Peripheral artery disease (PAD) is strongly associated with coronary artery disease and poor outcomes after coronary revascularization. The aim of this study was to test the hypothesis that patients with PAD diagnosed by a low ankle-brachial index (ABI; ≤0.90) have more complex coronary artery disease and more myocardium at risk than patients with normal ABIs (1.00 to 1.40) and that subsequent coronary revascularization is less complete. Adults referred for coronary angiography underwent ABI measurement using a standard Doppler ultrasound technique. Blinded reviewers calculated SYNTAX scores and Duke jeopardy scores at baseline and 3 months after angiography. Of 814 patients, 8% had PAD (ABI ≤0.90), 9% had borderline PAD (ABI 0.91 to 0.99), 77% were normal (ABI 1.00 to 1.40), and 7% had vascular calcification artifact (ABI >1.40). Patients with PAD were more likely to have high SYNTAX scores (≥33), with an odds ratio of 4.3 (95% confidence interval 1.2 to 14.9), compared with those with normal ABIs after adjustment for traditional cardiovascular risk factors. Similarly, there was a positive association between baseline high Duke jeopardy score (≥8) and PAD (adjusted odds ratio 3.5, 95% confidence interval 1.7 to 7.1). Postrevascularization high Duke jeopardy scores (≥5) were also positively associated with PAD (adjusted odds ratio 3.0, 95% confidence interval 1.1 to 8.8). In conclusion, PAD is associated with higher SYNTAX scores, more myocardium at risk, and less complete coronary revascularization than in patients with normal ABIs. More complex coronary artery disease and incomplete revascularization may contribute to worse cardiovascular outcomes in patients with PAD.
Lower-extremity peripheral artery disease (PAD) is strongly associated with coronary artery disease (CAD) and poor outcomes after coronary revascularization. PAD has also shown a strong correlation with the number coronary lesions and diseased vessels observed through angiography. Although completeness of coronary revascularization is associated with improved survival in patients with CAD, it is not known whether patients with PAD are more likely to have incomplete coronary revascularization and whether that may contribute to worse outcomes. Coronary disease complexity is frequently measured using the Synergy Between PCI With TAXUS and Cardiac Surgery (SYNTAX) score, while the Duke jeopardy score conveys the volume of myocardium distal to the lesion that is likely underperfused and at risk for necrosis. We hypothesized that patients with PAD, as determined by a low ankle-brachial index (ABI), have more complex CAD (as evidenced by higher SYNTAX scores) and more myocardium at risk (as determined by higher Duke jeopardy scores), than patients with normal ABIs and subsequently have less complete coronary revascularization.
Methods
Adult patients ≥18 years of age referred for coronary angiography for CAD were consecutively sampled from March 2010 to September 2012. Subjects underwent initial eligibility screening on the basis of their indications for coronary angiography on the procedure requisition form. Subjects being assessed for heart transplantation, valve disease, pulmonary hypertension, or congenital heart disease were excluded, as were unstable cases. Potential subjects were then approached to participate and underwent a second eligibility screening on the basis of their responses and chart information. Subjects with known CAD were included, while those with previous coronary artery bypass graft surgery, those who were unable to communicate in English, and those who were unable to undergo ABI measurement were excluded at the secondary screening. All eligible participants provided written informed consent. The Health Research Ethics Board of the University of Alberta approved the research protocol.
ABI was assessed by a trained doctoral student on each patient before coronary angiography. With the patient in a supine position, manual nonsimultaneous systolic blood pressure was measured bilaterally at the brachial, posterior tibial, and dorsalis pedis arteries using an L150 Summit Doppler (Wallach Surgical, Trumbull, Connecticut) with an 8-MHz vascular probe. Demographic and co-morbidity data were collected from the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH) database, a prospective database that records all coronary catheterizations performed in Alberta. ABI was calculated by dividing the highest pressure of the posterior tibial or dorsalis pedis arteries in each leg by the highest brachial pressure. The lowest ABI value was used except when the lower value was normal and the higher value was >1.40, in which case the higher value was used. ABI ≤0.90 was considered diagnostic for PAD, ABI 0.90 to 0.99 indicated borderline PAD, ABI 1.0 to 1.40 was normal, and ABI >1.40 was considered to represent hardening of the arteries by calcification.
SYNTAX and Duke jeopardy scores were calculated after the baseline angiographic procedure before revascularization. SYNTAX scores were calculated using an on-line calculator ( http://www.syntaxscore.com ). A SYNTAX score of 0 indicates no measurable coronary disease, while a score ≥1 indicates the presence of CAD, with CAD complexity increasing as the SYNTAX score increases. For Duke jeopardy scoring, the coronary circulation was divided into 6 arterial segments, and each segment with a proximal lesion >70% was considered jeopardized, to a maximum score of 12. Duke jeopardy scores were updated 3 months after the index procedure to reflect any revascularization. Research team members calculating the SYNTAX and Duke jeopardy scores were blinded to the patients’ ABIs and PAD histories. Patients underwent telephone follow-up at 30 days, 6 months, and 1 year from study entry. Data were collected for outcomes of myocardial infarction, stroke, target vessel revascularization, and death. Outcome data were also collected from the APPROACH database, which is linked to Alberta Vital Statistics and provincial administrative databases, to optimize completeness of follow-up.
Comparisons between ABI groups and the variables listed in Table 1 were analyzed using Fisher’s exact test and 1-way analysis of variance with Tukey’s post hoc test. The association between SYNTAX score and ABI group was examined using stepwise logistic regression, while relations between Duke jeopardy scores and ABI groups were examined using purposeful selection methods in logistic regression. The threshold level for a high SYNTAX score was based on previous research, while Duke jeopardy score thresholds were calculated using the entire sample mean plus 1 SD, rounded to the nearest integer. Outcome data were analyzed using a Cox proportional-hazards model with forward stepwise regression adjusted for age and gender.
| Variable | PAD ABI ≤ 0.90 | Borderline PAD ABI 0.91 to 0.99 | Normal ABI 1.00 to 1.40 | Vascular calcification artifact ABI > 1.40 | p value |
|---|---|---|---|---|---|
| No. of patients | 62 | 69 | 625 | 58 | |
| Male | 35 (57%) | 42 (61%) | 466 (75%) | 50 (86%) | <0.001 |
| Mean age (years) | 69.9 (11.8) | 65.3 (11.7) | 61.0 (11.3) | 65.5 (10.9) | <0.001 |
| Hypertension | 51 (89.5) | 58 (86.6) | 408 (74.5) | 47 (83.9) | 0.006 |
| Hyperlipidemia | 49 (86.0) | 57 (87.7) | 472 (85.4) | 47 (83.9) | 0.948 |
| Diabetes | 20 (47.6) | 23 (39.7) | 149 (32.3) | 26 (52.0) | 0.012 |
| Heart failure | 9 (21.4) | 4 (7.8) | 29 (6.8) | 9 (23.1) | 0.001 |
| Cerebrovascular disease | 4 (10.5) | 4 (8.0) | 11 (2.7) | 3 (7.9) | 0.012 |
| Chronic obstructive pulmonary disease | 8 (20.0) | 8 (15.7) | 50 (11.9) | 1 (2.6) | 0.083 |
| Renal insufficiency | 8 (20.5) | 7 (13.7) | 30 (7.7) | 10 (25.0) | 0.001 |
| Family history of CAD | 16 (35.6) | 21 (39.6) | 227 (48.4) | 19 (45.2) | 0.276 |
| Claudication classification ∗ | |||||
| Classic | 23 (28.8) | 8 (10.0) | 47 (58.8) | 2 (2.5) | <0.001 |
| Atypical | 2 (10.5) | 5 (26.3) | 11 (57.9) | 1 (5.3) | 0.045 |
| Smoker | |||||
| Never | 6 (12.0) | 16 (25.4) | 118 (23.8) | 10 (22.7) | 0.267 |
| Current | 23 (46.0) | 24 (38.1) | 158 (31.9) | 7 (15.9) | 0.012 |
| Former | 21 (42.0) | 23 (36.5) | 219 (44.2) | 27 (61.4) | 0.079 |
| Indication for catheterization | |||||
| ST segment elevated myocardial infarction | 3 (4.9) | 5 (7.4) | 69 (11.1) | 2 (3.4) | 0.132 |
| Non-ST segment elevated myocardial infarction | 26 (42.6) | 21 (30.9) | 185 (29.8) | 23 (39.7) | 0.105 |
| Unstable angina | 7 (11.5) | 10 (14.7) | 104 (16.7) | 6 (10.3) | 0.514 |
| Stable angina | 18 (30%) | 25 (37%) | 202 (33%) | 18 (31%) | 0.837 |
Results
The baseline characteristics of the study population, stratified by ABI group, are listed in Table 1 . Patients with PAD were significantly older than the normal group (69.9 vs 61.0 years), significantly fewer were men (57% vs 75%), and there was a higher prevalence of hypertension (90% vs 75%). Diabetes prevalence was significantly higher in the group with vascular calcification artifact compared with all others. Patients with vascular calcification artifact had a significantly lower prevalence of current smoking compared with the other 3 groups, but there was no difference in smoking status between patients with PAD and those with normal ABIs.
Measures of CAD complexity and myocardium at risk, stratified by ABI group, are listed in Table 2 . The overall mean SYNTAX score was 11.4 ± 11.4, with a SYNTAX scores of 0 found in 24% of patients (n = 192). Sixty percent of the cohort (n = 492) had low SYNTAX scores (1 to 22), 10% (n = 80) had intermediate SYNTAX scores (23 to 33), and 6% (n = 50) had high SYNTAX scores (≥33). The prevalence of PAD increased as SYNTAX score increased, with a prevalence of 8% (n = 35) in patients with low SYNTAX scores, 13% (n = 11) in patients with intermediate SYNTAX scores, and 20% (n = 10) in patients with high SYNTAX scores. Patients with PAD or vascular calcification artifact had significantly higher SYNTAX scores than patients with normal ABIs (p <0.001 and p = 0.032). Duke jeopardy scores were also highest in patients with PAD before and after revascularization (6.3 ± 4.1 and 3.3 ± 3.3, respectively).
| Variable | PAD ABI ≤ 0.90 | Borderline PAD ABI 0.91 to 0.99 | Normal ABI 1.00 to 1.40 | Vascular calcification artifact ABI > 1.40 | p value |
|---|---|---|---|---|---|
| Mean SYNTAX score | 17.6 (12.4) | 12.4 (11.7) | 10.3 (10.7) | 14.5 (14.5) | <0.001 |
| Mean initial Duke Jeopardy Score | 6.3 (4.1) | 4.4 (4.1) | 3.5 (3.5) | 4.6 (4.3) | <0.001 |
| Mean post revascularization Duke Jeopardy Score | 3.3 (3.3) | 2.1 (2.4) | 1.8 (2.3) | 2.7 (2.6) | 0.001 |
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