Metaloproteinases no tecido laminar do casco de equinos submetidos à obstrução intraluminal do cólon menor / Metalloproteinases in hoof laminar tissue of equine submitted to intraluminal small colon obstruction

O objetivo deste estudo foi avaliar a expressão das MMP-2 e MMP-9 no tecido laminar do casco e o perfil leucocitário de equinos submetidos à obstrução intraluminal do cólon menor. Realizaram-se laparotomia e obstrução do cólon menor de oito equinos hígidos, utilizando-se uma bola inserida no lúmem intestinal. A bola foi inflada à pressão de 80mmHg e a obstrução foi mantida por quatro horas. Foram realizadas coletas sanguíneas antes da obstrução (M0), imediatamente após a desobstrução (M4) e a cada 12 horas após M4, até completar 72 horas (M12, M24, M36, M48, M60 e M72). As biópsias de casco foram realizadas em M0, M4 e M72, e as amostras foram submetidas à análise zimográfica. Foi observado aumento nos leucócitos em M12 e M24, decorrente do aumento de neutrófilos segmentados e bastonetes, os quais diminuíram a partir de M36. Segundo a técnica zimográfica, não se observaram alterações nos valores de MMP-2 e -9, possivelmente devido à baixa intensidade das lesões ocasionadas no cólon menor. Com isso, conclui-se que as alterações inflamatórias decorrentes da obstrução do cólon menor não foram suficientes para ocasionar alterações na expressão das MMP-2 e -9 no tecido laminar podal.(AU)

The aim of this study was to evaluate the blood leukocytes and the MMP-2 and -9 expression in the hoof laminar tissue of horses undergoing intraluminal small colon obstruction. Laparotomy and the small colon obstruction was performed in eight healthy horses, inserting a ball in the intestinal lumen. The ball was inflated to 80 mmHg pressure and the occlusion was maintained for 4 hours. The blood was collectedBlood samples were taken before the obstruction (M0), immediately after intestinal clearance (M4), and every 12 hours until completeuntil 72 hours (M12, M24, M36, M48, M60 and M72). The hoof biopsies were performed at M0, M4, and M72 and the samples were subjected to zymography analysis. There was an increase in leukocytes in M12 and M24, due to the increase in segmented neutrophils and band neutrophils, which decreased as of M36. According to zymography technique not observed changes were not not observed in MMP-2 and -9, possibly due to the low intensity of the small colon lesions. Wherefore, it is concludedIn conclusion, that the inflammatory changes resulting from small colon obstruction were not enough to cause changes in the expression of MMP-2 and -9 in the hoof laminar tissue.(AU)

Clinical classification criteria for neurogenic claudication caused by lumbar spinal stenosis. The N-CLASS criteria.

BACKGROUND CONTEXT: Because imaging findings of lumbar spinal stenosis (LSS) may not be associated with symptoms, clinical classification criteria based on patient symptoms and physical examination findings are needed. PURPOSE: The objective of this study was to develop clinical classification criteria that identify patients with neurogenic claudication (NC) caused by LSS. STUDY DESIGN: This study is a two-stage process that includes Phase 1, the Delphi process, and Phase 2, the cross-sectional study. PATIENT SAMPLE: Outpatients were recruited from spine clinics in five countries. OUTCOME MEASURE: The outcome measure includes items from the patients' history and physical examination. METHODS: In Phase 1, a list of potential predictors of NC caused by LSS was based on the available literature and was evaluated through a Delphi process involving 17 spine specialists (surgeons and non-surgeons) from eight countries. In Phase 2, 19 different clinical spine specialists from five countries identified patients they classified as having (1) NC caused by LSS, (2) radicular pain caused by lumbar disc herniation (LDH), or (3) non-specific low back pain (NSLBP) with radiating leg pain. The patients completed survey items and the specialists documented the examination signs. Coefficients from general estimating equation models were used to select predictors, to generate a clinical classification score, and to obtain a receiver operating characteristic curve. Conduction of the Delphi process, data management, and statistical analysis were partially supported by an unrestricted grant of less than 15,000 US dollars from Merck Sharp & Dohme. No fees were allocated to participating spine specialists. RESULTS: Phase 1 generated a final list of 46 items related to LSS. In Phase 2, 209 patients with leg pain caused by LSS (n=63), LDH (n=89), or NSLBP (n=57) were included. Criteria that independently predicted NC (p<.05) were age over 60 years, positive 30-second extension test, negative straight leg test, pain in both legs, leg pain relieved by sitting, and leg pain decreased by leaning forward or flexing the spine. A classification score using a weighted set of these criteria was developed. The proposed N-CLASS score ranged from 0 to 19 and had an area under the curve of 0.92, and the cutoff (>10/19) to obtain a specificity of >90.0% resulted in a sensitivity of 82.0%. CONCLUSIONS: Clinical criteria independently associated with neurogenic claudication due to LSS were identified. The use of these symptom and physical variables as a classification score for clinical research could improve homogeneity among enrolled patients.

Managing claudication in the community setting.

Advances made in medical management and treatment options in addressing lower extremity claudication and vascular disease have skyrocketed during the last decade. Given the recent advances in treatment options, there is often the perception within the medical community and general community that to get the most "cutting edge" treatment, one must go to an academic center or practitioner. The goal of this portion of the discussion is to explore the question of what differences in treatment options there are between a community practice and an academic practice within those members of the vascular surgery specialty. Are there really any differences in the types of treatments offered or availability of the different modalities, and what drives us as practitioners to one over the other?

Predictive ability of the Society for Vascular Surgery Wound, Ischemia, and foot Infection (WIfI) classification system following infrapopliteal endovascular interventions for critical limb ischemia.

OBJECTIVE: The Society for Vascular Surgery (SVS) Lower Extremity Guidelines Committee has composed a new threatened lower extremity classification system that reflects the three major factors that impact amputation risk and clinical management: Wound, Ischemia, and foot Infection (WIfI). Our goal was to evaluate the predictive ability of this scale following any infrapopliteal endovascular intervention for critical limb ischemia (CLI). METHODS: From 2004 to 2014, a single institution, retrospective chart review was performed at the Beth Israel Deaconess Medical Center for all patients undergoing an infrapopliteal angioplasty for CLI. Throughout these years, 673 limbs underwent an infrapopliteal endovascular intervention for tissue loss (77%), rest pain (13%), stenosis of a previously treated vessel (5%), acute limb ischemia (3%), or claudication (2%). Limbs missing a grade in any WIfI component were excluded. Limbs were stratified into clinical stages 1 to 4 based on the SVS WIfI classification for 1-year amputation risk, as well as a novel WIfI composite score from 0 to 9. Outcomes included patient functional capacity, living status, wound healing, major amputation, major adverse limb events, reintervention, major amputation, or stenosis (RAS) events (> ×3.5 step-up by duplex), amputation-free survival, and mortality. Predictors were identified using Kaplan-Meier survival estimates and Cox regression models. RESULTS: Of the 596 limbs with CLI, 551 were classified in all three WIfI domains on a scale of 0 (least severe) to 3 (most severe). Of these 551, 84% were treated for tissue loss and 16% for rest pain. A Cox regression model illustrated that an increase in clinical stage increases the rate of major amputation (hazard ratio [HR], 1.6; 95% confidence interval [CI], 1.1-2.3). Separate regression models showed that a one-unit increase in the WIfI composite score is associated with a decrease in wound healing (HR, 1.2; 95% CI, 1.1-1.4) and an increase in the rate of RAS events (HR, 1.2; 95% CI, 1.1-1.4) and major amputations (HR, 1.4; 95% CI, 1.2-1.8). CONCLUSIONS: This study supports the ability of the SVS WIfI classification system to predict 1-year amputation, RAS events, and wound healing in patients with CLI undergoing endovascular infrapopliteal revascularization procedures.

El impacto de la enfermedad arterial periférica: propuesta de una nueva clasificación / The impact of peripheral arterial disease: A proposal for a new classification

La claudicación intermitente, estación evolutiva intermedia de la enfermedad arterial periférica, se ha considerado tradicionalmente como un estadio benigno, atendiendo al hecho exclusivo de la clínica de dolor que se produce durante la marcha. En este artículo pretendemos llamar la atención sobre las posibles consecuencias asociadas al dolor isquémico y el consiguiente estrés oxidativo desencadenado por su «sombra», el fenómeno isquemia/reperfusión. Durante el mismo se produce deficiente manejo del calcio y aparición incontrolada de radicales libres de oxígeno, con daño mitocondrial y aumento del fenómeno inflamatorio que podría estar asociado a una progresión acelerada de la arteriosclerosis sistémica con aumento del riesgo cardiovascular, directamente proporcional a la disminución del índice tobillo/brazo. Ante estos acontecimientos, proponemos una nueva clasificación integradora de las actuales de Fontaine y Rutherford, que considera las posibles consecuencias sistémicas expuestas y sirva para modificar nuestro manejo tradicional de la enfermedad arterial periférica

Clasically, intermittent claudication, an intermediate stage in peripheral arterial disease, has been considered as a benign condition when considering only the muscular pain on walking. In this paper our aim is to attract attention about the effects linked to ischemic pain and the oxidative injury resulting from episodes of ischemia/reperfusion. Throughout this process alterations in calcium homeostasis as well as uncontrolled generation of reactive oxygen species, in association with the mitochondrial dysfunction and inflammatory phenomena, could lead to accelerate atherosclerosis, with an increased cardiovascular risk stated by means of a reduced ankle-brachial index. Taking this idea into account we propose a possible new classification for the management of the peripheral arterial disease, combining the Fontaine and Rutherford classifications and thinking about the described systemic effects in order to change the traditional management of peripheral arterial disease

[Is our management of patients with claudicatio intermittens correct?]. / Liecime správne pacientov s claudicatio intermittens?

Claudicatio intermittens is the major symptom of peripheral arterial disease of extremities. At the same time it is an important manifestation of systemic atherosclerosis. In spite of the fact that the diagnosis of claudicatio intermittens requires only simple, non-invasive, and inexpensive diagnostic methods, the disease is still underdiagnosed and often goes untreated. Proper treatment of patients with claudicatio intermittens prevents the progression of the disease and development of critical limb ischemia as well as reduces other complications of systemic atherosclerosis, including cardiovascular death.

[Physical activity and peripheral arterial obstructive disease]. / Exercice physique et artériopathie oblitérante des membres inférieurs.

Intermittent claudication (IC) is the most common clinical manifestation of atherosclerotic peripheral arterial disease. Exercise training plays a major role in treating patients with IC. Regular exercise increases functional walking capacity, reduces cardiovascular mortality and improves quality of life. This seems to be achieved by: favorable effect on cardiovascular risk factors, anti-inflammatory effect, increased collateral blood flux, improved rheology profile, endothelial function, fibrinolysis, and muscular metabolism. However, exact mechanisms underlying beneficial effect of exercise remain largely unknown. Exercise modalities will be discussed in this article.

[Correlation between quantitative sensory testing and questionnaires on neuropathic pain for chronic ischemic pain in peripheral arterial disease]. / Zusammenhang von Quantitativer Sensorischer Testung und Fragebögen zu neuropathischen Schmerzen am Beispiel chronischer Ischämieschmerzen bei PAVK.

BACKGROUND: A neuropathic component to chronic ischemic pain in peripheral arterial disease (PAD) has recently been shown using quantitative sensory testing (QST) and pain questionnaires. The aim of this study was to examine correlations between QST and pain questionnaires in patients with chronic ischemic pain. METHODS: A total of 10 patients with severe PAD (Fontaine stages III and IV) without diabetes mellitus answered a questionnaire and were examined with QST. The questionnaire consisted of several validated instruments which were used to examine the intensity of pain, quality of pain and neuropathic pain (VAS, SF-MPQ, S-LANSS, NPSI). RESULTS: The results of the QST confirmed previously published data. Several terms of the SF-MPQ showed a correlation with parameters of the QST, such as Allodynia (QST) which correlated with the term tender (SF-MPQ) (Spearman's correlation coefficient 0.911; p< or =0.001) and the NPSI subscore evoked pain correlated with the QST parameter wind-up ratio (0.683; p=0.042). CONCLUSION: The results suggest that there might be correlations between psychophysical tests (QST) and pain questionnaires. Subjective perceptions of pain might be represented by a certain pattern in the QST. These connections could contribute to further clarify the pathophysiologic mechanisms leading to the perception of pain.

Clinical endpoints in peripheral endovascular revascularization trials: a case for standardized definitions.

BACKGROUND: Endovascular therapy is a rapidly expanding option for the treatment of patients with peripheral arterial disease (PAD), leading to a myriad of published studies reporting on various revascularization strategies. However, these reports are often difficult to interpret and compare because they do not utilize uniform clinical endpoint definitions. Moreover, few of these studies describe clinical outcomes from a patients' perspective. METHODS AND RESULTS: The DEFINE Group is a collaborative effort of an ad-hoc multidisciplinary team from various specialties involved in peripheral arterial disease therapy in Europe and the United States. DEFINE's goal was to arrive at a broad based consensus for baseline and endpoint definitions in peripheral endovascular revascularization trials for chronic lower limb ischemia. In this project, which started in 2006, the individual team members reviewed the existing pertinent literature. Following this, a series of telephone conferences and face-to-face meetings were held to agree upon definitions. Input was also obtained from regulatory (United States Food and Drug Administration) and industry (device manufacturers with an interest in peripheral endovascular revascularization) stakeholders, respectively. The efforts resulted in the current document containing proposed baseline and endpoint definitions in chronic lower limb PAD. Although the consensus has inevitably included certain arbitrary choices and compromises, adherence to these proposed standard definitions would provide consistency across future trials, thereby facilitating evaluation of clinical effectiveness and safety of various endovascular revascularization techniques. CONCLUSION: This current document is based on a broad based consensus involving relevant stakeholders from the medical community, industry and regulatory bodies. It is proposed that the consensus document may have value for study design of future clinical trials in chronic lower limb ischemia as well as for regulatory purposes.

Type-D personality and ankle brachial index as predictors of impaired quality of life and depressive symptoms in peripheral arterial disease.

BACKGROUND: Patient-based outcomes, such as impaired quality of life (QOL) and depression, may adversely affect the clinical course of patients with peripheral arterial disease (PAD). Disease severity indices, including the ankle brachial index, are only partially associated with these outcomes. OBJECTIVE: To examine whether individual differences in personality would predict impaired QOL and depression above and beyond PAD severity. DESIGN: A prospective follow-up study. SETTING: Vascular outpatient clinic of a teaching hospital. PATIENTS: Consecutive patients with newly diagnosed PAD (n = 150). Diagnosis and severity of PAD were based on history, physical examination, treadmill walking distance, and ankle brachial index. At their first visit, all patients completed the 14-Item Type-D Personality Scale, the World Health Organization Quality of Life Assessment Instrument-100, and the Center for Epidemiological Studies Depression Scale to assess distressed (type-D) personality, QOL, and depressive symptoms, respectively. The QOL and depression scales were repeated after 6 months' follow-up. MAIN OUTCOME MEASURES: Impaired QOL and depressive symptoms at follow-up. RESULTS: Indices of PAD severity (ankle brachial index and walking distance) did not predict impaired QOL or depressive symptoms at follow-up. In contrast, type-D personality predicted poor physical health (odds ratio, 3.94; 95% confidence interval, 1.60-9.67; P = .003), decreased level of independence (odds ratio, 4.26; 95% confidence interval, 1.69-10.73; P = .002), and poor overall QOL (odds ratio, 4.72; 95% confidence interval, 1.73-12.88; P<.01) after controlling for age, sex, PAD severity, and cardiovascular risk factors. Type-D personality also independently predicted increased risk of depressive symptoms (odds ratio, 8.55; 95% confidence interval, 3.01-24.25; P<.001). CONCLUSIONS: Type-D personality independently predicted individual differences in impaired QOL and depressive symptoms in patients with PAD above and beyond ankle brachial index. It is important to account for personality when evaluating patient-based outcomes in the context of PAD.

Clinical classification of patients with lumbar spinal stenosis based on their leg pain syndrome: its correlation with 2-year surgical outcome.

STUDY DESIGN: Prospective follow-up and retrospective review of 174 patients surgically treated for degenerative lumbar spinal stenosis. OBJECTIVE: To examine whether the type of leg pain syndrome associated with lumbar spinal stenosis is correlated with outcome. SUMMARY OF BACKGROUND DATA: Although classifying patients based on their leg pain syndrome is useful in planning surgical decompression, there is no validated method of classification and its prognostic significance remains unknown. METHODS: Based on the type of leg pain, the patients were classified into 2 groups: unilateral and bilateral. Improvement in functional status was evaluated using the Quebec Back Pain Disability Scale; the symptoms were rated on a visual analog scale and the change from baseline to 2-year evaluation was noted. Associations between score changes and baseline variables were examined using multivariate analysis. RESULTS: The type of leg pain was independently associated with improvements in function and leg symptom scores but was not associated with improvement in the back pain score. After surgery, patients with unilateral leg pain had significantly greater improvements in function and leg symptoms than patients with bilateral leg pain. CONCLUSION: In patients undergoing surgery for degenerative lumbar spinal stenosis, the preoperative type of leg pain predicts function and leg symptom outcomes.

High-intensity interval training for intermittent claudication in a vascular rehabilitation program.

This article reports an observational study investigating the safety and effectiveness of a high-intensity interval exercise program for patients with peripheral arterial disease. Patients were asked to walk on a treadmill to maximal claudication pain six times in each exercise session, with 3-minute rests in between. Once a patient could walk continuously for 6 minutes without reaching maximal pain, speed and/or grade was increased. To account for the changes in speed and grade, patients' walking ability was measured as a rehabilitation score, calculated as the product of the two. A total of 47 patients were included in the study. Results showed overall improvement in the rehabilitation score with participation in the program, and specifically showed that participation in more exercise sessions led to greater improvement. Moreover, no adverse events occurred in the study patients, suggesting patients with peripheral arterial disease can safely tolerate high-intensity exercise programs.

Popliteal artery entrapment syndrome: morphological classification utilizing MR imaging.

OBJECTIVE: To retrospectively analyze magnetic resonance (MR) findings in patients with popliteal arterial entrapment syndrome. MATERIALS AND METHODS: This study was a retrospective MRI and CT scan review of 12 patients with 23 limbs with popliteal artery entrapment syndrome (PAES) treated over a 10-yr period. All 12 patients (23 limbs) were evaluated with MR and CT scan (11 patients - bilateral sides; one patient - unilateral side). All cases were classified as to various types of anomalous relationships between the popliteal artery and the neighboring muscles. The PAES was classified to gastrocnemius medial head and lateral head anomaly. Gastrocnemius medial head anomaly was classified according to the classification made by Whelan and Rich, from type 1 to type 6 [12, 13]. Gastrocnemius lateral head anomaly was defined as popliteal artery entrapment due to medially inserted gastrocnemius lateral head or aberrant accessory head of gastrocnemius lateral head. RESULTS: The gastrocnemius medial head anomaly was found in 14 limbs (14/23). The classic type 1 was found in none, type 2 in five patients (six limbs), type 3 in four patients (five limbs), type 4 in none, type 5 in one patient (one limb) and type 6 in one patient (two limbs). The uncommon type, i.e. lateral head of gastrocnemius anomaly, was found in five patients (eight limbs). CONCLUSION: The gastrocnemius medial head anomaly was the cause of PAES, and PAES was classified by medial head anomaly. However the gastrocnemius lateral head anomaly was also the cause of PAES, and most cases of gastrocnemius lateral head anomaliy showed aberrant accessory slip which entrapped the popliteal artery and vein.

Leg blood flow and long-term cardiovascular prognosis in men with typical and atypical intermittent claudication.

OBJECTIVES: To compare leg blood flow and the long-term cardiovascular prognosis in men with typical and atypical intermittent claudication (IC) according to Rose's questionnaire. METHODS: Leg blood flow during reactive hyperaemia was assessed at 55 years of age by calf plethysmography. Measurement of the systolic ankle-arm pressure index was used to assess the prevalence of peripheral arterial disease (PAD) at 68 years of age. Mortality and incidence of cardiac events is based on record linkage with regional and national registers. RESULTS: Twenty-one (3%) out of 700 men had typical IC at 55 years of age. Sixteen (76%) of these had normal plethysmography, with a mean peak flow (95% CI) of 24.6 (19.3-30.0) ml/min/100 ml. Peak flows were similar and normal in men with atypical IC (mean 22.5; 95% CI 21.3-23.6) and men having no pain (mean 23.8; 95% CI 23.1-24.4). Mortality rates were increased in men with typical IC but who had normal leg blood flow (49.5 deaths/1000 person years; p = 0.008), and men having atypical IC (35.3 deaths/1000 person years; p = 0.007) in comparison with men having no leg pain (27.4 deaths/1000 person years). This could not be accounted for by an increased cardiac event rate. The prevalence of PAD at 68 years of age was not increased in either of these two groups. CONCLUSIONS: Only 12% of subjects with exertional pain fulfilled all criteria for typical IC. Typical and atypical claudication in absence of objective evidence of PAD was associated with a reduced life expectancy, but not with an increased cardiovascular risk. To properly assess the prognosis, non-invasive assessment of PAD should be used in addition to questionnaires.

Efficacy of a short-course intensive rehabilitation program in patients with moderate-to-severe intermittent claudication.

BACKGROUND: Many rehabilitation programs for intermittent claudication include physical training for several months, since the outcome of short-course protocols is still unclear. The aim of this study was to evaluate the efficacy of a short course of exercise therapy in patients with moderate-to-severe intermittent claudication in terms of walking distance variations. METHODS: Twenty-six patients (males 88%, mean age 59 +/- 8 years, ankle-brachial index < or = 0.8 and < or = 0.5 before and after exercise respectively) were evaluated. Moderate-to-severe stenoses or occlusions were localized at color Doppler scanning of the abdominal aorta/iliac arteries and femoral/popliteal/tibial arteries in 15 and 31% of patients respectively, while in 54% of cases both the proximal and distal sites were involved. The initial and absolute claudication distances were recorded by means of the constant treadmill test (3 km/hour speed, 0% grade) at the time of presentation and after a short-course comprehensive rehabilitation program (4 week duration) including physical training, educational intervention, psychological support, and cardiovascular risk management. RESULTS: At the end of the program, 1 patient (4%) became asymptomatic (walked > 1000 m without pain). In 25 patients who still developed pain, the average increase in the initial claudication distance was 132% (from 75 to 174 m). Among these, 20 patients (77%) were still unable to complete the treadmill test due to maximal claudication pain, but the absolute claudication distance increased by 87% from 204 to 381 m (p < 0.05). No cardiovascular complication occurred during the study period. Major clinical variables failed to predict an unsatisfactory increase in walking capacity. CONCLUSIONS: Short-course training programs enhance the walking ability even in patients with moderate-to-severe intermittent claudication and seem to be well tolerated, supporting their widespread use in rehabilitation centers.

[Peripheral arterial occlusive disease. Symptoms, basic diagnosis and staged therapy]. / Periphere arterielle Verschlusskrankheit (pAVK). Symptomatik, Basisdiagnostik und Stufentherapie.

Intermittent claudication or rest pain are typical symptoms of peripheral arterial occlusive disease (PAOD) affecting the lower limbs. The pain is localized one level below that of the occlusion. Initial investigations should determine skin temperature and color, pulse status, stenotic sounds and Doppler occlusive pressures. If intermittent claudication is present, angiography of the pelvis and legs then follows. Treatment is stage-dependent: while in stages I and IIa conservative treatment such as cessation of smoking, administration of acetylsalicylic acid and walking training suffices, stages IIb and higher require invasive measures extending from PTA to amputation of gangrenous parts of the limb.

Tratamiento médico de la claudicacion intermitente / The medical treatment of intermittent claudication

Introducción. El diagnóstico de claudicación intermitente por afectación arteriosclerótica de las arterias de las extremidades inferiores (EEII) implica un incremento significativo del riesgo de complicaciones cardiovasculares (CCV), así como una limitación importante de la calidad de vida. Objetivo. Considerar la modificación de los factores de riesgo de progresión de la arteriosclerosis como factor prioritario de tratamiento. Conclusiones. La aspirina constituye el fármaco de primera elección en la prevención secundaria de las CCV en pacientes con enfermedad arterial periférica, y el clopidogrel, con efecto potencialmente más eficaz, representa una alternativa en pacientes con isquemia crónica de las EEII. Los datos actuales son insuficientes para recomendar el uso sistemático de un fármaco específico en todos los pacientes con claudicación (AU)

Natural history of claudication: long-term serial follow-up study of 1244 claudicants.

OBJECTIVE: The purpose of this study was to delineate the natural history of claudication and determine risk factors for ischemic rest pain (IRP) and ischemic ulceration (IU) among patients with claudication. METHODS: We prospectively collected data on 1244 men with claudication during a 15-year period, including demographics, clinical risk factors, and ankle-brachial index (ABI). We followed these patients serially with ABIs, self-reported walking distance (WalkDist), and monitoring for IRP and IU. We used Kaplan-Meier and proportional hazards modeling to find independent predictors of IRP and IU. RESULTS: Mean follow-up was 45 months; statistically valid follow-up could be carried out for as long as 12 years. ABI declined an average of 0.014 per year. WalkDist declined at an average rate of 9.2 yards per year. The cumulative 10-year risks of development of IU and IRP were 23% and 30%, respectively. In multivariate analysis using several clinical risk factors, we found that only DM (relative risk [RR], 1.8) and ABI (RR, 2.2 for 0.1 decrease in ABI) predicted the development of IRP. Similarly, only DM (RR, 3.0) and ABI (RR, 1.9 for 0.1 decrease in ABI) were significant predictors of IU. CONCLUSION: This large serial study of claudication is, to our knowledge, the longest of its kind. We documented an average rate of ABI decline of 0.014 per year and a decline in WalkDist of 9.2 yards per year. Two clinical factors, ABI and DM, were found to be associated with the development of IRP and IU. Our findings may be useful in predicting the clinical course of claudication.