Our study shows a high prevalence (56.8%) of atherosclerotic renal artery stenosis (ARAS) in patients with combined heart and renal failure, defined as having a stenosis >50%. When taken a stricter cut-point (> 70% stenosis) the prevalence of ARAS was still as high as 21.8% in this population. The presence of ARAS was not associated with the extent in abnormalities in left ventricular function or myocardial fibrosis based on cardiac MRI findings with late gadolinium enhancement (LGE), when compared to patients with combined CHF/CKD without ARAS. Neither did we observe a difference in the presence of an ischemic pattern of LGE. Furthermore; we found a weak association between eGFR and the severity of ARAS and observed a negative association between diabetes mellitus and ARAS. This could indicate that our small cohort may consist of two different groups of cardiorenal patients: non-diabetic patients in which ARAS is highly prevalent and diabetic patients with a much lower ARAS prevalence.
ARAS is very common in patients with manifestations of non-renal atherosclerosis, particularly in patients with peripheral arterial and aortic disease. A recent literature review found a pooled prevalence of 25.3% in patients with peripheral arterial disease and 33.1% in patients with aortic aneurysm [7
]. Only few, small, studies determined the prevalence of ARAS in patients with CHF. McDowall et al. reported a prevalence of 34% of ARAS in patients with CHF and deSilva et al. found a prevalence of up to 54% [9
]. In both studies, ARAS was defined as a stenosis of >50% by magnetic resonance angiography (MRA). About the prevalence of ARAS in combined CHF/CKD, even fewer studies are published. DeSilva et al. reported a prevalence of 68% in 97 patients with CHF that had renal dysfunction. The study by deSilva et al. included only patients with HFREF. However, HFPEF is known to have a similar poor prognosis as HFREF and to be more prevalent in older patients and in patients with diabetes and/or hypertension [21
]. Our study included an ambulant stable outpatient clinic patient population with combined chronic heart failure and chronic kidney disease and mild anaemia. We included patients both with HFREF and HFPEF, treated with renin angiotensin (RAS) inhibitors and β- blockers according to present guidelines. In this cohort we demonstrate a high prevalence of ARAS (56.8%). A more severe degree of ARAS, defined as a unilateral stenosis of >70% and/or bilateral stenosis >50% was found in 43.2% of the patients. These results are similar to those of deSilva et al., confirming this high prevalence of ARAS in combined CHF/CKD in patients with both HFREF and HFPEF.
According to the present American Heart Association guidelines for the management of patients with peripheral arterial disease, the indication for percutaneous renal revascularization with stent placement (PTA) of ARAS is limited to “flash pulmonary oedema, recurrent episodes of unexplained congestive heart failure or unstable angina” [23
]. There is debate however whether PTA could benefit CHF patients with ARAS. In patients with stable CKD and/or hypertension it has been reported several times that PTA does not
affect renal function [5
]. On the other hand, a small retrospective study showed that in patients referred for renal revascularization close to one-third had CHF (mainly HFPEF) and that revascularization was associated with better control of heart failure [25
]. The results of the sub analysis of the Angioplasty for Renal Artery Lesions (ASTRAL) study of a predefined group of patients with CKD and reduced ejection fraction are not yet available.
Nonetheless, diagnosing ARAS can be important for more reasons than to find patients suitable for PTA. One could interpret the presence of ARAS as a marker of “atherosclerotic burden” associated with a high risk of cardiovascular events, which would warrant more aggressive medical therapy [8
]. Indeed, in a follow up study of elderly people with ARAS, the annual incidence of coronary events, heart failure and death were as high as 30%, 19% and 17% respectively [26
]. A recent retrospective study in elderly patients with ARAS presented a very high morbidity and mortality (49% suffered a primary event and 37% died during median follow-up of 3.3
years), which was negatively associated with the use of statins.
In addition to determining the prevalence of ARAS in patients with both CHF and CKD, we determined whether there is an association between left ventricular structure and function and the presence of ARAS. Although one could hypothesize that ARAS would be associated more often, and to a greater extent, with cardiac abnormalities, such as left ventricular hypertrophy, we found no differences in left ventricular mass index, left ventricular volumes and LVEF in patients with and without ARAS. We also hypothesized that the existence of ARAS represents an “atherosclerotic burden”, representing one of the mechanisms of combined CHF/CKD. However, we found no difference in the presence of ischemic aetiology of CHF. Moreover, we could not demonstrate a difference in the presence, the location and the extent of fibrosis, as depicted by LGE. The study by Wright et al. showed more diastolic dysfunction and left ventricular hypertrophy in patients with ARAS when compared with a matched control group with similar renal dysfunction [12
]. In contrast, our study only included patients with known CHF and CKD. In those patients with combined CHF and CKD, the presence of ARAS was not associated with a more severely impaired cardiac function, more severe left ventricular hypertrophy or the presence of fibrosis.
Coincidentally we found a negative association between diabetes and ARAS; the patients with combined CHF/CKD without ARAS were markedly more likely to have diabetes mellitus than those patients with ARAS (Figure ). Some studies identified diabetes mellitus as a predictor for ARAS [27
], whereas others showed that diabetes mellitus was not associated with ARAS [28
]. The negative association between diabetes and ARAS may point to a mechanistic difference in the pathophysiology of combined CHF/CKD in patients with and without diabetes. However, alternatively, the difference may result from survival bias.
A point of debate is the definition of ARAS, since no uniform definition exists. Previously, most studies defined ARAS as >50% stenosis [19
]. Indeed, the American Heart Association Guidelines [23
] are based on studies using this definition. However, more recent guidelines from the European Society of Cardiology define ARAS as having a stenosis >60% [33
], based on the fact that MRA (and CT angiography) tend to overestimate the degree of stenosis. More recent PTA studies often combine this definition with additional haemodynamic measurements, e.g. a systolic pressure gradient [34
], measurement of the fractional flow reserve [35
] or use a more strict cut-point of >70%. In this study we used the definition of ARAS as defined >50%, in accordance with the STAR study [19
]. However, if we also apply the more stringent definition of >70% stenosis we still find a prevalence of 21.8% of ARAS. Except for a significant decline in renal function in patients with a more severe ARAS versus a moderate ARAS, we found no other differences in clinical profile between a moderate or severe ARAS.
Some limitations of this study need to be acknowledged. The small study population, due to the complexity of the study design, consists of a selected group of stable ambulant patients, almost all using RAS inhibitors which, in addition to the exclusion of uncontrolled hypertension and patients with flash pulmonary oedema, may have led to underestimation of the prevalence of ARAS in CRS. However, despite this small study population, we believe that these data are valuable and robust, due to a paucity of data in the present literature about this subject and the reliable assessment with cardiac MRI. Furthermore, the data are baseline data from a randomized intervention study, which precludes spontaneous follow-up.