High-sensitivity cardiac troponin and natriuretic peptide with risk of lower-extremity peripheral artery disease: the Atherosclerosis Risk in Communities (ARIC) Study.

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. <3 ng/L) and NT-proBNP (≥258.3 vs. <51.5 pg/mL) showed ∼8- and 10-20-fold higher risk of PAD and CLI, respectively. Even after adjusting for potential confounders and each other, hazard ratios were greater for CLI than for PAD (7.74 95% confidence interval [95% CI 4.43-13.55] vs. 2.84 [2.02-4.00] for the highest vs. reference hs-cTnT category and 4.63 [2.61-8.23] vs. 3.16 [2.23-4.49] for the highest vs. reference NT-proBNP category). The addition of these cardiac markers improved c-statistics for CLI. Conclusion: High-sensitivity cTnT and NT-proBNP were independently associated with incident PAD, particularly its severe form, CLI. Although future studies are warranted to investigate pathophysiological mechanisms behind these associations, our study suggests the usefulness of cardiac markers to identify individuals at high risk of CLI.

Baseline assessment and comparison of arterial anatomy, hyperemic flow, and skeletal muscle perfusion in peripheral artery disease: The Cardiovascular Cell Therapy Research Network "Patients with Intermittent Claudication Injected with ALDH Bright Cells" (CCTRN PACE) study.

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 ALDHbr 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.

Extracranial Systemic Embolic Events in Patients With Nonvalvular Atrial Fibrillation: Incidence, Risk Factors, and Outcomes.

BACKGROUND: Nonvalvular atrial fibrillation is a major cause of thromboembolic events. In comparison with atrial fibrillation-related stroke, extracranial systemic embolic events (SEEs) remain poorly defined. METHODS AND RESULTS: All suspected SEEs reported among 37 973 participants of 4 large contemporary randomized clinical trials of anticoagulation in atrial fibrillation were independently readjudicated for clinical and objective evidence of sudden loss of perfusion of a limb or organ. Over 91 746 patient-years of follow-up, 221 SEEs occurred in 219 subjects. The SEE incidence was 0.24 of 100 and stroke incidence was 1.92 of 100 patient-years. In comparison with patients with stroke, those with SEE were more often female (56% versus 47%; P=0.01) and had comparable mean age (73.1±8.5 versus 73.5±8.8 years; P=0.57) and mean CHADS2 scores (2.4±1.3 versus 2.5±1.2; P=0.33). SEEs more frequently involved the lower extremity (58%) than visceral-mesenteric (31%) or upper extremity (10%). SEE-related care involved clinic assessment alone in 5%, 30% were hospitalized without procedures, 60% underwent endovascular or surgical intervention, and 5% underwent amputation. Within 30 days, 54% of patients recovered fully, 20% survived with deficits, and 25% died. Thirty-day mortality was greater after visceral-mesenteric than lower- or upper-extremity SEE (55%, 17%, and 9%, respectively, P≤0.0001). The relative risk of death throughout follow-up was 4.33 (95% confidence interval, 3.29-5.70) after SEE versus 6.79 (95% confidence interval, 6.22-7.41) after stroke in comparison with patients without either event. CONCLUSIONS: SEE constituted 11.5% of clinically recognized thromboembolic events in patients with atrial fibrillation and was associated with high morbidity and mortality. SEE mortality was comparable to that of ischemic stroke and varied by anatomic site.

Nutritional status and body composition in patients with peripheral arterial disease: A cross-sectional examination of disease severity and quality of life.

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.

The Society for Vascular Medicine: the first quarter century.

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 impact of prolonged lower limb ischemia on amputation, mortality, and functional status: the FRIENDS registry.

BACKGROUND: Peripheral artery disease (PAD) is a major cause of cardiovascular ischemic events and amputation. Knowledge gaps exist in defining and measuring key factors that predict these events. The objective of this study was to assess whether duration of limb ischemia would serve as a major predictor of limb and patient survival. METHODS: The FReedom from Ischemic Events: New Dimensions for Survival (FRIENDS) registry enrolled consecutive patients with limb-threatening peripheral artery disease at a single tertiary care hospital. Demographic information, key clinical care time segments, functional status and use of revascularization, and pharmacotherapy data were collected at baseline, and vascular ischemic events, cardiovascular mortality, and all-cause mortality were recorded at 30 days and 1 year. RESULTS: A total of 200 patients with median (interquartile range) age of 76 years (65-84 years) were enrolled in the registry. Median duration of limb ischemia was 0.75 days for acute limb ischemia (ALI) and 61 days for chronic critical limb ischemia (CLI). Duration of limb ischemia of <12, 12 to 24, and >24 hours in patients with ALI was associated with much higher rates of first amputation (P = .0002) and worse amputation-free survival (P = .037). No such associations were observed in patients with CLI. CONCLUSIONS: For individuals with ischemic symptoms <14 days, prolonged limb ischemia is associated with higher 30-day and 1-year amputation, systemic ischemic event rates, and worse amputation-free survival. No such associations are evident for individuals with chronic CLI. These data imply that prompt diagnosis and revascularization might improve outcomes for patients with ALI.

Rationale and design for PACE: patients with intermittent claudication injected with ALDH bright cells.

Peripheral artery disease (PAD) is recognized as a public health issue because of its prevalence, functional limitations, and increased risk of systemic ischemic events. Current treatments for claudication, the primary symptom in patients with PAD, have limitations. Cells identified using cytosolic enzyme aldehyde dehydrogenase (ALDH) may benefit patients with severe PAD but has not been studied in patients with claudication. PACE is a randomized, double-blind, placebo-controlled clinical trial conducted by the Cardiovascular Cell Therapy Research Network to assess the safety and efficacy of autologous bone marrow-derived ALDH(br) cells delivered by direct intramuscular injections in 80 patients with symptom-limiting intermittent claudication. Eligible patients will have a significant stenosis or occlusion of infrainguinal arteries and a resting ankle-brachial index less than 0.90 and will be randomized 1:1 to cell or placebo treatment with a 1-year follow-up. The primary end points are the change in peak walking time and leg collateral arterial anatomy, calf muscle blood flow, and tissue perfusion as determined by magnetic resonance imaging at 6 months compared with baseline. The latter 3 measurements are new physiologic lower extremity tissue perfusion and PAD imaging-based end points that may help to quantify the biologic and mechanistic effects of cell therapy. This trial will collect important mechanistic and clinical information on the safety and efficacy of ALDH(br) cells in patients with claudication and provide valuable insight into the utility of advanced magnetic resonance imaging end points.

Epidemiology of peripheral arterial disease and critical limb ischemia in an insured national population.

BACKGROUND: Critical limb ischemia (CLI) represents the most severe clinical manifestation of peripheral arterial disease (PAD) and is the major cause of ischemic amputation in the United States. Risk factors and the associated incidence and prevalence of CLI have not been well described in the general population. This study describes the risk factors for PAD progression to CLI and estimates the annual incidence and prevalence of CLI in a representative United States patient cohort. METHODS: This was a retrospective cohort analysis of adults with commercial, Medicare supplemental, or Medicaid health insurance who had at least one PAD or CLI health care claim from January 1, 2003, through December 31, 2008, and 12 months of continuous coverage. Two subgroups of CLI presentation were identified: primary CLI (patients without any prior PAD or subsequent PAD diagnostic code >30 days after CLI diagnostic code) and secondary CLI (patients with prior PAD or subsequent PAD diagnostic codes ≤30 days of a CLI diagnostic code). Patterns of presentation, annual incidence, and prevalence of CLI were stratified by health care plan. Risk factors for progression to CLI were compared by presentation type. RESULTS: From 2003 to 2008, the mean annual incidence of PAD was 2.35% (95% confidence interval [CI], 2.34%-2.36%) and the incidence of CLI was 0.35% (95% CI, 0.34%-0.35%) of the eligible study population, with primary and secondary presentations occurring at similar rates. The mean annualized prevalence of PAD was 10.69% (95% CI, 10.67%10.70%) and the mean annualized prevalence of CLI was 1.33% (95% CI, 1.32%-1.34%) of the eligible study population, and two-thirds of the cases presented as secondary CLI. CLI developed in 11.08% (95% CI, 11.30%-11.13%) of patients with PAD. A multivariable model demonstrated that diabetes, heart failure, stroke, and renal failure were stronger predictors of primary rather than secondary CLI presentation. CONCLUSIONS: These data establish new national estimates of the incidence and prevalence of CLI and define key risk factors that contribute to primary or secondary presentations of CLI within a very large contemporary insured population cohort in the United States.

Effect of tirasemtiv, a selective activator of the fast skeletal muscle troponin complex, in patients with peripheral artery disease.

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. CLINICALTRIALSGOV IDENTIFIER NCT01131013:

Development of administrative data algorithms to identify patients with critical limb ischemia.

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.

A 16-month community-based intervention to increase aspirin use for primary prevention of cardiovascular disease.

INTRODUCTION: Cardiovascular diseases are the leading causes of disability and death in the United States. Primary prevention of these events may be achieved through aspirin use. The ability of a community-based intervention to increase aspirin use has not been evaluated. The objective of this study was to evaluate an educational intervention implemented to increase aspirin use for primary prevention of cardiovascular disease in a small city in Minnesota. METHODS: A community-based intervention was implemented during 16 months in a medium-sized community in Minnesota. Messages for aspirin use were disseminated to individuals, health care professionals, and the general population. Independent cross-sectional samples of residents (men aged 45-79, women aged 55-79) were surveyed by telephone to identify candidates for primary prevention aspirin use, examine their characteristics, and determine regular aspirin use at baseline and after the campaign at 4 months and 16 months. RESULTS: In primary prevention candidates, regular aspirin use rates increased from 36% at baseline to 54% at 4 months (odds ratio = 2.05; 95% confidence interval, 1.09-3.88); the increase was sustained at 52% at 16 months (odds ratio = 1.89; 95% confidence interval, 1.02-3.49). The difference in aspirin use rates at 4 months and 16 months was not significant (P = .77). CONCLUSION: Aspirin use rates for primary prevention remain low. A combined public health and primary care approach can increase and sustain primary prevention aspirin use in a community setting.

Global variation in the prevalence of elevated cholesterol in outpatients with established vascular disease or 3 cardiovascular risk factors according to national indices of economic development and health system performance.

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<0.001, for both). Countries in the highest tertile of out-of-pocket health expenditures had higher odds of elevated cholesterol than those in the lowest tertile (P<0.001). No significant associations were found for patients without history of hyperlipidemia. 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.

Supervised exercise versus primary stenting for claudication resulting from aortoiliac peripheral artery disease: six-month outcomes from the claudication: exercise versus endoluminal revascularization (CLEVER) study.

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<0.001 for the comparison of SE versus OMC, 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.

Correlation of patient-reported symptom outcomes and treadmill test outcomes after treatment for aortoiliac claudication.

PURPOSE: To examine the relationship between objective treadmill test outcomes and subjective symptom outcomes among patients with claudication treated with stent revascularization (ST) compared with supervised exercise (SE). MATERIALS AND METHODS: Five scales of the Peripheral Artery Questionnaire and Walking Impairment Questionnaire were correlated with peak walking time and treadmill claudication onset time. RESULTS: The correlation between change in disease-specific quality of life (QOL) and change in peak walking time differed according to treatment group, with statistically significant correlations for all five scales for the ST group and weaker trends for the SE group, only one of which was statistically significant. In contrast, improvements in disease-specific QOL correlated well with increases in claudication onset time, with no significant interaction with treatment group for any of the five scales. CONCLUSIONS: Disease-specific QOL results at 6 months in the Claudication: Exercise Vs. Endoluminal Revascularization (CLEVER) study show that improved maximal treadmill walking in patients with claudication treated with SE correlated poorly with self-reported symptom relief. Conversely, patients treated with ST showed good correlation between improved maximal treadmill walking and self-reported symptom improvement. The correlation between claudication onset time and self-reported symptom relief was good across treatment groups. This finding indicates that traditional objective treadmill test outcomes may not correlate well with symptom relief in patients with claudication. Future studies should investigate these data and improve understanding of patient relevance of traditional objective treadmill-based treatment outcomes.

The FReedom from Ischemic Events-New Dimensions for Survival (FRIENDS) registry: design of a prospective cohort study of patients with advanced peripheral artery disease.

BACKGROUND: Advanced lower extremity peripheral artery disease (PAD), whether presenting as acute limb ischemia (ALI) or chronic critical limb ischemia (CLI), is associated with high rates of cardiovascular ischemic events, amputation, and death. Past research has focused on strategies of revascularization, but few data are available that prospectively evaluate the impact of key process of care factors (spanning pre-admission, acute hospitalization, and post-discharge) that might contribute to improving short and long-term health outcomes. METHODS/DESIGN: The FRIENDS registry is designed to prospectively evaluate a range of patient and health system care delivery factors that might serve as future targets for efforts to improve limb and systemic outcomes for patients with ALI or CLI. This hypothesis-driven registry was designed to evaluate the contributions of: (i) pre-hospital limb ischemia symptom duration, (ii) use of leg revascularization strategies, and (iii) use of risk-reduction pharmacotherapies, as pre-specified factors that may affect amputation-free survival. Sequential patients would be included at an index "vascular specialist-defined" ALI or CLI episode, and patients excluded only for non-vascular etiologies of limb threat. Data including baseline demographics, functional status, co-morbidities, pre-hospital time segments, and use of medical therapies; hospital-based use of revascularization strategies, time segments, and pharmacotherapies; and rates of systemic ischemic events (e.g., myocardial infarction, stroke, hospitalization, and death) and limb ischemic events (e.g., hospitalization for revascularization or amputation) will be recorded during a minimum of one year follow-up. DISCUSSION: The FRIENDS registry is designed to evaluate the potential impact of key factors that may contribute to adverse outcomes for patients with ALI or CLI. Definition of new "health system-based" therapeutic targets could then become the focus of future interventional clinical trials for individuals with advanced PAD.

Correlates of delayed recognition and treatment of acute type A aortic dissection: the International Registry of Acute Aortic Dissection (IRAD).

BACKGROUND: In acute aortic dissection, delays exist between presentation and diagnosis and, once diagnosed, definitive treatment. This study aimed to define the variables associated with these delays. METHODS AND RESULTS: Acute aortic dissection patients enrolled in the International Registry of Acute Aortic Dissection (IRAD) between 1996 and January 2007 were evaluated for factors contributing to delays in presentation to diagnosis and in diagnosis to surgery. Multiple linear regression was performed to determine relative delay time ratios (DTRs) for individual correlates. The median time from arrival at the emergency department to diagnosis was 4.3 hours (quartile 1-3, 1.5-24 hours; n=894 patients) and from diagnosis to surgery was 4.3 hours (quartile 1-3, 2.4-24 hours; n=751). Delays in acute aortic dissection diagnosis occurred in female patients; those with atypical symptoms that were not abrupt or did not include chest, back, or any pain; patients with an absence of pulse deficit or hypotension; or those who initially presented to a nontertiary care hospital (all P<0.05). The largest relative DTRs were for fever (DTR=5.11; P<0.001) and transfer from nontertiary hospital (DTR=3.34; P<0.001). Delay in time from diagnosis to surgery was associated with a history of previous cardiac surgery, presentation without abrupt or any pain, and initial presentation to a nontertiary care hospital (all P<0.001). The strongest factors associated with operative delay were prolonged time from presentation to diagnosis (DTR=1.35; P<0.001), race other than white (DTR=2.25; P<0.001), and history of coronary artery bypass surgery (DTR=2.81; P<0.001). CONCLUSIONS: Improved physician awareness of atypical presentations and prompt transport of acute aortic dissection patients could reduce crucial time variables.

Peripheral artery disease and CKD: a focus on peripheral artery disease as a critical component of CKD care.

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.

An evidence-based score to detect prevalent peripheral artery disease (PAD).

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.

Late outcomes after carotid artery stenting versus carotid endarterectomy: insights from a propensity-matched analysis of the Reduction of Atherothrombosis for Continued Health (REACH) Registry.

BACKGROUND: In patients with carotid artery disease, carotid endarterectomy (CEA) and carotid stenting (CAS) are treatment options. Controversy exists as to the relative efficacy of the 2 techniques in preventing late events. METHODS AND RESULTS: The Reduction of Atherothrombosis for Continued Health (REACH) Registry recruited > 68,000 outpatients ≥ 45 years of age with established atherothrombotic disease or ≥ 3 risk factors for atherothrombosis. Patients with CAS or CEA were chosen and followed up prospectively for the occurrence of cardiovascular events. Propensity score matching was performed to assemble a cohort of patients in whom all baseline covariates would be well balanced. Primary outcome was defined as death or stroke at the 2-year follow-up. Secondary outcome was stroke or transient ischemic attack. Tertiary outcome was a composite of death, myocardial infarction, or stroke and the individual outcomes. Of the 68 236 patients with atherothrombosis, 3412 patients (5%) had a history of carotid artery revascularization (70% asymptomatic carotid stenosis), 1025 (30%) with CAS and 2387 (70%) with CEA. Propensity score analyses matched 836 CAS patients with 836 CEA patients. At the end of 2 years of follow-up, in the propensity score-matched cohort, CAS was associated with a risk similar to CEA for the primary (hazard ratio [HR], 0.85; 95% confidence interval [CI], 0.57 to 1.26), secondary (HR, 1.20; 95% CI, 0.73 to 1.96), and tertiary (HR, 0.72; 95% CI, 0.51 to 1.01) composite outcome, death (HR, 0.63; 95% CI, 0.40 to 1.00), and stroke (HR, 1.48; 95% CI, 0.79 to 2.80). CONCLUSIONS: In a real-world cohort of patients with a history of carotid artery revascularization, CAS was comparable to CEA for late outcomes.

The role of preoperative coronary angiography in the setting of type A acute aortic dissection: insights from the International Registry of Acute Aortic Dissection.

BACKGROUND: Performing preoperative coronary angiography (CA) before surgical repair of a type A acute aortic dissection (TA-AAD) remains controversial. Although the information provided by CA may be useful in planning the surgical approach, the potential delay to surgery and complications of CA may confer added risk of death before definitive repair of the aorta. METHODS: We analyzed 1,343 patients from January 27, 1996, to May 3, 2010, with TA-AAD from the International Registry of Acute Aortic Dissection who underwent surgical or endovascular repair during the index hospitalization, with (n = 156) or without (n = 1,187) preoperative CA. The main outcomes measured were in-hospital complications and in-hospital and long-term mortality. RESULTS: Patients who underwent preoperative CA were more likely to have a history of atherosclerosis and present with electrocardiographic signs of myocardial ischemia/infarction. In the preoperative CA group, significant delays from the onset of symptoms to the time of surgery occurred. In-hospital postoperative complications and mortality rates were largely similar between the 2 groups. On multivariable logistic regression analysis, preoperative CA had no significant effect on in-hospital risk-adjusted mortality when compared to the validated International Registry of Acute Aortic Dissection risk score. Long-term mortality was similar between patients receiving preoperative CA and those who did not; long-term rehospitalization rates were higher, although largely insignificantly, among preoperative CA recipients through 5 years of follow-up. CONCLUSIONS: Preoperative CA is infrequently performed on patients with TA-AAD, except, occasionally, on patients at high risk for myocardial ischemia. When performed, preoperative CA was not associated with any significant changes in in-hospital and long-term mortality.