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Diabetes is associated with unique pathological mechanisms in heart failure.

Session Poster Session 3

Speaker Jasper Tromp

Event : Heart Failure 2019

  • Topic : heart failure
  • Sub-topic : Chronic Heart Failure: Comorbidities
  • Session type : Poster Session

Authors : J Tromp (Singapore,SG), AA Voors (Groningen,NL), A Sharma (Montreal,CA), JP Ferreira (Nancy,FR), W Ouwerkerk (Amsterdam,NL), HL Hillege (Groningen,NL), P Van Der Harst (Groningen,NL), DJ Van Veldhuisen (Groningen,NL), P Van Der Meer (Groningen,NL), I Sama (Groningen,NL)

J Tromp1 , AA Voors2 , A Sharma3 , JP Ferreira4 , W Ouwerkerk5 , HL Hillege2 , P Van Der Harst2 , DJ Van Veldhuisen2 , P Van Der Meer2 , I Sama2 , 1National Heart Centre Singapore, Cardiology - Singapore - Singapore , 2University Medical Center Groningen - Groningen - Netherlands (The) , 3Mcgill University - Montreal - Canada , 4Clinical Investigation Centre Pierre Drouin (CIC-P) - Nancy - France , 5Academic Medical Center of Amsterdam - Amsterdam - Netherlands (The) ,


Background. Diabetes mellitus (DM) adversely affects clinical outcomes and complicates treatment in patients with heart failure (HF). A clear understanding of the pathophysiologic processes involved with DM type 2 in HF is lacking.

Methods. We performed network analyses and pathway over-representation analysis to identify unique pathological pathways in patients with HF and DM using 92 biomarkers from different pathophysiological domains measured in 1572 patients with HF (32% DM) and reduced ejection fraction (HFrEF; LVEF <40%). We validated our results in an independent cohort of 729 patients with HFrEF (30% DM). In addition, we investigated the association of DM with a composite outcome with all-cause mortality or hospitalization for HF within 2 years and whether this association was modified by biomarkers significantly related to DM.

Results. In both the index and validation cohort, 8 proteins were up-regulated and 1 protein was down-regulated in HF patients with diabetes compared to non-diabetics Network analyses identified epidermal growth factor receptor (EGFR) as a central protein in patients with DM and HF (Figure 1A). Biological pathways upregulated in patients with HF and DM were related to inflammation and protein phosphorylation (Figure 1B). DM conferred worse outcomes after correction for an establish risk model (hazard ratio [HR] 1.20; 95% CI 1.01-1.42). These differences in outcome were modified by differences in biomarker levels.

Conclusion. Concomitant DM in patients with HFrEF worsens clinical outcomes and is associated with pathological processes related to inflammation and protein phosphorylation. The role of EGFR in the relationship between DM and HF warrants further evaluation.

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