217Metabolomic profile of patients with new onset heart failure; more microvascular dysfunction in patients with preserved ejection fraction compared to reduced ejection fraction - the PREFERS Study

Abstract

Abstract Background Heart failure with preserved (HFpEF) and reduced (HFrEF) ejection fraction are both associated with metabolic derangements which may have different pathophysiological implications Purpose To identify metabolites and pathways differentially altered with the potential to differentiate HFpEF from HFrEF. Methods In the PREFERS Stockholm study (Preserved and Reduced Ejection Fraction Epidemiological Regional Study) 121 endogenous plasma metabolites were assessed by targeted mass spectrometry. Partial Least Squares Discriminant Analysis (PLS-DA) was used to identify metabolites differentially altered in new onset HF divided into HFpEF (EF ≥50%, n=46) versus HFrEF (ÈF<40%, n=75) patients. Multivariable logistic regression was used to assess independent associations between HF group and selected metabolites, including sex, age and eGFR as co-variates. Results Compared to HFrEF, HFpEF patients were older; 77 vs 65 years (p<0.001), more often female 54% vs 46% (p=0.004) with hypertension 60% vs 40% (p<0.001) and diabetes 63% vs 37% (p=0.007), and lower NT-proBNP 720 vs 1295 ng/L (p=0.014) and eGFR 63 vs 72 mL/min/1.73 m2 (p<0.001). HFpEF patients had higher levels of hydroxyproline, cysteine, symmetric dimethyl arginine, alanine, kynurenine and acylcarinitines and lower levels of cAMP, lysoPC, L-carnitine, arginine, cGMP, serine and lactate (Figure). HFpEF was independently associated with reduced levels of cGMP (OR 0.98 [95% CI: 0.97–0.99; p=0.008]), serine (0.97 [0.95–1.00; 0.047]) and cAMP (0.97 [0.94–0.99; 0.009]). Figure 1 Conclusions In new onset HF patients, HFpEF was associated with decreased cGMP, cAMP and serine indicating increased oxidative stress, impaired innate immune function and myocardial hypertrophy. HFpEF patients displayed a distinct metabolic profile reflecting increased endothelial dysfunction, hypoxia, inflammation and myocardial fibrosis pointing towards more involvement of microvascular dysfunction compared to HFrEF. Acknowledgement/Funding Science for Life Laboratory–Astra Zeneca; Mölndal, Sweden collaborative grant No. 1377