Background: Remote ischaemic pre-conditioning (RIC) has cardioprotective effects, however its mechanisms are incompletely understood.
Purpose: To determine whether RIC enhances coronary endothelial function in patients with coronary artery disease (CAD).
Methods: 75 patients with stable angina undergoing elective invasive management were prospectively enrolled, and randomised to RIC or sham prior to angiography. RIC comprised 4 cycles of intermittent arm sphygmomanometer cuff inflation (200mg for 5 minutes), followed by a rest interval (5 minutes). Sham involved cuff placement without inflation (5 minutes). Endothelial function testing by a blinded operator, involved a control intracoronary (IC) saline infusion, followed by IC acetylcholine (ACh) in incremental doses [10–6, 10–5, 10–4 M] via a 3F infusion catheter. Endothelial independent vasodilation was tested with IC glyceryl trinitrate bolus. Venous blood pre- and post-RIC/sham was obtained and analysed for circulating molecules regulating endothelial function (MPO, IL-6, tPA, vWF). Quantitative coronary angiography (QCA) was performed (blinded) to assess mean coronary luminal diameter change in the coronary segment distal to the infusion catheter or the main epicardial segment demonstrating the most marked diameter change. The primary outcome was the mean percentage change in coronary luminal diameter following ACh infusion. Results are expressed as mean (SD) and were analysed by an independent statistician using an ANOVA model. A two-sided p value <0.05 was considered significant. NCT02666235.
Results: 75 patients provided consent, and 60 (mean age 57.5 years, 80% male) were eligible and completed the protocol (n=30 RIC, n=30 sham) The LAD, LCx and RCA were evaluated in 13 (21.7%), 20 (33.3%), and 27 (45.0%) patients, respectively. The mean percentage change in coronary luminal diameter was -13.3% (22.3) and -2.0% (17.2) in the sham and RIC groups respectively, with a significant mean percentage difference (11.32%, 95% CI: 1.2 to 21.4, p=0.0317). There were no between-group changes in non-endothelial dependent vasodilation or the circulating markers of endothelial function.
Conclusion: RIC improves coronary artery endothelial function in patients with stable CAD. Potentially, enhanced coronary endothelial function may contribute to the cardioprotective effects of RIC in patients with CAD. This result is not associated with changes circulating molecules that reflect endothelial function.