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1.  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
2.  Serum Phosphorus Levels and the Spectrum of Ankle-Brachial Index in Older Men 
American Journal of Epidemiology  2010;171(8):909-916.
A higher serum phosphorus level is associated with cardiovascular disease (CVD) events among community-living populations. Mechanisms are unknown. The ankle-brachial index (ABI) provides information on both atherosclerosis and arterial stiffness. In this cross-sectional study (2000–2002), the authors evaluated the association of serum phosphorus levels with low (<0.90) and high (≥1.40 or incompressible) ABI as compared with intermediate ABI in 5,330 older US men, among whom the mean serum phosphorus level was 3.2 mg/dL (standard deviation, 0.4), 6% had a low ABI, and 5% had a high ABI. Each 1-mg/dL increase in serum phosphorus level was associated with a 1.6-fold greater prevalence of low ABI (95% confidence interval (CI): 1.2, 2.1; P < 0.001) and a 1.4-fold greater prevalence of high ABI (95% CI: 1.0, 1.9; P = 0.03) in models adjusted for demographic factors, traditional CVD risk factors, and kidney function. However, the association of phosphorus with high ABI differed by chronic kidney disease (CKD) status (in persons with CKD, prevalence ratio = 2.96, 95% CI: 1.61, 5.45; in persons without CKD, prevalence ratio = 1.14, 95% CI: 0.81, 1.61; interaction P = 0.04). In conclusion, among community-living older men, higher phosphorus levels are associated with low ABI and are also associated with high ABI in persons with CKD. These associations may explain the link between serum phosphorus levels and CVD events.
doi:10.1093/aje/kwq020
PMCID: PMC2877442  PMID: 20237150
ankle brachial index; cardiovascular diseases; kidney diseases; phosphorus
3.  Distribution of the Ankle-Brachial Index and Associated Cardiovascular Risk Factors in a Population of Middle-Aged and Elderly Koreans 
Journal of Korean Medical Science  2005;20(3):373-378.
The Doppler ankle-brachial pressure index (ABI) is an objective and efficient tool that can be used to determine the presence and severity of peripheral arterial disease in the lower extremities. The ABI value is inversely associated with other cardiovascular risk factors. To date, there have been no studies of the distribution of ABI in Korea. We performed a cross-sectional study of 1,943 subjects (681 men and 1,262 women; 45-74 yr old) in Namwon, Korea. The prevalence of a low ABI (<0.90) was 2.2% in men and 1.8% in women, and a high ABI (≥1.30) was prevalent in 3.1% of men and 0.8% of women. Age, smoking habits, waist circumference, hypertension, and blood pressure were associated with ABI values in both sexes. The presence of carotid plaques was associated with ABI values only in men, whereas pulse pressure was associated with ABI values only in women (p<0.05). Although the prevalence of a low ABI in the present study was lower than those reported previously for Western populations and Japanese men, our results suggest that the ABI might be used as an indicator of cardiovascular risk factors in adult Koreans.
doi:10.3346/jkms.2005.20.3.373
PMCID: PMC2782189  PMID: 15953855
Peripheral Vascular Diseases; Prevalence; Ankle-brachial Index; Risk Factors
4.  The Ankle-Brachial Index and Incident Cardiovascular Events in the Multi-Ethnic Study of Atherosclerosis (MESA) 
Objectives
The purpose of this study was to examine the association of both a low and a high ankle-brachial index (ABI) with incident cardiovascular events in a multi-ethnic cohort.
Background
Abnormal ankle-brachial indices (ABIs), both low and high, are associated with elevated cardiovascular disease (CVD) risk. However, it is unknown whether this association is consistent across different ethnic groups, and whether it is independent of both newer biomarkers and other measures of subclinical atherosclerotic CVD.
Methods
6647 non-Hispanic white, African-American, Hispanic, and Chinese men and women aged 45–84 years from free-living populations in six United States field centers and free of clinical CVD at baseline had extensive measures of traditional and newer biomarker risk factors, and measures of subclinical CVD, including the ABI. Incident CVD, defined as coronary disease, stroke, or other atherosclerotic CVD death, was determined over a mean follow-up of 5.3 years.
Results
Both a low (<1.00) and a high (≥ 1.40) ABI were associated with incident CVD events. Gender- specific and ethnic-specific analyses showed consistent results. Hazard ratios were 1.77 (p<.001) for a low and 1.85 (p=.050) for a high ABI after adjustment for both traditional and newer biomarker CVD risk factors, and the ABI significantly improved risk discrimination. Further adjustment for coronary artery calcium score, common and internal carotid intimal medial thickness, and major ECG abnormalities only modestly attenuated these hazard ratios.
Conclusions
In this study both a low and a high ABI were associated with elevated CVD risk in persons free of known CVD, independent of standard and novel risk factors, and independent of other measures of subclinical CVD. Further research should address the cost-effectiveness of measuring the ABI in targeted population groups.
doi:10.1016/j.jacc.2010.04.060
PMCID: PMC2962558  PMID: 20951328
peripheral arterial disease; ankle-brachial index; cardiovascular events; risk factors; subclinical atherosclerosis
5.  A High Ankle Brachial Index is Associated with Greater Left Ventricular Mass: The Multi-Ethnic Study of Atherosclerosis 
Background
Arterial stiffness leads to left ventricular (LV) mass through non-atherosclerotic pathways in mice. In humans, a high ankle brachial index (ABI) indicates stiff peripheral arteries, and is associated with cardiovascular disease (CVD) events. Whether high ABI is associated with LV mass in humans, and whether this may reflect consequences of arterial stiffness, atherosclerosis, or both is unknown.
Methods
Among 4,972 MESA participants without clinical CVD, we used linear regression to evaluate the association of low (< 0.90) and high (>1.40 or incompressible) ABI with LV mass by cardiac magnetic resonance imaging (MRI). Intermediate ABIs served as the reference category. To determine the effect of subclinical atherosclerosis, models were adjusted for common and internal carotid intima media thickness (cIMT) and log-transformed coronary artery calcification (Ln[CAC+1]).
Results
Compared to subjects with intermediate ABI, LV mass was higher with either low (2.70g/m2 higher, 95% CI 0.65–4.75) or high ABI (6.84 g/m2 higher, 95% CI 3.2–10.47) after adjustment for traditional CVD risk factors, kidney function, and CRP. However, further adjustment for cIMT and CAC substantially attenuated the association of low ABI with LVMI (1.24 g/m2 higher, 95% CI −0.84–3.33), whereas the association of high ABI was minimally altered (6.01 g/m2 higher, 95% CI 2.36–9.67).
Conclusions
High ABI is associated with greater LV mass; an association that is not attenuated with adjustment for subclinical atherosclerosis in non-peripheral arterial beds. High ABI may lead to greater LV mass through non-atherosclerotic pathways.
doi:10.1016/j.jacc.2009.11.010
PMCID: PMC2837506  PMID: 20117440
vascular stiffness; medial arterial calcification; left ventricular mass; heart failure; cardiovascular disease
6.  Is Diabetic Retinopathy Related to Subclinical Cardiovascular Disease? 
Ophthalmology  2010;118(5):860-865.
OBJECTIVE
Persons with diabetic retinopathy (DR) have an increased risk of clinical cardiovascular events. Our study aimed to determine whether DR is associated with a range of measures of subclinical cardiovascular disease (CVD) in persons without clinical CVD.
DESIGN
Population-based, cross-sectional epidemiologic study
PARTICIPANTS
Nine hundred and twenty seven persons with diabetes without clinical CVD in the Multi-Ethnic Study of Atherosclerosis.
METHODS
DR was ascertained from retinal photographs according to modification of the Airlie House Classification system. Vision threatening DR (VTDR) was defined as severe non-proliferative DR, proliferative DR or clinically significant macular edema. Subclinical CVD measures were assessed and defined as follows: high coronary artery calcium (CAC) score, defined as CAC score≥400; low ankle-brachial index (ABI), defined as ABI<0.9; high ABI, defined as ABI≥1.4; high carotid intima-media thickness (IMT), defined as highest 25% of IMT; and carotid stenosis, defined as >25% stenosis or presence of carotid plaque.
MAIN OUTCOME MEASURES
Associations between DR and subclinical CVD measures.
RESULTS
The prevalence of DR and VTDR in this sample was 30.0% and 7.2%, respectively. VTDR was associated with a high CAC score (odds ratio [OR] 2.33, 95% condifence interval [CI] 1.15–4.73), low ABI (OR 2.54; 95%CI, 1.08–5.99) and high ABI (OR 12.6, 95% CI, 1.14, 140.6), after adjusting for risk factors including hemoglobin A1c level and duration of diabetes. The association between VTDR and high CAC score remained significant after further adjustment for hypoglycemic, anti-hypertensive and cholesterol-lowering medications. DR was not significantly associated with measures of carotid artery disease.
CONCLUSIONS
In persons with diabetes without a history of clinical CVD, the presence of advanced stage of DR is associated with subclinical coronary artery disease. These findings emphasize the need to be careful about the use of anti-vascular endothelial growth factor for the treatment of DR.
doi:10.1016/j.ophtha.2010.08.040
PMCID: PMC3087839  PMID: 21168222
7.  Inflammation and Oxidative Stress are Associated with the Prevalence of High Aankle-brachial Index in Metabolic Syndrome Patients without Chronic Renal Failure 
Aims: High ankle-brachial index (ABI) is marker of increased cardiovascular morbidity and mortality, while the relationship and mechanism between high ABI and metabolic syndrome (MetS) are unclear. The objectives of this study were to determine the relationship and possible mechanism of MetS with high ABI.
Methods: 341 participants without CRF were recruited. Among these participants, 58 participants (ABI ≥ 1.3) were include in high ABI group and the other 283 participants (0.9 < ABI < 1.3) were include in normal ABI group. Furthermore, these 341 participants were also divided into MetS group (n = 54) and non-MetS group (n = 287). All participants received examinations including body mass index (BMI), ABI and related biochemical parameters.
Results: Compared with non-MetS group, the prevalence of high ABI was higher in MetS group (27.8% vs. 15%, p < 0.05). Participants with 3-4 metabolic risk factors had higher prevalence of high ABI than those with 0-1 metabolic risk factors (27.8% vs. 12.7%, p < 0.05). The prevalence of high ABI in overweight participants was higher than those with normal body weight. And the participants with hypertension also had higher prevalence of high ABI than normotensive participants. BMI, high-sensitivity C-reactive protein (hsCRP) and superoxide dismutase (SOD) were all higher in high ABI group than normal ABI group (p < 0.05).
Conclusions: More metabolic risk factors have increased the risk of high ABI. Inflammation and oxidative stress are associated with prevalence of high ABI in metabolic syndrome patients without chronic renal failure.
doi:10.7150/ijms.5308
PMCID: PMC3547217  PMID: 23329891
High ankle-brachial index; metabolic syndrome; inflammation; oxidative stress; metabolic risk factors
8.  Ankle-brachial index in HIV infection 
Prognosis for patients with the human immunodeficiency virus (HIV) has improved with the introduction of highly active antiretroviral therapy (HAART). Evidence over recent years suggests that the incidence of cardiovascular disease is increasing in HIV patients. The ankle-brachial index (ABI) is a cheap and easy test that has been validated in the general population. Abnormal ABI values are associated with increased cardiovascular mortality. To date, six series of ABI values in persons with HIV have been published, but none was a prospective study. No agreement exists concerning the risk factors for an abnormal ABI, though its prevalence is clearly higher in these patients than in the general population. Whether this higher prevalence of an abnormal ABI is associated with a higher incidence of vascular events remains to be determined.
doi:10.1186/1742-6405-6-6
PMCID: PMC2679059  PMID: 19397788
9.  Oscillometric measurement of the ankle-brachial index 
INTRODUCTION
Peripheral arterial disease is a coronary risk equivalent; a low ankle-brachial index (ABI) is indicative of systemic vascular disease, and should place a patient in the high-risk category. Few physicians measure ABI because it is technically challenging and time consuming. Oscillometric blood pressure monitors are readily available and easy to use. The use of a simple method of documenting ABI was assessed and compared with the conventional method.
METHODS
The oscillometric ABI (OABI) was measured for normal volunteers, patients attending a cardiovascular risk clinic (Cardiovascular Risk Factor Reduction Unit [CRFRU] at the University of Saskatchewan, Saskatoon) and patients referred to a vascular laboratory (vasc lab). The latter group had Doppler ABI (DABI) measurements and served to validate OABI. An Omron HEM 711C oscillometric system (Omron Canada Inc) with appropriate cuff size for arm and leg circumference was used.
RESULTS
The mean ± SEM OABI was 1.13±0.08 in normal volunteers (n=26), 1.10±0.10 in CRFRU patients (n=11, P not significant) and 1.03±0.14 in vasc lab patients (n=57, P<0.05 compared with normal volunteers). No difference was found between sexes, and there was no correlation with age. In the vasc lab group, the correlation with DABI was 0.71 (P<0.05). The sensitivity of OABI to detect DABI of less than 0.9 was 0.71, and the specificity was 0.89. OABI was found to be less sensitive at detecting low values in patients with nonpalpable pulses on physical examination.
CONCLUSION
The OABI is feasible and operator-independent, but does not detect low ABI efficiently. If OABI is abnormal, low DABI is likely. The OABI is less likely to detect disease in patients with nonpalpable peripheral pulses. Such patients are better referred directly to a vascular laboratory for DABI testing.
PMCID: PMC2631249  PMID: 18209769
Ankle-brachial index; Atherosclerosis; Diagnosis; Peripheral vascular disease; Risk factors
10.  Ethnic differences in Ankle Brachial Index are Present in Middle-Aged Individuals without Peripheral Arterial Disease 
Introduction
To better understand the basis for previously reported ethnic differences in ankle brachial index (ABI), we investigated whether these differences were present in individuals without known peripheral arterial disease (PAD).
Methods
We used data from National Health and Nutrition Examination surveys (NHANES 1999–2004) to determine whether ethnic differences were present in respondents without PAD (1≤ABI≤1.3). We assessed whether ethnicity was an independent predictor of ABI and ankle systolic blood pressure (SBP) in linear regression models that adjusted for conventional and novel cardiovascular risk factors. To minimize effects of atherosclerosis on ABI, we studied adults aged ≤ 60 years, and also repeated our analyses in a subset aged ≤ 50 years that did not have risk factors for PAD.
Results
3348 participants aged ≤ 60 years were included in the study. Mean ABI was 1.11 in non-Hispanic Blacks (NHB) and 1.13 in non-Hispanic Whites (NHW) (P <0.0001). In multivariable linear regression analysis that adjusted for age, gender, ethnicity, smoking, height, diabetes, brachial SBP, dyslipidemia, diabetes, renal function, concurrent cardiovascular disease, and plasma levels of homocysteine, fibrinogen and C-reactive protein, NHB had lower ABI than NHW (β= − 0.03± 0.004, P < 0.00001). Although, NHBs had higher ankle SBP than NHWs (by 5.3 mm Hg), NHBs had a lower mean ankle SBP (β= − 3.663 mm Hg ± 0.500, P <.0001) after adjusting for clinical covariates, including brachial SBP, in multivariable analysis.
Conclusion
Ethnic differences in ABI are present in middle-aged adults at low risk for peripheral atherosclerosis.
doi:10.1016/j.ijcard.2011.05.068
PMCID: PMC3174274  PMID: 21652099
ankle brachial index; ethnicity
11.  Ethnicity and Risk Factors for Change in the Ankle-Brachial Index: The Multi-Ethnic Study of Atherosclerosis 
Background
The aim of this study was to determine the risk factors for conversion from a normal to either a low or high ABI.
Methods
Participants in the Multi-Ethnic Study of Atherosclerosis who had two separate measurements of the ABI over a 3-year time period were assessed.
Results
At baseline, the mean age was 62 years and 50% were women, 28% African American, 12% Chinese, 22% Hispanic and 38% non-Hispanic White. Of the 5,514 participants with a baseline ABI between 0.90 and 1.40, 89 (1.6%) had an ABI ≤ 0.90 (“low ABI group”) and 71 (1.3%) had an ABI ≥ 1.40 (“high ABI group”) three years later. On multivariable analysis, the odds for having progressed into the low ABI group were significantly increased for higher baseline age, hypertension, diabetes, greater pack-years of cigarette smoking and homocysteine levels. The odds for progression into the high ABI group were increased for male gender and higher body mass index. Compared to non-Hispanic Whites, African Americans had a significantly higher odds for progression to the low ABI group (OR: 2.24, 95% CI: 1.29 – 3.88) while having a reduced odds for progression to the high ABI group (OR: 0.50, 95% CI: 0.24 – 1.00). Neither Chinese nor Hispanic ethnicity was significantly associated with progression to either ABI group.
Conclusions
The risk factors for progression to a low or high ABI were distinct and African Americans were at increased risk for progression to a low ABI but at decreased risk for progression into the high ABI group.
doi:10.1016/j.jvs.2009.05.061
PMCID: PMC2783523  PMID: 19628357
12.  Alcohol Consumption and Ankle-to-Brachial Index: Results from the Cardiovascular Risk Survey 
PLoS ONE  2010;5(12):e15181.
Background and Methodology
A low ankle-to-brachial index (ABI) is a strong correlate of cardiovascular disease and subsequent mortality. The relationship between ABI and alcohol consumption remains unclear. Data are from the Cardiovascular Risk Survey (CRS), a multiple-ethnic, community-based, cross-sectional study of 14 618 Chinese people (5 757 Hans, 4 767 Uygurs, and 4 094 Kazakhs) aged 35 years and over at baseline from Oct. 2007 to March 2010. The relationship between alcohol intake and ABI was determined by use of analysis of covariance and multivariable regressions.
Principal Findings
In men, alcohol consumption was significantly associated with ABI (P<0.001). After adjusted for the confounding factors, such as age, sex, ethnicity, body mass index, smoking, work stress, diabetes, and fasting blood glucose, the difference remained significant (P<0.001); either the unadjusted or multivariate-adjusted odds ratio (OR) for peripheral artery disease (PAD) was significantly higher in men who consumed >60.0 g/d [OR  = 3.857, (95% CI: 2.555–5.824); OR = 2.797, (95% CI: 1.106–3.129); OR = 2.878, (95% CI: 1.215–4.018); respectively] and was significantly lower in men who consumed 20.1–40.0 g/d [OR  = 0.330, (95% CI: 0.181–0.599); OR = 0.484, (95% CI: 0.065–0.894); OR = 0.478, (95% CI: 0.243–1.534); respectively] and 40.1–60.0 g/d [OR  = 0.306, (95% CI: 0.096–0.969); OR = 0.267, (95% CI: 0.087–0.886); OR = 0.203, (95% CI: 0.113–0.754); respectively] compared with never drinking, respectively (all P<0.01). Neither in unadjusted nor in multivariate-adjusted model was the association between ABI and alcohol consumption significant (all P>0.05) in women. Similarly, PAD was not correlated with alcohol intake in women (all P>0.05).
Conclusions/Significance
Our results indicated that in Chinese men, alcohol consumption was associated with peripheral artery disease, and consumption of less than 60 g/d had an inverse association with peripheral atherosclerosis whereas consumption of 60 g/d or more had a positive association.
doi:10.1371/journal.pone.0015181
PMCID: PMC2996294  PMID: 21152041
13.  The association of the ankle-brachial index with incident coronary heart disease: the Atherosclerosis Risk In Communities (ARIC) study, 1987–2001 
Background
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.
Methods
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.
Results
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.
Conclusion
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.
doi:10.1186/1471-2261-7-3
PMCID: PMC1784111  PMID: 17227586
14.  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.
15.  The Prevalence and Predictors of an Abnormal Ankle-Brachial Index in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Trial 
Diabetes Care  2011;34(2):464-467.
OBJECTIVE
To examine ankle-brachial index (ABI) abnormalities in patients with type 2 diabetes and coronary artery disease (CAD).
RESEARCH DESIGN AND METHODS
An ABI was obtained in 2,240 patients in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Trial. ABIs were classified as: normal, 0.91–1.3; low, ≤0.9; high, >1.3; or noncompressible artery (NC). Baseline characteristics were examined according to ABI and by multivariate analysis.
RESULTS
ABI was normal in 66%, low in 19%, and high in 8% of patients, and 6% of patients had NC. Of the low ABI patients, 68% were asymptomatic. Using normal ABI as referent, low ABI was independently associated with smoking, female sex, black race, hypertension, age, C-reactive protein, diabetes duration, and lower BMI. High ABI was associated with male sex, nonblack race, and higher BMI; and NC artery was associated with diabetes duration, higher BMI, and hypertension.
CONCLUSIONS
ABI abnormalities are common and often asymptomatic in patients with type 2 diabetes and CAD.
doi:10.2337/dc10-1734
PMCID: PMC3024368  PMID: 21270200
16.  Association of Serum Myeloperoxidase with Peripheral Arterial Disease 
Myeloperoxidase (MPO) is an enzymatic mediator of several inflammatory cascades and higher serum levels have been associated with increased risk of adverse cardiovascular events. We investigated the association of serum MPO with the ankle-brachial index (ABI) and peripheral arterial disease (PAD), in a bi-ethnic cohort of African-Americans and non-Hispanic whites. Participants included 1324 African-Americans (64 y, 71% women) and 1237 non- Hispanic whites (59 y, 57% women) belonging to hypertensive sibships. Plasma levels of MPO were measured by solid phase sandwich immunoassay. ABI was measured using a standard protocol and PAD defined as ABI <0.90. Multivariable regression analysis using generalized estimating equations (GEE) were performed to assess whether serum MPO levels were associated with ABI and the presence of PAD. After adjustment for age and sex, higher MPO levels were significantly associated with lower ABI and presence of PAD in African-Americans (P=0.004 and P=0.005, respectively) and in non-Hispanic whites (P=0.001and P=0.021, respectively). After additional adjustment for conventional risk factors (diabetes, smoking status, total and HDL cholesterol, waist circumference, hypertension), prior history of myocardial infarction or stroke, and medication use (statins, aspirin, estrogen), higher MPO levels remained significantly associated with lower ABI and presence of PAD in both African- Americans (P=0.008 and P=0.012, respectively) and non-Hispanic whites (P=0.001and P=0.029, respectively). We conclude that higher MPO levels are associated with lower ABI and the presence of PAD in African-Americans and non-Hispanic whites.
doi:10.1177/1358863X08101999
PMCID: PMC2752685  PMID: 19651670
peripheral arterial disease; inflammation; ankle-brachial index; myeloperoxidase
17.  The Association Between Physical Activity and Subclinical Atherosclerosis 
American Journal of Epidemiology  2008;169(4):444-454.
Prior reports regarding the association between physical activity and subclinical cardiovascular disease have not been consistent. The authors assessed physical activity and walking pace via questionnaire among 6,482 US adults aged 45–84 years without prior clinical cardiovascular disease participating in the Multi-Ethnic Study of Atherosclerosis from 2000 to 2002. Ankle-brachial index (ABI), coronary artery calcification, and internal and common carotid intima-media thickness (IMT) were measured. Metabolic equivalent-hours/week of physical activity were calculated. These data were analyzed by using multivariable linear or relative prevalence regression in gender-specific strata. After adjustment for age, race/ethnicity, clinic site, education, income, and smoking (model 1), increasing total, moderate + vigorous, and intentional-exercise physical activity were not associated with IMT or coronary artery calcification in either gender. These factors were associated with increased ABI (P < 0.05) in women only. Walking pace was associated favorably with common carotid IMT, ABI, and coronary artery calcification in men and with common carotid IMT and ABI in women (all P < 0.05) after adjustment for model 1 variables. These associations were attenuated and, for common carotid IMT, no longer significant when lipids, hypertension, diabetes, and body mass index were added to the model. These data suggest that walking pace is associated with less subclinical atherosclerosis; these associations may be mediated by cardiovascular disease risk factors.
doi:10.1093/aje/kwn350
PMCID: PMC2726643  PMID: 19075250
atherosclerosis; carotid arteries; coronary vessels; exercise; motor activity; peripheral vascular diseases
18.  Endothelial function in a cardiovascular risk population with borderline ankle–brachial index 
Introduction:
The diagnosis of peripheral arterial disease (PAD) can be made by measuring the ankle–brachial index (ABI). Traditionally ABI values > 1.00–1.40 have been considered normal and ABI ≤ 0.90 defines PAD. Recent studies, however, have shown that individuals with ABI values between 0.90–1.00 are also at risk of cardiovascular events. We studied this cardiovascular risk population subgroup in order to determine their endothelial function using peripheral arterial tonometry (PAT).
Methods:
We selected 66 individuals with cardiovascular risk and borderline ABI. They all had hypertension, newly diagnosed glucose disorder, metabolic syndrome, obesity, or a ten year risk of cardiovascular disease death of 5% or more according to the Systematic Coronary Risk Evaluation System (SCORE). Subjects with previously diagnosed diabetes or cardiovascular disease were excluded. Endothelial function was assessed by measuring the reactive hyperemia index (RHI) from fingertips using an Endo-PAT device.
Results:
The mean ABI was 0.95 and mean RHI 2.11. Endothelial dysfunction, defined as RHI < 1.67, was detected in 15/66 (23%) of the subjects. There were no statistically significant differences in RHI values between subjects with different cardiovascular risk factors. The only exception was that subjects with impaired fasting glucose (IFG) had slightly lower RHI values (mean RHI 1.91) than subjects without IFG (mean RHI 2.24) (P = 0.02).
Conclusions:
In a cardiovascular risk population with borderline ABI nearly every fourth subject had endothelial dysfunction, indicating an elevated risk of cardiovascular events. This might point out a subgroup of individuals in need of more aggressive treatment for their risk factors.
doi:10.2147/VHRM.S17249
PMCID: PMC3049545  PMID: 21415923
peripheral arterial disease; ankle–brachial index; cardiovascular risk; endothelial dysfunction
19.  Abnormally Low and High Ankle-Brachial Indices Are Independently Associated with Increased Left Ventricular Mass Index in Chronic Kidney Disease 
PLoS ONE  2012;7(9):e44732.
Abnormally low and high ankle-brachial indices (ABIs) are associated with high cardiovascular morbidity and mortality in patients with chronic kidney disease (CKD), but the mechanisms responsible for the association are not fully known. This study is designed to assess whether there is a significant correlation between abnormal ABI and echocariographic parameters in patients with CKD stages 3–5. A total of 684 pre-dialysis CKD patients were included in the study. The ABI was measured using an ABI-form device. Patients were classified into ABI <0.9, ≥0.9 to <1.3, and ≥1.3. Clinical and echocariographic parameters were compared and analyzed. Compared with patients with ABI of ≥0.9 to <1.3, the values of left ventricular mass index (LVMI) were higher in patients with ABI <0.9 and ABI ≥1.3 (P≤0.004). After the multivariate analysis, patients with ABI <0.9 (β = 0.099, P = 0.004) and ABI ≥1.3 (β = 0.143, P<0.001) were independently associated with increased LVMI. Besides, increased LVMI (odds ratio, 1.017; 95% confidence interval, 1.002 to 1.033; P = 0.031) was also significantly associated with ABI <0.9 or ABI ≥1.3. Our study in patients of CKD stages 3–5 demonstrated abnormally low and high ABIs were positively associated with LVMI. Future studies are required to determine whether increased LVMI is a causal intermediary between abnormal ABI and adverse cardiovascular outcomes in CKD.
doi:10.1371/journal.pone.0044732
PMCID: PMC3434147  PMID: 22957102
20.  The reliability of the ankle-brachial index in the Atherosclerosis Risk in Communities (ARIC) study and the NHLBI Family Heart Study (FHS) 
Background
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.
Methods
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.
Results
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.
Conclusion
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.
doi:10.1186/1471-2261-6-7
PMCID: PMC1435775  PMID: 16504033
21.  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
22.  Abdominal Aortic Calcium and Multi-Site Atherosclerosis: The Multiethnic Study of Atherosclerosis 
Atherosclerosis  2011;214(2):436-441.
Background
Abdominal aortic calcification (AAC) is a measure of subclinical cardiovascular disease (CVD). Data are limited regarding its relation to other measures of atherosclerosis.
Methods
Among 1,812 subjects (49% female, 21% black, 14% Chinese, and 25% Hispanic) within the population-based Multiethnic Study of Atherosclerosis, we examined the cross-sectional relation of AAC with coronary artery calcium (CAC), ankle brachial index (ABI), and carotid intimal medial thickness (CIMT), as well as multiple measures of subclinical CVD.
Results
AAC prevalence ranged from 34% in those aged 45–54 to 94% in those aged 75–84 (p<0.0001), was highest in Caucasians (79%) and lowest in blacks (62%) (p<0.0001). CAC prevalence, mean maximum CIMT ≥ 1 mm, and ABI<0.9 was greater in those with vs. without AAC: CAC 60% vs 16%, CIMT 38% vs 7%, and ABI 5% vs 1% for women and CAC 80% vs 37%, CIMT 43% vs 16%, and ABI 4% vs 2% for men (p<0.01 for all except p<0.05 for ABI in men). The presence of multi-site atherosclerosis (≥ 3 of the above) ranged from 20% in women and 30% in men (p<0.001), was highest in Caucasians (28%) and lowest in Chinese (16%) and ranged from 5% in those aged 45–54 to 53% in those aged 75–84 (p<0.01 to p<0.001). Finally, increased AAC was associated with 2 to 3-fold relative risks for the presence of increased CIMT, low ABI, or CAC.
Conclusions
AAC is associated with an increased likelihood of other vascular atherosclerosis. Its additive prognostic value to these other measures is of further interest.
doi:10.1016/j.atherosclerosis.2010.09.011
PMCID: PMC3040451  PMID: 21035803
atherosclerosis; calcification; cardiovascular disease; epidemiology
23.  Lower limb arterial incompressibility and obstruction in rheumatoid arthritis 
Annals of the Rheumatic Diseases  2004;64(3):425-432.
Background: Despite increased cardiovascular morbidity and mortality in rheumatoid arthritis, the peripheral arteries remain understudied.
Objective: To examine the lower limb arteries in age and sex matched, non-smoking subjects with and without rheumatoid arthritis.
Methods: The ankle-brachial index (ABI) was measured at the posterior tibial and dorsal pedal arteries. Arteries were classified as obstructed with ABI ⩽0.9, normal with ABI >0.9 but ⩽1.3, and incompressible with ABI >1.3. Multinomial logistic regression was used to estimate differences in ABI between patients and controls, adjusting for cardiovascular risk factors, rheumatoid arthritis manifestations, inflammation markers, and glucocorticoid dose.
Results: 234 patients with rheumatoid arthritis and 102 controls were studied. Among the rheumatoid patients, 66 of 931 arteries (7%) were incompressible and 30 (3%) were obstructed. Among the controls, three of 408 arteries (0.7%) were incompressible (p = 0.002) and four (1%) were obstructed (p = 0.06). At the person level, one or more abnormal arteries occurred among 45 rheumatoid patients (19%), v five controls (5%, p = 0.001). The greater frequency of arterial incompressibility and obstruction in rheumatoid arthritis was independent of age, sex, and cardiovascular risk factors. Adjustment for inflammation markers, joint damage, rheumatoid factor, and glucocorticoid use reduced rheumatoid arthritis v control differences. Most arterial impairments occurred in rheumatoid patients with 20 or more deformed joints. This subgroup had more incompressible (15%, p⩽0.001) and obstructed arteries (6%, p = 0.005) than the controls, independent of covariates.
Conclusions: Peripheral arterial incompressibility and obstruction are increased in rheumatoid arthritis. Their propensity for patients with advanced joint damage suggests shared pathogenic mechanisms.
doi:10.1136/ard.2003.018671
PMCID: PMC1755423  PMID: 15271772
24.  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
25.  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

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