Effects of Lower Extremity Revascularization on the Endothelial Functions Measured With Noninvasive Brachial Artery Flow-Mediated Dilatation

The effect of superficial femoral artery stenting and some atherosclerosis risk factors on changes in selected global endothelial function tests in patients with chronic lower limb ischemia. A pilot study

“…The presented results indicate that similarly to other cardiologic syndromes (such as acute coronary syndromes or cardiogenic shock) most benefits from the medical interventions (in this case SFA stenting and intensification of pharmacotherapy) are observed in patients at the highest risk, such as patients with uncontrolled risk factors. Our results are partially consistent with limited data from the literature that confirm the beneficial effect of peripheral artery revascularization (involving mainly lower limbs and renal arteries) on all-cause and cardiovascular mortality [5,6,8,10,15,19,33] and improvement of global endothelial function [21,22]. In a randomized prospective study Husmann et al [21] demonstrated in 17 patients treated with a percutaneous procedure and pharmacotherapy due to peripheral arterial disease of the lower limbs that FMD values increased after 4 weeks of observation in contrast to patients treated only with pharmacotherapy (n = 16), in whom these values remained unchanged.…”

“…In a randomized prospective study Husmann et al [21] demonstrated in 17 patients treated with a percutaneous procedure and pharmacotherapy due to peripheral arterial disease of the lower limbs that FMD values increased after 4 weeks of observation in contrast to patients treated only with pharmacotherapy (n = 16), in whom these values remained unchanged. On the other hand, Unal et al [22] found in a group of 54 patients that revascularization with the use of a femoro-popliteal PTFE prosthesis led to a significant rise of FMD values and decrease of the following markers in blood: nitric oxide, high-sensitivity C-reactive protein, interleukin-6 and tumor necrosis factor α (TNF-α). The authors of these studies proposed several potential mechanisms to explain the beneficial effect of peripheral revascularization on the global endothelial function: (a) secondary to increased physical activity increase of the shear stress, which is the most potent stimulus for endothelial production of nitric oxide [21], (b) reduction of oxidative stress caused by exertional ischemia before the procedure and by numerous episodes of post-ischemic reperfusion in the lower limb muscles [21], …”

“…and (c) decreased activity of the inflammatory processes dependent on oxidative stress, cytokines and adhesion molecules released from the ischemic area [22,49]. Other studies showed that oxidative stress causing oxidation of LDLs is a key factor for the processes of atherogenesis (oxidative hypothesis of atherosclerosis).…”

“…However, there are reports which demonstrate a positive relationship between revascularization of the peripheral arteries and reduced frequency of acute incidents in other vascular beds, such as other peripheral arteries, coronary arteries or intracranial arteries [5][6][7][8][9][10][11][12][13][14][15][16][17][18]. The positive effect of peripheral artery stenting on all-cause and cardiovascular mortality is explained by: (a) increase of the anklebrachial index (ABI), which is an important risk factor of death and cardiovascular events [1,2], (b) diagnosis of atherosclerosis followed by implementation of optimal pharmacotherapy [19], (c) improvement of patients' functional status and increase of the walking distance [5,8], (d) initiation of previously impossible cardiac rehabilitation [20], (e) improved quality of life [5,8] and (f) improved global endothelial function [21][22][23][24][25]. Endothelial dysfunction is the endpoint for all risk factors of atherosclerosis and promotes the processes of atherogenesis through the influence on vasodilation mechanisms, stimulation of arterial thrombosis as well as migration and proliferation of vascular wall cells [26].…”

“…The degree of FMD and PAT values reduction in response to ischemia was proportional to the number of risk factors present in the studied groups of patients and predicted the occurrence of cardiovascular incidents [6,14,15,17,33] including even venous thrombosis [34]. Smoking cessation [33,[35][36][37], hypertension [32,37,38], treatment of hyperlipidemia [39][40][41][42], diabetes control [43], body mass reduction [44], improvement of physical activity [31,45,46] as well as peripheral revascularization involving lower extremities [16,[21][22][23]26] and renal arteries [24,25] were shown to improve the markers of endothelial function not only in the culprit lesion, but also in other vascular beds. In this context it is logical to hypothesize that control of individual risk factors of atherosclerosis may modify the course of changes of global endothelial function after percutaneous revascularization of the lower extremities.…”