Improvement of endothelial function parameters during cardiac rehabilitation predicts cardiovascular death and heart failure hospitalization in patients with HFpEF: 3 years follow up
Authors: Deljanin Ilic M , Kocic G , Simonovic D , Ilic S , Djordjevic B , Stojanovic M , Stojanovic S 
Published: November 2023

Abstract

Purpose
To evaluate the effects of cardiac rehabilitation on Dipeptidyl peptidase 4 (DPP4), circulating Insulin-like growth factor binding protein 1 (IGF BP1) levels and circulating blood marker of endothelial function, nitric oxide (NOx) and to assess their prognostic significance on composite endpoint cardiovascular death (CVD) and heart failure (HF) hospitalization.

Methods
88 patients (pts) (62,3±5,7 years) with HFpEF who were admitted at residential rehabilitation center were enrolled in the study. All pts underwent a supervised 3 weeks exercise training. At baseline and after 3 weeks 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 was documented, and for this analysis, we focused on CVD death and HF hospitalization.

Results
After follow-up period, 34 (38,6%) patients experienced composite endpoint (CE group: 11 CVD and 23 HF hospitalization), while 54 (61,4%) pts did not report any deterioration in health status (non-CE group). Baseline values of DPP4, IGF BP1 and NOx did not differ between the examined groups. After 3 weeks of exercise training DPP4 decreased significantly in both group (CE group, from 782,14±124,76 to 642,17±110,53 μg/L, p&lt;0,001; non-CE group, from 774,12±98,65 to 554,71±88,12 μg/L, p&lt;0,001); also IGF BP1 (CE group, from 904,77±115,34 to 689,14±96,55 ng/mL, p&lt;0,001; non-CE group from 898,17±108,55 to 558,18±88,62 ng/mL, p&lt;0,001); and NOx increased (CE group, from 35,4±6,5 to 41,4±5,2 µmol/L, p&lt;0,001; non-CE group, from 36,1±5,2 to 47,2±4,7 µmol/L, p&lt;0,001). All second values od DPP4, IGF BP1 and NOx differ significantly between the examined groups (p&lt;0,001 for all). Exercise capacity (METs) has increased significantly in both groups, but second value in CE group was significantly lower than in non-CE group (P&lt;0.001). A positive correlation was found between IGF BP1 decrease and NOx increase (r=0.554, P&lt;0.01), between IGF BP1 decrease and DPP 4 decrease (r=0.685, P&lt;0.01), between IGF BP1 decrease and METs increase (r=0.653, P&lt;0.01), between DPP4 decrease and NOx increase (r=0.775, P&lt;0.001), between DPP 4 decrease and METs increase (r=0.708, P&lt;0.01), and between METs increase and NOx increase (r=0.746, P&lt;0.001). After adjusment for age and gender, univaried COX-regression analyses showed that NOx increase (OR 0.832, CI 0.462-0.994, p&lt;0.01), DPP4 decrease (OR 0.718, CI 0.614–0.926, p=0.01), IGF BP1 decrease (OR 0.952, CI 0.889–0.999, p=0.002) and METS increase (OR 0.921, CI 0.774-0.977, p=0.014) significantly predict composite endpoint (CV death and HF hospitalization).

Conclusion
Residential CV rehabilitation, in patients with HFpEF, improved endothelial function. Pts 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 at lower risk of CV death and HF hospitalization.