PENK levels reflect cardiorenal status in acute HF and are prognostic for worsening renal function and in-hospital mortality as well as mortality during follow-up.

This study shows marked differences in composition of the HDL proteome between HF survivors and deaths. The strongest differences were seen in proteins reflecting crosslinking of actin filaments and alveolar capillary membrane function, posing potential pathophysiological mechanisms underlying the association between HDL and clinical outcome in HF.

The opioid system is activated in heart failure, which may be cardioprotective but may also be counter-regulatory. Recently, systemic proenkephalin activation has been investigated in various conditions predicting mortality and kidney injury. In acute heart failure, proenkephalin independently predicts mortality and heart failure rehospitalization in addition to traditional risk markers. It also predicts worsening renal function, increasingly recognized as an important risk predictor for poor outcome in heart failure. This article explores the role of enkephalins and delta-opioid receptors in the heart, then reviews studies measuring proenkephalin levels in the circulation and their associations with prognosis.

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Aims To provide insights into pathogenesis of disease progression and potential novel treatment targets for patients with heart failure by investigation of the plasma proteome using network analysis. Methods and results The plasma proteome of 50 patients with heart failure who died or were rehospitalised were compared with 50 patients with heart failure, matched for age and sex, who did not have an event. Peptides were analysed on two‐dimensional liquid chromatography coupled to tandem mass spectrometry (2D LC ESI‐MS/MS) in high definition mode (HDMSE). We identified and quantified 3001 proteins, of which 51 were significantly up‐regulated and 46 down‐regulated with more than two‐fold expression changes in those who experienced death or rehospitalisation. Gene ontology enrichment analysis and protein–protein interaction networks of significant differentially expressed proteins discovered the central role of metabolic processes in clinical outcomes of patients with heart failure. The findings revealed that a cluster of proteins related to glutathione metabolism, arginine and proline metabolism, and pyruvate metabolism in the pathogenesis of poor outcome in patients with heart failure who died or were rehospitalised. Conclusions Our findings show that in patients with heart failure who died or were rehospitalised, the glutathione, arginine and proline, and pyruvate pathways were activated. These pathways might be potential targets for therapies to improve poor outcomes in patients with heart failure.

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Background Proenkephalin (PENK), a stable endogenous opioid biomarker related to renal function, has prognostic utility in acute and chronic heart failure. We investigated the prognostic utility of PENK in heart failure with preserved ejection fraction (HFpEF), and its relationship to renal function, Body Mass Index (BMI), and imaging measures of diastolic dysfunction. Methods In this multicentre study, PENK was measured in 522 HFpEF patients (ejection fraction > 50%, 253 male, mean age 76.13 ± 10.73 years) and compared to 47 age and sex-matched controls. The primary endpoint was 2-years composite of all-cause mortality and/or heart failure rehospitalisation (HF). A subset ( n = 163) received detailed imaging studies. Results PENK levels were raised in HFpEF (median [interquartile range] 88.9 [62.1–132.0]) compared to normal controls (56.3 [47.9–70.5]). PENK was correlated to urea, eGFR, Body Mass Index and E / e ′ ( r s 0.635, − 0.741, − 0.275, 0.476, respectively, p < 0.0005). During 2 years follow-up 144 patients died and 220 had death/HF endpoints. Multivariable Cox regression models showed PENK independently predicted 2 year death/HF [hazard ratio (for 1 SD increment of log-transformed biomarker) HR 1.45 [95% CI 1.12–1.88, p = 0.005]], even after adjustment for troponin (HR 1.59 [1.14–2.20, p = 0.006]), and Body Mass Index (HR 1.63 [1.13–2.33, p = 0.009]). PENK showed no interaction with ejection fraction status for prediction of poor outcomes. Net reclassification analyses showed PENK significantly improved classification of death/HF outcomes for multivariable models containing natriuretic peptide, troponin and Body Mass Index ( p < 0.05 for all). Conclusions In HFpEF, PENK levels are related to BMI, and measures of diastolic dysfunction and are prognostic for all-cause mortality and heart failure rehospitalisation. Electronic supplementary material The online version of this article (10.1007/s00392-019-01424-y) contains supplementary material, which is available to authorized users.

Providing a molecular characterisation of cardiometabolic syndrome (CMS) could improve our understanding of its pathogenesis and pathophysiology, and provide a step toward the development of better treatments. To this end, we performed a deep phenotyping analysis of 185 blood donors, 10 obese, and 10 lipodystrophy patients.We analysed transcriptomes and epigenomes of monocytes, neutrophils, macrophages and platelets. Additionally, plasma metabolites including lipids and biochemistry measurements were quantified.Multi-omics integration of this data allowed us to identify combinations of features related to patient status and to order the donor population according to their molecular similarity to patients. We also performed differential analyses on epigenomic, transcriptomic and plasma proteomic data collected from obese individuals before and six months after bariatric surgery. These analyses revealed a pattern of abnormal activation of immune cells in obese individuals and lipodystrophy patients, which was partially reverted six months after bariatric surgery.