The prevalence of atherosclerotic peripheral artery disease is increasing. Incidence in the population over 60 years of age is about 20% (1). In high-risk patients suffering from diabetes, arterial hypertension, and coronary and cerebrovascular disease, the incidence can be up to 30%. Peripheral artery disease (PAD) also increases with age, so the incidence in those over 85 years of age is as high as 50% (2). Numerous comorbidities, especially at an advanced age, not only modify the typical clinical presentation but also occasionally influence the treatment outcomes, increasing the already very high cardiovascular risk in this population. Given the vulnerability of this population due to cardiovascular risk and very common comorbidities, it is important to follow the guidelines for the diagnosis and treatment of PAD, and a personalized approach should be used in choosing the optimal treatment with the goal of achieving the maximum effect with minimal side-effects (3). Diagnostics and monitoring the clinical course in patients with PAD is based on assessing functional status, anamnesis, clinical status, plethysmography, and ankle brachial index (ABI). Ultrasound examination in PAD diagnosis can objectivize the anatomic and hemodynamic significance of the atherosclerotic process. Imaging methods (MSCT or MR angiography) are an integral part of the diagnostic algorithm when anatomic imaging is necessary for planning and decision-making regarding the optimal method of revascularization. The specificity of ABI is approximately 95% if its value is below 0.9, and the sensitivity is 79-95% in comparison with angiography as a method of discovering occlusive arterial disease (4). ABI values and disease symptoms are often uncorrelated, so it is sometimes necessary to perform an exertion test and measure ABI after the test. Functional diagnostics and anamnesis are often neglected in assessing the severity of the clinical presentation, often due to over-implementation of technically sophisticated diagnostic methods such as MR and MSCT, which undoubtably have a role in diagnostics but are not without certain limitations (4-6). Classification of PAB according to Fontaine and Rutherford is based on assessing the status and functional capacity of the patient. Fontaine stage I comprises patients with PAD who do not have limiting symptoms and pain while walking. Stage II comprises patients who have intermittent claudication symptoms. The II A subgroup has a walking distance (WD) over 200 m, whereas patients in subgroup II B report pain in the extremities at walking distances below 200 m. Stage III comprises patients who report rest pain, and stage IV comprises patients with ulcerations or gangrene. Stage III and IV undoubtably represent patients in whom revascularization is absolutely indicated due to danger to the extremities. Stage I requires monitoring and lifestyle modification with correction and treatment of risk factors, whereas the optimal treatment choice for patients with stable claudication (Fontaine II) requires a detailed clinical assessment with the application of medication treatment and structured walking exercises with supervision. Due to lack of financial support from healthcare funds for the implementation of structured supervised walking exercises, patients usually conduct trainings arbitrarily, which is often not sufficiently effective (4). The decision on implementing revascularization is based on clinical assessment, disease progression, comorbidities, patient age, and the clinical course of the disease, especially when physiotherapy and pharmacological treatments are not effective. In addition to risk factor correction, nicotine abstinence, and regulation of body weight, blood sugar levels, blood pressure, LDL cholesterol, and triglycerides, treating stable course intermittent claudication also requires daily walking and supervised physical exercises. It is also necessary to include the application of antiaggregant medication as well as statins and ACE inhibitors in symptomatic phases of the disease (4, 7). Physical activity consisting of walking training with supervision is certainly recommended, since its effectiveness is comparable to endovascular revascularization methods if the training is properly conducted. This is the reason for clinical dilemmas in deciding on treatment choice; optimal medication treatment and walking exercises, endovascular or surgical revascularization (8-10). Revascularization in Fontaine stage II is indicated if claudication reduces quality of life despite the application of optimal medication treatment and risk factor modification (11). The past decade was marked by a tripling of endovascular revascularizations due to increased disease prevalence, improved diagnostics, but also due to improved technical options for endovascular treatment, resulting in increased application of endovascular instead of surgical methods for more complex lesions (12, 13). The goal of this retrospective study was to analyze ABI and walking distance values, parameters which should be routinely used in the functional assessment of the immediate and delayed effects of endovascular revascularization. The analysis was conducted in a group of patients who had undergone percutaneous endovascular revascularization leading to a good angiographic effect, with the goal of studying the dynamics of changes in ABI and WD parameters in the periods before and after angiointervention and during follow-up.

We used data from medical documentation of patients treated at the Clinic for Cardiovascular Diseases and the Clinical Institute for Diagnostic and Interventional Radiology at the University Hospital Centre Zagreb. Out of a total of 135 patients treated with endovascular revascularization methods in 2018, only 67 fulfilled the inclusion criteria for this retrospective study, which were: a clinical picture with Fontaine stage II intermittent claudication, lack of response to conservative treatment in the initial 6-month period, application of percutaneous endovascular revascularization with good angiographic results, availability of postprocedural follow-up data in 3- to 6-month intervals. Before revascularization, all patients underwent a 6-month interval of treatment that involved statins, ACE inhibitors, and aspirin, nicotine abstinence, and a motivational conversation on the need for daily walks lasting at least 30 minutes at a pace that provoked pain in the extremities. The patients were also informed of the nature of their disease, the treatment method, and the need for daily walks via a leaflet designed for patients suffering from PAD. Patients were re-evaluated 6 months after the establishment of the diagnosis. Due to lack of treatment response or even deterioration of functional status, walking distance, and ABI after 6 months of treatment, MSCT angiography was used to allow the vascular team to asses suitability for angiointerventional treatment. Although all patients had bilateral atherosclerotic changes in arteries of the lower extremities, revascularization was performed only on the symptomatic leg. The ABI of all patients was measured within 48 h of successful completion of the procedure, followed by postprocedural ABI measurements at 3- to 6-month follow-up when the walking distance was noted based on the patient’s self-assessment. Bilateral revascularization was performed in a small number of patients, so these patients were not included in the study, and neither were patients at Fontaine stage III or IV with life-endangering critical ischemia and those in whom the angiointervention was not technically successful. All patients were treated with aspirin 100 mg and clopidogrel 75 mg daily for a minimum of one month after intervention, followed by long-term treatment with aspirin and high doses of statins as well as adjusted doses of ACE inhibitors as the treatment standard for PAD. Walking exercises were still part of the usual standard recommendations. All patients underwent ABI measurement 24 to 48 h after the procedure and at 3- to -6-month follow-up.

Measurements were performed using the Vaso Guard Viasys device for standard flow assessment based on plethysmography, segmental pressure measurement, and determining ABI. The test was performed after the patient had a 10-minute rest in a space at room temperature.

Anamnesis regarding walking distance was considered relevant and was included in the analysis. Pain-free walking distance was expressed in meters and data before the intervention and 3 to 6 months after the procedure were analysed.

SPSS 20.0 and Python version 3.7.1 were used for statistical analysis. The Friedman and Wilcoxon tests were used for determining significance for parameters with continuous variables. The Spearman regression analysis test and the Chi-squared test were used to compare categorical variables. The level of significance was set at p<0.05.

Data from 67 patients with symptomatic Fontaine stage II disease and unilateral endovascular intervention with good angiographic results were included in the analysis. The disease was bilateral in all the patients, and the intervention was performed only on the leg that was symptomatic and therefore a limiting factor for patient quality of life. The results were analysed chronologically: before intervention, immediately after intervention, and at 3- to 6-month follow-up after percutaneous transluminal angioplasty (PTA). Complications associated with the procedure were present in 5 (7.4%) of patients and included one retroperitoneal haemorrhage, 3 puncture site hematomas that did not require transfusion treatment, and 1 arteriovenous fistula. Patient characteristics are shown in Table 1.

ABI values measured immediately after intervention, i.e. within 48 h, were statistically significantly higher in comparison with values before the procedure (0.65±0.19 before, 0.84±0.18 after; p<0.05). The statistically significant difference remained constant during the follow-up examination 3 to 6 months later. A positive effect of revascularization in the postprocedural 3- to 6-month follow-up period was observed on both legs; both the leg on which the procedure was performed and on the contralateral side (Table 2, Table 3, and Table 4). Change in postinterventional follow-up ABI values in the leg on which revascularization was performed also had a positive correlation with ABI values in the other leg in the follow-up period (Spearman correlation coefficient=0.45; p<0.01).

Angiointerventional treatment with angiographically successful results lead to a significant increase in ABI and walking distance values in patients who showed lack of response to conservative treatment in a 6-month period before the intervention. ABI changes immediately after successful PTA with stable, unchanged values during follow-up and statistically significant increase in walking distance during follow-up represent evidence for the stability of successful angiointerventional procedures in the general patient population.

The results of previous studies (8, 14, 15) as well as those from the present study confirm that walking training and pharmacotherapy can be expected to lead to clinical and functional improvement of PAD given that this study has found an increase in ABI values on the leg that did not undergo revascularization.

Increase in ABI values on the contralateral leg was statistically significant although the difference in ABI value increase cannot be considered functionally relevant, because the ABI increase in the left leg was 0.1 on average. Sobieszczyk et al. (16) believed that an ABI increase of 0.15 represents a clinically significant change that reflects improved arterial flow. There is insufficient data on ABI changes that would represent a discriminating difference in improvement for conservative, non-interventional treatment. Increase in ABI values is the result of increased blood pressure due to restitution of flow in the main artery. There is insufficient evidence for ABI changes with improvement of total perfusion through the formation of new collaterals, which is usually the expected result of applying conservative treatment measures (15, 16). The issue of lack of effect from conservative treatment measures prior to PTA is associated with patient selection common in clinical practice, despite the patients having been treated according to guidelines for PAD (4). Increase in ABI values in the leg where the endovascular revascularization was not performed is likely the consequence of improved patient compliance and the compounded effect of pharmacotherapy application, application of dual antiplatelet therapy, but also of higher-quality physical training that is being more rigorously applied due to increased walking distance after PTA on the symptomatic leg. These results are in line with ESC guidelines for PAD treatment (4).

The population in the present study was exposed to multiple comorbidities, most commonly arterial hypertension. The presence of different comorbidities did not affect the results of the intervention or the study parameters, namely walking distance and ABI. Normal blood pressure was present in only 9% of participants, which points to a strong association between occlusive arterial disease and elevated arterial pressure (17, 18).

In the subgroup of participants with diabetes, high ABI values prior to intervention were expected because the arteries affected by medial sclerosis in diabetics become incompressible, leading to high ABI values. However, angiointervention led to ABI increase even in this subgroup, as well as to increased walking distance, which is in agreement with results reported by other authors (19).

Good effects from angiointerventional revascularization on walking distance and ABI increase were achieved only in participants above 65 years of age. The explanation for this difference could be the smaller sample of patients younger than 65 years of age (37%), but also their initially better ABI values before intervention, which led to there being no significant difference in postinterventional values. Increase in walking distance in the same group was statistically significant (p < 0.001). Despite the fact that walking distance is a parameter that was not verified with measurements in controlled conditions but was obtained through self-reporting, there was a statistically significant increase in walking distance with change in functional status after PTA in all patient categories. Increase in walking distance was achieved in all age groups and regardless of the presence of comorbidities, with a high level of both clinical and statistical significance. Increase in ABI after angiointervention was statistically significant in the total population (p<0.05), but did not parallel the statistically significant increase in walking distance for certain study categories and group characteristics. There was a lack of correspondence, albeit proportionally small, for the following variables: age, patients who did not have arterial hypertension, and in the group in which PTA was performed on the lower leg. Variable ABI values were observed in many studies. Results from the PORTRAIT PAD registry indicated that maximum walking distance and claudication-free walking distance represent a reproducible marker of functional status in patients both in their everyday life and in clinical practice, whereas ABI values were of questionable value in functional assessment, but not in the screening and early detection for PAD, where the importance of ABI is beyond question (4, 20).

Results reported by Amighi et al. showed that controlled exercise programs and conservative treatment methods can achieve a reduction in symptoms with an improvement in quality of life, as well as increased walking distance from an initial 100 m to 650 m within a year, but with no significant change in ABI values (7). The sensitivity of ABI for measuring flow after revascularization can also be achieved through the application of an ABI stress test, which would certainly represent valuable and reproducible data (21).

Successful endovascular revascularization (PTA) in comparison with standard pharmacotherapy and unsupervised walking exercises in patients with Fontaine stage II resulted in increased walking distance and ABI. Presence of comorbidities did not affect the results of the study parameters. Changes in ABI during the follow-up period in the leg where the revascularization was performed were significant and expected. The successfulness and “stability” of successful revascularization assessed through ABI values and walking distance was also observed during follow-up. ABI values in the contralateral leg were increased in the follow-up period and correlated with ABI increase in the leg on which angiointervention was performed. Based on these results, walking distance assessment represents a commonly neglected factor that should be reevaluated and considered as an important parameter in monitoring revascularization successfulness and functional status of patients with PAD.