Insulin Growth Factor Phenotypes in Heart Failure With Preserved Ejection Fraction, an INSPIRE Registry and CATHGEN Study

Background:The insulin like growth factor (IGF) axis emerged as an important pathway in heart failure with preserved ejection (HFpEF).We aimed to identify IGF phenotypes associated with HFpEF in the context high-dimensional proteomic profiling. Methods:From the Intermountain INSPIRE Registry, we identified 96 patients with HFpEF and matched controls.We performed targeted proteomics including IGF-1,2, IGF binding proteins (IGFBP) 1-7 and 111 other proteins (EMD Millipore and ELISA).We used partial least square discriminant analysis (PLS-DA) to identify a set of proteins associated with prevalent HFpEF, pulmonary hypertension (PH) and 5-year-all-cause mortality.K-mean clustering was used to identify IGF phenotypes.Results: Patients with HFpEF had a high prevalence of systemic hypertension (95%) and coronary artery disease (74%).Using PLS-DA, we identified a set of biomarkers including IGF1,2 and IGFBP-1,2,7 that provided a strong discrimination of HFPEF, PH and mortality with an AUC of 0.91, 0.77 and 0.83, respectively.Using K mean clustering, we identified three IGF phenotypes that were independently associated with all-cause 5-year mortality after adjustment for age, NT-proBNP and kidney disease (p=0.004).Multivariable analysis validated the prognostic value of IGFBP-1 and 2 in the CATHGEN biorepository. Conclusion:IGF phenotypes were associated with PH and mortality in HFpEF.