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1.  The Relation Between Ankle-Brachial Index (ABI) and Coronary Artery Disease Severity and Risk Factors: An Angiographic Study 
ARYA Atherosclerosis  2011;7(2):68-73.
The current study aims to determine the relation between ankle–brachial index (ABI) and angiographic findings and major cardiovascular risk factors in patients with suspected coronary artery diseases (CAD) in Isfahan.
In this cross-sectional descriptive-analytic research, patients with suspected CAD were studied. Characteristics of studied subjects including demographics, familial history, past medical history and atherosclerotic risk factors such as diabetes mellitus, hypertension, hyperlipidemia and smoking were obtained using a standard questionnaire. ABI was measured in all studied patients. ABI≤0.9 (ABI+) was considered as peripheral vessel disease and ABI>0.9 (ABI-) was considered as normal. Then, all studied patients underwent coronary artery angiography. The results of the questionnaire and angiographic findings were compared in ABI+ and ABI- groups. Data were analyzed by SPSS 15 using ANOVA, t-test, Spearman's rank correlation coefficient, and discriminant analysis.
In this study, 125 patients were investigated. ABI≤0.9 was seen in 25 patients (20%). The prevalence of ABI+ among men and women was 25.9% and 7.5%, respectively (P=0.01). The prevalence of atherosclerotic risk factors was significantly higher in ABI+ patients than in ABI- ones (P<0.05). ABI+ patients had more significant stenosis than ABI- ones. The mean of occlusion was significantly higher in ABI+ patients with left main artery (LMA), right coronary artery (RCA), left anterior descending artery (LAD), diagonal artery 1 (D1) and left circumflex artery (LCX) involvements (P<0.05).
The findings of this research indicated that ABI could be a useful method in assessing both the atherosclerotic risk factors and the degree of coronary involvements in suspected patients. However, in order to make more accurate decisions for using this method in diagnosing and preventing CAD, we should plan further studies in large sample sizes of general population.
PMCID: PMC3347847  PMID: 22577449
Ankle–Brachial Index; Angiography; Atherosclerotic Risk Factors.
2.  Relation between the ankle-brachial index and the complexity of coronary artery disease in older patients 
In the elderly, the ankle-brachial index (ABI) has greater than 90% sensitivity and specificity for peripheral artery disease identification. A well-known relation exists between peripheral artery disease and the number of diseased coronary vessels. Yet, other anatomical characteristics have important impacts on the type of treatment and prognosis.
To determine the relation between ABI and the complexity of coronary artery disease, by different anatomical classifications.
This study was a prospective analysis of patients ≥65 years old who were undergoing elective coronary angiography for ischemic coronary disease. The ABI was calculated for each leg, as the ratio between the lowest ankle pressure and the highest brachial pressure. The analysis of coronary anatomy was performed by three interventional cardiologists; it included classification of each lesion with >50% diameter stenosis, according to the American Heart Association criteria, and calculation of the SYNTAX score.
The study recruited 204 consecutive patients (median age: 72.5 years). Stable angina was present in 51% of patients. Although only 1% of patients reported peripheral artery disease, 45% exhibited an abnormal ABI. The number of lesions per patient, the number of patients with complex lesions, and the median SYNTAX scores were greater in the group with abnormal ABI. However, among 144 patients with obstructive coronary artery disease, despite abnormal ABI being able to identify a higher rate of patients with B2 or C type lesions (70.9% versus 53.8%; P=0.039), the mean SYNTAX scores (13 versus 9; P=0.14), and the proportion of patients with SYNTAX score >16 (34.2% versus 27.7%; P=0.47), were similar, irrespective of ABI.
In patients ≥65 years old the presence of peripheral artery disease could discriminate a group of patients with greater occurrence of B2 and C type lesions, but similar median SYNTAX score.
PMCID: PMC3854920  PMID: 24324332
ankle-brachial index; coronary artery disease; peripheral artery disease; elderly health
3.  Stenting for Peripheral Artery Disease of the Lower Extremities 
Executive Summary
In January 2010, the Medical Advisory Secretariat received an application from University Health Network to provide an evidentiary platform on stenting as a treatment management for peripheral artery disease. The purpose of this health technology assessment is to examine the effectiveness of primary stenting as a treatment management for peripheral artery disease of the lower extremities.
Clinical Need: Condition and Target Population
Peripheral artery disease (PAD) is a progressive disease occurring as a result of plaque accumulation (atherosclerosis) in the arterial system that carries blood to the extremities (arms and legs) as well as vital organs. The vessels that are most affected by PAD are the arteries of the lower extremities, the aorta, the visceral arterial branches, the carotid arteries and the arteries of the upper limbs. In the lower extremities, PAD affects three major arterial segments i) aortic-iliac, ii) femoro-popliteal (FP) and iii) infra-popliteal (primarily tibial) arteries. The disease is commonly classified clinically as asymptomatic claudication, rest pain and critical ischemia.
Although the prevalence of PAD in Canada is not known, it is estimated that 800,000 Canadians have PAD. The 2007 Trans Atlantic Intersociety Consensus (TASC) II Working Group for the Management of Peripheral Disease estimated that the prevalence of PAD in Europe and North America to be 27 million, of whom 88,000 are hospitalizations involving lower extremities. A higher prevalence of PAD among elderly individuals has been reported to range from 12% to 29%. The National Health and Nutrition Examination Survey (NHANES) estimated that the prevalence of PAD is 14.5% among individuals 70 years of age and over.
Modifiable and non-modifiable risk factors associated with PAD include advanced age, male gender, family history, smoking, diabetes, hypertension and hyperlipidemia. PAD is a strong predictor of myocardial infarction (MI), stroke and cardiovascular death. Annually, approximately 10% of ischemic cardiovascular and cerebrovascular events can be attributed to the progression of PAD. Compared with patients without PAD, the 10-year risk of all-cause mortality is 3-fold higher in patients with PAD with 4-5 times greater risk of dying from cardiovascular event. The risk of coronary heart disease is 6 times greater and increases 15-fold in patients with advanced or severe PAD. Among subjects with diabetes, the risk of PAD is often severe and associated with extensive arterial calcification. In these patients the risk of PAD increases two to four fold. The results of the Canadian public survey of knowledge of PAD demonstrated that Canadians are unaware of the morbidity and mortality associated with PAD. Despite its prevalence and cardiovascular risk implications, only 25% of PAD patients are undergoing treatment.
The diagnosis of PAD is difficult as most patients remain asymptomatic for many years. Symptoms do not present until there is at least 50% narrowing of an artery. In the general population, only 10% of persons with PAD have classic symptoms of claudication, 40% do not complain of leg pain, while the remaining 50% have a variety of leg symptoms different from classic claudication. The severity of symptoms depends on the degree of stenosis. The need to intervene is more urgent in patients with limb threatening ischemia as manifested by night pain, rest pain, ischemic ulcers or gangrene. Without successful revascularization those with critical ischemia have a limb loss (amputation) rate of 80-90% in one year.
Diagnosis of PAD is generally non-invasive and can be performed in the physician offices or on an outpatient basis in a hospital. Most common diagnostic procedure include: 1) Ankle Brachial Index (ABI), a ratio of the blood pressure readings between the highest ankle pressure and the highest brachial (arm) pressure; and 2) Doppler ultrasonography, a diagnostic imaging procedure that uses a combination of ultrasound and wave form recordings to evaluate arterial flow in blood vessels. The value of the ABI can provide an assessment of the severity of the disease. Other non invasive imaging techniques include: Computed Tomography (CT) and Magnetic Resonance Angiography (MRA). Definitive diagnosis of PAD can be made by an invasive catheter based angiography procedure which shows the roadmap of the arteries, depicting the exact location and length of the stenosis / occlusion. Angiography is the standard method against which all other imaging procedures are compared for accuracy.
More than 70% of the patients diagnosed with PAD remain stable or improve with conservative management of pharmacologic agents and life style modifications. Significant PAD symptoms are well known to negatively influence an individual quality of life. For those who do not improve, revascularization methods either invasive or non-invasive can be used to restore peripheral circulation.
Technology Under Review
A Stent is a wire mesh “scaffold” that is permanently implanted in the artery to keep the artery open and can be combined with angioplasty to treat PAD. There are two types of stents: i) balloon-expandable and ii) self expandable stents and are available in varying length. The former uses an angioplasty balloon to expand and set the stent within the arterial segment. Recently, drug-eluting stents have been developed and these types of stents release small amounts of medication intended to reduce neointimal hyperplasia, which can cause re-stenosis at the stent site. Endovascular stenting avoids the problem of early elastic recoil, residual stenosis and flow limiting dissection after balloon angioplasty.
Research Questions
In individuals with PAD of the lower extremities (superficial femoral artery, infra-popliteal, crural and iliac artery stenosis or occlusion), is primary stenting more effective than percutaneous transluminal angioplasty (PTA) in improving patency?
In individuals with PAD of the lower extremities (superficial femoral artery, infra-popliteal, crural and iliac artery stenosis or occlusion), does primary stenting provide immediate success compared to PTA?
In individuals with PAD of the lower extremities (superficial femoral artery, infra-popliteal, crural and iliac artery stenosis or occlusion), is primary stenting associated with less complications compared to PTA?
In individuals with PAD of the lower extremities (superficial femoral artery, infra-popliteal, crural and iliac artery stenosis or occlusion), does primary stenting compared to PTA reduce the rate of re-intervention?
In individuals with PAD of the lower extremities (superficial femoral artery, infra-popliteal, crural and iliac artery stenosis or occlusion) is primary stenting more effective than PTA in improving clinical and hemodynamic success?
Are drug eluting stents more effective than bare stents in improving patency, reducing rates of re-interventions or complications?
Research Methods
Literature Search
A literature search was performed on February 2, 2010 using OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, OVID EMBASE, the Cochrane Library, and the International Agency for Health Technology Assessment (INAHTA). Abstracts were reviewed by a single reviewer and, for those studies meeting the eligibility criteria, full-text articles were obtained. Reference lists were also examined for any additional relevant studies not identified through the search. The quality of evidence was assessed as high, moderate, low or very low according to GRADE methodology.
Inclusion Criteria
English language full-reports from 1950 to January Week 3, 2010
Comparative randomized controlled trials (RCTs), systematic reviews and meta-analyses of RCTs
Proven diagnosis of PAD of the lower extremities in all patients.
Adult patients at least 18 years of age.
Stent as at least one treatment arm.
Patency, re-stenosis, re-intervention, technical success, hemodynamic (ABI) and clinical improvement and complications as at least an outcome.
Exclusion Criteria
Non-randomized studies
Observational studies (cohort or retrospective studies) and case report
Feasibility studies
Studies that have evaluated stent but not as a primary intervention
Outcomes of Interest
The primary outcome measure was patency. Secondary measures included technical success, re-intervention, complications, hemodynamic (ankle brachial pressure index, treadmill walking distance) and clinical success or improvement according to Rutherford scale. It was anticipated, a priori, that there would be substantial differences among trials regarding the method of examination and definitions of patency or re-stenosis. Where studies reported only re-stenosis rates, patency rates were calculated as 1 minus re-stenosis rates.
Statistical Analysis
Odds ratios (for binary outcomes) or mean difference (for continuous outcomes) with 95% confidence intervals (CI) were calculated for each endpoint. An intention to treat principle (ITT) was used, with the total number of patients randomized to each study arm as the denominator for each proportion. Sensitivity analysis was performed using per protocol approach. A pooled odds ratio (POR) or mean difference for each endpoint was then calculated for all trials reporting that endpoint using a fixed effects model. PORs were calculated for comparisons of primary stenting versus PTA or other alternative procedures. Level of significance was set at alpha=0.05. Homogeneity was assessed using the chi-square test, I2 and by visual inspection of forest plots. If heterogeneity was encountered within groups (P < 0.10), a random effects model was used. All statistical analyses were performed using RevMan 5. Where sufficient data were available, these analyses were repeated within subgroups of patients defined by time of outcome assessment to evaluate sustainability of treatment benefit. Results were pooled based on the diseased artery and stent type.
Summary of Findings
Balloon-expandable stents vs PTA in superficial femoral artery disease
Based on a moderate quality of evidence, there is no significant difference in patency between primary stenting using balloon-expandable bare metal stents and PTA at 6, 12 and 24 months in patients with superficial femoral artery disease. The pooled OR for patency and their corresponding 95% CI are: 6 months 1.26 (0.74, 2.13); 12 months 0.95 (0.66, 1.38); and 24 months 0.72 (0.34. 1.55).
There is no significant difference in clinical improvement, re-interventions, peri and post operative complications, mortality and amputations between primary stenting using balloon-expandable bare stents and PTA in patients with superficial femoral artery. The pooled OR and their corresponding 95% CI are clinical improvement 0.85 (0.50, 1.42); ankle brachial index 0.01 (-0.02, 0.04) re-intervention 0.83 (0.26, 2.65); complications 0.73 (0.43, 1.22); all cause mortality 1.08 (0.59, 1.97) and amputation rates 0.41 (0.14, 1.18).
Self-expandable stents vs PTA in superficial femoral artery disease
Based on a moderate quality of evidence, primary stenting using self-expandable bare metal stents is associated with significant improvement in patency at 6, 12 and 24 months in patients with superficial femoral artery disease. The pooled OR for patency and their corresponding 95% CI are: 6 months 2.35 (1.06, 5.23); 12 months 1.54 (1.01, 2.35); and 24 months 2.18 (1.00. 4.78). However, the benefit of primary stenting is not observed for clinical improvement, re-interventions, peri and post operative complications, mortality and amputation in patients with superficial femoral artery disease. The pooled OR and their corresponding 95% CI are clinical improvement 0.61 (0.37, 1.01); ankle brachial index 0.01 (-0.06, 0.08) re-intervention 0.60 (0.36, 1.02); complications 1.60 (0.53, 4.85); all cause mortality 3.84 (0.74, 19.22) and amputation rates 1.96 (0.20, 18.86).
Balloon expandable stents vs PTA in iliac artery occlusive disease
Based on moderate quality of evidence, despite immediate technical success, 12.23 (7.17, 20.88), primary stenting is not associated with significant improvement in patency, clinical status, treadmill walking distance and reduction in re-intervention, complications, cardiovascular events, all cause mortality, QoL and amputation rates in patients with intermittent claudication caused by iliac artery occlusive disease. The pooled OR and their corresponding 95% CI are: patency 1.03 (0.56, 1.87); clinical improvement 1.08 (0.60, 1.94); walking distance 3.00 (12.96, 18.96); re-intervention 1.16 (0.71, 1.90); complications 0.56 (0.20, 1.53); all cause mortality 0.89 (0.47, 1.71); QoL 0.40 (-4.42, 5.52); cardiovascular event 1.16 (0.56, 2.40) and amputation rates 0.37 (0.11, 1.23). To date no RCTs are available evaluating self-expandable stents in the common or external iliac artery stenosis or occlusion.
Drug-eluting stent vs balloon-expandable bare metal stents in crural arteries
Based on a very low quality of evidence, at 6 months of follow-up, sirolimus drug-eluting stents are associated with a reduction in target vessel revascularization and re-stenosis rates in patients with atherosclerotic lesions of crural (tibial) arteries compared with balloon-expandable bare metal stent. The OR and their corresponding 95% CI are: re-stenosis 0.09 (0.03, 0.28) and TVR 0.15 (0.05, 0.47) in patients with atherosclerotic lesions of the crural arteries at 6 months follow-up. Both types of stents offer similar immediate success. Limitations of this study include: short follow-up period, small sample and no assessment of mortality as an outcome. Further research is needed to confirm its effect and safety.
PMCID: PMC3377569  PMID: 23074395
4.  Aortic Augmentation Index is Associated with the Ankle Brachial Index; A Community Based Study 
Atherosclerosis  2007;195(2):248-253.
Increased arterial stiffness has been associated with greater risk of cardiovascular events. We investigated whether aortic augmentation index (AIx), a measure of arterial stiffness and wave reflection, was associated with the ankle-brachial index (ABI), a measure of peripheral arterial disease (PAD).
AIx and ABI were measured in a community-based sample of 475 adults without prior history of heart attack or stroke (mean age 59.3 years, 46.5% men). Radial artery pulse waveforms were obtained by applanation tonometry and an ascending aortic pressure waveform derived by a transfer function. AIx is the difference between the first and second systolic peak of the ascending aortic pressure waveform indexed to the central pulse pressure. ABI was measured using a standard protocol, and subjects with non-compressible vessels (ABI >1.5) were excluded from the analyses. Multivariable linear and logistic generalized estimating equations (GEE) analyses were used to assess whether AIx was associated with ABI and ABI <1.00 respectively, independent of conventional risk factors.
Mean (± SD) values were: AIx, 29.3±11.6 %; ABI, 1.12±0.13; 59 (12.4%) participants had an ABI <1.00. Variables associated with a lower ABI (and ABI <1.00) included older age, shorter height, female sex, higher total cholesterol, hypertension medication use, history of smoking, and higher AIx. After adjustment for mean arterial pressure and the above variables, higher AIx remained associated with a lower ABI (P=0.015) and ABI <1.00 (P=0.002). A significant interaction (P=0.007) was present between AIx and age in the prediction of ABI; the (inverse) association of AIx with ABI was stronger in older subjects (>65 years).
AIx, a measure of arterial stiffness and wave reflection, was independently associated with a lower ABI in asymptomatic subjects from the community, and this association was modified by age.
PMCID: PMC3249443  PMID: 17254587
arterial stiffness; ankle-brachial index; arteries
5.  The Relationship among Pulse Wave Velocity, Ankle-Brachial Pressure Index and Heart Rate Variability in Adult Males 
Korean Journal of Family Medicine  2011;32(7):406-411.
Pulse wave velocity (PWV) and ankle-brachial pressure index (ABI) are non-invasive tools to measure atherosclerosis and arterial stiffness. Heart rate variability (HRV) has proven to be a non-invasive powerful tool in the investigation of the autonomic cardiovascular control. Therefore, the purpose of this study was to determine the relationship among PWV, ABI, and HRV parameters in adult males.
The study was carried out with 117 males who visited a health care center from April, 2009 to May, 2010. We conducted blood sampling (total cholesterol, triglyceride, high density lipoprotein, cholesterol, fasting glucose) and physical examination. We studied brachial-ankle PWV (baPWV) and ABI. We examined HRV parameters including standard deviation of NN interval (SDNN), low frequency (LF), high frequency (HF), LF/HF ratio. We analyzed the relationship among baPWV, ABI, and HRV parameters.
SDNN had a significant negative correlation with age, systolic blood pressure and heart rate. LF and HF had a significant negative correlation with age, and age and heart rate, respectively. baPWV was significantly and positively associated with age, systolic and diastolic blood pressures, total cholesterol, fasting glucose and heart rate. ABI was negative correlated significantly with systolic and diastolic blood pressures and heart rate. After adjusting for all associated variables, baPWV was not correlated with HRV parameters, but there was a significant positive association between SDNN and ABI (r = 0.195, P = 0.014).
SDNN of HRV parameters had a significant positive correlation with ABI.
PMCID: PMC3383151  PMID: 22745879
Heart Rate Variability; Pulse Wave Velocity; Ankle-Brachial Pressure Index
6.  Distribution of a subclinical marker of cardiovascular risk, the ankle brachial index, in a rural African population: SASPI study 
In sub-Saharan Africa, hypertension and stroke are emerging as an important cause of death and disability whereas coronary heart disease appears to still be uncommon. The aim of our study was to measure for the first time in an African population the ankle brachial index which is known to be a good marker of subclinical atheroma and of the risk of future cardiovascular events.
The study was part of the Southern African Stroke Prevention Initiative (SASPI). It comprised a cross-sectional survey conducted in rural north-east South Africa in the sub-district of Agincourt in which the demography of the population has been closely monitored. A stratified sample of 10 villages were selected and within these a random sample was chosen of 526 men and women 35 years and older. Subjects were visited on up to three occasions to be interviewed and have a clinical examination by specially trained nurses. This included assessment of cardiovascular risk factors and measurement of the ankle brachial index (ABI) (ratio of ankle: brachial systolic pressure) using a Doppler ultrasound machine.
The sample comprised 322 subjects in which the mean ABI (lower of either leg) was 1.05 in both men and women. The distribution of ABI was negatively skewed and a low ABI of ≤ 0.9, indicative of significant atheroma and higher cardiovascular risk, increased with age from 3.9% in 40-49 year olds to 39.7% in those 70 years and older. Lower ABI was related to current cigarette smoking (p = 0.02) and higher systolic and diastolic blood pressure (p < 0.01, p = 0.02 respectively) but not total cholesterol levels which were relatively low in this population (mean 4.47 mmol/L).
The distribution of the ABI in this rural African population was very similar to that reported in Western populations and suggests that this population has subclinical peripheral atheroma and is at increased risk of future cardiovascular events, thus providing further evidence of an epidemiological transition towards cardiovascular disease.
PMCID: PMC2833984  PMID: 17143129
Cardiovascular disease; subclinical; peripheral arterial disease; ankle brachial index; cross sectional survey; rural; sub-Saharan Africa; South Africa
7.  Plasma C-Terminal Pro-Endothelin-1 Is Associated With Target-Organ Damage in African Americans With Hypertension 
American journal of hypertension  2010;23(11):1204-1208.
Endothelin-1 (ET-1) is a vasoactive peptide with vasoconstrictor and mitogenic properties. We investigated whether plasma levels of C-terminal pro-ET-1 (CT-proET-1), a newly described stable fragment of the ET-1 precursor, are associated with target-organ damage in hypertension.
Participants included 981 African Americans (65 ± 9 years, 71% women) and 812 non-Hispanic whites (61 ± 9 years, 54% women) ascertained from sibships with hypertension. We measured plasma CT-proET-1 by an immunoluminometric assay. Measures of target-organ damage included the ankle-brachial index (ABI) and urinary albumin:creatinine ratio (UACR). Multivariable regressions analyses were employed to assess whether plasma CT-proET-1 levels were independently associated with ABI and UACR.
In hypertensive African Americans, higher plasma levels of CT-proET-1 were significantly associated with lower ABI (P < 0.01) and higher UACR (P < 0.01). After adjustment for age, sex, body mass index, systolic blood pressure (SBP) and diastolic blood pressure (BP), diabetes, serum glucose, insulin use, estimated glomerular filtration rate (eGFR), history of smoking, total and high-density lipoprotein cholesterol, medication use, and previous history of myocardial infarction (MI) or stroke, higher plasma levels of CT-proET-1 remained significantly associated with lower ABI (P < 0.01) and higher UACR (P = 0.02). In non-Hispanic white hypertensives, higher plasma levels of CT-proET-1 were weakly associated with higher UACR (P = 0.02) and with lower ABI (P = 0.07). After adjustment for the relevant covariates, no statistically significant associations between CT-proET-1 and ABI or UACR were present in whites.
Plasma levels of CT-proET-1 were independently associated with lower ABI and greater UACR in African American but not non-Hispanic white adults with hypertension.
PMCID: PMC2957561  PMID: 20634796
ankle-brachial index; blood pressure; endothelin; hypertension; target-organ damage; urinary albumin:creatinine ratio
8.  Post-Exercise Ankle-Brachial Pressure Index Demonstrates Altered Endothelial Function in the Elderly 
The ankle-brachial pressure index (ABI), the ratio of the systolic blood pressure of the ankle to the systolic brachial pressure, is commonly measured at rest, but ABI values post-exercise enhance the sensitivity of the test and can be used to identify atherosclerotic vascular damage. However, it has not been established whether or not enhanced post-exercise ABI is also associated with endothelial dysfunction. We hypothesized that a decrease in post-exercise ABI is related to impaired endothelial function.
To investigate alterations in post-exercise ABI values and endothelial dysfunction in the elderly.
The study population comprised 35 men and women aged 51–77 years (mean age: 66 years). Patients with peripheral arterial disease or a history of heart failure were excluded. The ABI was estimated at rest and immediately after exercise. The exercise protocol comprised 2.5 min of active pedal flexion exercises at a speed of 60 times/min. Endothelial function was assessed by measuring flow-mediated vasodilation (FMD) in the brachial artery using ultrasound imaging.
No correlation was found between FMD and the ABI at rest. However, a weak correlation was found between FMD and post-exercise ABI (r = 0.46, P = 0.06). A strong correlation was observed between FMD and a decrease in post-exercise ABI compared to baseline readings (r = −0.52, P = 0.01). Multiple linear regression analysis was used to generate a prediction equation for FMD using the percentage decrease in post-exercise ABI. Significant correlations were observed between the ultrasound imaging-measured FMD and the predicted FMD (R2 = 0.27, P = 0.001).
Post-exercise ABI appears to be a simple surrogate marker for endothelial function in the elderly, although larger studies are required for validation.
PMCID: PMC3699488  PMID: 23885186
ABI; endothelial function; elder; FMD; exercise
9.  Cardiovascular Risk Factors and Distributions of the Ankle-Brachial Index among Type 2 Diabetes Mellitus Patients 
Background. The aim of present study is to observe the association between the levels of ankle-brachial index (ABI) and cardiovascular risk factors among people with type 2 diabetes mellitus in north India. A cross-sectional study was carried out at a centre for heart and diabetic clinic in the state of Punjab on 1121 subjects (671 males and 450 females) with type 2 diabetes mellitus. History of symptoms related to cardiovascular diseases was noted, and blood pressure and anthropometric measurements were recorded. Ankle-brachial index (ABI) was measured using ultrasonic Doppler flow detector. Subjects with ABI ≤0.9 and ≥1.30 were classified as having low and high ABI, respectively. Females had a higher BMI and brachial-ankle pulse wave velocity (P < 0.001). Whereas, males had higher diastolic blood pressure and duration of type 2 diabetes mellitus. The differences of systolic blood pressure and ankle-brachial index were not found significant between the sexes. The prevalence of low ABI (<0.9) was 4.47% in men and 4.67% in women and high ABI (≥1.30) was prevalent in 14% of men and 10.45% of women. Age, BMI, baPWV, and blood pressures were significantly associated with ABI value in both sexes. The results suggested that the ABI might be used as a strong indicator for cardiovascular risk factors in type 2 diabetic subjects.
PMCID: PMC3420126  PMID: 22919466
10.  Correlation between Changes in Leg Blood Flow and Ankle-Brachial Pressure Index: A Study Using Laser Doppler Flowmeter —The 1st Report— 
Annals of Vascular Diseases  2011;4(2):79-86.
Objective: The objective of this study was to use non-invasive laser Doppler flowmeter to measure changes in blood flow in peripheral vessels in the legs before and after stress induced by leg elevation stress test and investigate correlations with the ankle-brachial pressure index (ABI).
Methods: Subjects included 28 patients over 20 years of age (mean, 73 years) who reported chiefly of leg symptoms such as intermittent claudication, numbness, chills, or cramps had been examined at the study institution, and agreed to participate in the study. The ABI of both legs was measured, and patients were divided into two groups: low ABI (ABI ≤0.9) and normal ABI (ABI ≥0.9). Blood flow in the big toe was measured using a box-type laser Doppler flowmeter before, during, and after leg-elevation stress. Amplitude of the recorded waveform and changes in blood flow were compared.
Results: Average ABI was 1.09 ± 0.10 in the normal ABI group (33 legs) and 0.68 ± 0.17 in the low ABI group (21 legs). Amplitude before and during stress was significantly smaller in the low ABI group than in the normal ABI group (p<0.01), and there was a significant correlation with ABI before and during stresses (r= 0.4606, r= 0.5048, respectively; p<0.05). Change in blood flow during stress was significantly lower in the low ABI group than in the normal ABI group (p<0.05). There was a significant correlation between change in blood flow during stress and ABI in both groups (r= 0.5073; p<0.05). There was also a significant correlation between change in blood flow and change in amplitude in both groups (r= 0.5477; p<0.05).
Conclusion: Results of this study show, that comparing amplitude and change in blood flow before and after leg extension and elevation stress, there was a correlation between change in blood flow and amplitude, and ABI during stress. A box-type laser Doppler flowmeter may provide a means of screening for peripheral arterial disease.
PMCID: PMC3595823  PMID: 23555434
peripheral arterial disease; ankle-brachial pressure index; laser Doppler flowmeter; intermittent claudication; lumbar spinal stenosis
11.  The reliability of the ankle-brachial index in the Atherosclerosis Risk in Communities (ARIC) study and the NHLBI Family Heart Study (FHS) 
A low ankle-brachial index (ABI) is associated with increased risk of coronary heart disease, stroke, and death. Regression model parameter estimates may be biased due to measurement error when the ABI is included as a predictor in regression models, but may be corrected if the reliability coefficient, R, is known. The R for the ABI computed from DINAMAP™ readings of the ankle and brachial SBP is not known.
A total of 119 participants in both the Atherosclerosis Risk in Communities (ARIC) study and the NHLBI Family Heart Study (FHS) had repeat ABIs taken within 1 year, using a common protocol, automated oscillometric blood pressure measurement devices, and technician pool.
The estimated reliability coefficient for the ankle systolic blood pressure (SBP) was 0.68 (95% CI: 0.57, 0.77) and for the brachial SBP was 0.74 (95% CI: 0.62, 0.83). The reliability for the ABI based on single ankle and arm SBPs was 0.61 (95% CI: 0.50, 0.70) and the reliability of the ABI computed as the ratio of the average of two ankle SBPs to two arm SBPs was estimated from simulated data as 0.70.
These reliability estimates may be used to obtain unbiased parameter estimates if the ABI is included in regression models. Our results suggest the need for repeated measures of the ABI in clinical practice, preferably within visits and also over time, before diagnosing peripheral artery disease and before making therapeutic decisions.
PMCID: PMC1435775  PMID: 16504033
12.  Association of Diabetes and Hemodialysis With Ankle Pressure and Ankle-Brachial Index in Japanese Patients With Critical Limb Ischemia 
Diabetes Care  2012;35(10):2000-2004.
To investigate whether diabetes and regular hemodialysis are associated with false elevation of ankle systolic blood pressure and ankle-brachial systolic pressure index (ABI) because of their arterial calcification in patients with critical limb ischemia (CLI).
We recruited 269 Japanese patients who underwent endovascular therapy for CLI. Ankle systolic blood pressure and ABI were assessed before endovascular therapy. Arterial stenosis and calcification were evaluated angiographically. We investigated the associations among clinical comorbidities, arterial calcification, and measurements of ankle systolic blood pressure and ABI.
Ankle systolic blood pressure was 85 ± 56 mmHg, and ABI was 0.59 ± 0.37. Arterial calcification was observed in 69% of the patients. The prevalence of diabetes and regular hemodialysis was 71 and 47%. Diabetes and regular hemodialysis were both significantly associated with the presence of arterial calcification; their adjusted odds ratios were 2.33 (P = 0.01) and 7.40 (P < 0.01), respectively. However, there was no significant difference in ankle systolic blood pressure or ABI level between those with and without these comorbidities. Furthermore, the presence of arterial calcification was not associated with ankle systolic blood pressure or ABI level, whereas arterial stenoses of all segments in the lower body had independent associations with reduced ankle systolic blood pressure and ABI level.
Diabetes and regular hemodialysis were significantly associated with arterial calcification, but not with elevated measurements of ankle systolic blood pressure or ABI, in CLI patients.
PMCID: PMC3447830  PMID: 22723344
13.  Why Is ABI Effective in Detecting Vascular Stenosis? Investigation Based on Multibranch Hemodynamic Model 
The Scientific World Journal  2013;2013:185691.
The ankle-brachial index (ABI), defined as the ratio of systolic pressure in the ankle arteries and that in the brachial artery, was a useful noninvasive method to detect arterial stenoses. There had been a lot of researches about clinical regularities of ABI; however, mechanism studies were less addressed. For the purpose of a better understanding of the correlation between vascular stenoses and ABI, a computational model for simulating blood pressure and flow propagation in various arterial stenosis circumstances was developed with a detailed compartmental description of the heart and main arteries. Particular attention was paid to the analysis of effects of vascular stenoses in different large-sized arteries on ABI in theory. Moreover, the variation of ABI during the increase of the stenosis severity was also studied. Results showed that stenoses in lower limb arteries, as well as, brachial artery, caused different variations of blood pressure in ankle and brachial arteries, resulting in a significant change of ABI. Furthermore, the variation of ABI became faster when the severity of the stenosis increased, validating that ABI was more sensitive to severe stenoses than to mild/moderate ones. All these in findings revealed the reason why ABI was an effective index for detecting stenoses, especially in lower limb arteries.
PMCID: PMC3780660  PMID: 24089601
14.  Borderline peripheral arterial disease 
Peripheral arterial disease (PAD), along with coronary artery disease and cerebrovascular disease, is a manifestation of systemic atherosclerosis. These cardiovascular diseases (CVDs) are the leading cause of death in the world, representing 30% of all global deaths. Although population-based studies indicate that PAD has a relatively benign course in the legs, patients with PAD show more cardiovascular comorbidity and have at least twofold risk of fatal coronary artery disease and cerebrovascular accidents compared with the general population. These studies suggest that noninvasive testing using the ankle-brachial index (ABI) is also an accurate marker of subclinical CVD and thus may hold promise for early identification of individuals at the greatest risk for major CVD events.
The Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II) defines a cutoff ABI value of 0.90 or less for diagnosing PAD at rest. This threshold value has been reported to be 95% sensitive in detecting angiogram-positive PAD and almost 100% specific in identifying apparently healthy individuals. In persons without PAD, arterial pressures increase with greater distance from the heart, resulting in higher systolic blood pressures at the ankle than at the the brachial arteries. Thus, persons without atherosclerosis typically have an ABI greater than 1.00. But what is the significance of ABI values between 0.91 to 1.00, which are conventionally regarded as ‘no disease’? The present article gives an overview of current knowledge of borderline PAD (ie, an ABI of 0.91 to 1.00).
PMCID: PMC2728920  PMID: 22477444
Ankle-brachial index; Borderline peripheral arterial disease; Cardiovascular disease; Cardiovascular risk; Peripheral arterial disease
15.  Prevalence of Low Ankle Brachial Index and Its Association With Pulse Pressure in an Elderly Chinese Population: A Cross-Sectional Study 
Journal of Epidemiology  2012;22(5):454-461.
We investigated the prevalence of low ankle brachial index (ABI) and the association of low ABI with pulse pressure among elderly community residents in China.
This population-based cross-sectional study was conducted in Beijing and recruited 2982 participants who were aged 60 years or older in 2007. Low ABI was defined as an ABI value less than 0.9 in either leg. Participants with or without stroke or coronary heart disease (CHD) were analyzed separately. The association between pulse pressure and low ABI was examined by using multiple logistic regression models.
The prevalence of low ABI was 5.65% (4.24% among men and 6.52% among women; P = 0.0221) among participants without stroke or CHD and 10.91% (13.07% among men and 9.49% among women; P = 0.1328) among those with stroke or CHD. After adjusting for confounders, the odds ratio (95% CI) for each 5-mm Hg increase in pulse pressure was 1.19 (1.07, 1.33) and 1.10 (1.02, 1.20) for men and women, respectively, among participants without stroke or CHD and 1.17 (1.03, 1.34) and 1.15 (1.02, 1.30) for men and women with stroke or CHD. When pulse pressure was classified into quartiles and the lowest quartile was used as reference, the association between pulse pressure and low ABI remained positive in men and women.
Low ABI was prevalent among elderly Chinese, and pulse pressure was positively associated with low ABI.
PMCID: PMC3798641  PMID: 22813646
pulse pressure; ankle brachial index; cross-sectional study
16.  Alternative ankle-brachial index method identifies additional at-risk individuals 
To determine whether utilization of an alternative ankle-brachial index (ABI) calculation method improves mortality risk prediction compared to traditional methods.
The ABI is used to diagnose peripheral arterial disease (PAD), and to identify those at risk for cardiovascular events. Traditionally, the ABI is calculated using the higher of the dorsalis pedis and posterior tibial ankle arteries. Studies directly comparing calculation methods are limited.
The ABI was calculated at baseline in 1,413 study participants undergoing non-emergent coronary angiography subsequently followed for all-cause and cardiovascular mortality. There were 224 individuals assigned to the traditional-PAD group (ABI < 0.90) using the traditional ABI method. Of those remaining, an alternative ABI method utilizing the lower of the two ankle pressures assigned 282 patients to the alternative-PAD group. The 862 individuals not assigned to PAD by either method were the no-PAD group.
There were 163 mortalities during a median follow-up of 5.0 years. Adjusted Cox regression models showed that the alternative-PAD group had an increased risk for all-cause (HR=1.49; 95% CI, 1.01-2.19) and cardiovascular mortality (HR=3.21; 95% CI, 1.53-6.37) versus the no-PAD group. Additionally, in the no-PAD group, there was an 11% (HR=1.11; 95% CI, 1.05-1.17) increased risk of all-cause mortality per 1mm Hg increased difference between the left and right brachial systolic pressures.
The implementation of an alternative ABI method and use of the brachial difference identifies individuals at an increased risk for mortality who are currently missed using traditional ABI methods. Current ABI protocols may need to be evaluated.
PMCID: PMC3732795  PMID: 23707317
peripheral artery disease; mortality; diagnosis
17.  Ankle-brachial index and the incidence of cardiovascular events in the Mediterranean low cardiovascular risk population ARTPER cohort 
Peripheral arterial disease (PAD) of the lower limbs is a cardiovascular disease highly prevalent particularly in the asymptomatic form. Its prevalence starts to be a concern in low coronary risk countries like Spain. Few studies have analyzed the relationship between ankle-brachial index (ABI) and cardiovascular morbi-mortality in low cardiovascular risk countries like Spain where we observe significant low incidence of ischemic heart diseases together with high prevalence of cardiovascular risk factors. The objective of this study is to determine the relationship between pathological ABI and incidence of cardiovascular events (coronary disease, cerebrovascular disease, symptomatic aneurism of abdominal aorta, vascular surgery) and death in the >49 year population-based cohort in Spain (ARTPER).
Baseline ABI was measured in 3,786 randomly selected patients from 28 Primary Health Centers in Barcelona, distributed as: ABI<0.9 peripheral arterial disease (PAD), ABI ≥1.4 arterial calcification (AC), ABI 0.9-1.4 healthy; and followed during 4 years.
3,307 subjects were included after excluding those with previous vascular events. Subjects with abnormal ABI were older with higher proportion of men, smokers and diabetics. 260 people presented cardiovascular events (incidence 2,117/100,000 person-years) and 124 died from any cause (incidence 978/100,000 person-years). PAD had two-fold greater risk of coronary disease (adjusted hazard ratio (HR) = 2.0, 95% confidence interval (CI) 1.3-3.2) and increased risk of vascular surgery (HR = 5.6, 95%CI 2.8-11.5) and mortality (HR = 1.8, 95%CI 1.4-2.5). AC increased twice risk of cerebrovascular events (HR = 1.9, 95%CI 1.0-3.5) with no relationship with ischemic heart disease.
PAD increases coronary disease risk and AC cerebrovascular disease risk in low cardiovascular risk Mediterranean population. ABI could be a useful tool to detect patients at risk in Primary Health Care.
PMCID: PMC3878485  PMID: 24341531
Peripheral arterial disease; Ankle-brachial index; Cardiovascular diseases; Incidence; Primary health care; Cohort studies
18.  The effect of exercise training on ankle-brachial index in type 2 diabetes 
Atherosclerosis  2013;230(1):125-130.
Though being physically active has associated with a healthier ankle-brachial index (ABI) in observational studies, ABI usually does not change with exercise training in patients with peripheral artery disease (PAD). Less is known about the effect of exercise training on ABI in patients without PAD but at high risk due to the presence of type 2 diabetes (T2DM).
Participants (n=140) with uncomplicated T2DM, and without known cardiovascular disease or PAD, aged 40–65 years, were randomized to supervised aerobic and resistance training 3 times per week for 6 months or to a usual care control group. ABI was measured before and after the intervention.
Baseline ABI was 1.02±0.02 in exercisers and 1.03±0.01 in controls (p=0.57). At 6 months, exercisers vs. controls improved ABI by 0.04±0.02 vs. −0.03±0.02 (p=0.001). This change was driven by an increase in ankle pressures (p<0.01) with no change in brachial pressures (p=0.747). In subgroup analysis, ABI increased in exercisers vs. controls among those with baseline ABI<1.0 (0.14±0.03 vs. 0.02±0.02, p=0.004), but not in those with a baseline ABI≥1.0 (p=0.085). The prevalence of ABI between 1.0–1.3 increased from 63% to 78% in exercisers and decreased from 62% to 53% in controls. Increased ABI correlated with decreased HbA1c, systolic and diastolic blood pressure, but the effect of exercise on ABI change remained significant after adjustment for these changes (β=0.061, p=0.004).
These data suggest a possible role for exercise training in the prevention or delay of PAD in T2DM, particularly among those starting with an ABI <1.0.
PMCID: PMC3775271  PMID: 23958264
exercise; peripheral artery disease; ankle-brachial index; type 2 diabetes
19.  Aortic Pulse Wave Velocity Is Associated With Measures of Subclinical Target Organ Damage 
JACC. Cardiovascular imaging  2011;4(7):10.1016/j.jcmg.2011.04.011.
Our goal was to evaluate the associations of central arterial stiffness, measured by aortic pulse wave velocity (aPWV), with subclinical target organ damage in the coronary, peripheral arterial, cerebral, and renal arterial beds.
Arterial stiffness is associated with adverse cardiovascular outcomes. We hypothesized that aPWV is associated with subclinical measures of atherosclerosis—coronary artery calcification (CAC) and ankle-brachial index (ABI) and arteriolosclerosis—brain white matter hyperintensity (WMH) and urine albumin-creatinine ratio (UACR).
Participants (n = 812; mean age 58 years; 58% women, 71% hypertensive) belonged to hypertensive sibships and had no history of myocardial infarction or stroke. aPWV was measured by applanation tonometry, CAC by electron beam computed tomography, ABI using a standard protocol, WMH volume by brain magnetic resonance, and UACR by standard methods. WMH was log-transformed, whereas CAC and UACR were log-transformed after adding 1 to reduce skewness. The associations of aPWV with CAC, ABI, WMH, and UACR were assessed by multivariable linear regression using generalized estimating equations to account for the presence of sibships. Covariates included in the models were age, sex, body mass index, history of smoking, hypertension and diabetes, total and high-density lipoprotein cholesterol, estimated glomerular filtration rate, use of aspirin and statins, and pulse pressure.
The mean ± SD aPWV was 9.8 ± 2.8 m/s. After adjustment for age, sex, conventional cardiovascular risk factors, and pulse pressure, higher aPWV (1 m/s increase) was significantly associated with higher log (CAC + 1) (β ± SE = 0.14 ± 0.04; p = 0.0003), lower ABI (β ± SE =−0.005 ± 0.002; p = 0.02), and greater log (WMH) (β ± SE = 0.03 ± 0.009; p = 0.002), but not with log (UACR + 1) (p = 0.66).
Higher aPWV was independently associated with greater burden of subclinical disease in coronary, lower extremity, and cerebral arterial beds, highlighting target organ damage as a potential mechanism underlying the association of arterial stiffness with adverse cardiovascular outcomes. (J Am Coll Cardiol Img 2011;4:754–61)
PMCID: PMC3862768  PMID: 21757166
arterial stiffness; arteriosclerosis; coronary artery calcification; hypertension; leukoariosis; peripheral arterial disease; pulse wave velocity; target organ damage
20.  Relation of Plasma Midregional Proatrial Natriuretic Peptide to Target Organ Damage in Adults With Systemic Hypertension 
The American journal of cardiology  2009;103(9):1255-1260.
We tested the hypothesis that, in adults with essential hypertension, plasma levels of midregional proatrial natriuretic peptide (MR-proANP) are associated with target organ damage. MR-proANP is a newly described stable fragment of N-terminal proatrial natriuretic peptide. Participants included 1,919 adults with hypertension identified from the community (1,037 African-Americans, 65 ± 9 years of age, 72% women; 882 non-Hispanic whites, 61 ± 9 years of age, 55% women). We measured MR-proANP by an immunoluminometric assay. Measurements of target organ damage included the ankle–brachial index (ABI), urinary albumin–creatinine ratio (UACR), and left ventricular (LV) mass (available only in African-Americans). Generalized estimating equations were used to assess whether plasma MR-proANP was associated with measurements of target organ damage, independent of potential confounding variables. In African-Americans, higher MR-proANP was significantly associated with lower ABI (p < 0.0001), higher UACR (p<0.0001), and greater LV mass (indexed to height to the power of 2.7, p < 0.0001). After adjustment for age, gender, body mass index, systolic blood pressure, estimated glomerular filtration rate, smoking history, diabetes mellitus, total and high-density lipoprotein cholesterols, medication (blood pressure lowering, statin, and aspirin) use, and previous myocardial infarction or stroke, higher MR-proANP levels remained significantly associated with lower ABI (p = 0.01), higher UACR (p = 0.0007), and greater LV mass index (p<0.0001). In non-Hispanic whites, higher MR-proANP levels were significantly associated with lower ABI (p = 0.002) and greater UACR (p = 0.001), but not after adjustment for the covariates listed earlier. In conclusion, plasma MR-proANP may be a marker of target organ damage in the setting of hypertension, especially in African-Americans.
PMCID: PMC2956127  PMID: 19406268
21.  Peripheral Arterial Disease and Ankle-Brachial Index Abnormalites in Young and Middle-Aged HIV-Positive Patients in Lower Silesia, Poland 
PLoS ONE  2014;9(12):e113857.
Peripheral arterial disease (PAD) is a clinical manifestation of atherosclerosis and mainly refers to elderly patients, having a negative impact on their functionality and quality of life. The findings of previous studies in HIV-infected patients have shown that cardiovascular risk is higher and PAD occurs more frequently than in the general population. There are also contradictory observations. Much less is known about the ankle-brachial index (ABI) value in asymptomatic HIV-infected patients. The aim of this study was to evaluate the prevalence of PAD and ankle-brachial index abnormalities as well as to determine risk factors related to the disease in a group of Polish HIV–positive patients.
Methods and Findings
One hundred and eleven young to middle aged HIV–positive subjects and 40 noninfected subjects were enrolled into the study. Resting ABI measurements were performed and cardiovascular risk was analysed as well. Subgroups were created according to the ABI values: low (PAD), borderline, normal, high and altered ABI. Symptomatic PAD was observed in 2 HIV–positive patients, asymptomatic PAD was not diagnosed. The ABI value is lower and more varied, in 22.5% of the study group altered ABI values were found. Six subjects demonstrated borderline ABI, and 15 high ABI, including >1.4. In the control group no low or very high values were reported. A relation between low ABI and cardiovascular family history and between altered ABI and high–density–lipoprotein cholesterol (HDL–C) level was demonstrated.
In young and middle–aged HIV–positive patients, symptomatic PAD prevalence is comparable to that observed in the overall population. Among asymptomatic patients PAD is not reported. The ABI value in HIV–positive patients is more varied compared to the HIV–negative subjects; the altered ABI shows a strong relation with low HDL–C levels and metabolic syndrome.
PMCID: PMC4264742  PMID: 25503743
22.  Role of ankle-brachial pressure index as a predictor of coronary artery disease severity in patients with diabetes mellitus 
The Canadian Journal of Cardiology  2009;25(9):e301-e305.
Previous studies have reported a close correlation between low ankle-brachial pressure index (ABPI) and various cardiovascular risk factors. However, despite the well-established potential hazards of consequent coronary artery disease (CAD), no data exist on the relationship between ABPI and the severity of CAD, particularly in patients with diabetes mellitus (DM).
A total of 840 patients ranging from 35 to 87 years of age (mean [± SD] 63.9±10.2 years) with suspected CAD in a clinical practice were enrolled. All patients underwent ABPI measurements and coronary angiography. Patients were divided into four groups according to the results of ABPI measurements and the presence or absence of DM: group A had an ABPI value of at least 0.9 but no DM (A−/D−); group B had an ABPI value of at least 0.9 and DM (A−/D+); group C had an ABPI of less than 0.9 but no DM (A+/D−); and group D had an ABPI value of less than 0.9 and DM (A+/D+).
Age was significantly higher in the A+ (groups C and D) than the A− patients (groups A and B). Moreover, men predominated in all four groups. Comparisons of sex distribution among the four groups revealed that group D had the highest percentage of women, while group A had the lowest. Total cholesterol level did not differ among the four groups, although group D tended to have the highest result. Patients in group D had the highest percentages of hypertension, hypercholesterol, hypertriglyceride, low high-density lipoprotein cholesterol and high low-density lipoprotein cholesterol among the four groups. Group D exhibited the highest triglyceride and uric acid levels, the lowest high-density lipoprotein cholesterol level, and the highest metabolic syndrome criteria number and percentage of metabolic syndrome. Furthermore, group D had the highest mean lesion numbers, mean numbers of target vessel involvement, stenoses with type C classification and complex morphology lesions (chronic total occlusion, diffuse or calcified lesions) among the four groups. There were still significant differences in lesion numbers (P<0.001) and numbers of target vessel involvement (P<0.001) for ABPI predicting CAD severity after controlling for the effects of DM and age. The sensitivity, specificity, positive predictive value and negative predictive value of using an ABPI of less than 0.9 to predict CAD differed significantly between patients with and without DM.
ABPI is a useful noninvasive tool for predicting CAD severity, even in patients with DM.
PMCID: PMC2780910  PMID: 19746248
Ankle-brachial pressure index; Coronary artery disease; Peripheral artery disease
23.  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 
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).
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: Unique identifier: NCT01072500.
PMCID: PMC3886743  PMID: 24222666
aging; exercise; peripheral vascular disease
24.  The association of the ankle-brachial index with incident coronary heart disease: the Atherosclerosis Risk In Communities (ARIC) study, 1987–2001 
Peripheral arterial disease (PAD), defined by a low ankle-brachial index (ABI), is associated with an increased risk of cardiovascular events, but the risk of coronary heart disease (CHD) over the range of the ABI is not well characterized, nor described for African Americans.
The ABI was measured in 12186 white and African American men and women in the Atherosclerosis Risk in Communities Study in 1987–89. Fatal and non-fatal CHD events were ascertained through annual telephone contacts, surveys of hospital discharge lists and death certificate data, and clinical examinations, including electrocardiograms, every 3 years. Participants were followed for a median of 13.1 years. Age- and field-center-adjusted hazard ratios (HRs) were estimated using Cox regression models.
Over a median 13.1 years follow-up, 964 fatal or non-fatal CHD events accrued. In whites, the age- and field-center-adjusted CHD hazard ratio (HR, 95% CI) for PAD (ABI<0.90) was 2.81 (1.77–4.45) for men and 2.05 (1.20–3.53) for women. In African Americans, the HR for men was 4.86 (2.76–8.47) and for women was 2.34 (1.26–4.35). The CHD risk increased exponentially with decreasing ABI as a continuous function, and continued to decline at ABI values > 1.0, in all race-gender subgroups. The association between the ABI and CHD relative risk was similar for men and women in both race groups. A 0.10 lower ABI increased the CHD hazard by 25% (95% CI 17–34%) in white men, by 20% (8–33%) in white women, by 34% (19–50%) in African American men, and by 32% (17–50%) in African American women.
African American members of the ARIC cohort had higher prevalences of PAD and greater risk of CHD associated with ABI-defined PAD than did white participants. Unlike in other cohorts, in ARIC the CHD risk failed to increase at high (>1.3) ABI values. We conclude that at this time high ABI values should not be routinely considered a marker for increased CVD risk in the general population. Further research is needed on the value of the ABI at specific cutpoints for risk stratification in the context of traditional risk factors.
PMCID: PMC1784111  PMID: 17227586
25.  Low Lifetime Recreational Activity is a Risk Factor for Peripheral Arterial Disease 
The relationship between lifetime physical activity and the risk of developing peripheral arterial disease (PAD) is not known.
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.
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.
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.
PMCID: PMC3152670  PMID: 21664093
Intermittent claudication; exercise; vascular disease; atherosclerosis

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