GLP-1 vasodilatation in humans with coronary artery disease is not adenosine mediated

Q: What does this research mean for the field?

The coronary vasodilatory effect of GLP-1 in patients with coronary artery disease is not mediated by adenosine. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Muhammad Aetesam‐ur‐Rahman; Joel P. Giblett; Bharat Khialani; S. Kyranis; Sophie Clarke; Tian Zhao; Denise Braganza; Sarah Clarke; Nick E.J. West; Martin R. Bennett; Stephen P. Hoole

doi:10.1186/s12872-021-02030-5

May 1, 2021BMC Cardiovascular DisordersOpen Access

GLP-1 vasodilatation in humans with coronary artery disease is not adenosine mediated

View Full Paper

Ask AI

Bookmark

Share

Why the study?

Although GLP-1 is known to be a coronary vasodilator, whether this effect is mediated by adenosine remained unknown.

Does GLP-1 infusion reduce coronary microvascular resistance via an adenosine-mediated mechanism in patients having PCI for stable angina?

Structured PICO

Does GLP-1 infusion reduce coronary microvascular resistance via an adenosine-mediated mechanism in patients having PCI for stable angina?

P

Population

41 patients having percutaneous coronary intervention (PCI) for stable angina. Most patients were not diabetic.

I

Intervention

GLP-1 infusion (n=10) or GLP-1 + Theophylline infusion (n=10) administered following successful PCI

C

Comparator

Placebo (normal saline infusion, n=11) or Theophylline infusion alone (n=10)

O

Outcome

Coronary distal pressure and flow velocity (thermodilution transit time-Tmn) at rest and hyperaemia, and derived basal and index of microvascular resistance (BMR and IMR)surrogate

GLP-1 induces coronary vasodilatation through an adenosine-independent mechanism in patients with stable angina undergoing PCI.

Implication

Challenges adenosine mediation of GLP-1 coronary effects; hypothesis-generating for microvascular actions in stable angina PCI.

Abstract

BACKGROUND: Incretin therapies appear to provide cardioprotection and improve cardiovascular outcomes in patients with diabetes, but the mechanism of this effect remains elusive. We have previously shown that glucagon-like peptide (GLP)-1 is a coronary vasodilator and we sought to investigate if this is an adenosine-mediated effect. METHODS: We recruited 41 patients having percutaneous coronary intervention (PCI) for stable angina and allocated them into four groups administering a specific study-related infusion following successful PCI: GLP-1 infusion (Group G) (n = 10); Placebo, normal saline infusion (Group P) (n = 11); GLP-1 + Theophylline infusion (Group GT) (n = 10); and Theophylline infusion (Group T) (n = 10). A pressure wire assessment of coronary distal pressure and flow velocity (thermodilution transit time-Tmn) at rest and hyperaemia was performed after PCI and repeated following the study infusion to derive basal and index of microvascular resistance (BMR and IMR). RESULTS: There were no significant differences in the demographics of patients recruited to our study. Most of the patients were not diabetic. GLP-1 caused significant reduction of resting Tmn that was not attenuated by theophylline: mean delta Tmn (SD) group G - 0.23 s (0.27) versus group GT - 0.18 s (0.37), p = 0.65. Theophylline alone (group T) did not significantly alter resting flow velocity compared to group GT: delta Tmn in group T 0.04 s (0.15), p = 0.30. The resulting decrease in BMR observed in group G persisted in group GT: - 20.83 mmHg s (24.54 vs. - 21.20 mmHg s (30.41), p = 0.97. GLP-1 did not increase circulating adenosine levels in group GT more than group T: delta median adenosine - 2.0 ng/ml (- 117.1, 14.8) versus - 0.5 ng/ml (- 19.6, 9.4); p = 0.60. CONCLUSION: The vasodilatory effect of GLP-1 is not abolished by theophylline and GLP-1 does not increase adenosine levels, indicating an adenosine-independent mechanism of GLP-1 coronary vasodilatation. TRIAL REGISTRATION: The local research ethics committee approved the study (National Research Ethics Service-NRES Committee, East of England): REC reference 14/EE/0018. The study was performed according to institutional guidelines, was registered on http://www.clinicaltrials.gov (unique identifier: NCT03502083) and the study conformed to the principles outlined in the Declaration of Helsinki.