According to the most recent data, currently there are approximately 71 million people in the United States with some form of cardiovascular disease (CVD).¹ The burden of CVD on the society is enormous. CVD has been the number one killer disease in the United States every year since 1900 except 1918.¹ It kills more Americans every year than the next four leading causes of death combined together (cancer, chronic lower respiratory tract disease, accidents, and diabetes).¹

The spectrum of CVD includes hypertension (HTN), angina, myocardial infarction (MI), heart failure, cerebrovascular accidents, etc. Of this, the prevalence of coronary artery disease (CAD), which includes angina and MI, is estimated to be approximately 13 million.¹ Considering the diffuse nature of atherosclerotic vascular disease, it would be reasonable to expect patients with CAD to have a systemic distribution of arterial disease. In fact, it has been recognized since the middle of the 20th century that patients with atherosclerotic vascular disease in one vascular bed are likely to develop disease in other arteries as well and clinically manifest symptoms of such disease.²

When studying incidence of CAD, data suggest that the incidence of single and multiple vessel CAD (defined as >50% angiographic stenosis) is as high as 21% to 41%, respectively, regardless of the principal vascular diagnosis (AAA, PAD, carotid artery disease).³ Manifestations of arterial disease frequently seen in patients with CAD include renal artery stenosis (RAS), peripheral arterial disease (PAD), carotid artery disease, and aneurysms of the aorta and its branches (subclavian artery, celiac trunk, superior mesenteric artery, and inferior mesenteric artery).

Recently, the REACH database, which included 67 888 patients from an international population, demonstrated that of patients with symptomatic atherothrombotic disease almost 16% had significant polyvascular disease.⁴ It should be noted that the prevalence of polyvascular arterial disease would have been much higher had these patients also been screened for asymptomatic vascular disease.⁴

With this in mind, it should not be surprising that the risk of angiographically significant RAS increases with multi-vessel CAD.⁵ Presence of significant CAD with more than two vessel involvement has been shown to be a predictor of RAS with a sensitivity of 0.84 and specificity of 0.77.⁶ It has been further demonstrated that the risk of significant RAS (defined as >50% stenosis of a renal artery) ranges from 22% to 89% in patients with CAD.^7,8 In patients with prior history of percutaneous coronary intervention, the prevalence of significant RAS is around 39%⁹ (Table 12-1).

Patients with CAD also tend to have a higher incidence of underlying carotid arterial occlusive disease and approximately 11% of patients with CAD have been reported to have significant carotid stenosis (defined as >70%).¹⁰

Along the same lines, it has been reported that individuals with CAD also tend to have a higher prevalence of PAD. One Finnish study reported that the relative risk of intermittent claudication (IC) in women and men with angina pectoris was 4 to 7 times higher, respectively, as compared to controls.¹¹ The Framingham heart study suggests that CAD confers almost a threefold increase in the risk of developing IC.¹² In a study that looked at patients hospitalized with medically stable CAD, Dieter et al.¹³ found that as many as 40% of such patients had significant PAD (as defined by an ankle-brachial index [ABI] of <0.9 or history of revascularization for PAD).¹³ Similarly, others have reported that one out of three patients aging 62 or older and with CAD also have underlying PAD.¹⁴ The Cardiovascular Health Study demonstrated that there is a significant association between ABI and MI, congestive heart failure, and angina.¹⁵ The TASC II data suggest that as many as 10% to 30% of patients with ischemic heart disease will have underlying PAD¹⁶ (Table 12-2).

RAS is the most common cause of secondary HTN.¹⁷ Until recently, estimating RAS in a population required invasive technique (e.g., angiography) and therefore a population- based study estimate of the prevalence of RAS had been difficult. Most of the estimates available were obtained either from necropsy reports or from angiographic evidence gathered during evaluation of other vascular regions. From a recent population-based study, the prevalence of RAS amongst the elderly Americans (65 years or older) was reported to be 6.8%.¹⁸ In fact, atherosclerosis of the renal arteries is the most common disease to affect the renal arteries.¹⁹

RAS is much more common in patients who have clinical evidence of atherosclerotic arterial disease in vascular territory excluding the renal arteries (such as PAD, CAD, carotid occlusive disease, etc.). Various studies have demonstrated that once a diagnosis of arterial atherosclerotic disease has been made somewhere else in the arterial tree, the risk of having atherosclerotic RAS ranges from 26% to 50%.^{5,9,20,21,22,23} It has been observed that approximately 31% of patients with mild atherosclerotic narrowing (<50% occlusion) of a renal artery have clinical evidence of symptomatic arterial disease in the coronary, cerebrovascular, or peripheral vascular circulation.²⁴ Moreover, in patients with moderate to severe stenosis of renal artery (>50%), 49% had clinical symptoms of extra-renal atherosclerotic arterial disease.²⁴ It has been observed that patients with RAS have a higher likelihood of having underlying CAD and more stenotic coronary segments have been observed in those with significant RAS as compared to those without RAS (3.8+−1.2 vs. 2.3+−1.3; p < 0.001).⁶ Further, on average 58% of patients with 50% or greater RAS have been shown to have clinically overt CAD (ECG changes, symptoms, etc.)²³ It has been demonstrated that of patients with unilateral RAS requiring surgical intervention, as many as 14% of patients required myocardial revascularization when the coronary anatomy was evaluated after the diagnosis of RAS was made. This number was significantly worse in the bilateral RAS group which had as many as 40% of patients who needed myocardial revascularization or had advanced coronary disease²⁵ (Table 12-3).

As alluded to earlier, just as there is significant overlap between patients with RAS and CAD, there is also significant overlap between RAS, carotid artery disease, and PAD. In fact, it has been demonstrated that there is an association between the degree of RAS and the extent of disease in the extracranial carotids and lower extremity arteries.^26,27 It has been noted that among patients with renovascular HTN caused by occlusive renal arterial disease, as many as 83% had some degree of carotid arterial stenosis compared to 43% of patients with essential hypertension (EH). Hemodynamically significant carotid stenosis was seen in 10% of patients with renovascular HTN as compared to a 3% risk in patients with EH.²⁶ Further, it has also been demonstrated that 40% to 46% of patients with significant RAS tend to have moderate to severe occlusion of the carotid circulation^17,28 (Table 12-4). Carotid artery lesions are not only more common but also more severe and occur at a younger age in patients with renovascular HTN. Further exacerbating the situation, these plaques in patients with renovascular HTN tend to be more heavily calcified as compared to their counterpart with EH.²⁶ It has been observed that as the severity of RAS progresses from mild to severe, there is a fourfold increase in the prevalence of severe carotid artery disease.²⁷

Similarly, patients are more likely to have moderate or severe lower extremity PAD in the presence of severe RAS.²⁷ In patients with moderate to severe RAS, as many as three out of four have been found to have PAD with ABI less than 0.95.¹⁷ Yet another study looked at patients with atherosclerotic RAS of variable degree and concluded that as many as 69% of these patients suffered from PAD²⁹ (Table 12-5).

It is well known that the atherosclerotic disease of the celiac and mesenteric arteries is the most common cause for their obstruction.³⁰ Consequently, such patients present with the clinical symptomatology of postprandial abdominal pain (referred to as “intestinal angina”), which was first described in 1957 by Mikklesen.³¹ The celiac, superior, and inferior mesenteric arteries are interconnected and the intestines are usually well perfused by a comprehensive network of collaterals. Therefore, an obstruction of one of the three vessels is usually well tolerated. It has been suggested that the classical symptoms of this disease process become evident when at least two of the three main intestinal arteries are obstructed, although cases of intestinal ischemia from obstruction of just the superior mesenteric artery have also been documented.³² The clinical presentation of intestinal ischemia remains rare despite the relative commonness of this disease in the general population.³³ As a result, symptomatic mesenteric ischemia requiring surgical intervention or other diagnostic studies remains rare and therefore literature available for this disease process and overlap with other atheromatous disease processes remains sparse.

From unselected autopsy studies, it has been concluded that significant intestinal atherosclerotic obstruction is present in 6% to 10% of the population. This incidence has been reported to be as high as 14% to 24% in patients undergoing abdominal arteriography.³² Coexistent arterial disease involving other arterial beds (cerebrovascular, renal, or lower extremity) has been seen in as many as 85% of patients with mesenteric ischemia requiring surgical intervention.³⁴ In patients with stenosis of both the celiac trunk and the superior mesenteric artery, as many as 71% have been reported to have RAS as well.³⁵

Along the same lines, CAD has been seen in as many 33% to 50% of patients with chronic mesenteric occlusive disease.^34,35

The prevalence of underlying PAD is also high in patients with mesenteric ischemia and is even more significant in those who have symptoms severe enough to require bypass graft. Underlying PAD has been observed in as many as 78% of patients undergoing surgical revascularization of the mesenteric vessels for history of ischemia³⁶ (Table 12-6).

PAD is a common syndrome affecting 8 to 12 million Americans. It is estimated that symptomatic PAD has a negative impact on the quality of life of as many as 2 million adult Americans.³⁷ The burden of asymptomatic PAD is hard to ignore and is also associated with significant cardiovascular morbidity and mortality. The prevalence of PAD is expected to continue to increase as the population continues to grow and the average life expectancy increases.