1 Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL
2 Department of Family and Preventive Medicine, University of California at San Diego, La Jolla, CA
3 Department of Public Health Sciences, School of Medicine, Wake Forest University, Winston-Salem, NC
4 Department of Medicine, School of Medicine, University of California at Los Angeles, Los Angeles, CA
5 Epidemiology and Biometry Program, Division of Epidemiology and Clinical Applications, National Heart, Lung, and Blood Institute, Bethesda, MD
6 Department of Medicine, School of Medicine and Public Health, Columbia University, New York, NY
7 Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD
Correspondence to Dr. Mary McGrae McDermott, Feinberg School of Medicine, Northwestern University, 675 North St. Clair Street, Suite 18-200, Chicago, IL 60611 (e-mail: mdm608{at}northwestern.edu).
Received for publication November 1, 2004. Accepted for publication March 3, 2005.
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ABSTRACT |
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arterial occlusive diseases; arteriosclerosis; carotid artery diseases; coronary disease; heart diseases
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INTRODUCTION |
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In general medical practice, the prevalence of ABI <0.90 is 2530 percent among patients selected for older age or a history of diabetes or smoking (46
). ABI <0.90 is associated with a two- to threefold increased risk of cardiovascular morbidity and mortality (7
, 8
). The prevalence and significance of borderline ABI (i.e., ABI 0.900.99), low-normal ABI (i.e., ABI 1.001.09), and elevated ABI (i.e., ABI
1.30) are less well studied.
We studied the prevalence of a priori defined categories of ABI: PAD (ABI <0.90), borderline ABI (ABI 0.900.99), low-normal ABI (ABI 1.001.09), normal ABI (ABI 1.101.29), and high ABI (ABI 1.30) in an ethnically diverse group of men and women participating in the Multi-Ethnic Study of Atherosclerosis (MESA). We studied associations between these ABI categories and severity of subclinical atherosclerosis in the carotid and coronary arterial beds. We hypothesized that borderline ABI, low-normal ABI, definite PAD, and possibly high ABI would be associated with more severe subclinical atherosclerosis in other vascular beds in comparison with normal ABI values. We also evaluated whether there were ethnic differences in associations between ABI and subclinical atherosclerosis in the carotid and coronary arterial beds.
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MATERIALS AND METHODS |
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Measurements
Height and weight were measured during the study visit. Body mass index was calculated as weight (kg)/height (m)2. Systolic blood pressure was measured three times in the seated position with a Dinamap model pro 100 automated oscillometric sphygmomanometer (Critikon, Inc., Tampa, Florida) (10). The final two systolic blood pressure measurements were used in the analyses.
Cigarette smoking was defined on the basis of self-report. Participants brought their medication bottles to study appointments. Medication names were recorded, coded, and categorized. Diabetes mellitus was defined on the basis of self-report, a fasting glucose level greater than or equal to 126 mg/dl, or reported use of diabetes medication. Fasting glucose level was measured once.
Plasma lipids
Total plasma cholesterol and triglyceride levels were measured using a cholesterol oxidase method and Triglyceride GB reagent, respectively (Roche Diagnostics, Indianapolis, Indiana), with a Roche COBAS FARA centrifugal analyzer in the Collaborative Studies Clinical Laboratory at Fairview-University Medical Center (Minneapolis, Minnesota). High density lipoprotein cholesterol was measured in ethylenediaminetetraacetic acid plasma using the cholesterol oxidase method (Roche Diagnostics) after precipitation of non-high density lipoprotein cholesterol with magnesium/dextran. Low density lipoprotein cholesterol was calculated in plasma specimens that had a triglyceride value less than 400 mg/dl, using the formula of Friedewald et al. (11).
Coronary artery calcium score
Computed tomography of coronary arteries was performed with cardiac-gated electron-beam scanners at three field centers (Imatron C-150; Imatron, Inc., San Francisco, California) (12) or with a prospectively electrocardiogram-triggered scan acquisition at 50 percent of the R-R interval with multidetector scanners (13
) at the remaining three centers. A previous study showed that these scanners in MESA were comparable in their ability to measure calcium (14
). Participants were scanned along with phantoms of known physical calcium concentration. Scans were read centrally at Harbor-University of California Medical Center (Los Angeles, California) for quantification of Agatston coronary artery calcium (CAC) score. We defined significant CAC as a score greater than 20, on the basis of a previous study (15
).
Carotid artery intima-media thickness
Images of bilateral common carotid and internal carotid arteries were obtained using high-resolution B-mode ultrasonography. Images of near and far walls were obtained, on the basis of a previous study (16). A Logiq 700 ultrasound machine (GE Medical Systems, Waukesha, Wisconsin) was used at all centers. Central reading of intima-media thickness (IMT) was done at the Tufts-New England Medical Center (Boston, Massachusetts) (17
, 18
).
Ankle-brachial index
Measurements for calculation of ABI were obtained using a hand-held Doppler instrument with a 5-mHz probe (Nicolet Vascular, Golden, Colorado). Systolic blood pressure measurements were obtained from bilateral brachial, dorsalis pedis, and posterior tibial arteries (19). Brachial artery pressures were averaged to obtain the ABI denominator. When the two brachial artery pressures differed by 10 mmHg or more, the highest brachial artery pressure was used as the denominator (19
). For each lower extremity, the ABI numerator used was the highest pressure (dorsalis pedis or posterior tibial) from that leg. The lower of the right and left ABI values was used to classify the participant into an ABI category.
We defined five ABI categories. Definite PAD was defined as ABI <0.90, on the basis of previous studies showing that an ABI less than 0.90 is 94 percent sensitive and 99 percent specific for angiographically diagnosed PAD (3) and is associated with increased risk of cardiovascular morbidity and mortality (7
, 8
). Borderline ABI was defined as ABI 0.900.99, since participants without lower extremity atherosclerosis should have an ABI greater than 1.0 (1
). Low-normal ABI was defined as ABI 1.001.09. Normal ABI was defined as ABI 1.101.29. High ABI (possibly indicative of calcified lower extremity arteries) was defined as ABI
1.30 (20
). Some previous studies have used ABI
1.50 to define the upper limit of normal (7
, 8
, 21
, 22
). However, the optimal upper limit of normal ABI is unknown. Higher ABI values are considered indicative of medial arterial calcinosis and inability to accurately gauge the lower extremity arterial obstruction. Recently, ABI >1.30 has been suggested as the upper limit of normal for ABI (20
).
Statistical analyses
Age-adjusted mean values for participant characteristics by ABI group were determined using analysis of covariance. To assess the linear trend of the relation of ABI as a continuous variable with body mass index, lipid levels, and systolic and diastolic blood pressures, we used linear regression analysis, adjusting for age. For diabetes, hypertension, and smoking, we assessed linear associations using the Mantel-Haenszel correlation chi-square test, adjusting for age in 10-year strata.
Analyses of covariance were used to estimate adjusted mean values by ABI group for common carotid IMT and internal carotid IMT. Logistic regression was used to estimate the adjusted odds of CAC scores greater than 20 and CAC scores greater than 0 for each ABI group as compared with the normal ABI group (reference group, 1.10 ABI
1.29). For each subclinical atherosclerotic endpoint, results were first adjusted for age only and then fully adjusted for age, race, low density lipoprotein cholesterol, high density lipoprotein cholesterol, systolic blood pressure, body mass index, use of cholesterol-lowering medication, diabetes, and cigarette smoking status (current/former/never). Linear trend was evaluated using linear regression or logistic regression models, with ABI as a continuous variable. The possibility of a quadratic or U-shaped trend was evaluated by including an ABI squared term in the trend model, in addition to an ABI term. For identification of ethnic differences in the associations between ABI and subclinical atherosclerosis in the coronary and carotid arterial beds, analyses relating ABI to carotid IMT and CAC scores greater than 20 were repeated within each ethnic subgroup. The z test was used to compare the significance of differences in slopes between ethnic groups for each relation between ABI and subclinical atherosclerosis.
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RESULTS |
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The prevalence of definite PAD was 3.7 percent among women and 3.7 percent among men. The prevalence of borderline ABI was more than twice as high in women as in men (10.3 percent vs. 4.0 percent; p < 0.001). Low-normal ABI was also more common in women (35.5 percent vs. 21.1 percent; p < 0.001). These sex differences did not change substantially after we adjusted for height or after we repeated age-adjusted gender prevalence analyses within the entire cohort.
Figure 1 shows the proportion of subjects in each ABI category within each ethnic group for men and women. Among women, prevalences of PAD and borderline ABI were lowest among Hispanics and highest in African Americans. Among men, prevalences of PAD and borderline ABI were lowest among Chinese and highest among African Americans.
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In fully adjusted analyses among women, lower ABI categories were associated with higher odds ratios for CAC scores greater than 20. In fully adjusted pairwise comparisons, definite PAD was associated with a significantly higher odds ratio for CAC > 20 than was normal ABI among women. In fully adjusted analyses among men, odds ratios for CAC > 20 were significantly associated with ABI. In pairwise comparisons among men, definite PAD, borderline ABI, and high ABI were each associated with significantly higher odds ratios for CAC > 20 in comparison with the normal ABI group. When analyses were repeated using CAC > 0 as the dependent variable, results for men and women were comparable to those shown in table 2.
Linear associations between ABI and subclinical atherosclerosis were generally consistent across ethnic groups in women and men, respectively (table 3). However, among women, ABI and internal carotid artery IMT were significantly less inversely associated in Chinese women than in Caucasian women (p = 0.016 for the difference in regression coefficients between Chinese and Caucasian women). ABI and internal carotid IMT were also less inversely associated in Chinese women than in Hispanic women (p = 0.012 for the difference in regression coefficients between Chinese and Hispanic women). Among men, associations between ABI and internal carotid IMT were significantly less inverse in Caucasians than in African Americans (p = 0.02 for the difference in regression coefficients between Caucasian and African-American men).
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DISCUSSION |
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Among men and women in MESA, African Americans had substantially higher prevalences of definite PAD and borderline ABI than did non-African Americans. Previous studies have shown that African Americans have a higher prevalence of PAD than Caucasians (7, 22
, 24
27
), an excess only partially explained by a higher prevalence of diabetes and hypertension in African Americans (28
). While data reported here for women showed that Hispanics had the lowest prevalence of PAD and borderline ABI, previous studies of persons identified in clinical settings have shown comparable prevalences of PAD between Caucasians and Hispanics (5
, 27
, 29
). Inverse associations between ABI and subclinical atherosclerosis were generally consistent across ethnic groups. However, among women, inverse associations between ABI and subclinical atherosclerosis were less strong in Chinese than in Caucasians and African Americans. Among men, associations between ABI and subclinical atherosclerosis were stronger in African Americans than in Caucasians. The results presented here did not allow us to determine reasons for these ethnic differences in associations between ABI and subclinical atherosclerosis.
Prior studies have assessed associations between ABI as a continuous variable and carotid IMT (3032
). However, to our knowledge, only one prior study has assessed associations between borderline or low-normal ABI and carotid IMT. In the Atherosclerosis Risk in Communities Study, an ABI less than 0.90 was associated with higher carotid IMT among African-American women and White men after adjustment for age, low density lipoprotein cholesterol, hypertension, and diabetes (30
). However, in contrast to our findings here, this relation was not observed among African-American men or White women. To our knowledge, only one prior study has assessed associations between borderline or low-normal ABI and CAC scores (33
). In the Rotterdam Coronary Calcification Study population (2,013 participants), men and women with ABI <0.90 had significantly higher CAC scores than participants with ABI
1.20. Among men, but not among women, ABI 0.900.99 was also associated with a higher CAC score than was ABI
1.20 (33
). However, linear associations between ABI categories and CAC scores were not observed. To our knowledge, no prior studies have assessed ethnic differences in associations between ABI and subclinical atherosclerosis in the coronary and carotid arterial beds.
The prevalence of definite PAD was relatively low in the MESA cohort in comparison with previous studies in which participants were recruited among community-dwelling men and women (22, 34
). For example, in the Cardiovascular Health Study, the prevalence of ABI <0.90 was 12 percent among men and women aged 65 years or more (22
). In contrast to prior studies, a history of clinically evident cardiovascular disease was an exclusion criterion for MESA. Furthermore, the Cardiovascular Health Study excluded persons under age 65 years. Increasing age is a well-documented risk factor for PAD (22
, 34
). The exclusion of persons with clinically evident cardiovascular disease and the inclusion of persons under age 65 years in the MESA cohort are likely contributors to the relatively low prevalence of definite PAD observed in MESA.
The variability of the ABI measure is approximately 12 percent (35). While this may have resulted in some misclassification of participants into other ABI categories, systematic bias is unlikely. Based on the findings reported here, further study is needed to determine whether persons with borderline and low-normal ABIs have increased rates of cardiovascular events as compared with persons with normal ABI.
Similar to findings from the Cardiovascular Health Study and the Systolic Hypertension in the Elderly Program, prevalences of ABI <0.90 in MESA were comparable between men and women (7, 20
). Gender differences in the prevalence of PAD appear to be smaller in populations that include persons with relatively mild PAD (36
), which is consistent with findings in the MESA cohort. In MESA, women had significantly higher prevalences of borderline and low-normal ABI than did men. These findings are consistent with a previous study by Hiatt et al. (29
), in which average ABIs were 7 percent lower in women than in men among 403 San Luis Valley Diabetes Study participants with low cardiovascular risk. In the Atherosclerosis Risk in Communities cohort, average ABI values were 1.12 in women and 1.18 in men (37
). Because systolic blood pressures increase with greater distance from the heart, these sex differences in ABI could be explained by greater height in men than in women. In the San Luis Valley Diabetes Study and in MESA, adjustment for height did not eliminate gender differences in ABI. Thus, an unidentified factor may account for the gender difference in low-normal and borderline ABI values reported here.
In conclusion, borderline and low-normal ABI values were common in the MESA cohort. In both men and women, borderline ABI values were associated with a significantly higher prevalence of subclinical atherosclerosis in comparison with normal ABI values (ABI 1.101.29). Low-normal ABI values were associated with a significantly higher prevalence of subclinical atherosclerosis in men. Based on the findings reported here, further study is needed to determine whether persons with borderline ABI and men with low-normal ABI have a higher incidence of cardiovascular events than persons with normal ABI, and whether intensive atherosclerotic risk factor intervention comparable to that currently recommended for patients with clinically evident PAD is important for persons with borderline and low-normal ABI in order to prevent the progression of subclinical atherosclerosis.
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ACKNOWLEDGMENTS |
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References |
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