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Background. Early and accurate diagnosis of peripheral atherosclerosis is of paramount importance for global management of patients with known coronary artery disease (CAD). We sought to retrospectively evaluate the role of the invasive cardiologist in the diagnosis and management of clinical relevance significant subclavian artery stenosis (SAS) and abdominal vessel stenosis or aneurysm (AVA) diagnosed by coincident peripheral angiography in patients undergoing coronary angiography in whom CAD is detected. Methods. Medical records of consecutive patients underwent coronary angiography at two public institutions over a 12-month period were evaluated. Angiographic results of patients underwent coincident diagnostic abdominal aorta angiography to evaluate abdominal vessels or subclavian angiography on the basis of clinical and angiographic criteria were analyzed. Results. During the study period, 724 consecutive patients (535 males, mean age 68.1± 11 years) were enrolled (Table 2). A significant atherosclerotic disease of at least one arterial segment was observed in 198 patients (27.3%). Angiographically significant SAS was observed in 18/220 patients (8.1%) undergoing concomitant subclavian artery angiography and candidates to coronary surgery using the internal mammary artery. AVA was reported in 180 (35.7%) of 504 consecutive patients; renal artery stenosis was found in 13.1% of cases (66 patients), aortoiliac artery disease in 13.7% (69 patients), and aortic aneurismal disease in 8.9% (45 patients). Logistic regression analyses revealed >3-vessel CAD (odds ratio[OR] 9.917 , p=0.002), age >60 years old (OR 3.817, p=0.036), >3 risk factors (OR 2.8, p=0.048) as independent predictors of SAS and AVA. Conclusion. The role of the invasive cardiologist and coincident peripheral angiography in the management of patients with multivessel CAD and concomitant PVD seems not to be trivial due to the high prevalence of PVD in aged patients with multivessel CAD. It suggests the usefulness of a more global and comprehensive cardiovascular approach and calls for the creation of multidisciplinary endovascular teams. Key words: coronary disease, catheterization, angiography, peripheral vascular disease

INTRODUCTION
An early and accurate diagnosis of peripheral atherosclerosis (renal, abdominal and aortoiliac localizations) is of paramount importance for global management and prognosis due to its major additional mortality impact in patients with known coronary artery disease^1-2, especially those who are candidates to coronary or cardiac revascularization (CAD).^3-4 We sought to retrospectively evaluate the role of the invasive cardiologist in the diagnosis and management of clinically relevant significant subclavian artery stenosis (SAS) and abdominal vessel stenosis or aneurysm (AVA) diagnosed by coincident peripheral angiography in patients undergoing coronary angiography in whom CAD is detected.

MATERIALS AND METHODS
Medical records of consecutive patients who underwent coronary angiography at two 700-bed public institutions over a 12-month period were reviewed. On the basis of clear clinical and angiographic criteria (Table 1), patients underwent coincident diagnostic subclavian artery angiography in order to assess subclavian and internal mammary artery (IMA) in patient candidates for coronary surgery, using IMA or abdominal aorta angiography to evaluate renal, abdominal and iliac vessels. These patients were enrolled in a retrospective registry and analyzed. Written, informed consent was obtained from all patients. Pretreatment with 0.45% saline at a rate of 1ml/kg/hr for 12 h was administered to all patients. Repeated serum creatinine was obtained during admission and every two weeks until return to baseline values in patients exhibiting a procedure-related kidney dysfunction (increase in serum creatinine of > 0.5 mg/dl).
For subclavian artery angiography with visualization of LIMA, peripheral angiographic protocol included the use of a diagnostic modified or standard 5F Judkins right diagnostic catheter through the femoral or brachial artery, positioned at the origin of subclavian artery in anterior-posterior view and using the powered injection of > 4-8 ml of Iopromide (Ultravist 370, Schering, Milan, Italy). For abdominal angiography, a pigtail catheter was positioned at the level of the L1 vertebral body in the anterior-posterior to depict the abdominal aorta slightly above the renal arteries, to the origin of femoral arteries, using the powered injection of >30 ml of Iopromide (Ultravist 370, Schering, Milan, Italy). Alternatively, a Judkins Right coronary catheter has been used for selective renal artery angiography in the 20-25° left or right oblique projections using 4-8 ml. Digital subtractive technique was preferentially used. Moderate to severe vascular arterial stenosis (>50% stenosis), vessel occlusion, and aneurysmal vessels were noted as significant angiographic findings. Contrast-induced nephropathy was defined as a rise in serum creatinine of >25% from baseline.

STATISTICAL ANALYSIS
Data are expressed as mean ± SD and as percentages. Univariate and multivariate logistic regression analyses were employed to determine independent predictors of extra-cardiac atherosclerotic involvement. A significant level was defined when p< 0.05. All analyses were performed using SPSS 10.0 (SPSS Inc., Chicago, IL).

RESULTS
During the study period, 724 consecutive patients (535 males, mean age 68.1± 11 years) were enrolled (Table 2). A significant atherosclerotic disease at least one arterial segment was observed in 198 patients (27.3%). Angiographically-significant SAS was observed in 18 of 220 patients (8.1%) who underwent concomitant subclavian artery angiography and were candidates for coronary surgery using the internal mammary artery. Ten patients (55.5%) with subclavian artery stenosis and upper limb ischemia underwent subclavian artery angioplasty and stenting, and bypass surgery using LIMA. Angiographically significant AVA was observed in 180 of 504 (35.7%) patients undergoing concomitant abdominal aorta angiography. Renal artery stenosis was found in 13.1% of cases (66 patients), aortoiliac artery disease in 13.7% (69 patients), and aortic aneurismal disease in 8.9% (45 patients) including patients with combined renal artery and aortic stenosis, renal artery stenosis and abdominal aneurysm, and iliac stenosis/occlusion and thoracoabdominal aneurysmal disease. Significant AVA was associated with CAD in 98.8% (Table 3). Complications of combined coronary and subclavian or abdominal vessel angiography included 6 contrast-induced nephropathy. No case required renal replacement therapy. The additional contrast volume used for subclavian artery angiography was 8±2.6 ml, while for abdominal aorta and/or renal angiography, it was 38±15 ml. Cumulative additional fluoroscopy time was 5.0±1.1 minutes.

Ten patients (55.5%) with subclavian artery stenosis and upper limb ischemia underwent subclavian artery angioplasty and stenting, and bypass surgery using LIMA. In patient candidates for coronary surgery (89/180, 49.4%), abdominal angiography was useful in determining the need for prior percutaneous peripheral interventions in 48 patients, concomitant or staged vascular surgery in 41 patients, and unsuitability for any post-cardiac surgery aortic balloon counterpulsation in 14 patients. Globally, on the basis of standard clinical indications, an endovascular treatment was necessary in 40% (72 patients) and surgical vascular repair in 22.2% (40 patients) of cases. The remaining patients were medically managed for peripheral vascular disease and are currently being followed. Multivariate logistic regression analyses revealed:
• >3-vessel CAD (odds ratio[OR] 9.917; 95% confidence interval [CI] 2.2 to 43.8; p=0.002);
• Age >60 years (OR 3.817; 95% CI 2.2 to 6.5.8; p=0.036);
• and >3 risk factors (OR 2.8; CI 95% 0.63–9.1; p=0.048) as independent predictors of SAS and/or AVA (Table 4).

DISCUSSION
Although no definitive evidence of a clinical benefit of a combined coronary and peripheral angiography can be drawn from this registry, due to the retrospective nature and the clear limitations in selecting patients, data reported in this study suggest that the association of SAS/AVA with CAD is high and clinically relevant in patients undergoing coronary angiography. The role of the invasive cardiologist and coincident peripheral angiography in management of patients with multivessel CAD and concomitant PVD seems to be not trivial, especially in those scheduled for coronary revascularization.

Some differences exist in current literature in regard to the prevalence of the association of CAD with different sites of atherosclerotic involvement. Proximal subclavian artery occlusive disease in the presence of a patent internal mammary artery used as a conduit for a coronary artery bypass graft procedure may cause the reversal of the internal mammary artery flow (coronary-subclavian steal), leading to myocardial ischemia.⁵ Visualization of the subclavian artery by duplex ultrasound is possibly in nearly all cases, at least for the distal part of the vessel. The proximal part of the right subclavian artery, as well as the distal part of the innominate artery are visible in most cases, but the origin of the left subclavian artery, where lesions are three times as likely to occur, is almost never directly visible by duplex ultrasound. Thus, all patients undergoing cardiac catheterization prior to coronary artery bypass grafting using the internal mammary artery should be evaluated for the presence of upper extremity and cerebrovascular ischemia, the presence of cervical or supraclavicular bruits, and an upper extremity blood pressure differential of 10–20 mm Hg or greater.⁵ Patients with these findings or with evidence of diffuse atherosclerotic vascular disease should have brachiocephalic arteriography at the time of coronary arteriography to identify significant subclavian artery occlusive disease. Moreover, although very unusual, atherosclerotic lesions of the internal mammary artery have been reported in patients undergoing coronary angiography.^6-9 Angiography of subclavian artery and internal mammary artery at the time of coronary angiography seems effective in preventing any coronary-subclavian steal syndrome as well as in assessing the suitability of LIMA as a bypass conduit. It is more effective in patients with upper extremity and cerebrovascular ischemia, cervical or supraclavicular bruits, and an upper extremity blood pressure differential of 20 mm Hg or greater, as well as those who have had previous thoracic or neck brachytherapy, or thoracic surgery.^10–11

Renal artery stenosis (RAS) is a relatively uncommon but potential cause of renal failure, as well as being a cause of refractory hypertension and recurrent pulmonary edema. It is independently associated with mortality in patients undergoing coronary artery angiography and its severity has an incremental effect on survival prognosis. Four-year unadjusted survival for patients with RAS is 65% compared with 86% for patients undergoing catheterization without significant RAS. Factors associated with decreased 4-year survival include increased age, increased serum creatinine, the presence of RAS, peripheral vascular disease, congestive heart failure, diabetes, hypertension, and reduced ejection fraction.¹² Progression of even mild stenosis is reported in a large number of patients.¹³ Moreover, RAS has been reported to have a high prevalence in patients with CAD.^14-15 Not surprisingly, many authors have advocated the usefulness of renal angiography screening in patients undergoing coronary angiography, especially those with unexplained renal insufficiency, uncontrolled or severe hypertension, and previous vascular surgery or clinical history of cerebral ischemic attack and hypertensive pulmonary edema.^16–26 Recent reports24 have demonstrated that a severe RAS may be present in 7% of patients with severe atherosclerosis, 3% of patients with renal dysfunction, 9% with hypertension, 22% with acute pulmonary edema and hypertension, and 39% with proteinuria.

As recently reported, CAD was associated with aortoiliac lesions in 40.5% of patients undergoing coronary angiography and in a significant proportion of patients with aortic aneurismal disease.²⁷ The extent of the coronary disease was directly related to the frequency and extent of the aortoiliac lesions. Frequencies of aortoiliac lesions were strongly related to a history of smoking and intermittent claudication, and directly related to the extent of CAD. The prevalence of the association of aortic aneurysmal disease with CAD has been reported to range from 4.4 to 7%.^28-29 A knowledge of aortic involvement in such atherosclerotic phenomena may influence the operative strategy in patients undergoing urgent coronary angiography, privileging complete revascularization. This reduces the risk of cardiac events in patients undergoing thoracic aortic surgery, or in the case of severe thoraco-abdominal aneurysm, by referring the patient for combined surgical management, which has low mortality and good event-free survival rates.^30-35 Abdominal aortography should be considered not only for assessing the renal artery but also for evaluating aortoiliac diseases.^36-37

Differences in the entry criteria, imaging techniques and protocols, and lesion severity evaluation methods may contribute to this variety of results. Although no definitive conclusions can be drawn from the the analysis of our angiographic data, the prevalence of angiographically significant SAS or AVA associated with CAD seems to be high and clinically relevant in patients undergoing coronary angiography. Our study may contribute to show that combined coronary and peripheral angiography may be more efficient in over 60-year old patients with multivessel CAD and multiple risk factors. Patients with multivessel CAD in our series were frequently aged, had a high-risk profile and multiple vascular atherosclerotic distributions. It suggests the usefulness of a more global and comprehensive cardiovascular approach and calls for the creation of multidisciplinary endovascular teams.

Acknowledgements
The authors wish to thank Mrs Anne Holdstock for her invaluable help in language editing.

Dr. Gianluca Rigatelli can be contacted at jackyheart@hotmail.com