William R Hiatt

University of Colorado, Denver, Colorado, United States

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Publications (267)2034.58 Total impact

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    ABSTRACT: The Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC) guidelines were last updated in 2007 (TASC II) and represented the collaboration of international vascular specialties involved in the management of patients with peripheral arterial disease (PAD). Since the publication of TASC II, there have been innovations in endovascular revascularization strategies for patients with PAD. The intent of this publication is to provide a complete anatomic lower limb TASC lesion classification, including the infrapopliteal segment, and an updated literature review of new endovascular techniques and practice patterns employed by vascular specialists today. © The Author(s) 2015.
    Journal of Endovascular Therapy 08/2015; DOI:10.1177/1526602815592206 · 3.59 Impact Factor
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    ABSTRACT: Randomized controlled trials (RCTs) in pediatric venous thromboembolism (VTE) treatment have been challenged by unsubstantiated design assumptions and/or poor accrual. Pilot/feasibility (P/F) studies are critical to future RCT success. Kids-DOTT is a multicenter RCT investigating non-inferiority of a 6-week (shortened) vs. 3-month (conventional) duration of anticoagulation in patients <21 years old with provoked venous thrombosis. Primary efficacy and safety endpoints are symptomatic recurrent VTE at 1 year and anticoagulant-related, clinically-relevant bleeding. In the P/F phase, 100 participants were enrolled in an open, blinded endpoint, parallel-cohort RCT design. No eligibility violations or randomization errors occurred. Of enrolled patients, 69% were randomized, 3% missed the randomization window, and 28% were followed in pre-specified observational cohorts for completely occlusive thrombosis or persistent antiphospholipid antibodies. Retention at 1 year was 82%. Inter-observer agreement between local vs. blinded central determination of venous occlusion by imaging at 6 weeks post-diagnosis was strong (ĸ-statistic=0.75; 95% confidence interval [CI] 0.48-1.0). Primary efficacy and safety event rates were 3.3% (95% CI 0.3-11.5%) and 1.4% (0.03-7.4%). The P/F phase of Kids-DOTT has demonstrated validity of vascular imaging findings of occlusion as a randomization criterion, and defined randomization, retention, and endpoint rates to inform the fully-powered RCT. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Journal of Thrombosis and Haemostasis 06/2015; DOI:10.1111/jth.13038 · 5.55 Impact Factor
  • Cecilia C Low Wang · Jeffrey L Galinkin · William R Hiatt
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    ABSTRACT: R118 is an experimental compound that completed preclinical development as a potential medical therapy for the exercise limitation in peripheral artery disease. Animal studies established that R118 provided partial and reversible mitochondrial complex I inhibition with consequent increases in AMP kinase activation in liver and skeletal muscle. After demonstration of improved exercise performance in a mouse model and safety in rodent and primate models, a Phase I trial was performed in 24 subjects randomized to R118 vs placebo (5:1) in escalating doses. Plasma lactic acid levels were transiently elevated in 20% of subjects at the lowest dose and in 100% of subjects using a different formulation at the highest dose, which was associated with hospitalization in all subjects and severe metabolic acidosis requiring prolonged intubation in 2 subjects. Thus inhibition of mitochondrial complex I with R118 resulted in severe lactic acidosis representing unacceptable toxicity from this mechanism of action. This article is protected by copyright. All rights reserved. © 2015 American Society for Clinical Pharmacology and Therapeutics.
    Clinical Pharmacology &#38 Therapeutics 06/2015; DOI:10.1002/cpt.178 · 7.39 Impact Factor
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    ABSTRACT: Non-Valvular Atrial Fibrillation (AF) patients show high residual cardiovascular risk despite oral anticoagulants. Urinary 11-dehydro-thromboxane B2 (TxB2) is associated with an increased risk of cardiovascular events (CVEs), but its predictive value in anticoagulated AF patients is unknown.
    American Heart Journal 05/2015; DOI:10.1016/j.ahj.2015.05.011 · 4.56 Impact Factor
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    ABSTRACT: To investigate the relationship between Ankle-Brachial Index (ABI) and renal function progression in patients with atrial fibrillation (AF). Observational prospective multicentre cohort study. Atherothrombosis Center of I Clinica Medica of 'Sapienza' University of Rome; Department of Medical and Surgical Sciences of University Magna Græcia of Catanzaro; Atrial Fibrillation Registry for Ankle-Brachial Index Prevalence Assessment-Collaborative Italian Study. 897 AF patients on treatment with vitamin K antagonists. The relationship between basal ABI and renal function progression, assessed by the estimated Glomerular Filtration Rate (eGFR) calculated with the CKD-EPI formula at baseline and after 2 years of follow-up. The rapid decline in eGFR, defined as a decline in eGFR >5 mL/min/1.73 m(2)/year, and incident eGFR<60 mL/min/1.73 m(2) were primary and secondary end points, respectively. Mean age was 71.8±9.0 years and 41.8% were women. Low ABI (ie, ≤0.90) was present in 194 (21.6%) patients. Baseline median eGFR was 72.7 mL/min/1.73 m(2), and 28.7% patients had an eGFR<60 mL/min/1.73 m(2). Annual decline of eGFR was -2.0 (IQR -7.4/-0.4) mL/min/1.73 m(2)/year, and 32.4% patients had a rapid decline in eGFR. Multivariable logistic regression analysis showed that ABI ≤0.90 (OR 1.516 (95% CI 1.075 to 2.139), p=0.018) and arterial hypertension (OR 1.830 95% CI 1.113 to 3.009, p=0.017) predicted a rapid eGFR decline, with an inverse association for angiotensin converting enzyme (ACE) inhibitors/angiotensin receptor blockers (OR 0.662 95% CI 0.464 to 0.944, p=0.023). Among the 639 patients with AF with eGFR >60 mL/min/1.73 m(2), 153 (23.9%) had a reduction of the eGFR <60 mL/min/1.73 m(2). ABI ≤0.90 was also an independent predictor for incident eGFR<60 mL/min/1.73 m(2) (HR 1.851, 95% CI 1.205 to 2.845, p=0.005). In patients with AF, an ABI ≤0.90 is independently associated with a rapid decline in renal function and incident eGFR<60 mL/min/1.73 m(2). ABI measurement may help identify patients with AF at risk of renal function deterioration. NCT01161251. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    BMJ Open 05/2015; 5(5):e008026-e008026. DOI:10.1136/bmjopen-2015-008026 · 2.06 Impact Factor
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    ABSTRACT: Patients with peripheral artery disease have a marked reduction in exercise performance and daily ambulatory activity irrespective of their limb symptoms of classic or atypical claudication. This review will evaluate the multiple pathophysiologic mechanisms underlying the exercise impairment in peripheral artery disease based on an evaluation of the current literature and research performed by the authors. Peripheral artery disease results in atherosclerotic obstructions in the major conduit arteries supplying the lower extremities. This arterial disease process impairs the supply of oxygen and metabolic substrates needed to match the metabolic demand generated by active skeletal muscle during walking exercise. However, the hemodynamic impairment associated with the occlusive disease process does not fully account for the reduced exercise impairment, indicating that additional pathophysiologic mechanisms contribute to the limb manifestations. These mechanisms include a cascade of pathophysiological responses during exercise-induced ischemia and reperfusion at rest that are associated with endothelial dysfunction, oxidant stress, inflammation, and muscle metabolic abnormalities that provide opportunities for targeted therapeutic interventions to address the complex pathophysiology of the exercise impairment in peripheral artery disease. © 2015 American Heart Association, Inc.
    Circulation Research 04/2015; 116(9):1527-39. DOI:10.1161/CIRCRESAHA.116.303566 · 11.09 Impact Factor
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    ABSTRACT: Despite the global burden of cardiovascular disease, investment in cardiovascular drug development has stagnated over the past 2 decades, with relative underinvestment compared with other therapeutic areas. The reasons for this trend are multifactorial, but of primary concern is the high cost of conducting cardiovascular outcome trials in the current regulatory environment that demands a direct assessment of risks and benefits, using clinically-evident cardiovascular endpoints. To work toward consensus on improving the environment for cardiovascular drug development, stakeholders from academia, industry, regulatory bodies, and government agencies convened for a think tank meeting in July 2014 in Washington, DC. This paper summarizes the proceedings of the meeting and aims to delineate the current adverse trends in cardiovascular drug development, understand the key issues that underlie these trends within the context of a recognized need for a rigorous regulatory review process, and provide potential solutions to the problems identified. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
    Journal of the American College of Cardiology 04/2015; 65(15):1567-1582. DOI:10.1016/j.jacc.2015.03.016 · 15.34 Impact Factor
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    ABSTRACT: The lack of consistent definitions and nomenclature across clinical trials of novel devices, drugs, or biologics poses a significant barrier to accrual of knowledge in and across peripheral artery disease therapies and technologies. Recognizing this problem, the Peripheral Academic Research Consortium, together with the U.S. Food and Drug Administration and the Japanese Pharmaceuticals and Medical Devices Agency, has developed a series of pragmatic consensus definitions for patients being treated for peripheral artery disease affecting the lower extremities. These consensus definitions include the clinical presentation, anatomic depiction, interventional outcomes, surrogate imaging and physiological follow-up, and clinical outcomes of patients with lower-extremity peripheral artery disease. Consistent application of these definitions in clinical trials evaluating novel revascularization technologies should result in more efficient regulatory evaluation and best practice guidelines to inform clinical decisions in patients with lower extremity peripheral artery disease. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
    Journal of the American College of Cardiology 03/2015; 65(9):931-941. DOI:10.1016/j.jacc.2014.12.036 · 15.34 Impact Factor
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    ABSTRACT: Supervised walking exercise is an effective treatment to improve walking ability of patients with peripheral artery disease (PAD), but few exercise programs in community settings have been effective. The aim of this study was to determine the efficacy of a community-based walking exercise program with training, monitoring and coaching (TMC) components to improve exercise performance and patient-reported outcomes in PAD patients. This was a randomized, controlled trial including PAD patients (n=25) who previously received peripheral endovascular therapy or presented with stable claudication. Patients randomized to the intervention group received a comprehensive community-based walking exercise program with elements of TMC over 14 weeks. Patients in the control group did not receive treatment beyond standard advice to walk. The primary outcome in the intent-to-treat (ITT) analyses was peak walking time (PWT) on a graded treadmill. Secondary outcomes included claudication onset time (COT) and patient-reported outcomes assessed via the Walking Impairment Questionnaire (WIQ). Intervention group patients (n=10) did not significantly improve PWT when compared with the control group patients (n=10) (mean±standard error: +2.1±0.7 versus 0.0±0.7 min, p=0.052). Changes in COT and WIQ scores were greater for intervention patients compared with control patients (COT: +1.6±0.8 versus -0.6±0.7 min, p=0.045; WIQ: +18.3±4.2 versus -4.6±4.2%, p=0.001). This pilot using a walking program with TMC and an ITT analysis did not improve the primary outcome in PAD patients. Other walking performance and patient self-reported outcomes were improved following exercise in community settings. Further study is needed to determine whether this intervention improves outcomes in a trial employing a larger sample size. © The Author(s) 2015.
    Vascular Medicine 03/2015; 20(4). DOI:10.1177/1358863X15572725 · 1.73 Impact Factor
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    ABSTRACT: 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 Author(s) 2015.
    Vascular Medicine 02/2015; 20(1):60-8. DOI:10.1177/1358863X14566042 · 1.73 Impact Factor
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    ABSTRACT: This White Paper provides a summary of presentations and discussions at a Cardiovascular Safety Outcome Trials Think Tank cosponsored by the Cardiac Safety Research Consortium, the US Food and Drug Administration, and the American College of Cardiology, held at American College of Cardiology's Heart House, Washington, DC, on February 19, 2014. Studies to assess cardiovascular (CV) risk of a new drug are sometimes requested by regulators to resolve ambiguous safety signals seen during its development or among other members of its class. Think Tank participants thought that important considerations in undertaking such studies were as follows: (1) plausibility-how likely it is that a possible signal indicating risk is real, based on strength of evidence, and/or whether a plausible mechanism of action for potential CV harm has been identified; (2) relevance-what relative and absolute CV risk would need to be excluded to determine that the drug had an acceptable benefit-to-risk balance for its use in the intended patient population; and (3) how plausibility and relevance influence the timing and approach to further safety assessment. Copyright © 2015 Elsevier Inc. All rights reserved.
    American Heart Journal 01/2015; 169(4). DOI:10.1016/j.ahj.2015.01.007 · 4.56 Impact Factor
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    ABSTRACT: Hypoxia inducible factor (HIF) stabilization by HIF-prolyl hydroxylase (PHD) inhibitors may improve ischemic conditions such as peripheral artery disease (PAD). This multicenter, randomized, placebo-controlled study evaluated the safety and efficacy of GSK1278863 (an oral PHD inhibitor) in subjects with PAD. The study assessed two active treatment paradigms: single dosing and subchronic daily dosing (300 mg single dose and 15 mg daily for 14 days, respectively). Neither regimen improved exercise performance compared with placebo (change from baseline in the 6-minute walk test (6MWT; feet), (GSK1278863, placebo): single dose (-46, -44), p=0.96; repeat dose (9, 8), p=0.99; change in number of contractions to onset of claudication (goniometry): single dose (4, -1), p=0.053; repeat dose (-2, 1), p=0.08). A calf-muscle biopsy substudy showed no increases in mRNA or protein levels of HIF target genes. More subjects receiving GSK1278863 than placebo experienced adverse events, particularly following the 300 mg single dose. Thus, assessing the safety of GSK1278863 in this setting would require a larger population exposed to the agent for a longer duration. These data do not support a benefit of GSK1278863 in PAD using the regimens tested. ClinicalTrials.gov Identifier: NCT01673555.
    Vascular Medicine 11/2014; 19(6). DOI:10.1177/1358863X14557151 · 1.73 Impact Factor
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    ABSTRACT: Although the relationship between physical activity and coronary heart disease is well characterized, a paucity of data exists on physical activity and vascular disease in other arterial territories. This study examined the prevalence of peripheral artery disease (PAD) and carotid artery stenosis (CAS) in association with physical activity.
    Arteriosclerosis Thrombosis and Vascular Biology 10/2014; 35(1). DOI:10.1161/ATVBAHA.114.304161 · 5.53 Impact Factor
  • William R. Hiatt
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    ABSTRACT: Background-Tremendous advances have occurred in therapies for peripheral vascular disease (PVD); until recently, however, it has not been possible to examine the entire clinical trial portfolio of studies for the treatment of PVD (both arterial and venous disease). Methods and Results-We examined interventional trials registered in ClinicalTrials.gov from October 2007 through September 2010 (n=40 970) and identified 676 (1.7%) PVD trials (n=493 arterial only, n=170 venous only, n=13 both arterial and venous). Most arterial studies investigated lower-extremity peripheral artery disease and acute stroke (35% and 24%, respectively), whereas most venous studies examined deep vein thrombosis/pulmonary embolus prevention (42%) or venous ulceration (25%). A placebo-controlled trial design was used in 27% of the PVD trials, and 4% of the PVD trials excluded patients >65 years of age. Enrollment in at least 1 US site decreased from 51% of trials in 2007 to 41% in 2010. Compared with noncardiology disciplines, PVD trials were more likely to be double-blinded, to investigate the use of devices and procedures, and to have industry sponsorship and assumed funding source, and they were less likely to investigate drug and behavioral therapies. Geographic access to PVD clinical trials within the United States is limited to primarily large metropolitan areas. Conclusions-PVD studies represent a small group of trials registered in ClinicalTrials.gov, despite the high prevalence of vascular disease in the general population. This low number, compounded by the decreasing number of PVD trials in the United States, is concerning and may limit the ability to inform current clinical practice of patients with PVD.
    Circulation 09/2014; 59(13). DOI:10.1161/CIRCULATIONAHA.114.011021 · 14.95 Impact Factor
  • William R Hiatt · R Kevin Rogers · Eric P Brass
    Circulation 07/2014; 130(1):69-78. DOI:10.1161/CIRCULATIONAHA.113.007003 · 14.95 Impact Factor
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    ABSTRACT: 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 PAD patients, have limitations. Cells identified usingcytosolic 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 (CCTRN) to assess the safety and efficacy of autologous bone marrow–derived ALDHbr 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 <0.90 and will be randomized 1:1 to cell or placebo treatment with a 1-year follow-up. The primary endpoints are the change in peak walking time and leg collateral arterial anatomy, calf muscle blood flow, and tissue perfusion as determined by magnetic resonance (MR) imaging at 6 months compared to baseline. The latter 3 measurements are new physiologic lower extremity tissue perfusion and PAD imaging-based endpoints 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 ALDHbr cells in patients with claudication and provide valuable insight into the utility of advanced MR imaging endpoints.
    American Heart Journal 07/2014; 168(5). DOI:10.1016/j.ahj.2014.07.021 · 4.56 Impact Factor
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    ABSTRACT: 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:
    Vascular Medicine 05/2014; 19(4). DOI:10.1177/1358863X14534516 · 1.73 Impact Factor
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    ABSTRACT: To determine the effect of ticagrelor compared to clopidogrel in patients with peripheral artery disease (PAD) and acute coronary syndromes (ACS). PLATO (n = 18,624) was a multicentre, double-blind, randomized trial in ACS, that showed a 16% reduction in cardiovascular death (CV-death), myocardial infarction (MI) and stroke with ticagrelor compared with clopidogrel, without significant increase in overall major bleeding. We performed a post-hoc analysis of cardiovascular and bleeding outcomes in PLATO according to reported PAD status at baseline. At one year, CV death, MI or stroke occurred in 19.3% of patients with PAD (n = 1144) compared to 10.2% in patients without PAD (p < 0.001). The Kaplan-Meier one year event rate for the primary endpoint of CV death, MI or stroke in PAD patients treated with ticagrelor as compared with clopidogrel, was 18% vs 20.6% (HR: 0.85 95% CI 0.64-1.11; for PAD status by treatment interaction, p = 0.99) and for death from any cause 8.7% vs 11.9%, (HR: 0.74 95% CI 0.50-1.08; interaction p = 0.73). PLATO-defined major bleeding event rates at one year were 14.8% for ticagrelor compared to 17.9% for clopidogrel, (HR: 0.81 95% CI 0.59-1.10; interaction p = 0.09). PAD patients have a high rate of ischaemic and bleeding events post ACS. The reduction of CV death, MI or stroke with ticagrelor compared with clopidogrel in PAD patients was consistent with the overall trial result although it did not reach statistical significance. Overall major bleeding was similar between the therapies.
    05/2014; 22(6). DOI:10.1177/2047487314533215
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    ABSTRACT: 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. 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. 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. 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.
    Journal of vascular surgery: official publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter 05/2014; 60(3). DOI:10.1016/j.jvs.2014.03.290 · 2.98 Impact Factor

Publication Stats

15k Citations
2,034.58 Total Impact Points

Institutions

  • 1998–2015
    • University of Colorado
      • • Division of Cardiology
      • • Department of Medicine
      Denver, Colorado, United States
  • 1989–2015
    • University of Colorado Hospital
      • Department of Medicine
      Denver, Colorado, United States
  • 2012–2013
    • Sapienza University of Rome
      • Department of Experimental Medicine
      Roma, Latium, Italy
  • 2011
    • University of Colorado at Boulder
      Boulder, Colorado, United States
  • 2008–2011
    • Harvard Medical School
      • Department of Medicine
      Boston, Massachusetts, United States
  • 2009
    • University of Pennsylvania
      • Division of Cardiovascular Medicine
      Philadelphia, PA, United States
  • 2007
    • Duke University Medical Center
      • Division of Cardiology
      Durham, NC, United States
    • University of Washington Seattle
      Seattle, Washington, United States
  • 1998–2007
    • Harbor-UCLA Medical Center
      • Department of Emergency Medicine
      Torrance, California, United States
  • 2006
    • Mental Health Center of Denver
      Denver, Colorado, United States
    • Colorado Center for Digestive Disorders
      Longmont, Colorado, United States
  • 2004
    • Icahn School of Medicine at Mount Sinai
      Manhattan, New York, United States
  • 2001–2004
    • University of California, San Diego
      • Department of Family and Preventive Medicine
      San Diego, California, United States
    • Mayo Clinic - Rochester
      Рочестер, Minnesota, United States
  • 2002
    • Uniformed Services University of the Health Sciences
      Maryland, United States
  • 1999
    • Universitätsspital Basel
      Bâle, Basel-City, Switzerland
  • 1994
    • Case Western Reserve University
      • Department of Medicine (University Hospitals Case Medical Center)
      Cleveland, Ohio, United States