Leg symptoms, the ankle-brachial index, and walking ability in patients with peripheral arterial disease

OBJECTIVE: To determine how functional status and walking ability are related to both severity of lower extremity peripheral arterial disease (PAD) and PAD-related leg symptoms. DESIGN: Cross-sectional study. SETTING: Academic medical center. PARTICIPANTS: Patients aged 55 years and older diagnosed with PAD in a blood flow laboratory or general medicine practice (n = 147). Randomly selected control patients without PAD were identified in a general medicine practice (n = 67). MEASUREMENTS: Severity of PAD was measured with the ankle-brachial index (ABI). All patients were categorized according to whether they had (1) no exertional leg symptoms; (2) classic intermittent claudication; (3) exertional leg symptoms that also begin at rest (pain at rest), or (4) exertional leg symptoms other than intermittent claudication or pain at rest (atypical exertional leg symptoms). Participants completed the 36-Item Short-Form Health Survey (SF-36) and the Walking Impairment Questionnaire (WIQ). The WIQ quantifies patient-reported walking speed, walking distance, and stair-climbing ability, respectively, on a scale of 0 to 100 (100 = best). MAIN RESULTS: In multivariate analyses patients with atypical exertional leg symptoms, intermittent claudication, and pain at rest, respectively, had progressively poorer scores for walking distance, walking speed, and stair climbing. The ABI was measurably and independently associated with walking distance (regression coefficient = 2.87/0.1 ABI unit, p =.002) and walking speed (regression coefficient = 2.09/0.1 ABI unit, p =.015) scores. Among PAD patients only, pain at rest was associated independently with all WIQ scores and six SF-36 domains, while ABI was an independent predictor of WIQ distance score. CONCLUSIONS: Both PAD-related leg symptoms and ABI predict patient-perceived walking ability in PAD.     

Peripheral arterial disease symptom subtype and walking impairment

Walking impairment is common in patients with peripheral arterial disease (PAD). The purpose of this study was to compare specific leg symptoms and walking impairment in a racially diverse cohort of patients with PAD. Patients who were receiving care at the Michael E DeBakey Veterans Affairs Medical Center or in the Harris County Hospital District were screened for PAD, which was diagnosed in the office setting by blood pressure measurements that were used to calculate the ankle-brachial index (a level <0.90 was defined as disease). To define leg symptoms, we asked patients to complete the San Diego Claudication Questionnaire. Based on the questionnaire results, leg symptoms were categorized as: asymptomatic, atypical, and intermittent claudication. The patients also completed the Walking Impairment Questionnaire. Among 403 patients screened (136 Caucasians, 136 African Americans and 131 Latinos), 67 were found to have PAD (18 Caucasians, 31 African Americans and 18 Latinos). The mean age of the cohort was 63.8 years (standard deviation (SD) 7.3). Walking distance, speed and stair climbing scores were lower (p < 0.0001) for patients with PAD and leg pain on exertion or at rest when compared with patients with PAD without leg symptoms or with symptoms of intermittent claudication. For patients with PAD and leg pain on exertion and at rest, the walking distance score was 27.1 +/- SD 37.7 compared with 41.0 +/- 38.4 for those with asymptomatic disease who were inactive, and with 38.5 +/- 42.7 for those with intermittent claudication (p = 0.02). In an ethnically diverse primary care clinic population, patients with PAD and leg pain on exertion and at rest had greater compromise in their walking ability when compared with patients with intermittent claudication. The reasons for the significant impairment in walking among patients with PAD and these atypical leg symptoms may stem from coexisting illnesses or other as yet undefined factors. Future research should focus on methods to improve daily walking in patients with PAD and atypical leg symptoms.     

Association of anger proneness, depression and low social support with peripheral arterial disease: the Atherosclerosis Risk in Communities Study

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

Functional status measured by walking impairment questionnaire and cardiovascular risk prediction in peripheral arterial disease: results of the Peripheral Arteriopathy and Cardiovascular Events (PACE) study

The prognostic impact of the functional status of patients with intermittent claudication is still obscure. From the lists of seven general practitioners, we identified all subjects aged 40-80 years (n = 4352). Of those reporting leg symptoms while walking on the Rose questionnaire (n = 760), 60 had a qualifying diagnosis of peripheral arterial disease (PAD). All of them received the Walking Impairment Questionnaire (WIQ). For each patient affected by PAD, three sex- and age-matched controls were selected randomly. After a 24-month follow-up, survival curves showed that PAD patients with WIQ scores > median had a higher cardiovascular risk than controls, and patients with WIQ scores < median had an even poorer prognosis (p < 0.001 for all WIQ domains). In PAD, after adjustment for age, sex, ankle-brachial index and comorbidity, two WIQ domains (ie walking speed and stair-climbing) were associated with cardiovascular events. The cardiovascular risk of claudicants who had a score > median for at least three WIQ domains was intermediate versus the risk of controls and PAD patients with a WIQ score < median, also when adjusted for the covariates indicated above (RR = 3.26, p = 0.019). In intermittent claudication, a worse functional status entails a greater risk of ischemic events versus low functional impairment.     

The prevalence of peripheral arterial disease in a racially diverse population

BACKGROUND: The purpose of this study was to determine the prevalence of peripheral arterial disease (PAD) in white, African American, and English- and Spanish-speaking Hispanic patients. METHODS: We screened patients older than 50 years for PAD at 4 primary care clinics located in the Houston Veterans Affairs Medical Center and the Harris County Hospital District. The disease was diagnosed by an ankle-brachial index of less than 0.9. Patients also completed questionnaires to ascertain symptoms of intermittent claudication, walking difficulty, medical history, and quality of life. RESULTS: We enrolled 403 patients (136 whites; 136 African Americans; and 131 Hispanics, 81 of whom were Spanish speaking). The prevalence of PAD was 13.2% among whites, 22.8% among African Americans, and 13.7% among Hispanics (P =.06). African Americans had a significantly higher prevalence of PAD than whites and Hispanics combined (P =.02). Among all patients who were diagnosed as having PAD on the basis of their ankle-brachial index, only 5 (7.5%) had symptoms of intermittent claudication. CONCLUSIONS: Peripheral arterial disease is a prevalent illness in the primary care setting. Its prevalence varies by race and is higher in African Americans than in whites and Hispanics. Relative to the prevalence of PAD, the prevalence of intermittent claudication is low. Since measurement of the ankle-brachial index is not part of the routine clinic visit, many patients with PAD are not diagnosed unless they develop symptoms of intermittent claudication. Because of this, it is likely that many patients remain undiagnosed. Efforts are needed to improve PAD detection in the primary care setting.     

Leg Symptom Categories and Rates of Mobility Decline in Peripheral Arterial Disease

OBJECTIVES: To determine whether asymptomatic lower extremity peripheral arterial disease (PAD) and leg symptoms other than intermittent claudication (IC) in PAD are associated with faster functional decline than in people with both PAD and IC. DESIGN: Prospective, observational study. SETTING: Chicago‐area medical center. PARTICIPANTS: Four hundred fifteen people with PAD followed annually for up to 7 years. MEASUREMENTS: At baseline, patients with PAD were categorized into symptom categories, including IC; leg pain on exertion and rest; participants who could walk through exertional leg pain (pain/carry on); and participants who never experienced exertional leg pain, even during the 6‐minute walk (always asymptomatic). Outcomes included mobility loss (becoming unable to walk one‐quarter of a mile or walk up and down one flight of stairs without assistance) and becoming unable to complete the 6‐minute walk without stopping. Analyses adjusted for age, sex, comorbidities, ankle brachial index, and other confounders. RESULTS: Always‐asymptomatic participants (hazard ratio (HR)=2.94, 95% confidence interval (CI)=1.39–6.19, P=.005) and those with leg pain on exertion and rest (HR=2.89, 95% CI=1.47–5.68, P=.002) had greater mobility loss than participants with IC. Participants with PAD with leg pain/carry on were less likely (P=.047) to become unable to walk for 6 minutes continuously without stopping than participants with IC. CONCLUSION: The ABI identifies patients with asymptomatic PAD and those with atypical leg symptoms who are at risk for greater mobility decline than participants without PAD and participants with PAD with IC.     

Abnormal circulating levels of metalloprotease 9 and its tissue inhibitor 1 in angiographically proven peripheral arterial disease: relationship to disease severity

BACKGROUND: Peripheral arterial disease (PAD) is associated with adaptive changes in the vascular and muscle extracellular matrix (ECM) in response to reduced blood flow. Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs), are key modulators of ECM turnover. We hypothesized that patients with intermittent claudication (with low ankle-brachial blood pressure index, <0.8), and critical ischaemia would have raised circulating levels of MMP-9, TIMP-1 and TIMP-2 compared with healthy controls, reflecting an increase in proteolytic activity which may be related to ECM turnover in PAD. METHODS: We studied 36 patients (23 males; 65 +/- 9 years) with intermittent claudication and 43 (25 males; 68 +/- 12) patients with critical ischaemia. All patients had angiographic evidence confirming significant PAD. RESULTS: Circulating levels of MMP-9 and TIMP-1 were higher (both P < 0.0001) in the PAD patient groups compared with the controls. Patients with critical ischaemia had MMP-9 and TIMP-1 levels that were significantly higher than those with intermittent claudication. There were no differences in circulating TIMP-2 levels between patients and controls. There was a modest positive correlation between the white cell count (WCC) and MMP-9, both patients with intermittent claudication (Spearman, r = 0.398, P = 0.016) and critical ischaemia (r = 0.378, P = 0.014). CONCLUSION: We demonstrate higher levels of circulating MMP-9 and TIMP-1 in patients with intermittent claudication and critical ischaemia. Circulating concentrations of both markers can be related to disease severity, being higher in critical ischaemia compared with levels in intermittent claudication.     

Progression of asymptomatic peripheral artery disease over 1 year

The pathophysiology and time course of an individual converting from asymptomatic peripheral artery disease (PAD) to symptomatic claudication is unclear. The objectives of this study were: (1) to characterize the extent of atherosclerotic disease in individuals with an abnormal ankle-brachial index (ABI), but without claudication; and over 1 year of follow-up to (2) evaluate the progression of PAD using ultrasound imaging, (3) determine changes in the ABI and leg pain symptoms, and (4) correlate PAD progression with changes in the ABI and leg symptoms. We hypothesized that PAD progression would be associated with the development of claudication and changes in the ABI, 6-minute walk distance (6-MWD), and walking quality of life. Individuals with a reduced ABI but without typical intermittent claudication noted on community screening were invited to undergo baseline and 1-year follow-up assessment, including duplex ultrasound. The initial and repeat evaluations included measurement of the ABI, lower extremity duplex arterial mapping, and assessment of leg pain and functional status. Of the 50 people studied, 44 (88%) had significant atherosclerotic lesions in the lower extremity arteries, affecting 80 legs. A total of 33 of 50 individuals (66%) returned for the 1-year follow-up visit. On ultrasound examination, two of 18 normal legs developed PAD, and in 48 legs with PAD at baseline, 17 legs (35%) developed new or progressive lesions. Thirteen legs developed new claudication. Overall, there was no significant worsening in the ABI, 6-MWD, or the Walking Impairment Questionnaire (WIQ). However, legs with new lesions or lesion progression were significantly more likely to develop claudication, and the 13 legs (seven subjects) developing claudication showed a significant decline in the 6-MWD. In conclusion, these data indicate that a significant number of people with asymptomatic PAD show progression over 1 year, that such individuals are more likely to develop claudication, and that those developing claudication have a significant decrease in their 6-MWD.     

The ankle-brachial pressure index and a standardized questionnaire are easy and useful tools to detect peripheral arterial disease in non-claudicating patients at high risk.

AIM: This observational study (Survey of Peripheral Arterial Disease Epidemiology, SPADE) evaluated the prevalence of asymptomatic peripheral arterial disease (PAD) in general practice. METHODS: PAD was determined as an ankle-brachial pressure index (ABI) <0.9 measured with Doppler ultrasound. Included patients had a history of ischemic events and/or risk factors for PAD, but no spontaneous complaints of intermittent claudication. Patients with an ABI <0.9 filled in a standardized questionnaire and their drug use was registered. A total of 4 536 patients was included. RESULTS: The prevalence of PAD was 18.7% for the total population, 26.5% for those with a history of ischemic events and 15.2% for those without such history. The prevalence increased with age, but was independent of gender. A standard questionnaire revealed leg pain when walking uphill or when hurrying in 2/3 of patients with an ABI <0.9 and in 45% criteria for claudication were met. CONCLUSION: ABI detects PAD in a considerable number of asymptomatic patients at increased risk and followed in general practice. When properly questioned almost half of these patients appear to have intermittent claudication.     

The prevalence of occult peripheral arterial disease among patients referred for orthopedic evaluation of leg pain

AbstractLower extremity peripheral arterial disease (PAD) and musculoskeletal conditions both produce symptoms of leg pain, and may coexist. This study assesses the prevalence of PAD among patients referred to orthopedic surgery for evaluation of lower extremity pain. Fifty consecutive patients aged 50 years or more who had a chief complaint of leg pain, no history of trauma, and no previous history of PAD were studied prospectively. The presence of known risk factors for PAD and classic claudication symptoms was assessed by telephone interview and medical record review. Individuals were then evaluated by measurement of the ankle-brachial index (ABI) using Doppler and pulse volume recordings (PVR). A patient was deemed to have PAD if the ABI was below 0.9 or if the PVR demonstrated significant abnormalities. Occult PAD was detected in 10 of the 50 patients (20%) on the basis of the non-invasive vascular studies. There were no differences between patients with PAD and those without PAD regarding the presence of risk factors for PAD. None of the patients without PAD had claudication, while only one of the 10 patients with PAD had symptoms of classic claudication. In conclusion, 20% of patients referred by primary care providers to the orthopedic surgery clinic for lower extremity pain were discovered to have occult PAD. The majority of these patients did not have claudication. Orthopedic surgeons and primary care providers must maintain an appropriately high index of suspicion for PAD when evaluating patients with non-traumatic lower extremity pain.     

Do age and comorbidity affect quality of life or PTA-induced quality-of-life improvements in patients with symptomatic pad?

PURPOSE: To elucidate whether age or comorbidity influences (1) quality of life (QoL) or (2) the gain in QoL due to percutaneous angioplasty procedures in symptomatic peripheral arterial disease (PAD) patients. METHODS: One hundred two consecutive patients (81 men; mean age 66.3+/-9.1 years, range 44-83) with symptomatic PAD (83.2% with intermittent claudication, 16.8% with chronic critical limb ischemia) were tested cross-sectionally for their self-reported QoL and degree of leg pain during walking or rest according to standardized scales. A subgroup of 48 patients with a comparable clinical profile was prospectively investigated before and shortly after angioplasty. Quantitative indices of comorbidity burden and hemodynamic parameters were also obtained. RESULTS: QoL impairment significantly increased with a greater comorbidity burden and greater degree of leg pain during exercise or at rest, but decreased with advancing age (R = 0.91, p < 0.0001, stepwise regression). The angioplasty-associated gain in QoL, however, was positively correlated with the initial degree of QoL impairment and the degree of improvement in intermittent claudication (R = 0.873, p < 0.0001, multiple regression). By contrast, neither age nor comorbidity burden adversely affected angioplasty-induced QoL improvements. CONCLUSIONS: PAD patients with higher levels of leg pain or a greater comorbidity burden generally have more pronounced QoL impairment. They can gain considerable QoL benefits from percutaneous procedures, especially if they have greater QoL impairment initially, and experience substantial improvements in exertional leg pain after treatment. In general, neither age nor comorbidity should negatively influence the decision for percutaneous therapy in symptomatic PAD patients.     

Peripheral arterial disease

Prevalence of peripheral arterial disease (PAD) is high and patients with PAD have a high rate of cardiovascular mortality. Most patients are clinically asymptomatic, therefore it is important to screen persons using ankle-brachial index. It is useful to combine functional and morphological measurements to diagnose leg perfusion and for planning various treatment options. Treatment of cardiovascular risk factors is central to improve prognosis. Moreover, thrombocyte aggregation inhibitors are indicated. Patients with intermittent claudication should perform an exercise training program. In addition drugs can be used to improve walking distance. In patients with intermittent claudication peripheral intervention can be useful. However, in stable patients surgical treatment should be restricted to single cases. In patients with critical limb ischemia (pain at rest or ulcer/gangrene) percutaneous intervention or bypass surgery must be performed immediately. After successful improvement of leg perfusion the high risk PAD patients should be followed by a regular program for all their life.     

Periphere arterielle Verschlusskrankheit

Prevalence of peripheral arterial disease (PAD) is high and patients with PAD have a high rate of cardiovascular mortality. Most patients are clinically asymptomatic, therefore it is important to screen persons using ankle-brachial index. It is useful to combine functional and morphological measurements to diagnose leg perfusion and for planning various treatment options. Treatment of cardiovascular risk factors is central to improve prognosis. Moreover, thrombocyte aggregation inhibitors are indicated. Patients with intermittent claudication should perform an exercise training program. In addition drugs can be used to improve walking distance. In patients with intermittent claudication peripheral intervention can be useful. However, in stable patients surgical treatment should be restricted to single cases. In patients with critical limb ischemia (pain at rest or ulcer/gangrene) percutaneous intervention or bypass surgery must be performed immediately. After successful improvement of leg perfusion the high risk PAD patients should be followed by a regular program for all their life.     

Knowledge and attitudes regarding cardiovascular disease risk and prevention in patients with coronary or peripheral arterial disease

BACKGROUND: We compared perceptions regarding risk of cardiovascular events and benefits of cardiovascular disease (CVD) risk factor reduction between patients with peripheral arterial disease (PAD), patients with coronary artery disease (CAD), and patients without atherosclerosis (no disease). METHODS: Participants with no disease (n = 142) had a normal ankle-brachial index and no clinically evident atherosclerosis (group 1). The PAD participants (n = 136) had an ankle-brachial index less than 0.90 and no other clinically evident atherosclerosis (group 2). Participants with CAD (n = 70) had a normal ankle-brachial index and a history of heart disease (group 3). Participants were interviewed regarding risk of mortality, CVD, and the importance of CVD risk factor reduction for hypothetical patients with PAD and CAD. RESULTS: All groups reported that risks of myocardial infarction, stroke, and death were higher for a patient with CAD than for a patient with PAD. Group 2 was less likely than group 3 to believe that PAD is associated with an extremely high risk of stroke (13.3% vs 28.7%; P =.005) or mortality (10.9% vs 26.6%; P =.003). Group 2 was less likely than group 1 to believe that a patient with PAD has a very high risk of myocardial infarction (13.1% vs 23.8%; P =.02), stroke (13.3% vs 27.5%; P =.003), or mortality (10.9% vs 24.3%; P =.004). Compared with group 3, a smaller percentage of patients in group 2 reported that cholesterol lowering was very important in PAD (57.5% vs 75.8%; P =.005). CONCLUSIONS: Compared with other patients, those with PAD underestimated the high risk of cardiovascular events associated with PAD and the benefits of cholesterol-lowering therapy. These findings may help explain the low rates of CVD risk factor control previously reported in patients with PAD.     

Classic intermittent claudication is an uncommon manifestation of lower extremity peripheral arterial disease in hospitalized patients with coronary artery disease

Synchronous peripheral arterial disease (PAD) and coronary artery disease (CAD) is common. Standardized questionnaires such as the Rose/WHO questionnaire and later the Edinburgh modification of this questionnaire were developed to screen for PAD. Little data are available on the sensitivity of these questionnaires in hospitalized patients with CAD. The aim of this study was to determine the accuracy of these questionnaires and the prevalence of classic intermittent claudication in hospitalized patients with CAD. Medically stable patients with CAD were invited to participate before hospital discharge. The patients answered both the Rose/WHO and Edinburgh modification claudication questionnaires and had an ankle-brachial index (ABI) measured. An ABI less than or equal to 0.9 was considered to be indicative of significant PAD. Patients who had undergone previous lower extremity revascularization for PAD and had a corrected ABI greater than 0.9 were excluded. Ninety-five patients (66 men) were recruited. By measuring the ABI, 35 patients (25 men) were found to have significant PAD. An additional 3 patients who had an ABI corrected by lower extremity revascularization were excluded from the analysis. The Rose/WHO questionnaire had a sensitivity, specificity, and overall accuracy (95% CI) of 14.3% (2.7-25.9%), 96.7% (92.1-100%), and 66.3% (56.8-75.8%), respectively. The Edinburgh modification of the Rose/WHO questionnaire had a sensitivity, specificity, and overall accuracy (95% CI) of 28.6% (13.6-43.5%), 90.0% (82.4-97.6%), 67.4% (57.9-76.8%), respectively. Despite the high incidence of synchronous PAD in hospitalized patients with CAD, traditional claudication questionnaires are insensitive to PAD detection. Classic claudication is an uncommon manifestation of PAD in hospitalized patients with CAD.     

Mild peripheral neuropathy prevents both leg muscular ischaemia and activation of exercise-induced coagulation in Type 2 diabetic patients with peripheral artery disease.

AIM: To study the influence of peripheral neuropathy on intermittent claudication in patients with Type 2 diabetes (T2DM). METHODS: Twenty-five patients with T2DM were grouped according to the ankle/brachial index (ABI): 10 with ABI > 0.9 without peripheral artery disease (PAD; group T2DM) and 15 with ABI < 0.9 with PAD (group T2DM + PAD). Twelve individuals without T2DM with PAD (group PAD without T2DM) were also enrolled. Tests for peripheral neuropathy were performed in all patients. ABI, rate pressure product, prothrombin fragments 1 + 2 (F1+2), thrombin-anti-thrombin complex (TAT), and d-dimer were measured before and after a treadmill test. During exercise both initial and absolute claudication distance and electrocardiogram readings were recorded. RESULTS: We found mild peripheral neuropathy in 20% of group T2DM and 46.7% of group T2DM + PAD (P < 0.01). After exercise, the rate pressure product increased in each group; ABI fell in T2DM + PAD (P < 0.0001) and in PAD without T2DM (P = 0.0005); the fall was greater in the latter group. Initial and absolute claudication distances were similar in PAD patients. In group T2DM + PAD, absolute claudication distance was longer in the subgroup without peripheral neuropathy (P < 0.05), whereas ABI and rate pressure products were similar. F1+2 values at rest were higher in group T2DM + PAD. After exercise, F1+2 values and TAT increased only in group PAD without T2DM. CONCLUSION: Only group PAD without T2DM experienced muscular ischaemia, whereas group T2DM + PAD did not. Mild peripheral neuropathy may have prevented them from reaching the point of muscular ischaemia during the treadmill test, because they stopped exercising with the early onset of pain. Reaching a false absolute claudication distance may induce ischaemic preconditioning. These findings suggest a possible protective role of mild peripheral neuropathy in T2DM patients with intermittent claudication, by preventing further activation of coagulation during treadmill testing.     

Prevalence and significance of unrecognized lower extremity peripheral arterial disease in general medicine practice

OBJECTIVE: To determine the prevalence of unrecognized lower extremity peripheral arterial disease (PAD) among men and women aged 55 years and older in a general internal medicine (GIM) practice and to identify characteristics and functional performance associated with unrecognized PAD. DESIGN: Cross-sectional. SETTING: Academic medical center. PARTICIPANTS: We identified 143 patients with known PAD from the noninvasive vascular laboratory, and 239 men and women aged 55 and older with no prior PAD history from a GIM practice. Group 1 consisted of patients with PAD consecutively identified from the noninvasive vascular laboratory (n = 143). Group 2 included GIM practice patients found to have an ankle brachial index less than 0.90, consistent with PAD (n = 34). Group 3 consisted of GIM practice patients without PAD (n = 205). MEASUREMENTS AND MAIN RESULTS: Leg functioning was assessed with the 6-minute walk, 4-meter walking velocity, and Walking Impairment Questionnaire (WIQ). Of GIM practice patients, 14% had unrecognized PAD. Only 44% of patients in Group 2 had exertional leg symptoms. Distances achieved in the 6-minute walk were 1,130, 1,362, and 1,539 feet for Groups 1, 2, and 3, respectively, adjusting for age, gender, and race (P <.001). The degree of difficulty walking due to leg symptoms as reported on the WIQ was comparable between Groups 2 and 3 and significantly greater in Group 1 than Group 2. In multiple logistic regression analysis including Groups 2 and 3, current cigarette smoking was associated independently with unrecognized PAD (odds ratio [OR], 6.82; 95% confidence interval [95% CI], 1.55 to 29.93). Aspirin therapy was nearly independently associated with absence of PAD (OR, 0.37; 95% CI, 0.12 to 1.12). CONCLUSION: Unrecognized PAD is common among men and women aged 55 years and older in GIM practice and is associated with impaired lower extremity functioning. Ankle brachial index screening may be necessary to diagnose unrecognized PAD in a GIM practice.     

Treatment of intermittent claudication with beraprost sodium,an orally active prostaglandin I2 analogue: a double-blinded,randomized, controlled trial

OBJECTIVES: In the current study, we hypothesized that beraprost would: 1) improve treadmill exercise performance and quality of life; and 2) decrease rates of ischemic events in patients with intermittent claudication. BACKGROUND: Previous trials with beraprost sodium, an orally active prostaglandin I(2) analogue, in the treatment of claudication in patients with peripheral arterial disease (PAD) have been inconsistent. METHODS: Patients with intermittent claudication (n = 897) were randomized to receive either 40 microg three times a day of beraprost with meals (n = 385) or placebo (n = 377) in a double-blinded manner for one year. The primary efficacy parameter was treadmill-measured maximum walking distance, as assessed at three and six months after randomization. Secondary efficacy parameters included treadmill-measured pain-free walking distance and change in quality of life. RESULTS: There was no significant improvement in maximum walking distance in the beraprost group (16.7%) as compared with the placebo group (14.6%, p = NS). Administration of beraprost did not improve the pain-free walking distance (p = NS between treatment groups), and there was no improvement in the quality-of-life measures between the treatment groups. The incidence of critical cardiovascular events was 7.3% in the beraprost group and 11.4% in the placebo group (p = NS). There was a significant reduction in the combination of cardiovascular death and myocardial infarction in the beraprost group (p = 0.01). CONCLUSIONS: Despite previous investigations suggesting efficacy, these results indicate that beraprost is not an effective treatment to improve symptoms of intermittent claudication in patients with PAD. The potential benefit of beraprost on critical cardiovascular events would require confirmation in a larger prospective investigation.     

Functional outcomes and quality of life in peripheral arterial disease: current status

This review examines current evidence for baseline functional impairment and changes with therapy in patients with peripheral arterial disease (PAD)--ranging from patients without claudication or critical limb ischemia (CLI) but other exertional leg symptoms (erroneously referred to as asymptomatic in the Fontaine classification system), to patients with claudication and those with CLI. The review points out that the status of functional outcomes research is markedly different in focus and development in the different levels of disease severity--paradoxically less studied in the more severe CLI population than in patients with claudication, for example.     

The effect of inhibition of acyl coenzyme A-cholesterol acyltransferase (ACAT) on exercise performance in patients with peripheral arterial disease

This study tested the hypothesis that avasimibe, an inhibitor of acyl coenzyme A-cholesterol acyltransferase (ACAT), would improve treadmill exercise performance in patients with claudication secondary to peripheral arterial disease (PAD). Four hundred and forty-two patients with PAD (ankle-brachial index in the index leg of < or =0.90 with a > or =20% reduction post-exercise) were enrolled from 39 centers in the USA. Patients were randomized to receive oral avasimibe 50 mg, 250 mg, 750 mg or placebo for a treatment period of 12 months. Changes from baseline in peak walking time (PWT) using a graded treadmill protocol were compared among groups after 6 and 12 months of treatment. Individual group comparisons were considered statistically significant if p < 0.0245 for the 50 mg and 250 mg groups and p < 0.001 for the 750 mg group. Patients randomized to the 50 mg group experienced a 0.76 min net increase over placebo in PWT, but this did not reach the pre-specified level of statistical significance (Hochberg procedure p = 0.027) using ANCOVA after 12 months of treatment after adjusting for multiple comparisons. This trend in PWT was supported by the changes in treadmill initial claudication time (ICT) (p = 0.026) and Walking Impairment Questionnaire (WIQ) walking distance score (p = 0.058). The 250 mg and 750 mg avasimibe dose groups failed to demonstrate an improvement in PWT over placebo after 6 months of treatment. In conclusion, while the ACAT inhibitor avasimibe did not show clear evidence of benefit on treadmill exercise performance in patients with PAD, the results add to our knowledge of the impact of treatments directed at atherosclerosis on functional endpoints.