Sex-based differences in cardiovascular proteomic profiles and their associations with adverse outcomes in patients with chronic heart failure

Biology of Sex Differences

Research

Folkert W. Asselbergs¹  Dimitris Rizopoulos²  Magdalena Harakalova³  Marie de Bakker⁴  K. Martijn Akkerhuis⁴  Navin Suthahar⁴  Rudolf A. de Boer⁴  Kadir Caliskan⁴  Eric Boersma⁴  Isabella Kardys⁴  Teun B. Petersen⁵  Victor A. Umans⁶  Tjeerd Germans⁶  Peter D. Katsikis⁷  Peter J. van der Spek⁸ 

[1] Amsterdam University Medical Centers, Department of Cardiology, University of Amsterdam, Amsterdam, The Netherlands;Health Data Research UK and Institute of Health Informatics, University College London, London, UK;Department of Biostatistics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands;Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands;Department of Cardiology, Division Heart and Lungs, Circulatory Health Research Center, University Medical Center Utrecht, University of Utrecht, Utrecht, The Netherlands;Regenerative Medicine Center Utrecht, University Medical Center Utrecht, University of Utrecht, Utrecht, The Netherlands;Department of Cardiology, Erasmus MC Cardiovascular Institute, University Medical Center Rotterdam, P.O. Box 2040, Room Na‐316, 3000 CA, Rotterdam, The Netherlands;Department of Cardiology, Erasmus MC Cardiovascular Institute, University Medical Center Rotterdam, P.O. Box 2040, Room Na‐316, 3000 CA, Rotterdam, The Netherlands;Department of Biostatistics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands;Department of Cardiology, Northwest Clinics, Alkmaar, The Netherlands;Department of Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands;Department of Pathology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands;

关键词: Sex differences;    Proteomics;    Heart failure;    HFrEF;   

DOI  :  10.1186/s13293-023-00516-9

 received in 2023-02-24, accepted in 2023-05-05,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundStudies focusing on sex differences in circulating proteins in patients with heart failure with reduced ejection fraction (HFrEF) are scarce. Insight into sex-specific cardiovascular protein profiles and their associations with the risk of adverse outcomes may contribute to a better understanding of the pathophysiological processes involved in HFrEF. Moreover, it could provide a basis for the use of circulating protein measurements for prognostication in women and men, wherein the most relevant protein measurements are applied in each of the sexes.MethodsIn 382 patients with HFrEF, we performed tri-monthly blood sampling (median follow-up: 25 [13–31] months). We selected all baseline samples and two samples closest to the primary endpoint (PEP: composite of cardiovascular death, heart transplantation, left ventricular assist device implantation, and HF hospitalization) or censoring. We then applied an aptamer-based multiplex proteomic assay identifying 1105 proteins previously associated with cardiovascular disease. We used linear regression models and gene-enrichment analysis to study sex-based differences in baseline levels. We used time-dependent Cox models to study differences in the prognostic value of serially measured proteins. All models were adjusted for the MAGGIC HF mortality risk score and p-values for multiple testing.ResultsIn 104 women and 278 men (mean age 62 and 64 years, respectively) cumulative PEP incidence at 30 months was 25% and 35%, respectively. At baseline, 55 (5%) out of the 1105 proteins were significantly different between women and men. The female protein profile was most strongly associated with extracellular matrix organization, while the male profile was dominated by regulation of cell death. The association of endothelin-1 (Pinteraction < 0.001) and somatostatin (Pinteraction = 0.040) with the PEP was modified by sex, independent of clinical characteristics. Endothelin-1 was more strongly associated with the PEP in men (HR 2.62 [95%CI, 1.98, 3.46], p < 0.001) compared to women (1.14 [1.01, 1.29], p = 0.036). Somatostatin was positively associated with the PEP in men (1.23 [1.10, 1.38], p < 0.001), but inversely associated in women (0.33 [0.12, 0.93], p = 0.036).ConclusionBaseline cardiovascular protein levels differ between women and men. However, the predictive value of repeatedly measured circulating proteins does not seem to differ except for endothelin-1 and somatostatin.

【 授权许可】

CC BY   
© The Author(s) 2023

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