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1.  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
We studied associations of borderline and low-normal ankle brachial index (ABI) values with functional decline over five-year follow-up.
Associations of borderline and low-normal ABI with functional decline are unknown.
The 666 participants included 412 with peripheral arterial disease (PAD). Participants were categorized as follows: Severe PAD (ABI < 0.50), moderate PAD (ABI 0.50-0.69), mild PAD (ABI 0.70 to 0.89), borderline ABI (0.90 to 0.99), low normal ABI (1.00 to 1.09), and normal ABI (ABI 1.10-1.30). Outcomes were assessed annually for five years. Mobility loss was defined as loss of the ability to walk ¼ mile or walk up and down one flight of stairs without assistance among those without baseline mobility impairment. Becoming unable to walk for six minutes continuously was defined as stopping during the six minute walk at follow-up among those who walked for six minutes continuously at baseline. Results adjust for age, sex, race, comorbidities, and other confounders.
Hazard ratios (HR) for mobility loss according to ABI category were as follows. Severe PAD: HR=4.16 (95% Confidence Interval (CI)=1.58-10.92), moderate PAD: HR=3.82 (95% CI=1.66-8.81), mild PAD: HR=3.22 (95% CI=1.43-7.21), borderline ABI: HR=3.07 (95% CI=1.21-7.84), low normal ABI: HR=2.61 (95% CI=1.08-6.32) (p trend=0.0018). Similar associations were observed for becoming unable to walk six-minutes continuously (p trend<0.0001).
At five-year follow-up, persons with borderline ABI values have a higher incidence of mobility loss and becoming unable to walk for six minutes continuously compared to persons with a normal baseline ABI. A low normal ABI is associated with an increased incidence of mobility loss compared to persons with a normal ABI.
We studied associations of borderline and low-normal ABI values with functional decline over five-year follow-up among 666 participants, including 412 with lower extremity peripheral arterial disease (PAD). At five year follow-up, participants with borderline ABI values at baseline (ABI 0.90 to 0.99) had significantly greater mobility loss and were more likely to become unable to walk for six-minutes continuously compared to those with a normal baseline ABI. Participants with low normal ABI values (ABI 1.00 to 1.09) had significantly greater mobility loss compared to those with a normal baseline ABI.
PMCID: PMC3215766  PMID: 19298919
ankle brachial index; physical functioning; peripheral arterial disease; intermittent claudication
3.  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.
PMCID: PMC3547217  PMID: 23329891
High ankle-brachial index; metabolic syndrome; inflammation; oxidative stress; metabolic risk factors
4.  The Ankle-Brachial Index and Incident Cardiovascular Events in the Multi-Ethnic Study of Atherosclerosis (MESA) 
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.
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.
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.
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.
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.
PMCID: PMC2962558  PMID: 20951328
peripheral arterial disease; ankle-brachial index; cardiovascular events; risk factors; subclinical atherosclerosis
5.  High-Sensitivity C-Reactive Protein and Ankle Brachial Index in a Finnish Cardiovascular Risk Population 
High-sensitivity C-reactive protein (hsCRP) has been previously linked to different forms of vascular disease. However, some studies have not found any relationship between hsCRP and atherosclerosis. Also, studies investigating correlation between hsCRP and ankle brachial index (ABI) are scarce. We studied hsCRP in a cardiovascular risk population with a special interest in correlation between hsCRP and ABI. All men and women aged 45 to 70 years from a rural town Harjavalta, Finland were invited to participate in a population survey. Diabetics and people with known vascular disease were excluded. Seventy-three percent (n = 2085) of the invited persons participated and 70% of the respondents (n = 1496) had at least one risk factor to cardiovascular diseases. These subjects were invited to further examinations. From them we measured ABI, hsCRP, leukocyte count, glucose tolerance, systemic coronary risk evaluation (SCORE), body mass index (BMI), and waist circumference. Mean hsCRP was 1.9 mg/L. Smokers had higher hsCRP (mean 2.2 mg/L) than nonsmokers (mean 1.8 mL/L). hsCRP in women was higher than in men (mean 2.0 mg/L versus 1.8 mg/L). Mean ABI was 1.10, and the prevalence of peripheral arterial disease was 3.1%. ABI correlated weakly with hsCRP (r = −0.077, p = 0.014), leukocyte count (r = −0.107, p = 0.001), and SCORE (r = −0.116, p = 0.001). It did not have correlation between age, weight, BMI, or waist circumference. hsCRP correlated with BMI (r = 0.208, p < 0.0001) and waist circumference (r = 0.325, p < 0.0001). When we excluded subjects with hsCRP >10 mg/L, ABI no longer correlated with hsCRP. In a cardiovascular risk population, hsCRP has only a weak correlation with ABI, and this correlation disappeared when we excluded subject with hsCRP >10 mg/L. Instead, hsCRP was correlated to the measures of obesity (waist circumference and BMI), indicating its role as a marker of adipose tissue–driven inflammation. hsCRP does not seem to be a suitable screening method for peripheral arterial disease.
PMCID: PMC3331626  PMID: 22532770
High sensitivity C-reactive protein; ankle brachial index; cardiovascular risk factors
6.  Associations of Non-Invasive Measures of Arterial Compliance and Ankle-Brachial Index: The Multi-Ethnic Study of Atherosclerosis (MESA) 
American journal of hypertension  2012;25(5):535-541.
The association between measures of arterial compliance and peripheral arterial disease (PAD) is unclear. Early changes in arterial wall compliance could be a useful marker of patients at high risk for developing lower extremity atherosclerosis.
We used linear and logistic regression models on baseline data from 2803 female and 2558 male participants in the Multi-Ethnic Study of Atherosclerosis (MESA) to study associations between tonometry-derived baseline measures of arterial compliance (large artery compliance [C1] and small artery compliance [C2]) and the baseline ankle-brachial index (ABI), as well as change in the ABI over approximately 3 years of follow up.
In cross-sectional analyses, lower C1 and C2 values, indicating poorer arterial compliance, were associated with lower ABI. There were significant linear trends across strata of ABI, especially in C2 which ranged from 3.7ml/mmHg × 100 (95% confidence interval (CI) 3.3 to 4.2) in women with an ABI < 0.90 to 4.2ml/mmHg × 100 (95% CI 4.1 to 4.3 p<0.001) in women with ABI 1.10 - <1.40. Similar significant trends (p<0.001) were seen in men. In prospective analyses, those with the lowest tertile of C2 values at baseline had a greater multivariable-adjusted odds for decline in ABI of ≥ 0.15 over 3 years compared to those with the highest C2 values at baseline (OR 1.80 95% CI 1.23–2.64).
We observed that less compliant arteries were significantly associated with low ABI in cross-sectional analysis and with greater decline in ABI over time.
PMCID: PMC3748962  PMID: 22357412
Ankle-Brachial Index; Arterial Compliance; Peripheral Arterial Disease
7.  Ankle-Brachial Index (ABI), Abdominal Aortic Calcification (AAC), and Coronary Artery Calcification (CAC): the Jackson Heart Study 
To examine the associations of peripheral atherosclerosis, assessed by the ABI at baseline with the extent of AAC and with CAC measured by MDCT at follow-up examination in the Jackson Heart Study cohort.
Four categories of ABI: <0.90, 0.90–0.99, 1.00–1.39; >1.40. Presence of CAC/AAC was defined as scoring above the 75th percentile among participants with non-zero CT calcium scores. We conducted multivariable log-binomial models for this analysis examining the relationship between ABI and the presence of CAC or AAC using normal ABI (1.0 ≤ ABI ≤ 1.39) as the reference group. We estimated prevalence ratios adjusted for age, smoking, HTN, DM, BMI, LDL, HDL, CRP, systolic and diastolic blood pressure, and use of lipid-lowering medication.
There were 2,398 patients in this analysis (women: 65%, average age 55 years). AAC scores were not significantly different between sex. CAC scores were significantly higher in males than females regardless of ABI groups. The prevalence of significant AAC was 1.7 times higher for ABI < 0.90 (PR=1.70; 95% CI=1.26–2.28; p=0.0004) and 1.57 times higher for ABI 0.90–0.99 (PR=1.57; 95% CI=1.20–2.03; p=0.0008) than the normal ABI; AAC prevalence did not differ between subjects with ABI > 1.40 compared to those with normal ABI. The prevalence of the significant CAC was higher for ABI <0.90 (PR=1.55; 95% CI=1.12–2.14; p-value=0.0081) and ABI 0.90–0.99 (PR=1.60; 95% CI=1.05–2.46; p=0.0402) compared to normal ABI; CAC prevalence did not differ between subjects with ABI > 1.40 compared to those with normal ABI
Lower ABI was significantly associated with the extent of AAC and CAC in this cohort. ABI can provide clinicians with an inexpensive additional tool to assess vascular health and cardiovascular risk without exposing the patient to ionizing radiation.
PMCID: PMC3712513  PMID: 23111408
Coronary Artery Calcium; Abdominal Aortic Calcium; Ankle-Brachial Index; Peripheral Arterial Disease
8.  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.
PMCID: PMC2877442  PMID: 20237150
ankle brachial index; cardiovascular diseases; kidney diseases; phosphorus
9.  Comparison of Novel Risk Markers for Improvement in Cardiovascular Risk Assessment in Intermediate Risk Individuals. The Multi-Ethnic Study of Atherosclerosis 
Risk markers including coronary artery calcium (CAC), carotid intima-media thickness (CIMT), ankle-brachial Index (ABI), brachial flow-mediated dilation (FMD), high sensitivity C -reactive protein (hs-CRP) and family history (FH) of coronary heart disease (CHD) have been reported to improve on the Framingham risk score (FRS) for prediction of CHD. However, there are no direct comparisons of these markers for risk prediction in a single cohort.
We compared improvement in prediction of incident CHD/cardiovascular disease (CVD) of these 6 risk markers within intermediate risk participants (5 % < FRS < 20%) in the Multi-Ethnic Study of Atherosclerosis (MESA).
Design, Setting and Participants
Of 6814 MESA participants from 6 US field centers, 1330 were intermediate risk, without diabetes mellitus, and had complete data on all 6 markers. Recruitment spanned July 2000 to September 2002; follow-up extended through May 2011. Probability- weighted Cox proportional hazard models were used to estimate hazard ratios (HR). Area under the receiver operator characteristic curve (AUC) and net reclassification improvement (NRI) were used to compare incremental contributions of each marker when added to the FRS + race/ethnicity.
Main Outcome Measures
Incident CHD defined as MI, angina followed by revascularization, resuscitated cardiac arrest or CHD death. Incident CVD additionally included stroke or CVD death.
After median follow-up of 7.6 years (IQR 7.3 – 7.8 years), 94 CHD and 123 CVD events occurred. CAC, ABI, hs-CRP and FH were independently associated with incident CHD in multivariable analyses [HR (95%CI: 2.60(1.94-3.50), 0.79(0.66-0.95), 1.28(1.00-1.64) and 2.18(1.38-3.42) respectively]. CIMT and FMD were not associated with incident CHD in multivariable analyses [HR (95%CI) 1.17(0.95- 1.45) and 0.95(0.78 −1.14) respectively]. Although the addition of the markers individually to the FRS +race/ethnicity improved the AUC, CAC afforded the highest increment (0.623 vs. 0.784) while FMD afforded the least [0.623 vs. 0.639]. For incident CHD, the NRI with CAC was 0.659, FMD 0.024, ABI 0.036, CIMT 0.102, FH 0.160 and hs-CRP 0.079. Similar results were obtained for incident CVD.
CAC, ABI, hs-CRP and FH are independent predictors of incident CHD/CVD in intermediate risk individuals. CAC provides superior discrimination and risk reclassification compared with other risk markers.
PMCID: PMC4141475  PMID: 22910756
10.  The Association Between Physical Activity and Both Incident Coronary Artery Calcification and Ankle Brachial Index Progression: The Multi-Ethnic Study of Atherosclerosis 
Atherosclerosis  2013;230(2):278-283.
Both coronary artery calcification (CAC) and the ankle brachial index (ABI) are measures of subclinical atherosclerotic disease. The influence of physical activity on the longitudinal change in these measures remains unclear. To assess this we examined the association between these measures and self-reported physical activity in the Multi-Ethnic Study of Atherosclerosis (MESA).
At baseline, the MESA participants were free of clinically evident cardiovascular disease. We included all participants with an ABI between 0.90 and 1.40 (n=5656). Predictor variables were based on self-reported measures with physical activity being assessed using the Typical Week Physical Activity Survey from which metabolic equivalent-minutes/week of activity were calculated. We focused on physical activity intensity, intentional exercise, sedentary behavior, and conditioning. Incident peripheral artery disease (PAD) was defined as the progression of ABI to values below 0.90 (given the baseline range of 0.90 to 1.40). Incident CAC was defined as a CAC score >0 Agatston units upon follow up with a baseline score of 0 Agatston units.
Mean age was 61 years, 53% were female, and mean body mass index was 28 kg/m2. After adjusting for traditional cardiovascular risk factors and socioeconomic factors, intentional exercise was protective for incident peripheral artery disease (Relative Risk (RR)= 0.85, 95% Confidence Interval (CI): 0.74 to 0.98). After adjusting for traditional cardiovascular risk factors and socioeconomic factors, there was a significant association between vigorous PA and incident CAC (RR=0.97, 95% CI: 0.94 to 1.00). There was also a significant association between sedentary behavior and increased amount of CAC among participants with CAC at baseline (Δlog(Agatston Units +25)=0.027, 95% CI 0.002, 0.052).
These data suggest that there is an association between physical activity/sedentary behavior and the progression of two different measures of subclinical atherosclerotic disease.
PMCID: PMC4085097  PMID: 24075757
Ankle Brachial Index; Coronary Artery Calcification; Physical Activity; Epidemiology; Prospective Cohort Study
11.  Combination of High Ankle–Brachial Index and Hard Coronary Heart Disease Framingham Risk Score in Predicting the Risk of Ischemic Stroke in General Population 
PLoS ONE  2014;9(9):e106251.
Our previous study showed that the patients with more metabolic risk factors had higher risk of high ankle–brachial index (ABI), but the relationship between high ABI and the risk of severe cardiovascular and cerebrovascular diseases is still under debate. This study aims to evaluate this association in the general population. 1486 subjects of South China were recruited in the study. 61 subjects were defined as high ABI group (ABI≥1.3) and 65 subjects were randomly selected as normal ABI group (0.9
PMCID: PMC4157777  PMID: 25198106
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
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.
PMCID: PMC2842203  PMID: 20042436
ankle brachial index; cardiovascular diseases; continental population groups; ethnic groups; peripheral vascular diseases
The aim of this study was to determine the risk factors for conversion from a normal to either a low or high ABI.
Participants in the Multi-Ethnic Study of Atherosclerosis who had two separate measurements of the ABI over a 3-year time period were assessed.
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.
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.
PMCID: PMC2783523  PMID: 19628357
Clinical chemistry  2008;54(11):1788-1795.
Higher plasma concentrations of soluble adhesion molecules have been shown to be associated with increased risk of cardiovascular events. We investigated the associations of soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) with the ankle-brachial index (ABI), a measure of peripheral arterial disease (PAD), in a bi-ethnic cohort of adults without known coronary heart disease or stroke.
Participants included 1102 blacks (63 y, 74% women) and 1013 non-Hispanic whites (58 y, 59% women) belonging to hypertensive sibships. Plasma concentrations of sICAM-1 and sVCAM-1 were measured using high-sensitivity immunoassays. ABI was measured using a standard protocol and PAD was defined as ABI <0.9. Generalized estimating equations (GEE) were used to assess whether sICAM-1 and sVCAM-1 were associated with ABI and with PAD, independent of conventional risk factors.
After adjustment for conventional risk factors, blacks with sICAM-1 and sVCAM-1 concentrations in the highest quartiles had lower ABI than those in the lowest quartiles (mean ABI: 1.02 vs. 0.98, P=0.007 and 1.02 vs. 0.99, P=0.003, respectively). In multivariable logistic regression analysis, sICAM-1 and sVCAM-1 concentrations in the highest quartiles were each associated with a higher odds ratio of having PAD, compared with the lowest quartiles: odds ratio (95% CI): 5.2 (1.8–15.2) and 2.2 (1.0–4.8), respectively. In contrast, in non-Hispanic whites, sICAM-1 and sVCAM-1 concentrations were not associated with ABI or with PAD.
Higher sICAM-1 and sVCAM-1 concentrations were independently associated with a lower ABI and with PAD in blacks, but not in non-Hispanic whites.
PMCID: PMC2752683  PMID: 18787016
ethnicity; sICAM-1; sVCAM-1; ankle-brachial index; peripheral arterial disease; hypertension
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.
PMCID: PMC3434147  PMID: 22957102
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
Ophthalmology  2010;118(5):860-865.
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.
Population-based, cross-sectional epidemiologic study
Nine hundred and twenty seven persons with diabetes without clinical CVD in the Multi-Ethnic Study of Atherosclerosis.
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.
Associations between DR and subclinical CVD measures.
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.
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.
PMCID: PMC3087839  PMID: 21168222
Psychoneuroendocrinology  2012;38(7):1036-1046.
To investigate the association between salivary cortisol and two markers of subclinical cardiovascular disease (CVD), coronary calcification (CAC), and ankle-brachial index (ABI).
Data from an ancillary study to the Multi-Ethnic Study of Atherosclerosis (MESA), the MESA Stress Study, were used to analyze associations of salivary cortisol data collected six times per day over three days with CAC and ABI. The authors used mixed models with repeat cortisol measures nested within persons to determine if specific features of the cortisol profile were associated with CAC and ABI.
total of 464 participants were included in the CAC analysis and 610 in the ABI analysis. The mean age of participants was 65.6 years. A 1-unit increase in log coronary calcium was associated with a 1.77% flatter early decline in cortisol (95% CI: 0.23, 3.34) among men and women combined. Among women low ABI was associated with a steeper early decline (−13.95% CI:−25.58, −3.39) and a marginally statistically significant flatter late decline (1.39% CI: −0.009, 2.81). The cortisol area under the curve and wake to bedtime slope were not associated with subclinical CVD.
This study provides weak support for the link between cortisol and measures of subclinical atherosclerosis. We found an association between some features of the diurnal cortisol profile and coronary calcification and ABI but associations were not consistent across subclinical measures. There are methodological challenges in detecting associations of cortisol measures at a point in time with health outcomes that develop over a lifetime. Studies of short-term mechanisms linking stress to physiological processes related to the development of early atherosclerosis may be more informative.
PMCID: PMC4020284  PMID: 23146655
salivary cortisol; ankle brachial index; coronary calcification; atherosclerosis; stress; cortisol awakening response; cortisol diurnal pattern; Multi-Ethnic Study of Atherosclerosis
Central obesity is associated with peripheral arterial disease (PAD), suggesting that ectopic fat depots may be associated with localized diseases of the aorta and lower extremity arteries. We hypothesized that individuals with greater amounts of peri-aortic fat are more likely to have clinical peripheral arterial disease (PAD) and a low ankle-brachial index (ABI).
Methods and Results
We quantified peri-aortic fat surrounding the thoracic aorta using a novel volumetric quantitative approach in 1205 individuals from the Framingham Heart Study Offspring cohort (mean age 65.9 years, 54% women); visceral abdominal fat (VAT) was also measured. Clinical PAD was defined as a history of intermittent claudication and ABI was dichotomized as low ABI≤0.9 or lower extremity revascularization vs normal ABI >0.9 to < 1.4. Regression models were created to examine the association between peri-aortic fat and intermittent claudication or low ABI (n=66 participants). In multivariable logistic regression, per 1 standard deviation increase in peri-aortic fat, the odds ratio (OR) for the combined end-point was 1.52 (p-value=0.004); these results were strengthened with additional adjustment for BMI (OR 1.69, p=0.002) or visceral abdominal fat (OR 1.67, p=0.009) whereas no association was observed for VAT (p=0.16). Similarly, per standard deviation increase in BMI or waist circumference, no association was observed after accounting for VAT (p=0.35 [BMI]; p=0.49 [waist circumference]).
Peri-aortic fat is associated with low ABI and intermittent claudication.
PMCID: PMC3060043  PMID: 20639302
obesity; atherosclerosis; peripheral arterial disease
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
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.
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.
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].
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.
PMCID: PMC2859852  PMID: 20307322
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
Atherosclerosis  2011;214(2):436-441.
Abdominal aortic calcification (AAC) is a measure of subclinical cardiovascular disease (CVD). Data are limited regarding its relation to other measures of atherosclerosis.
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.
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.
AAC is associated with an increased likelihood of other vascular atherosclerosis. Its additive prognostic value to these other measures is of further interest.
PMCID: PMC3040451  PMID: 21035803
atherosclerosis; calcification; cardiovascular disease; epidemiology
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.
PMCID: PMC2782189  PMID: 15953855
Peripheral Vascular Diseases; Prevalence; Ankle-brachial Index; Risk Factors

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