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1.  Surrogates of Large Artery versus Small Artery Stiffness and Ankle-Brachial Index 
Peripheral artery tonometry (PAT) is a novel method for assessing arterial stiffness of small digital arteries. Pulse pressure can be regarded as a surrogate of large artery stiffness. When ankle-brachial index (ABI) is calculated using the higher of the two ankle systolic pressures as denominator (ABI-higher), leg perfusion can be reliably estimated. However, using the lower of the ankle pressures to calculate ABI (ABI-lower) identifies more patients with isolated peripheral arterial disease (PAD) in ankle arteries. We aimed to compare the ability of PAT, pulse pressure, and different calculations of ABI to detect atherosclerotic disease in lower extremities. We examined PAT, pulse pressure, and ABI in 66 cardiovascular risk subjects in whom borderline PAD (ABI 0.91 to 1.00) was diagnosed 4 years earlier. Using ABI-lower to diagnose PAD yielded 2-fold higher prevalence of PAD than using ABI-higher. Endothelial dysfunction was diagnosed in 15/66 subjects (23%). In a bivariate correlation analysis, pulse pressure was negatively correlated with ABI-higher (r = −0.347, p = 0.004) and with ABI-lower (r = −0.424, p < 0.001). PAT hyperemic response was not significantly correlated with either ABI-higher (r = −0.148, p = 0.24) or with ABI-lower (r = −0.208, p = 0.095). Measurement of ABI using the lower of the two ankle pressures is an efficient method to identify patients with clinical or subclinical atherosclerosis and worth performing on subjects with pulse pressure above 65 mm Hg. The usefulness of PAT measurement in detecting PAD is vague.
doi:10.1055/s-0031-1284200
PMCID: PMC3331653  PMID: 22942632
Ankle-brachial index; peripheral arterial disease; hypertension
2.  Ankle Brachial Index Values, Leg Symptoms, and Functional Performance Among Community‐Dwelling Older Men and Women in the Lifestyle Interventions and Independence for Elders Study 
Background
The prevalence and significance of low normal and abnormal ankle brachial index (ABI) values in a community‐dwelling population of sedentary, older individuals is unknown. We describe the prevalence of categories of definite peripheral artery disease (PAD), borderline ABI, low normal ABI, and no PAD and their association with lower‐extremity functional performance in the LIFE Study population.
Methods and Results
Participants age 70 to 89 in the LIFE Study underwent baseline measurement of the ABI, 400‐m walk, and 4‐m walking velocity. Participants were classified as follows: definite PAD (ABI <0.90), borderline PAD (ABI 0.90 to 0.99), low normal ABI (ABI 1.00 to 1.09), and no PAD (ABI 1.10 to 1.40). Of 1566 participants, 220 (14%) had definite PAD, 250 (16%) had borderline PAD, 509 (33%) had low normal ABI, and 587 (37%) had no PAD. Among those with definite PAD, 65% were asymptomatic. Adjusting for age, sex, race, body mass index, smoking, and comorbidities, lower ABI was associated with longer mean 400‐m walk time: (definite PAD=533 seconds; borderline PAD=514 seconds; low normal ABI=503 seconds; and no PAD=498 seconds [P<0.001]). Among asymptomatic participants with and without PAD, lower ABI values were also associated with longer 400‐m walk time (P<0.001) and slower walking velocity (P=0.042).
Conclusion
Among older community‐dwelling men and women, 14% had PAD and 49% had borderline or low normal ABI values. Lower ABI values were associated with greater functional impairment, suggesting that lower extremity atherosclerosis may be a common preventable cause of functional limitations in older people.
Clinical Trial Registration
URL: http://clinicaltrials.gov/ Unique identifier: NCT01072500.
doi:10.1161/JAHA.113.000257
PMCID: PMC3886743  PMID: 24222666
aging; exercise; peripheral vascular disease
3.  To screen or not to screen for peripheral arterial disease in subjects aged 80 and over in primary health care: a cross-sectional analysis from the BELFRAIL study 
BMC Family Practice  2011;12:39.
Background
Peripheral arterial disease (PAD) is common in older people. An ankle-brachial index (ABI) < 0.9 can be used as an indicator of PAD. Patients with low ABI have increased mortality and a higher risk of serious cardiovascular morbidity. However, because 80% of the patients are asymptomatic, PAD remains unrecognised in a large group of patients. The aims of this study were 1) to examine the prevalence of reduced ABI in subjects aged 80 and over, 2) to determine the diagnostic accuracy of the medical history and clinical examination for reduced ABI and 3) to investigate the difference in functioning and physical activity between patients with and without reduced ABI.
Methods
A cross-sectional study embedded within the BELFRAIL study. A general practitioner (GP) centre, located in Hoeilaart, Belgium, recruited 239 patients aged 80 or older. Only three criteria for exclusion were used: urgent medical need, palliative situation and known serious dementia. The GP recorded the medical history and performed a clinical examination. The clinical research assistant performed an extensive examination including Mini-Mental State Examination (MMSE), Geriatric Depression Scale (GDS-15), Activities of Daily Living (ADL), Tinetti test and the LASA Physical Activity Questionnaire (LAPAQ). ABI was measured using an automatic oscillometric appliance.
Results
In 40% of patients, a reduced ABI was found. Cardiovascular risk factors were unable to identify patients with low ABI. A negative correlation was found between the number of cardiovascular morbidities and ABI. Cardiovascular morbidity had a sensitivity of 65.7% (95% CI 53.4-76.7) and a specificity of 48.6% (95% CI 38.7-58.5). Palpation of the peripheral arteries showed the highest negative predictive value (77.7% (95% CI 71.8-82.9)). The LAPAQ score was significantly lower in the group with reduced ABI.
Conclusion
The prevalence of PAD is very high in patients aged 80 and over in general practice. The clinical examination, cardiovascular risk factors and the presence of cardiovascular morbidity were not able to identify patients with a low ABI. A screening strategy for PAD by determining ABI could be considered if effective interventions for those aged 80 and over with a low ABI become available through future research.
doi:10.1186/1471-2296-12-39
PMCID: PMC3121584  PMID: 21605447
4.  Prevalence of peripheral arterial disease in patients at non-high cardiovascular risk. Rationale and design of the PANDORA study 
Background
Lower extremity peripheral arterial disease (PAD) is a marker of widespread atherosclerosis. Individuals with PAD, most of whom do not show typical PAD symptoms ('asymptomatic' patients), are at increased risk of cardiovascular ischaemic events. American College of Cardiology/American Heart Association guidelines recommend that individuals with asymptomatic lower extremity PAD should be identified by measurement of ankle-brachial index (ABI). However, despite its associated risk, PAD remains under-recognised by clinicians and the general population and office-based ABI detection is still poorly-known and under-used in clinical practice. The Prevalence of peripheral Arterial disease in patients with a non-high cardiovascular disease risk, with No overt vascular Diseases nOR diAbetes mellitus (PANDORA) study has a primary aim of assessing the prevalence of lower extremity PAD through ABI measurement, in patients at non-high cardiovascular risk, with no overt cardiovascular diseases (including symptomatic PAD), or diabetes mellitus. Secondary objectives include documenting the prevalence and treatment of cardiovascular risk factors and the characteristics of both patients and physicians as possible determinants for PAD under-diagnosis.
Methods/Design
PANDORA is a non-interventional, cross-sectional, pan-European study. It includes approximately 1,000 primary care participating sites, across six European countries (Belgium, France, Greece, Italy, The Netherlands, Switzerland). Investigator and patient questionnaires will be used to collect both right and left ABI values at rest, presence of cardiovascular disease risk factors, current pharmacological treatment, and determinants for PAD under-diagnosis.
Discussion
The PANDORA study will provide important data to estimate the prevalence of asymptomatic PAD in a population otherwise classified at low or intermediate risk on the basis of current risk scores in a primary care setting.
Trial registration number
Clinical Trials.gov Identifier: NCT00689377.
doi:10.1186/1471-2261-10-35
PMCID: PMC2927475  PMID: 20687927
5.  Survival in Patients with Poorly Compressible Leg Arteries 
Objective
Compare survival of patients with poorly compressible arteries (PCA) to those with a normal ankle-brachial index (ABI) and those with peripheral arterial disease (PAD).
Background
Limited data are available regarding survival in patients with PCA identified in the clinical setting by non-invasive lower extremity arterial evaluation.
Methods
We conducted a historical cohort study of consecutive patients who underwent outpatient, non-invasive lower extremity arterial evaluation at Mayo Clinic, Rochester, Minnesota, from January 1998 through December 2007, and were followed for a mean duration of 5.8±3.1 years. An ABI 1.00-1.30 was considered normal, PAD was defined as a resting or post-exercise ABI ≤0.90, and PCA defined as an ABI ≥1.4 and/or an ankle systolic blood pressure >255 mm Hg. Patients were followed for all-cause mortality through 09/30/2009.
Results
Of 16,493 individuals (mean age ± standard deviation = 67.8±13.0 years, 59% male); 29% had normal ABI, 54% had PAD, and 17% had PCA. During follow-up (mean duration = 5.8±3.1 years), 4365 patients (26%) died. The percent alive at the end of the study period was 88%, 70%, and 60% for normal ABI, PAD, and PCA respectively. After adjustment for age, sex, cardiovascular risk factors, comorbid conditions, and medication use, the hazard ratios (confidence interval) of death associated with PCA were 2.0 (1.8-2.2) and 1.3 (1.2-1.4) compared to normal ABI and PAD groups, respectively.
Conclusions
Patients identified by non-invasive vascular testing to have poorly compressible leg arteries have poor survival, worse than those with a normal ABI or those with PAD.
doi:10.1016/j.jacc.2011.09.055
PMCID: PMC3307094  PMID: 22261162
peripheral arterial disease; arterial calcification; mortality; ankle-brachial index
6.  The Relevance of Different Methods of Calculating the Ankle-Brachial Index 
American Journal of Epidemiology  2009;171(3):368-376.
The authors aimed to determine differences in the prevalence of peripheral arterial disease (PAD) and its associations with cardiovascular disease (CVD) risk factors, using different methods of calculating the ankle-brachial index (ABI). Using measurements taken in the bilateral brachial, dorsalis pedis, and posterior tibial arteries, the authors calculated ABI in 3 ways: 1) with the lowest ankle pressure (dorsalis pedis artery or posterior tibial artery) (“ABI-LO”), 2) with the highest ankle pressure (“ABI-HI”), and 3) with the mean of the ankle pressures (“ABI-MN”). For all 3 methods, the index ABI was the lower of the ABIs calculated from the left and right legs. PAD was defined as an ABI less than 0.90. Among 6,590 subjects from a multiethnic cohort (baseline examination: 2000–2002), in comparison with ABI-HI, the relative prevalence of PAD was 3.95 times higher in women and 2.74 times higher in men when ABI-LO was used. The relative magnitudes of the associations were largest between PAD and both subclinical atherosclerosis and CVD risk factors when ABI-HI was used, except when risk estimates for PAD were less than 1.0, where the largest relative magnitudes of association were found using ABI-LO. PAD prevalence and its associations with CVD risk factors and subclinical atherosclerosis measures depend on the ankle pressure used to compute the ABI.
doi:10.1093/aje/kwp382
PMCID: PMC2842203  PMID: 20042436
ankle brachial index; cardiovascular diseases; continental population groups; ethnic groups; peripheral vascular diseases
7.  Critical Review of the Ankle Brachial Index 
Current Cardiology Reviews  2008;4(2):101-106.
Ankle brachial index (ABI) has been utilized in the management of peripheral arterial disease (PAD).ABI is a surrogate marker of atherosclerosis and recent studies indicate its utility as a predictor of future cardiovascular disease and all-cause mortality. Even so, this critical test is underutilized. The purpose of this review is to summarize available evidence associated with ABI methodology variances, ABI usage in the treatment of PAD, and ABI efficacy in predicting cardiovascular disease. This review further evaluates how ABI is used in the prognosis and follow-up of lower extremity arterial disease.We reviewed the most current American College of Cardiology guidelines for the management of PAD, the Trans Atlantic Intersociety Consensus (TASC) working group recommendations, and searched the Medline for the following words: ankle brachial index, ABI sensitivity and specificity, and peripheral arterial disease.
The ABI is a simple, noninvasive clinical test that should not only be applied to diagnose PAD, but also to provide important prognostic information about future cardiovascular events. Although the ABI has been employed in clinical practice for some time, our review of various studies reveals a lack of standardization regarding both the method of measuring ABI and the cutoff point for abnormal ABI. It is extremely important that we understand all aspects of this crucial test, as it is now being recommended as part of a patient’s routine health risk assessment.
doi:10.2174/157340308784245810
PMCID: PMC2779349  PMID: 19936284
Peripheral arterial disease; Ankle Brachial index; ABI Sensitivity and Specificity; Atherosclerosis; Cardiovascular morbidity and mortality.
8.  Automated Ankle-Brachial Pressure Index Measurement by Clinical Staff for Peripheral Arterial Disease Diagnosis in Nondiabetic and Diabetic Patients 
Diabetes Care  2009;32(7):1231-1236.
OBJECTIVE
Peripheral arterial disease (PAD) is a prognostic marker in cardiovascular disease. The use of Doppler-measured ankle-brachial pressure index (Dop-ABI) for PAD diagnosis is limited because of time, required training, and costs. We assessed automated oscillometric measurement of the ankle-brachial pressure index (Osc-ABI) by nurses and clinical staff.
RESEARCH DESIGN AND METHODS
Clinical staff obtained Osc-ABI with an automated oscillometric device in 146 patients (83 with diabetes) at the time of Dop-ABI measurement and ultrasound evaluation.
RESULTS
Measurements were obtained in most legs (Dop-ABI 98%; Osc-ABI 95.5%). Dop- and Osc-ABI were significantly related in diabetic and nondiabetic patients with good agreement over a wide range of values. When Dop-ABI ≤0.90 was used as the gold standard for PAD, receiver operating characteristic curve analysis showed that PAD was accurately diagnosed with Osc-ABI in diabetic patients. When ultrasound was used to define PAD, Dop-ABI had better diagnostic performance than Osc-ABI in the whole population and in diabetic patients (P = 0.026). Both methods gave similar results in nondiabetic patients. The cutoff values for the highest sensitivity and specificity for PAD screening were between 1.0 and 1.1. Estimation of cost with the French medical care system fees showed a potential reduction by three of the screening procedures.
CONCLUSIONS
PAD screening could be improved by using Osc-ABI measured by clinical staff with the benefit of greater cost-effectiveness but at the risk of lower diagnostic performance in diabetic patients.
doi:10.2337/dc08-2230
PMCID: PMC2699730  PMID: 19366974
9.  Utility of Toe-brachial Index for Diagnosis of Peripheral Artery Disease 
Archives of Plastic Surgery  2012;39(3):227-231.
Background
The ankle brachial pressure index (ABI) is a simple, useful method for diagnosing peripheral artery disease (PAD). Although the ABI is an objective diagnostic method, it has limited reliability in certain scenarios. The aim of the present study was to determine the accuracy and reliability of the toe brachial index (TBI) as a diagnostic tool for detecting stenosis in PAD, associated with normal or low ABI values.
Methods
ABI and TBI values were measured in 15 patients with diabetic gangrene who were suspected of having lower extremity arterial insufficiency. The ABI and TBI values were measured using a device that allowed the simultaneous measurement of systolic blood pressure in the upper and lower extremities. In addition, the ABI and TBI values were compared pre- and post-angiography.
Results
Patients with an ABI of 0.9-1.3 showed almost no difference between the 2 measurements. The patients with TBI >0.6 had no arterial insufficiency. The patients with TBI <0.6 required vascular intervention with ballooning. After the angiography, the gangrenous wounds decreased in size more rapidly than they did prior to the intervention.
Conclusions
Our findings suggest that TBI is the method of choice for evaluating lower limb perfusion disorders. This result requires further studies of TBI in a larger number of patients. Future long-term studies should therefore evaluate the utility of TBI as a means of screening for PAD and the present findings should be regarded as preliminary outcomes.
doi:10.5999/aps.2012.39.3.227
PMCID: PMC3385338  PMID: 22783531
Toe brachial index; Ankle brachial index; Peripheral arterial disease
10.  Facilitators and Barriers to Implementation of the Ankle Brachial Index in Outpatient Physical Therapy Practice: A Qualitative Study 
Introduction
The ankle brachial index (ABI) is a valid and reliable measurement of lower extremity circulation and can be used as a screening tool for peripheral arterial disease (PAD), but the usage pattern in physical therapy practice is virtually unknown.
Purpose
This study was performed to describe the phenomenon of using the ABI in outpatient physical therapy practice.
Methods
Nine participants from 3 different outpatient physical therapy clinics were provided with a hand held Doppler and education on how to accurately perform an ABI. Over a 3-month period, participants performed the ABI on any patient presenting with age > 50 with at least two risk factors for PAD. Immediately following the 3-month data collection period, two focus group interviews were performed to examine the therapist's experience using the ABI. Transcripts were analyzed to identify facilitators and barriers to implementation.
Results
Facilitators identified include familiarity, ease of use, accuracy, and confidence with results. Barriers included flow and routine disruption, patient did not want/refused, and issues related to direct access.
Conclusion
Although some barriers to use of the ABI in an outpatient clinical setting need to be considered, most participants found the experience of using the ABI positive and feasible.
PMCID: PMC3677180  PMID: 23754934
ankle brachial index; peripheral arterial disease; physical therapy
11.  Family History of Peripheral Artery Disease is associated with Prevalence and Severity of Peripheral Artery Disease: The San Diego Population Study (SDPS) 
Objective
To determine the association of family history of peripheral artery disease (PAD) with PAD prevalence and severity.
Background
PAD is a significant public health problem. Shared genetic and environmental factors may play an important role in the development of PAD. However, family history of PAD has not been adequately investigated.
Methods
The San Diego Population Study (SDPS) enrolled 2404 ethnically diverse men and women aged 29–91 who attended a baseline visit from 1994–98 to assess PAD and venous disease. Ankle brachial index (ABI) measurement was performed at the baseline clinic examination and family history of PAD was obtained via questionnaire. Family history of PAD was primarily defined as having any 1st degree relative with PAD. Prevalent PAD was defined as ABI ≤ 0.90 and severe prevalent PAD as ABI ≤ 0.70, with both definitions also including any previous leg revascularization. Logistic regression was used to evaluate the association of family history of PAD with prevalent PAD.
Results
The mean (SD) age was 59 (11) years, 66% were women, and 58% were Caucasian with 42% comprising other racial/ethnic groups. Prevalence of PAD was 3.6%, and severe prevalent PAD was 1.9%. In fully adjusted models, family history of PAD was associated with a 1.83-fold higher odds of PAD (95% CI (1.03, 3.26), p=0.04), an association which was stronger for severe prevalent PAD (OR 2.42, 95% CI (1.13, 5.23), p=0.02).
Conclusions
Family history of PAD is independently strongly associated with PAD prevalence and severity. This indicates a role for genetic factors and/or other shared environmental factors contributing to PAD.
doi:10.1016/j.jacc.2011.06.023
PMCID: PMC3215334  PMID: 21920269
family history; peripheral artery disease; ankle brachial index
12.  Lower Extremity Nerve Function in Patients With Lower Extremity Ischemia 
Archives of internal medicine  2006;166(18):1986-1992.
Background
We determined whether lower extremity ischemia, as measured by the ankle brachial index (ABI), is associated with impaired lower extremity nerve function.
Methods
Participants included 478 persons with peripheral arterial disease (PAD) identified from noninvasive vascular laboratories and 292 persons without PAD identified from a general medicine practice and noninvasive vascular laboratories. Peripheral arterial disease was defined as an ABI lower than 0.90 (mild PAD: ABI, 0.70 to <0.90; moderate PAD: ABI, 0.50 to <0.70; and severe PAD: ABI, <0.50). The ABI and electrophysiologic measures of the peroneal, sural, and ulnar nerves were obtained.
Results
Among 546 participants without diabetes, PAD participants had significantly impaired peripheral nerve function in the upper and lower extremities compared with non-PAD participants. After adjusting for age, sex, race, smoking, height, body mass index, recruitment source, alcohol use, disk disease, spinal stenosis, cardiac disease, and cerebrovascular disease, these associations were not statistically significant. After adjusting for confounders among nondiabetic participants, those with severe PAD (ABI, <0.50) had poorer peroneal nerve conduction velocity (NCV) compared with participants without PAD (42.6 vs 44.8 m/s; P=.003) and poorer peroneal NCV compared with participants with mild PAD (42.6 vs 45.0 m/s; P=.001) or moderate PAD (42.6 vs 44.1 m/s; P=.03). Among 224 participants with diabetes, after adjusting for confounders, PAD was associated with poorer peroneal NCV (40.8 vs 43.5 m/s; P=.01), sural nerve amplitude (3.1 vs 4.8 μV; P=.045), and ulnar NCV (47.6 vs 50.2 m/s; P=.03) compared with those without PAD.
Conclusions
Our findings suggest that leg ischemia impairs peroneal nerve function. This association is less strong in patients with diabetes, perhaps because of the overriding influence of diabetes on peripheral nerve function. Clinicians should consider screening for PAD in patients with idiopathic peroneal nerve dysfunction. Peripheral arterial disease–associated nerve dysfunction may contribute to PAD-associated functional impairment.
doi:10.1001/archinte.166.18.1986
PMCID: PMC2645651  PMID: 17030832
13.  Contemporary Risk Factor Control and Walking Dysfunction in Individuals with Peripheral Arterial Disease: NHANES 1999-2004 
Atherosclerosis  2008;201(2):425-433.
Background
Lower extremity peripheral arterial disease (PAD) is a coronary heart disease (CHD) risk equivalent. Selected studies have demonstrated less intense risk factor management and diminished mobility in individuals with PAD as compared to individuals with clinical recognized CHD. However, comparable data have not been reported from a nationally representative population.
Objectives
To assess the prevalence, treatment, and control of cardiovascular risk factors among individuals with PAD as defined by an ankle-brachial index (ABI) <0.90 (but without recognized CHD) as compared with individuals with recognized CHD (but without PAD). A second objective was to evaluate the diagnostic accuracy of measures of walking dysfunction to identify individuals with PAD.
Design, Setting, and Participants
We analyzed data from 7,571 participants aged 40 or older who participated in the National Health and Nutrition Examination Survey (NHANES) 1999-2004, a nationally representative cross-sectional survey of the U.S. population.
Results
The prevalence of PAD without CHD was 4.1% (95%CI 3.6, 4.5) compared to 7.9% (7.1, 8.9) for CHD (without PAD). Hypertension prevalence was similar, but treatment and control rates were lower among individuals with PAD compared to CHD (treatment: 69% vs 84%, p<0.001; control: 50% vs 63%, p=0.01). Treatment of hypercholesterolemia was lower among individuals with PAD (54% vs 79%, p<0.001) but control was similar (83% vs 85%, p=0.78). Diabetes awareness, treatment, and control did not differ between the two groups. Walking mobility limitations were specific, but insensitive, for the identification of individuals with PAD.
Conclusion
PAD in the absence of clinically recognized CHD is under-treated and poorly controlled in the general U.S. population. Leg symptoms are not adequate to identify individuals with PAD, who are at high risk of ischemic events.
doi:10.1016/j.atherosclerosis.2008.02.002
PMCID: PMC2771432  PMID: 18395208
14.  Exercise-Ankle Brachial Pressure Index with One-Minute Treadmill Walking in Patients on Maintenance Hemodialysis 
Annals of Vascular Diseases  2012;6(1):52-56.
Background: The ankle-brachial pressure index (ABI) is widely used as a standard screening method for arterial occlusive lesion above the knee. However, the sensitivity of ABI is low in hemodialysis (HD) patients. Exercise stress (Ex-ABI) may reduce the false negative results.
Patients and Methods: After measuring resting ABI and toe-brachial pressure index (TBI), ankle pressure and ABI immediately after walking (Post-AP, Post-ABI) were measured using one-minute treadmill walking in 52 lower limbs of 26 HD patients. The definition of peripheral arterial occlusive disease (PAD) required an ABI value of less than 0.90, TBI value of less than 0.60, and decrease of more than 15% of the Post-ABI value and 20 mmHg of Post-AP in Ex-ABI. Computed tomographic angiography (CTA) was performed in 32 lower limbs of 16 HD patients. PAD is defined as presence of stenosis of more than 75% in the case of lesions from an iliac artery to knee on CTA.
Results: The accuracy of Ex-ABI (Sensitivity, 85.7%; Specificity, 77.7%) was higher than those of ABI (Sensitivity, 42.9%; Specificity, 83.3%) or TBI (Sensitivity, 78.6%; Specificity, 61.1%).
Conclusion: Ex-ABI with one-minute treadmill walking is the most useful tool for the screening of arterial occlusive lesions above the knee in maintenance HD patients.
doi:10.3400/avd.oa.12.00070
PMCID: PMC3635000  PMID: 23641284
peripheral arterial disease; exercise; diagnosis; screening; hemodialysis
15.  Low Lifetime Recreational Activity is a Risk Factor for Peripheral Arterial Disease 
Background
The relationship between lifetime physical activity and the risk of developing peripheral arterial disease (PAD) is not known.
Methods
We studied 1381 patients referred for elective coronary angiography in a point prevalence analysis. PAD was defined as ankle-brachial index (ABI) < 0.9 at the time or a history of revascularization of the lower extremities regardless of ABI measure. We used a validated physical activity questionnaire to retrospectively measure each patient's lifetime recreational activity (LRA). Multivariate and logistic regression analyses were used to assess the independent association of LRA to ABI and the presence of PAD.
Results
PAD was present in 19% (n=258) of all subjects. Subjects reporting no regular LRA had greater diastolic BP and were more likely to be female. They had lower average ABI, and a higher proportion had PAD (25.6%). In a regression model including traditional risk factors and LRA, multivariate analysis showed that age (p <0.001), female gender (p <0.001), systolic blood pressure (p =0.014), fasting glucose (p <0.001), serum triglycerides (p =0.02) and cumulative pack years (p <0.001) were independent negative predictors of ABI, and LRA was a positive predictor of ABI (p <0.001). History of sedentary lifestyle independently increased the odds ratio for PAD (OR =1.46; 95% CI, 1.0112.103) when assessed by logistic regression. Intriguingly, there is a correlation between physical activity and gender, such that women with low lifetime recreational activity are at greatest risk.
Conclusion
Recalled lifetime recreational activity is positively correlated to ABI and associated with PAD. Whereas the mechanism for this effect is not clear, LRA may be a useful clinical screening tool for PAD risk and strategies to increase adult recreational activity may reduce the burden of PAD later in life.
doi:10.1016/j.jvs.2011.02.052
PMCID: PMC3152670  PMID: 21664093
Intermittent claudication; exercise; vascular disease; atherosclerosis
16.  The validity of ankle-brachial index for the differential diagnosis of peripheral arterial disease and lumbar spinal stenosis in patients with atypical claudication 
European Spine Journal  2011;21(6):1165-1170.
Purpose
Claudication is a typical symptom of peripheral arterial disease (PAD) and lumbar spinal stenosis (LSS). Differential diagnosis of PAD and LSS is often difficult due to the subjective natures of symptoms and atypical signs. The authors aimed to determine the usefulness of ankle-brachial index (ABI) measurement for the differential diagnosis of PAD and LSS when the etiology of claudication is uncertain.
Methods
Forty-two consecutive patients who had been referred by spine surgeons to a lower extremity vascular surgeon for atypical claudication were retrospectively analyzed. Atypical claudication was defined as claudication not caused by PAD, as determined by clinical manifestations, or by LSS, as determined by MR imaging. A final diagnosis of PAD was established by CT angiography (CTA) and of LSS by excluding PAD. Diagnostic validity of ABI for PAD in atypical presentation was assessed.
Results
Sixty-two legs of 42 atypical claudication patients were analyzed. Mean patient age was 65.8 ± 8.2 years (38–85) and 29 (69.0%) had diabetes mellitus. Mean ABI was 0.73 ± 0.14 (0.53–0.94) in the PAD group and 0.92 ± 0.18 (0.52–1.10) in the LSS group (P < 0.001). Of the 33 legs with a low ABI (ABI < 0.9), 29 legs were diagnosed as true positives for PAD by CTA and 4 were false positives, and of the 29 legs with a high ABI, 5 were false negatives and 24 were true negatives. The sensitivity and specificity of ABI for the diagnosis of PAD in patients with atypical claudication were 85.3 and 85.7%, respectively, and its positive and negative predictive values were 87.9 and 82.8%.
Conclusions
ABI is a recommended screening test for the differential diagnosis of lower leg claudication when clinical symptoms are atypical.
doi:10.1007/s00586-011-2072-3
PMCID: PMC3366123  PMID: 22105308
Claudication; Peripheral arterial disease; Lumbar spinal stenosis; Ankle-brachial index; Validity
17.  Lower Extremity Ischemia, Calf Skeletal Muscle Characteristics, and Functional Impairment in Peripheral Arterial Disease 
OBJECTIVES
To determine whether lower ankle brachial index (ABI) levels are associated with lower calf skeletal muscle area and higher calf muscle percentage fat in persons with and without lower extremity peripheral arterial disease (PAD).
DESIGN
Cross-sectional.
SETTING
Three Chicago-area medical centers.
PARTICIPANTS
Four hundred thirty-nine persons with PAD (ABI<0.90) and 265 without PAD (ABI 0.90–1.30).
MEASUREMENTS
Calf muscle cross-sectional area and the percentage of fat in calf muscle were measured using computed tomography at 66.7% of the distance between the distal and proximal tibia. Physical activity was measured using an accelerometer. Functional measures included the 6-minute walk, 4-meter walking speed, and the Short Physical Performance Battery (SPPB).
RESULTS
Adjusting for age, sex, race, comorbidities, and other potential confounders, lower ABI values were associated with lower calf muscle area (ABI<0.50, 5,193 mm2; ABI 0.50–0.90, 5,536 mm2; ABI 0.91–1.30, 5,941 mm2; P for trend <.001). These significant associations remained after additional adjustment for physical activity. In participants with PAD, lower calf muscle area in the leg with higher ABI was associated with significantly poorer performance in usual- and fast-paced 4-meter walking speed and on the SPPB, adjusting for ABI, physical activity, percentage fat in calf muscle, muscle area in the leg with lower ABI, and other confounders (P<.05 for all comparisons).
CONCLUSION
These data support the hypothesis that lower extremity ischemia has a direct adverse effect on calf skeletal muscle area. This association may mediate previously established relationships between PAD and functional impairment.
doi:10.1111/j.1532-5415.2007.01092.x
PMCID: PMC2645649  PMID: 17341243
physical functioning; peripheral vascular disease; intermittent claudication; sarcopenia
18.  Correlation between peripheral arterial disease and coronary artery disease using ankle brachial index-a study in Indian population 
Indian Heart Journal  2012;64(1):2-6.
Objective
To study the prevalence of peripheral arterial disease (PAD) of the lower limbs in a high-risk population and its correlation with coronary artery disease (CAD), using the ankle brachial index (ABI).
Methods
The present study was conducted in randomly selected indoor patients >45 years of age with one or more risk factors for PAD admitted in the cardiology and medicine wards in a tertiary care institute.
Results
Based on ABI <0.9, PAD was diagnosed in 32 of the 182 (18%) patients. Coronary artery disease was present in 15 cases of PAD which was statistically significant.
Conclusion
There is a definite and strong correlation between PAD and CAD. Correct diagnosis and supervision of patients with PAD is important for preventing the local progression of the disease and effective secondary prevention of future coronary and cerebrovascular events.
doi:10.1016/S0019-4832(12)60002-9
PMCID: PMC3860717  PMID: 22572416
Ankle brachial index; Coronary artery disease; Peripheral arterial disease
19.  The Prevalence of Peripheral Arterial Disease in Korean Patients with Type 2 Diabetes Mellitus Attending a University Hospital 
Diabetes & Metabolism Journal  2011;35(5):543-550.
Background
Peripheral arterial disease (PAD) is a common manifestation of systemic atherosclerosis and is associated with significant morbidity and mortality. Diabetes is known to increase the risk of PAD two- to four-fold. The prevalence of PAD in Korean diabetic patients has not been established. In this study, we investigated the prevalence of PAD in Korean patients with type 2 diabetes attending a large university hospital and analyzed the factors associated with PAD.
Methods
A total of 2,002 patients with type 2 diabetes who underwent ankle-brachial index (ABI) measurement in an outpatient clinic were enrolled. PAD was defined as an ABI ≤0.9. Clinical characteristics of 64 patients with PAD were compared with those of 192 age- and sex-matched control patients without PAD.
Results
Of the 2,002 type 2 diabetic patients, 64 (3.2%) were diagnosed as having PAD. PAD was associated with higher prevalences of retinopathy, nephropathy, neuropathy, cerebrovascular and coronary artery disease. Patients with PAD had higher systolic blood pressure and serum triglyceride level and reported higher pack-years of smoking. Multivariate analysis showed that the presence of micro- and macrovascular complications and high systolic blood pressure are factors independently associated with PAD.
Conclusion
The prevalence of PAD in diabetic patients was 3.2%, suggesting that the prevalence in Korean diabetic patients is lower than that of patients in Western countries.
doi:10.4093/dmj.2011.35.5.543
PMCID: PMC3221031  PMID: 22111047
Diabetes mellitus, type 2; Peripheral arterial disease; Prevalence; Risk factors
20.  Peripheral artery disease assessed by ankle-brachial index in patients with established cardiovascular disease or at least one risk factor for atherothrombosis - CAREFUL Study: A national, multi-center, cross-sectional observational study 
Background
To investigate the presence of peripheral artery disease (PAD) via the ankle brachial index (ABI) in patients with known cardiovascular and/or cerebrovascular diseases or with at least one risk factor for atherothrombosis.
Methods
Patients with a history of atherothrombotic events, or aged 50-69 years with at least one cardiovascular risk factor, or > = 70 years of age were included in this multicenter, cross-sectional, non-interventional study (DIREGL04074). Demographics, medical history, physical examination findings, and physician awareness of PAD were analyzed. The number of patients with low ABI (< = 0.90) was analyzed.
Results
A total of 530 patients (mean age, 63.4 ± 8.7 years; 50.2% female) were enrolled. Hypertension and dyslipidemia were present in 88.7% and 65.5% of patients, respectively. PAD-related symptoms were evident in about one-third of the patients, and at least one of the pedal pulses was negative in 6.5% of patients. The frequency of low ABI was 20.0% in the whole study population and 30% for patients older than 70 years. Older age, greater number of total risk factors, and presence of PAD-related physical findings were associated with increased likelihood of low ABI (p < 0.001). There was no gender difference in the prevalence of low ABI, PAD symptoms, or total number of risk factors. Exercise (33.6%) was the most common non-pharmacological option recommended by physicians, and acetylsalicylic acid (ASA) (45.4%) was the most frequently prescribed medication for PAD.
Conclusion
Our results indicate that advanced age, greater number of total risk factors and presence of PAD-related physical findings were associated with increased likelihood of low ABI. These findings are similar to those reported in similar studies of different populations, and document a fairly high prevalence of PAD in a Mediterranean country.
doi:10.1186/1471-2261-11-4
PMCID: PMC3033857  PMID: 21247449
21.  Ankle-Brachial Index and Cardiovascular Outcomes in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Trial 
American heart journal  2012;164(4):585-590.e4.
Background
Peripheral arterial disease (PAD) increases cardiovascular risk in many patient populations. The risks associated with an abnormal ankle-brachial index (ABI) in patients with type 2 diabetes (T2D) and stable coronary artery disease (CAD) have not been well described with respect to thresholds and types of cardiovascular events.
Methods
We examined 2368 patients in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial that underwent ABIassessment at baseline. Death and major cardiovascular events (death, myocardial infarction (MI) and stroke) during follow-up (average 4.3 years) were assessed across the ABI spectrum and by categorizedABI: low (≤0.90), normal (0.91–1.3), high (>1.3), or non-compressible.
Results
A total of 12,568 person-years were available for mortality analysis. During follow-up, 316 patients died and 549 suffered major cardiovascular events. After adjustment for potential confounders, with normal ABI as the referent group, a low ABI conferred an increased risk of death (relative risk (RR) 1.6; C.I. 1.2, 2.2; p=.0005) and major cardiovascular events (RR 1.4; C.I. 1.1, 1.7; p=.004). Patients with a high ABI had similar outcomes as patients with a normal ABI, but risk again increased in patients with a non-compressible ABI with a risk of death (RR1.9; C.I. 1.3, 2.8; p=.001) and major cardiovascular event (RR 1.5, C.I. 1.1, 2.1; p=.01).
Conclusions
In patients with CAD and T2D ABI screening and identification of ABI abnormalities including a low ABI (<1.0) or non-compressible artery provide incremental prognostic information.
doi:10.1016/j.ahj.2012.06.017
PMCID: PMC3474978  PMID: 23067918
coronary disease; diabetes mellitus; peripheral vascular disease
22.  ASSOCIATIONS OF BORDERLINE AND LOW NORMAL ANKLE BRACHIAL INDEX VALUES WITH FUNCTIONAL DECLINE AT FIVE YEAR FOLLOW-UP 
Objectives
We studied associations of borderline and low-normal ankle brachial index (ABI) values with functional decline over five-year follow-up.
Background
Associations of borderline and low-normal ABI with functional decline are unknown.
Methods
The 666 participants included 412 with peripheral arterial disease (PAD). Participants were categorized as follows: Severe PAD (ABI < 0.50), moderate PAD (ABI 0.50-0.69), mild PAD (ABI 0.70 to 0.89), borderline ABI (0.90 to 0.99), low normal ABI (1.00 to 1.09), and normal ABI (ABI 1.10-1.30). Outcomes were assessed annually for five years. Mobility loss was defined as loss of the ability to walk ¼ mile or walk up and down one flight of stairs without assistance among those without baseline mobility impairment. Becoming unable to walk for six minutes continuously was defined as stopping during the six minute walk at follow-up among those who walked for six minutes continuously at baseline. Results adjust for age, sex, race, comorbidities, and other confounders.
Results
Hazard ratios (HR) for mobility loss according to ABI category were as follows. Severe PAD: HR=4.16 (95% Confidence Interval (CI)=1.58-10.92), moderate PAD: HR=3.82 (95% CI=1.66-8.81), mild PAD: HR=3.22 (95% CI=1.43-7.21), borderline ABI: HR=3.07 (95% CI=1.21-7.84), low normal ABI: HR=2.61 (95% CI=1.08-6.32) (p trend=0.0018). Similar associations were observed for becoming unable to walk six-minutes continuously (p trend<0.0001).
Conclusion
At five-year follow-up, persons with borderline ABI values have a higher incidence of mobility loss and becoming unable to walk for six minutes continuously compared to persons with a normal baseline ABI. A low normal ABI is associated with an increased incidence of mobility loss compared to persons with a normal ABI.
CONDENSED ABSTRACT
We studied associations of borderline and low-normal ABI values with functional decline over five-year follow-up among 666 participants, including 412 with lower extremity peripheral arterial disease (PAD). At five year follow-up, participants with borderline ABI values at baseline (ABI 0.90 to 0.99) had significantly greater mobility loss and were more likely to become unable to walk for six-minutes continuously compared to those with a normal baseline ABI. Participants with low normal ABI values (ABI 1.00 to 1.09) had significantly greater mobility loss compared to those with a normal baseline ABI.
doi:10.1016/j.jacc.2008.09.063
PMCID: PMC3215766  PMID: 19298919
ankle brachial index; physical functioning; peripheral arterial disease; intermittent claudication
23.  Elevated osteoprotegerin is associated with abnormal ankle brachial indices in patients infected with HIV: a cross-sectional study 
Background
Patients infected with HIV have an increased risk for accelerated atherosclerosis. Elevated levels of osteoprotegerin, an inflammatory cytokine receptor, have been associated with a high incidence of cardiovascular disease (including peripheral arterial disease, or PAD), acute coronary syndrome, and cardiovascular mortality. The objective of this study was to determine whether PAD is prevalent in an HIV-infected population, and to identify an association with HIV-specific and traditional cardiovascular risk factors, as well as levels of osteoprotegerin.
Methods
One hundred and two patients infected with HIV were recruited in a cross-sectional study. To identify the prevalence of PAD, ankle-brachial indices (ABIs) were measured. Four standard ABI categories were utilized: ≤ 0.90 (definite PAD); 0.91-0.99 (borderline); 1.00-1.30 (normal); and >1.30 (high). Medical history and laboratory measurements were obtained to determine possible risk factors associated with PAD in HIV-infected patients.
Results
The prevalence of PAD (ABI ≤ 0.90) in a young HIV-infected population (mean age: 48 years) was 11%. Traditional cardiovascular risk factors, including advanced age and previous cardiovascular history, as well as elevated C-reactive protein levels, were associated with PAD. Compared with patients with normal ABIs, patients with high ABIs had significantly elevated levels of osteoprotegerin [1428.9 (713.1) pg/ml vs. 3088.6 (3565.9) pg/ml, respectively, p = 0.03].
Conclusions
There is a high prevalence of PAD in young HIV-infected patients. A number of traditional cardiovascular risk factors and increased osteoprotegerin concentrations are associated with abnormal ABIs. Thus, early screening and aggressive medical management for PAD may be warranted in HIV-infected patients.
doi:10.1186/1758-2652-13-12
PMCID: PMC2859852  PMID: 20307322
24.  Risk Factors Related to Low Ankle-Brachial Index Measured by Traditional and Modified Definition in Hypertensive Elderly Patients 
Peripheral arterial disease (PAD) increases with age and ankle-brachial index (ABI) ≤ 0.9 is a noninvasive marker of PAD. The purpose of this study was to identify risk factors related to a low ABI in the elderly using two different methods of ABI calculation (traditional and modified definition using lower instead of higher ankle pressure). A cross-sectional study was carried out with 65 hypertensive patients aged 65 years or older. PAD was present in 18% of individuals by current ABI definition and in 32% by modified method. Diabetes, cardiovascular diseases, metabolic syndrome, higher levels of systolic blood pressure and pulse pressure, elevated risk by Framingham Risk Score (FRS), and a higher number of total and antihypertensive drugs in use were associated with low ABI by both definitions. Smoking and LDL-cholesterol were associated with low ABI only by the modified definition. Low ABI by the modified definition detected 9 new cases of PAD but cardiovascular risk had not been considered high in 3 patients when calculated by FRS. In conclusion, given that a simple modification of ABI calculation would be able to identify more patients at high risk, it should be considered for cardiovascular risk prediction in all elderly hypertensive outpatients.
doi:10.1155/2012/163807
PMCID: PMC3376503  PMID: 22720134
25.  Prevalence and Risk Factors of Asymptomatic Peripheral Arterial Disease in Patients with COPD in Taiwan 
PLoS ONE  2013;8(5):e64714.
Aim
Chronic obstructive pulmonary disease (COPD) is an independent risk factor for cardiovascular morbidity and mortality. The aim of this study was to determine the prevalence of asymptomatic peripheral arterial disease (PAD) and the associated risk factors for patients with COPD.
Methods
This prospective cross-sectional study enrolled 427 COPD patients (mean age: 70.0 years) without PAD symptoms consecutively. Demographic data, lung function and cardiovascular risk factors were recorded. The ankle-brachial index (ABI) was used to detect PAD (ABI<0.90).
Results
The overall prevalence of asymptomatic PAD in the COPD patients was 8% (2.5% in the younger participants (<65 years of age, n = 118) and 10% in the elderly participants (≥65 years of age, n = 309). The COPD patients with asymptomatic PAD had a significantly higher rate of hyperlipidemia (47.1% vs. 10.4%) and hypertension (79.4% vs. 45.8%) than those without asymptomatic PAD (p<0.05). There was no significant difference in lung function (forced vital capacity and forced expiratory volume in one second) between the two groups. In multivariate logistic regression, hyperlipidemia was the strongest independent factor for PAD (odds ratio (OR): 6.89, p<0.005), followed by old age (OR: 4.80), hypertension (OR: 3.39) and smoking burden (pack-years, OR: 1.02).
Conclusions
The prevalence of asymptomatic PAD among COPD patients in Taiwan is lower than in Western countries. Hyperlipidemia, old age, hypertension, and smoking burden were the associated cardiovascular risk factors. However, there was no association between lung function and PAD in the COPD patients.
doi:10.1371/journal.pone.0064714
PMCID: PMC3661545  PMID: 23717654

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