Does changes of dipeptidyl peptidase-4 and IGF binding protein 1 during cardiac rehabilitation can predict recurrent anginal pain – correlation with nitric oxide response – 3 years follow up
Authors: Simonovic D , Deljanin Ilic M , Ilic S , Kocic G , Petrovic D , Ilic B 
Published: November 2020

Abstract

Background
Dipeptidyl peptidase 4 (DPP4) is a proteolytic enzyme, and its expression and activity is increased in coronary artery disease (CAD). Insulin-like growth factor binding protein 1 (IGF BP1) can affect prognosis and mortality from cardiovascular diseases.

Purpose
To evaluate the effects of cardiac rehabilitation on DPP4 and circulating IGF BP1 levels, also on circulating blood marker of endothelial function, nitric oxide (NOx); to assess their relationship and prognostic significance on recurrent chest pain.

Methods
51 subjects; 31 pts with stable CAD (CAD group; 58.4±6.8 years) and 20 healthy controls (C group; 57.4±8.1 years) were studied. All patients underwent a supervised 3 weeks exercise training. At baseline and after 3 weeks in all pts values of DPP4, IGF BP1 and NOx were determined and exercise test was performed. Clinical long-term follow-up (3 years) was performed. All medical therapy were documented, and for this analysis, we focused on recurrent anginal chest pain.

Results
After follow-up period there were no cardiovascular (CV) hard end points (CV death, MI, stroke), however 18 pts (58%) had episodes of typical anginal chest pain while 13 pts (42%) were without anginal chest pain. Baseline value of DPP4 and IGF BP1 was significantly higher in CAD than in C group (P&lt;0.01 and P&lt;0.01), while NOx was lower (58.61±7.64 vs 77.28±29.86 μmol/L P=0.024). After 3 weeks of exercise training DPP4 decreased significantly in CAD group (from 762.32±185.76 to 604.88±206.18 μg/L, P&lt;0.001), as well as IGF BP1 (P=0.018) and NOx inreased (P&lt;0.01). Those changes resulted in no significant difference in DPP4, IGF BP1 and NOx after three weeks between CAD and C group. Exercise capacity (METs) at baseline was significantly lower in CAD than in C group (P&lt;0.001), and it significantly increase in CAD group after exercise period (P&lt;0.001).A positive correlation during exercise period was found between IGF BP1 decrease and NOx increase (r=0.790, P&lt;0.001), between IGF BP1 decrease and DPP 4 decrease (r=0.880, P&lt;0.001), between IGF BP1 decrease and METs increase (r=0.866, P&lt;0.001), between DPP 4 decrease and NOx increase (r=0.975, P&lt;0.001), between DPP 4 decrease and METs increase (r=0.718, P&lt;0.001), and between METs increase and NOx increase (r=0.846, P&lt;0.001). Univaried logistic regression analyses were performed and showed that NOx increase (OR 0.842, CI 0.562–0.944, p&lt;0.01), DPP4 decrease (OR 0.718, CI 0.644–0.826, p=0.01), IGF BP1 decrease (OR 0.695, CI 0.475–0.822, p=0.002) and METS increase (OR 0.924, CI 0.788–0.988, p=0.015) significantly predict a 3 years period without anginal chest pain.

Conclusion
Residential cardiovascular rehabilitation, in patients with stable CAD, improved endothelial function. Patients with higher increase of NOx and METs, and greater reduction in DPP4 and IGF BP1 after 3 weeks of specialized cardiac rehabilitation, during 3 years follow up, were without anginal chest pain and without any CV event.

Funding Acknowledgement
Type of funding source: None