Peripheral artery disease (PAD) or, commonly, lower-extremity artery disease (LEAD), is a complex cardiovascular condition whose symptomatology and severity may be greatly affected by other medical conditions, some of them not (directly) of cardiovascular nature. Diabetes and its many deleterious effects, including diabetic kidney disease (DKD), are one such example.
The association between PAD and diabetes is far from coincidental or insignificant as it has a profound effect on patients with both diseases. The Framingham Heart Study found that 20% of patients with PAD had diabetes, but that included only patients with the symptomatic form of the disease . This is significant additional information as there are considerably more asymptomatic than symptomatic patients. Only 10% of them have typical symptoms (intermittent claudication), while up to 40% have no symptoms and the rest have atypical symptoms that could be attributed to other medical conditions [2, 3]. The true number of patients with (asymptomatic) PAD and comorbid diabetes is therefore (likely) far higher.
Still, diabetic patients are far more likely to have intermittent claudication than non-diabetics: males are 3.5 times more at risk, while in females that number is 8.6 times more . Other negative effects are far worse. At least 50 % (estimates actually go as high as 76 %) of patients with critical limb ischaemia (CLI), the most serious form of PAD, have diabetes and they have higher rates of more severe outcomes like lower-extremity amputations and mortality than non-diabetics [5, 6, 7]. Statistically, the rates of major amputations are 5 to 15 times greater in patients with both diseases than in those with only PAD . On top of that, diabetes mellitus, particularly if poorly managed (improper glycaemic control), is associated with more complications and more severe outcomes post vascular surgery or endovascular intervention .
The deleterious effects of diabetes are not limited to the overall severity of PAD and the incidence of serious outcomes, but extend to “masking” the presence of PAD, even when modern diagnostic tools are used. For example, diabetic patients might not experience intermittent claudication due to the nerve damage caused by peripheral neuropathy, delaying proper and timely diagnosis until it may be already too late to manage the disease using conservative means . There are far more serious pathophysiological mechanisms at play in case of other diagnostic methods that do not rely solely on diagnosing intermittent claudication.
There are several diagnostic methods in use for diagnosing PAD, the most well-known being the Ankle-Brachial (pressure) Index (ABPI or ABI) assessment. Convenience and cost-efficiency coupled with good accuracy and specificity have made ABI a go-to method for use in both general and specialist practice, in the latter usually for preventive screening of at-risk individuals in lieu of more complex and expensive alternatives (i.e. angiography). Usage is also on the rise thanks to proliferation of oscillometric-plethysmographic diagnostic devices, which are superior to the (standard) Doppler probe/sphygmomanometer measuring method in speed and are user error-free [10, 11, 12].
However, for all its benefits ABI is not without a major drawback—it is unusable in patients with incompressible (stiff/calcified) arteries. Not all are affected equally as the condition is usually diagnosed in those with diabetes, end-stage renal disease (ESRD) and rheumatoid arthritis [13, 14, 15]. Of those three, two are intimately linked—diabetes and ESRD. Diabetic nephropathy is the most common cause (in combination with hypertensive nephropathy) of ESRD in both economically developed and developing countries . Additionally, it is estimated that between 20% and 40% of diabetics are affected by diabetic nephropathy .
These are worrisome statistics that do not end with the prevalence of renal issues in diabetic patients, but are merely an introduction to well-supported findings of increased incidence and severity of adverse outcomes in patients with additional PAD. It is estimated that about 24% of patients with renal insufficiency have PAD (defined as ABI <0.9) and they have far higher mortality rates than those with none or either disease [18, 19]. Amputation rates are likewise higher and patients with both conditions are more likely to require distal procedures and to present with limb-threatening infections than those without renal issues [20, 21].
The ABI assessment is very likely to return an abnormally high (ABI ≥1.30) result in those patients, precluding definite diagnosis. There is limited diagnostic value in such results: studies have demonstrated a U-shaped relationship between ABI and mortality, indicating that patients with high score had nearly equal mortality risk than those with low score (both groups still had 2 times greater mortality risk in comparison with those with intermediate scores) . Abnormally high ABI is also associated with an increased risk of myocardial infarction, but offers no clinically usable information about PAD .
Patients with incompressible arteries, particularly those with already diagnosed renal issues should, therefore, be given a Toe-Brachial Index (TBI) assessment. Toe arteries are rarely affected by calcification, making them suitable for blood pressure measurement, which is performed in a similar fashion as the one at the ankle, but with significantly smaller pressure cuffs . The TBI has the added benefit of better suitability for patients with excruciating pain in the lower extremities (contraindication for ABI measurement), whether due to ulceration (higher risk in patients with ESRD) or other causes [25, 26, 27]. The value of TBI in nephrology is well recognised with studies demonstrating its superiority in diagnosing PAD in patients with ESRD (in comparison with ABI) and usefulness as an informative predictor of mortality in dialysis patients [28, 29].
Screening for PAD in patients with nephropathic conditions on the basis of ABI should be supplemented with a TBI assessment, which is suitable even in those with incompressible arteries and has diagnostic value beyond diagnosing PAD.