The effect of external counterpulsation on angiopoietin-1 and angiopoietin-2 levels in nondiabetic patients with refractory angina
Authors: Witarsa T R , Arityanti D , Ambari A M 
Published: May 2023

Abstract

Funding Acknowledgements
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Health Research and Development of the Ministry of Health of Indonesia.

Background
External counterpulsation (ECP) is a noninvasive therapy that employs external compression on the lower extremities to augment coronary perfusion pressure. Numerous studies reported that ECP possesses potential benefits in enhancing the angiogenesis process by promoting expressions of several growth factors. Nondiabetic patients are believed to be more reliable in portraying the angiogenesis process. Unfortunately, the effect of ECP on angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) as angiogenesis markers has not been elucidated.

Purpose
The objective of this study is to evaluate the effect of ECP on Ang-1 and Ang-2 levels in nondiabetic patients with refractory angina.

Methods
This is a randomised, double-blind, sham-controlled clinical trial. Nondiabetic patients with refractory angina, who were not contraindicated to ECP therapy, were enrolled and randomised into ECP or sham groups. The treatment consisted of optimal medical therapy plus 35 sessions of ECP or sham, with an hour duration for each session. The pressure applied was up to 300 mmHg in the ECP group, while only 75 mmHg in the sham group. Subjective symptoms, laboratory, echocardiographic, and functional capacity parameters were measured before and after 35 sessions of treatment. Appropriate statistical tests were performed and a p-value of &lt;0.05 was considered statistically significant.

Results
A total of 26 nondiabetic patients with refractory angina were enrolled and randomised into ECP (n=11) and sham (n=15) groups. All patients successfully followed every treatment session until the 35th session. The baseline characteristics were comparable between the two groups (p&gt;0.05). After 35 sessions, there were increases in Ang-1 median levels in both ECP (1663.4 pg/ml versus 891.6 pg/ml, p=0.477) and sham groups (1577.0 pg/ml versus 1295.0 pg/ml, p=0.496). The Ang-2 median levels after the treatments were slightly lower in ECP (2849.5 pg/ml versus 2902.3 pg/ml, p=0.594), while higher in sham groups (2728.3 pg/ml versus 2376.2 pg/ml, p=0.826). Meanwhile, the ECP group also showed an improvement in the Canadian Cardiovascular Society (CCS) angina class from class III to class I/II in 18% (2 out of 11) patients, while in the sham group only 13% (2 out of 15) patients. Interestingly, the ECP group seemed to elicit a noticeable increase in Ang-1 median levels and a decrease in Ang-2 median levels. However, the effects of ECP shown in this study were not statistically significant (p&gt;0.05).

Conclusion
The ECP group exhibited a higher trend of increase in Ang-1 level compared to the sham group. The Ang-2 level was slightly lowered in the ECP group, while increased in the sham group. Although it was not statistically significant, the increasing trend in the Ang-1 level may provide an additional understanding of the ECP angiogenic effects. Therefore, further studies to validate these results are warranted.