that provide the basis for prevention of coronary and cerebrovascular ischemic events, and improve survival, but have limited impact on limb ischemia. If patients are not ideal candidates for revascularization, they often progress to amputation. Stimulating angiogenesis using protein, gene, or stem cell therapy is an attractive alternative in a disease caused by inadequate blood flow. Preclinical studies and clinical trials investigating the role of gene transfer for therapeutic angiogenesis in critical limb ischemia have been encouraging, but definitive proof of efficacy remains elusive. In this chapter, we aim to discuss the current gene transfer systems and angiogenic growth factors which may play an important role in the future management of critical limb ischemia.

The incidence of peripheral artery disease (PAD) is higher in patients with chronic kidney disease (CKD) than in the general population. PAD is a strong independent risk factor for increased cardiovascular disease mortality and morbidity, including limb amputation, in persons with CKD. Diagnosis of PAD in patients with CKD may be challenging in the absence of classic intermittent claudication or the presence of atypical leg symptoms. In addition, pedal artery incompressibility may decrease the accuracy of ankle-brachial index measurement, the most common PAD diagnostic tool. Alternative methods such as toe-brachial index should be used if clinical suspicion persists despite a normal ankle-brachial index value. Aggressive risk-factor modification, including treatment of diabetes, hyperlipidemia, and hypertension and smoking cessation, should be mandatory in all patients. Treatment of all individuals with PAD should include antiplatelet medications and prescribed supervised exercise programs and/or cilostazol for individuals with claudication symptoms. Preventive foot care measures and a multidisciplinary approach involving podiatrists and vascular and wound care specialists should be used to reduce amputations. Revascularization for critical limb ischemia is associated with poor outcomes in patients with CKD with PAD. Future investigation is recommended to evaluate the benefit of earlier treatment strategies in this high cardiovascular disease risk population with CKD.

SUMMARY Peripheral artery disease (PAD) is a common, chronic atherosclerotic disease affecting millions of individuals that causes a major impact on morbidity and cardiovascular mortality. Although the gender- and age-specific prevalence of PAD has been well-defined from published population-based studies, the clinical relevance of these data has not been fully recognized by the public and health professionals. These health facts are now revealing that women suffer the consequences of PAD at rates at least as high as those observed in men. Additionally, PAD is more common in African–Americans over the age of 50 years than in non-Hispanic caucasians, suggesting that African–American women are at particularly high risk for developing PAD. Cardiovascular disease is the leading cause of death in women, making it imperative that the contribution of PAD be included in all future women's 'heart health efforts'.

Comparative effectiveness research (CER) aims to provide decision makers with the evidence needed to evaluate the benefits and harms of alternative clinical management strategies. CER has become a national priority, with considerable new research funding allocated. Cardiovascular disease is a priority area for CER. This workshop report provides an overview of CER methods, with an emphasis on practical clinical trials and observational treatment comparisons. The report also details recommendations to the National Heart, Lung, and Blood Institute for a new framework for evidence development to foster cardiovascular CER, and specific studies to address 8 clinical issues identified by the Institute of Medicine as high priorities for cardiovascular CER.

Background— Elevated serum cholesterol accounts for a considerable proportion of cardiovascular disease worldwide. An understanding of the relationship between country-level economic and health system factors and elevated cholesterol may provide insight for prioritization of cardiovascular prevention programs. Methods and Results— Using hierarchical models, we examined the relationship between elevated total cholesterol (>200 mg/dL) in 53 570 outpatients from 36 countries, and tertiles of several country-level indices: (1) gross national income, (2) total expenditure on health as percentage of gross domestic product, (3) government expenditure on health as percentage of total expenditure on health, (4) out-of-pocket expenditures as percentage of private expenditure on health, and the World Health Organization indices of (5) Health System Achievement and (6) Performance/Efficiency. Overall, 38% of outpatients had total cholesterol >200 mg/dL (>5.18 mmol/L), and 9.3% of the total variability in elevated cholesterol was at the country level; this proportion was higher for patients with (12.1%) versus without (7.4%) history of hyperlipidemia. Among patients with history of hyperlipidemia, countries in the highest tertile of gross national income or World Health Organization Health System Achievement had lower odds of elevated cholesterol than lower tertiles ( P P Conclusions— Global variations in the prevalence of elevated cholesterol among patients with history of hyperlipidemia are associated with country-level economic development and health system indices. These results support the need for strengthening efforts toward effective cardiovascular disease prevention and control and may provide insight for health policy setting at the national level.

To evaluate systemic and limb ischemic event rates of PAD patients with prior leg amputation and determine predictors of adverse outcomes.The REduction of Atherothrombosis for Continued Health (REACH) Registry provided a prospective multinational cohort of 7996 outpatients with PAD enrolled from primary medical clinics in 44 countries in 2003-2004. 1160 patients (14.5%) had a prior leg amputation at any level. Systemic (myocardial infarction [MI], stroke, cardiovascular death) and limb (angioplasty, surgery, amputation) ischemic event rates were determined in a 3-year follow-up.PAD patients with leg amputations on entry had a 5-fold higher rate of a subsequent amputation (12.4% vs. 2.4%, P.001), lower rate of peripheral angioplasty (8.3% vs. 10.7%, P = .005), and similar rates of surgical revascularization procedures compared with PAD patients without amputation. A nearly 2-fold increase in rates of cardiovascular death (14.5% vs. 7.7%, P.001) and all-cause mortality (21.8% vs. 12.6%, P.001) and an increase in the composite outcome of MI, stroke, cardiovascular death, or hospitalization (48.7% vs. 40.0%, P.001) were noted. Recent (≤ 1 year) amputation was associated with higher rates of worsening PAD, subsequent lower extremity surgical revascularization procedures, re-amputation, non-fatal MI, and the composite outcome, including hospitalization. Adverse systemic and limb ischemic outcomes were similar regardless of amputation level.Individuals with a history of leg amputations have markedly elevated rates of systemic and limb-related outcomes. PAD patients with recent ischemic amputation have the highest risk of adverse events. A history of "minor" ischemic amputation may confer an identical systemic risk as "major" leg amputation.

Background— Claudication is a common and disabling symptom of peripheral artery disease that can be treated with medication, supervised exercise (SE), or stent revascularization (ST). Methods and Results— We randomly assigned 111 patients with aortoiliac peripheral artery disease to receive 1 of 3 treatments: optimal medical care (OMC), OMC plus SE, or OMC plus ST. The primary end point was the change in peak walking time on a graded treadmill test at 6 months compared with baseline. Secondary end points included free-living step activity, quality of life with the Walking Impairment Questionnaire, Peripheral Artery Questionnaire, Medical Outcomes Study 12-Item Short Form, and cardiovascular risk factors. At the 6-month follow-up, change in peak walking time (the primary end point) was greatest for SE, intermediate for ST, and least with OMC (mean change versus baseline, 5.8±4.6, 3.7±4.9, and 1.2±2.6 minutes, respectively; P P =0.02 for ST versus OMC, and P =0.04 for SE versus ST). Although disease-specific quality of life as assessed by the Walking Impairment Questionnaire and Peripheral Artery Questionnaire also improved with both SE and ST compared with OMC, for most scales, the extent of improvement was greater with ST than SE. Free-living step activity increased more with ST than with either SE or OMC alone (114±274 versus 73±139 versus −6±109 steps per hour), but these differences were not statistically significant. Conclusions— SE results in superior treadmill walking performance than ST, even for those with aortoiliac peripheral artery disease. The contrast between better walking performance for SE and better patient-reported quality of life for ST warrants further study. Clinical Trial Registration— URL: http://clinicaltrials.gov/ct/show/NCT00132743?order=1 . Unique identifier: NCT00132743.

Robert C. Hendel, MD, FACC, FAHA, Chair; Biykem Bozkurt, MD, PhD, FACC, FAHA; Gregg C. Fonarow, MD, FACC, FAHA; Jeffrey P. Jacobs, MD, FACC; Pamela N. Peterson, MD, FACC; Veronique L. Roger, MD, MPH, FACC, FAHA[∥∥∥][1]; Eric E. Smith, MD, MPH, FAHA; James E. Tcheng, MD, FACC, FSCAI; Tracy

Background Daily low‐dose aspirin is recommended for primary prevention of myocardial infarction and stroke in higher‐risk patients. Population trends in aspirin use for cardiovascular disease (CVD) prevention in an urban population (Minneapolis/St. Paul, 2010 population 2.85 million) from 1980 to 2009 were evaluated. Methods and Results Surveys of randomly selected adults aged 25 to 74 years were collected at 5‐year intervals. Self‐reports of regular aspirin use for CVD prevention and history of CVD were obtained. Six cross‐sectional surveys included 12 281 men and 14 258 women. Age‐adjusted aspirin use for primary prevention increased during this period from 1% to 21% among men and 1% to 12% among women. Aspirin use was highest in those aged 65 to 74 years. For secondary prevention, age‐adjusted aspirin use increased from 19% to 74% among men and 11% to 64% among women. While data are based on self‐report, a substudy using a biochemical indicator of aspirin use (serum thromboxane B 2 ) supports the validity of self‐report. Conclusions Aspirin for CVD prevention is commonly used by a large and growing portion of the general population. It is not known if this is based on professional advice or self‐prescribed use. It is also likely that many who would benefit do not use aspirin and others use aspirin inappropriately.