The metabolites urobilin and sphingomyelin (30:1) are associated with incident heart failure in the general population

ESC Heart Failure

Andrea Ganna¹  Per Svensson²  Patrik K.E. Magnusson³  Johan Sundström⁴  Lars Lind⁵  Tove Fall⁶  Markus Stenemo⁶  Erik Ingelsson⁶  Samira Salihovic⁶  Vilmantas Giedraitis⁷  Christoph Nowak⁸  Johan Ärnlöv⁸  Jessica E. Prenni⁹  Corey D. Broeckling⁹ 

[1] Analytic and Translational Genetics Unit Massachusetts General Hospital Boston MA USA;Department of Clinical Science and Education, Department of Cardiology Södersjukhuset, Karolinska Institutet Stockholm Sweden;Department of Medical Epidemiology and Biostatistics (MEB) Karolinska Institutet Stockholm Sweden;Department of Medical Sciences Uppsala University Uppsala Sweden;Department of Medical Sciences, Cardiovascular Epidemiology Uppsala University Uppsala Sweden;Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory Uppsala University EpiHubben, MTC‐huset 75185 Uppsala Sweden;Department of Public Health and Caring Sciences, Geriatrics Uppsala University Uppsala Sweden;Division of Family Medicine and Primary Care, Department of Neurobiology, Care Sciences and Society (NVS) Karolinska Institutet Stockholm Sweden;Proteomics and Metabolomics Facility Colorado State University Fort Collins CO USA;

关键词: Biomarkers;    Metabolomics;    Heart failure;    Risk prediction;    Epidemiology;   

DOI  :  10.1002/ehf2.12453

来源: DOAJ

【 摘 要 】

Abstract Aims We aimed to investigate whether metabolomic profiling of blood can lead to novel insights into heart failure pathogenesis or improved risk prediction. Methods and results Mass spectrometry‐based metabolomic profiling was performed in plasma or serum samples from three community‐based cohorts without heart failure at baseline (total n = 3924; 341 incident heart failure events; median follow‐up ranging from 4.6 to 13.9 years). Cox proportional hazard models were applied to assess the association of each of the 206 identified metabolites with incident heart failure in the discovery cohorts Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) (n = 920) and Uppsala Longitudinal Study of Adult Men (ULSAM) (n = 1121). Replication was undertaken in the independent cohort TwinGene (n = 1797). We also assessed whether metabolites could improve the prediction of heart failure beyond established risk factors (age, sex, body mass index, low‐density and high‐density lipoprotein cholesterol, triglycerides, lipid medication, diabetes, systolic and diastolic blood pressure, blood pressure medication, glomerular filtration rate, smoking status, and myocardial infarction prior to or during follow‐up). Higher circulating urobilin and lower sphingomyelin (30:1) were associated with incident heart failure in age‐adjusted and sex‐adjusted models in the discovery and replication sample. The hazard ratio for urobilin in the replication cohort was estimated to 1.29 per standard deviation unit, 95% confidence interval (CI 1.03–1.63), and for sphingomyelin (30:1) to 0.72 (95% CI 0.58–0.89). Results remained similar after further adjustment for established heart failure risk factors in meta‐analyses of all three cohorts. Urobilin concentrations were inversely associated with left ventricular ejection fraction at baseline in the PIVUS cohort (β = −0.70, 95% CI −1.03 to −0.38). No major improvement in risk prediction was observed when adding the top 2 metabolites (C‐index 0.787, 95% CI 0.752–0.823) or nine Lasso‐selected metabolites (0.790, 95% CI 0.754–0.826) to a modified Atherosclerosis Risk in Communities heart failure risk score model (0.780, 95% CI 0.745–0.816). Conclusions Our metabolomic profiling of three community‐based cohorts study identified associations of circulating levels of the haem breakdown product urobilin, and sphingomyelin (30:1), a cell membrane component involved in signal transduction and apoptosis, with incident heart failure.

【 授权许可】

Unknown