Search tips
Search criteria

Results 1-25 (1331445)

Clipboard (0)

Related Articles

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
2.  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
3.  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
4.  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
5.  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
6.  Ankle Brachial Index Values, Leg Symptoms, and Functional Performance Among Community‐Dwelling Older Men and Women in the Lifestyle Interventions and Independence for Elders Study 
The prevalence and significance of low normal and abnormal ankle brachial index (ABI) values in a community‐dwelling population of sedentary, older individuals is unknown. We describe the prevalence of categories of definite peripheral artery disease (PAD), borderline ABI, low normal ABI, and no PAD and their association with lower‐extremity functional performance in the LIFE Study population.
Methods and Results
Participants age 70 to 89 in the LIFE Study underwent baseline measurement of the ABI, 400‐m walk, and 4‐m walking velocity. Participants were classified as follows: definite PAD (ABI <0.90), borderline PAD (ABI 0.90 to 0.99), low normal ABI (ABI 1.00 to 1.09), and no PAD (ABI 1.10 to 1.40). Of 1566 participants, 220 (14%) had definite PAD, 250 (16%) had borderline PAD, 509 (33%) had low normal ABI, and 587 (37%) had no PAD. Among those with definite PAD, 65% were asymptomatic. Adjusting for age, sex, race, body mass index, smoking, and comorbidities, lower ABI was associated with longer mean 400‐m walk time: (definite PAD=533 seconds; borderline PAD=514 seconds; low normal ABI=503 seconds; and no PAD=498 seconds [P<0.001]). Among asymptomatic participants with and without PAD, lower ABI values were also associated with longer 400‐m walk time (P<0.001) and slower walking velocity (P=0.042).
Among older community‐dwelling men and women, 14% had PAD and 49% had borderline or low normal ABI values. Lower ABI values were associated with greater functional impairment, suggesting that lower extremity atherosclerosis may be a common preventable cause of functional limitations in older people.
Clinical Trial Registration
URL: Unique identifier: NCT01072500.
PMCID: PMC3886743  PMID: 24222666
aging; exercise; peripheral vascular disease
7.  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
8.  Ethnicity and Risk Factors for Change in the Ankle-Brachial Index: The Multi-Ethnic Study of Atherosclerosis 
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
9.  Change in ankle-brachial index over time and mortality in diabetics with proteinuria  
Clinical Nephrology  2012;78(5):335-345.
Peripheral arterial disease is common in diabetic chronic kidney disease (CKD) and is characterized either by abnormally low or high ankle-brachial index (ABI). Whether low or high ABI carries similar prognostic value is unknown. The association of baseline ABI with all-cause mortality over 40 ± 21 months (mean ± SD) was ascertained in 167 proteinuric diabetics (age 57 ± 7 years; median urine protein-creatinine, 2.5 mg/mg). Association of change in ABI with all-cause mortality was determined in 75 subjects with normal ABI (0.9 – 1.3) at baseline. Among 167 participants, 41% had an abnormal ABI: < 0.9, 18%; and > 1.3 or non-compressible arteries, 23%. Only individuals with low ABI had a significantly higher risk for all-cause mortality (hazards ratio (95% confidence interval), HR: 2.23 (1.07, 4.65)). In subjects with normal ABI at baseline with follow-up measurement (n = 75), vascular disease worsened in 39% over 23 ± 6 months: 17% had either a decrease in ABI by ≥ 0.1 or a final ABI < 0.9, and 21% had a final ABI > 1.3 or non-compressible arteries. Only individuals who had a decrease in ABI over time had a significantly higher risk for death (adjusted HR, 7.41 (1.63, 33.65)). Peripheral arterial disease is not uncommon and progresses rapidly in individuals with diabetes and proteinuria. Low or declining ABI is a strong predictor of all-cause mortality. Routine measurement of ABI is a simple bed-side procedure that may permit easy risk-stratification in diabetic CKD patients.
PMCID: PMC4407335  PMID: 22784559
all-cause mortality; ankle-brachial index; chronic kidney disease; peripheral arterial disease; proteinuria; Type 2 diabetes
10.  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
11.  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
12.  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
13.  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
14.  Associations of Diabetes Mellitus and Other Cardiovascular Disease Risk Factors with Decline in the Ankle Brachial Index 
We compared associations of diabetes mellitus (DM) and other cardiovascular disease (CVD) risk factors with decline in the ankle brachial index (ABI) over four years in participants with and without peripheral artery disease (PAD).
Five hundred sixty-six participants, 300 with PAD, were followed prospectively for four years.
Mean (SD) baseline ABI values were 0.70 (0.13) for participants with both PAD and DM, 0.67 (0.14) for participants with only PAD, 1.10 (0.13) for participants with only DM, and 1.10 (0.10) for participants with neither PAD nor DM. After adjusting for age, gender, and baseline ABI, corresponding ABI change from baseline to 4-year follow-up were -0.02, -0.04, +0.05, and +0.05 respectively. Compared to participants with neither PAD nor DM, participants with only PAD showed significantly more ABI decline (P < .01), while the decline in participants with both PAD and DM was borderline non-significant (P = .06). After adjustments for baseline ABI, age, gender, African-American ethnicity, and other cardiovascular disease (CVD) risk factors; independent factors associated with ABI decline in participants with PAD in the lower ABI leg were older age and elevated D-dimer. DM was not related to ABI decline.
Despite being an important risk factor for PAD, DM was not independently associated with ABI decline. This could reflect the effect of DM promoting both PAD and lower extremity arterial stiffness, resulting in a small decline in the ABI over time. In conclusion, ABI change over time in persons with diabetes may not accurately reflect underlying atherosclerosis.
PMCID: PMC4515111  PMID: 25358555
Peripheral artery disease; Ankle brachial index; Diabetes
15.  Peri-Aortic Fat Deposition Is Associated with Peripheral Arterial Disease: The Framingham Heart Study 
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
16.  Fibroblast Growth Factor 23, the Ankle-Brachial Index, and Incident Peripheral Artery Disease in the Cardiovascular Health Study 
Atherosclerosis  2014;233(1):91-96.
Fibroblast growth factor 23 (FGF23) has emerged as a novel risk factor for mortality and cardiovascular events. Its association with the ankle-brachial index (ABI) and clinical peripheral artery disease (PAD) is less known.
Using data (N=3,143) from the Cardiovascular Health Study (CHS), a cohort of community dwelling adults > 65 years of age, we analyzed the cross sectional association of FGF23 with ABI and its association with incident clinical PAD events during 9.8 years of follow up using multinomial logistic regression and Cox proportional hazards models respectively.
The prevalence of cardiovascular disease (CVD) and traditional risk factors like diabetes, coronary artery disease, and heart failure increased across higher quartiles of FGF23. Compared to those with ABI of 1.1–1.4, FGF23 at baseline was associated with prevalent PAD (ABI<0.9) although this association was attenuated after adjusting for CVD risk factors, and kidney function (OR 0.91, 95% CI 0.76–1.08). FGF23 was not associated with high ABI (>1.4) (OR 1.06, 95% CI 0.75–1.51). Higher FGF23 was associated with incidence of PAD events in unadjusted, demographic adjusted, and CVD risk factor adjusted models (HR 2.26, 95% CI 1.28–3.98; highest versus lowest quartile). The addition of estimated glomerular filtration and urine albumin to creatinine ratio to the model however, attenuated these findings (HR 1.46, 95% CI, 0.79–2.70).
In community dwelling older adults, FGF23 was not associated with baseline low or high ABI or incident PAD events after adjusting for confounding variables. These results suggest that FGF23 may primarily be associated with adverse cardiovascular outcomes through non atherosclerotic mechanisms.
PMCID: PMC3927151  PMID: 24529128
Fibroblast growth factor; peripheral artery disease; ankle-brachial index; chronic kidney disease; cardiovascular disease
17.  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
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
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
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
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
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
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
Low ankle brachial index (ABI) is associated with increases in serum creatinine. Whether low ABI is associated with the development of rapid estimated glomerular filtration rate (eGFR) decline, stage 3 chronic kidney disease (CKD), or microalbuminuria is uncertain.
Study Design
Prospective cohort study.
Setting & Participants
Framingham Offspring cohort participants who attended the sixth (1995-98) and eighth (2005-08) exams.
ABI, categorized as normal (>1.1 to <1.4), low-normal (>0.9 to 1.1), and low (≤0.9).
Rapid eGFR decline (eGFR decline ≥3mL/min/1.73m2 per year), incident stage 3 CKD (eGFR<60mL/min/1.73m2), incident microalbuminuria.
GFR was estimated using the serum creatinine-based CKD-EPI (CKD Epidemiology Collaboration) equation. Urinary albumin-creatinine ratio (UACR) was determined based on spot urine samples.
Over 9.5 years, 9.0% (232 of 2592) experienced rapid eGFR decline and 11.1% (270 of 2426) developed stage 3 CKD. Compared to a normal ABI, low ABI was associated with a 5.73-fold increased odds of rapid eGFR decline (95% CI, 2.77-11.85; p<0.001) after age, sex, and baseline eGFR adjustment; this persisted after multivariable adjustment for standard CKD risk factors (OR, 3.60; 95% CI, 1.65-7.87; p=0.001). After adjustment for age, sex, and baseline eGFR, low ABI was associated with a 2.51-fold increased odds of stage 3 CKD (OR, 2.51; 95% CI, 1.16-5.44; p=0.02), although this was attenuated after multivariable adjustment (OR, 1.68; 95% CI, 0.75-3.76; p=0.2). Among 1902 free of baseline microalbuminuria, low ABI was associated with an increased odds of microalbuminuria after adjustment for age, sex, and baseline UACR (OR, 2.81; 95% CI, 1.07-7.37; p=0.04), with attenuation upon further adjustment (OR, 1.88; p=0.1).
Limited number of events with a low ABI. Outcomes based on single serum creatinine and UACR measurements at each exam.
Low ABI is associated with an increased risk of rapid eGFR decline, suggesting that systemic atherosclerosis predicts decline in kidney function.
PMCID: PMC3517695  PMID: 22901770
Journal of Epidemiology  2012;22(5):454-461.
We investigated the prevalence of low ankle brachial index (ABI) and the association of low ABI with pulse pressure among elderly community residents in China.
This population-based cross-sectional study was conducted in Beijing and recruited 2982 participants who were aged 60 years or older in 2007. Low ABI was defined as an ABI value less than 0.9 in either leg. Participants with or without stroke or coronary heart disease (CHD) were analyzed separately. The association between pulse pressure and low ABI was examined by using multiple logistic regression models.
The prevalence of low ABI was 5.65% (4.24% among men and 6.52% among women; P = 0.0221) among participants without stroke or CHD and 10.91% (13.07% among men and 9.49% among women; P = 0.1328) among those with stroke or CHD. After adjusting for confounders, the odds ratio (95% CI) for each 5-mm Hg increase in pulse pressure was 1.19 (1.07, 1.33) and 1.10 (1.02, 1.20) for men and women, respectively, among participants without stroke or CHD and 1.17 (1.03, 1.34) and 1.15 (1.02, 1.30) for men and women with stroke or CHD. When pulse pressure was classified into quartiles and the lowest quartile was used as reference, the association between pulse pressure and low ABI remained positive in men and women.
Low ABI was prevalent among elderly Chinese, and pulse pressure was positively associated with low ABI.
PMCID: PMC3798641  PMID: 22813646
pulse pressure; ankle brachial index; cross-sectional study

Results 1-25 (1331445)