Background: In today's aging population and an increasing proportion of patients with peripheral artery disease (PAD), adequate treatment becomes more challenging. Conservative therapy methods become more popular, especially those including physical exertion like supervised treadmill training programs (STTPs).

Purpose: The aim of the current study was to ascertain determinants of the improvement of walking abilities and endothelial function in patients with PAD undergoing STTP.

Methods: The current study enrolled 66 patients (62.1% males) in the mean age 65.4±7.7 years with PAD who underwent a 3-month length STTP. We assessed the effect of the following factors on the change of the flow-mediated dilatation value (ΔFMD), maximal-walking time (ΔMWT) and pain-free walking time (ΔPFWT). The evaluation included urinary derivatives of arachidonic acid, lactates, pro-inflammatory markers, markers of angiogenesis and lipids. Among the others were anthropometric indices, blood pressure, age, comorbidities, cardiovascular interventions, ankle-brachial index, gender, smoking habit, claudication time, as well as the current pharmacotherapy. Linear regression for each of the variables was performed. Moreover the multi-factorial model analysis of variances (ANOVA) was adopted to select the most influential determinants.

Results: The mean FMD value improved after the STTP from 4.2±2.2% to 6.2±2.4% (p<0.00001), the MWT from 469±185.5 s to 900.1±345.7 s (p<0.00001) and the PFWT from 155±62.6 to 301.5±157.3 s (p<0.00001). The linear regression analysis (LRA) revealed that higher soluble-endogline (sEng) level is found to predict better the improvement of ΔMWT and lower fibrinogen level remains on the verge. The ANOVA confirmed sEng as a significant determinant. The LRA showed that higher fibrinogen level, BMI value are negative predictors of the better improvement of ΔPFWT, and higher sEng level is a determinant of ΔPFWT increase. Atherosclerosis located in iliac arteries and treatment with an angiotensin-converting enzyme or an aldosterone receptor blocker are also determinants of the ΔPFWT increase. Whereas hypertension is found to be a negative determinant of ΔPFWT decrease. The LRA demonstrated that coronary artery disease (CAD) and peracted percutaneous transluminal angioplasty (PTA) are determinants of ΔFMD increase, and length of claudication history is on the verge of significance. Also the treatment with β-blockers and age are on the verge. The ANOVA confirmed CAD, PTA, treatment with β-blocker and age as significant determinants of the ΔFMD increase. (Figure 1)

Conclusions: High level of sEng at baseline could serve as a determinant of better MWT and PFWT improvement after STTP in patients with PAD. Older patients and those treated with β-blocker respond worse on STTP in terms of the FMD improvement. Whereas coexistence of CAD and peracted PTA of lower limbs are positive determinants of ΔFMD increase after the STTP.