Effects of Remote Ischaemic Preconditioning on Arterial Stiffness in Patients Undergoing Lower Limb Angiographic Procedures: A Randomised Clinical Trial

Abstract

WHAT THIS PAPER ADDS This study evaluates for the first time the effects of remote ischaemic preconditioning (RIPC) on arterial stiffness parameters in patients with symptomatic peripheral arterial disease (PAD) undergoing digital subtraction angiography (DSA). The study shows that RIPC may modulate arterial stiffness and this effect is more pronounced in patients after stenting. As DSA is an additional risk factor in PAD patients with concomitant high cardiovascular risk, RIPC as adjunctive treatment may improve vascular function in these patients and have some clinical impact. Objectives: Remote ischaemic preconditioning (RIPC) is a phenomenon that promotes protection of tissues and organs against ischaemia reperfusion injury. RIPC has been shown to reduce myocardial and renal injury but its effect on arterial stiffness in patients undergoing lower limb digital subtraction angiography (DSA) is unknown. The aim of this study was to evaluate the effect of RIPC on arterial stiffness in patients with peripheral arterial disease (PAD) undergoing lower limb DSA. Methods: In the RIPC intervention, the blood pressure cuff on the arm was inflated to 200 mmHg or to 20 mmHg above systolic pressure, and in the sham intervention to 20 mmHg. For both, the procedure was repeated for four five minute cycles at five minute intervals between the cycles. Changes in heart rate corrected augmentation index (AIx@75), augmentation index (AIx), carotid femoral pulse wave velocity (PWV), and haemodynamic parameters were measured before and 24 h after DSA. Results: 111 (RIPC 54, sham 57) patients with symptomatic lower limb PAD scheduled for DSA were randomised. 102 patients (RIPC 47, sham 55) were included in final analysis. RIPC significantly improved AIx (À5.46% in RIPC and À1.45% in sham group; p ¼ .05), but not AIx@75 (À4.88% in RIPC and À1.38% in sham group; p ¼ .07) or PWV (À0.41 m/s in RIPC and À0.27 m/s in sham group; p ¼ .74). In the RIPC group a significant reduction in AIx (p ¼ .002) and AIx@75 (p ¼ .003) was noted after stenting when compared with the sham intervention. AIx (p ¼ .001), AIx@75 (p ¼ .002), mean arterial (p ¼ .01), peripheral (p ¼ .02), and central systolic blood pressure (p ¼ .006) were significantly reduced only in the RIPC group 24 h after DSA. Conclusion: This study evaluates for the first time the effects of RIPC on arterial stiffness parameters in patients with symptomatic PAD following DSA. RIPC may modulate arterial stiffness following a DSA procedure and is more pronounced in patients after stent placement.

Chronic Limb Remote Ischemic Conditioning may have an Antihypertensive Effect in Patients with Hypertension

“…The study of England et al showed that once-only LRIC therapy had neither short-term nor delayed effect on central arterial pressure in patients with acute ischemic stroke (AIS) [ 30 ]. Other studies also draw similar conclusions that once or twice LRIC treatment only was not enough to reduce BP in patients with CVD [ 23 , 31 - 33 ]. Meng et al compared changes in BP before and after each LRIC treatment in patients with symptomatic intracranial artery stenosis (SIAS) and found that LRIC had no short-term hypotensive effect.…”

“…First, different ranges of subjects were included. Both healthy volunteers and CVD patients were enrolled in 2 studies [ 25 , 26 ], healthy volunteers with normal BP were included in 6 studies [ 18 , 20 - 22 , 24 , 27 ], patients with hypertension or CVD were enrolled in 14 studies [ 11 - 16 , 19 , 23 , 28 - 33 ]. Second, different LRIC schemes were used.…”

“…Second, different LRIC schemes were used. LRIC therapy for once or twice only was performed in 10 studies [ 21 - 23 , 25 - 27 , 30 - 33 ], a long-term repeated LRIC therapy was applied in 12 studies [ 11 - 16 , 18 - 20 , 24 , 28 , 29 ]. Thus, we classified these relevant articles according to different participant selection and LRIC schemes to clarify whether LRIC has an antihypertensive effect in specific populations, the details of these studies are listed in Table 1 and 2 .…”

“…In summary of 8 clinical studies including 192 subjects, the first speculation is that neither LRIC performed once nor repeated for a long time has a significant BP-lowering effect on healthy volunteers with normal BP [ 18 , 20 - 22 , 24 - 27 ]. Secondly, after analyzing 8 studies involving 402 patients with CVD or hypertension, we confer that LRIC treatment performed only once seems insufficient to trigger the BP-lowering effect [ 23 , 25 , 26 , 28 , 30 - 33 ]. In addition, we presume that long-term repeated LRIC therapy may provide an alternative applicable intervention to treat hypertension, evidence of which was from 71 subjects involved in 8 studies [ 11 - 17 , 19 , 29 ].…”

Remote Ischaemic Preconditioning in Vascular Surgery: Relevant Perspective or a Holy Grail?

“…In their study, Kuusik et al have reported the results of a randomised, double blind, single centre trial in which 111 patients who underwent digital subtraction angiography were included either in a group that received remote ischaemic preconditioning (RIPC) or in a sham group, to evaluate the effects of RIPC on arterial stiffness parameters. 1 The authors showed that RIPC did not modify the carotid-femoral pulse wave velocity (PWV), considered to be the gold standard parameter of arterial stiffness, but decreased surrogate markers of arterial stiffness, such as the augmentation index (Aix), and augmentation index corrected to heart rate (Aix@75) in cases where stenting was performed. 1 These results are of importance regarding the controversy surrounding the efficacy of RIPC in vascular surgery and contribute to opening future research; however, many confounding factors might have biased the results, such as degree of ischaemia, site of atherosclerotic lesions, type and location of stents, as well as patient comorbidities.…”