Christian S. Hansen, MD, on the Effect of RIC on Vascular Function
Peripheral arterial disease (PAD) and diabetes mellitus are common comorbidities. Patients with severe disease can oftentimes need limb amputation due to poor circulation. In a new study, published in the Journal of the American Heart Association, researchers investigated the effect of remote ischemic conditioning (RIC) on patients with type 2 diabetes and PAD.
Cardiology Consultant caught up with lead author Christian S. Hansen, MD, PhD-student, from the Steno Diabetes Center Copenhagen in Denmark, to ask him about the study.
CARDIOLOGY CONSULTANT: You and your colleagues investigated a non-surgical option for improving vascular and neuronal function in patients with type 2 diabetes and PAD. How did this study come about, and what did the results show?
Christian Hansen: PAD is a major socioeconomic challenge in the diabetes community, and non-surgical treatment options are limited. PAD can lead to ischemic foot ulcers and lower limb amputations. Diabetic foot ulcers and their derived costs constitute the most expensive diabetic complication. In several countries, including the United Kingdom, we see a surge of costs related to this complication. Therefore, new preventive measures are needed. RIC may serve as a new treatment modality for PAD. Especially in patients with diabetes, new treatment options are needed. As RIC improves vascular function and attenuates ischemia-induced tissue damage, we wanted to investigate the efficacy of RIC on vascular and neuronal function in type 2 diabetes patients with PAD.
We enrolled 36 patients with type 2 diabetes with moderately reduced toe pressure (40 mmHg to 70 mmHg) in a randomized, placebo-controlled, double-blinded trial. Patients were randomly assigned to a 12-week, home-based, once-daily treatment of either RIC or similar sham device. The RIC treatment consisted of 4 cycles of 5-minute ischemia followed by 5-minute reperfusion. The primary outcome was transcutaneous tissue oxygen tension (TcPO2) of the instep of the foot. Secondary outcomes were aortic pulse wave velocity, toe pressure, and toe-brachial index. Tertiary outcomes were markers of peripheral and autonomic nerve function.
We found no effect of RIC on study outcomes and concluded that long-term repeated RIC treatment has no effect on tissue oxygenation, or vascular or neuronal function in patients with type 2 diabetes and moderate PAD.
CARDIO CON: Can you give us some background on RIC? Is it currently being used in other areas of medicine?
CH: RIC is a non-invasive non-pharmacological treatment that attenuates tissue damage caused by ischemia-reperfusion injury. RIC is capable of reducing infarct size in patients with acute myocardial infarction, reducing organ damage in patients undergoing kidney transplantation, and having neuroprotective effects in patients with stroke.
RIC is achieved by brief repetitive periods of ischemia induced in an extremity (e.g., an arm). It is believed that the effect of RIC is mediated through both neuronal and humoral pathways. In addition to the effect on ischemia-reperfusion injury, RIC has been shown to have beneficial effects by attenuating platelet activation and aggregation, improving endothelial function, and improving microcirculation. Taken together, these findings led us to the hypothesis that RIC could have beneficial effects on the pathogenic mechanisms leading to PAD in patients with diabetes.
RIC is not used routinely in patient care but seems to have promising potential in patients with acute myocardial ischemia.
CARDIO CON: What is the next step in your research? What other non-surgical interventions might help improve outcomes in this patient population?
CH: We are not planning on doing new studies on diabetes patients with PAD. These patients may have too advanced cardiovascular disease to benefit from RIC treatment. However, we are planning to test the treatment on vascular function in patients with prediabetes and metabolic syndrome. These patients may benefit from RIC, as they only have very early stages of vascular dysfunction.
CARDIO CON: In general, what other clinical knowledge gaps exist in this area of medicine?
CH: We need more long-term studies investigating the efficacy of RIC. Most studies carried out are acute studies, and from these studies we cannot conclude that RIC may benefit patients in the long run. In addition, studies in pure diabetes cohorts are warranted because very few of these studies have been carried out.
Reference:
- Hansen CS, Jørgensen ME, Fleischer J, Bøtker HE, Rossing P. Efficacy of long‐term remote ischemic conditioning on vascular and neuronal function in type 2 diabetes patients with peripheral arterial disease [published online July 2, 2019]. J Am Heart Assoc. https://doi.org/10.1161/JAHA.118.011779.