Identification of sex-specific biomarkers predicting new-onset heart failure.

Raafs, Anne; Verdonschot, Job; Ferreira, João Pedro; Wang, Ping; Collier, TimothyORCID logo; Henkens, Michiel; Björkman, Jens; Boccanelli, Alessandro; Clark, Andrew L; Delles, Christian; +15 more...Diez, Javier; González, Arantxa; Girerd, Nicolas; Jukema, J Wouter; Pinet, Florence; Rossignol, Patrick; Thum, Thomas; Vodovar, Nicolas; de Boer, Rudolf A; van Empel, Vanessa; Staessen, Jan A; Hazebroek, Mark; Cleland, John; Zannad, Faiez; and Heymans, Stephane (2021) Identification of sex-specific biomarkers predicting new-onset heart failure. ESC heart failure, 8 (5). pp. 3512-3520. ISSN 2055-5822 DOI: 10.1002/ehf2.13476
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AIMS: Heart failure (HF) is common in both men and women, yet disease pathophysiology, presentation, and progression differ between sexes. Studies addressing whether biomarkers predict new onset HF sex-specifically are scarce. This study therefore aims to test the sex-specificity of 252 protein biomarkers for new-onset HF. METHODS AND RESULTS: A matched case-control design in patients selected from cohorts within the HOMAGE consortium was used. Cases (new-onset HF, n = 562) and controls (n = 780) were matched for cohort (PREDICTOR, HEALTH-ABC, & PROSPER), follow-up time (defined as time from entry to incident HF), and age. Incident HF was defined as first hospitalization for HF. Targeted plasma proteins (n = 252) were measured using Proximity Extension Assay technology from O-link. To look for sex differences for new onset HF, we adjusted for cohort, age, and baseline clinical parameters. At baseline, women had a biomarker profile reflecting activated metabolism and immune responses. However, none of the biomarkers had a significant interaction with sex in predicting new onset HF, but four biomarkers had a trend towards sex-specificity (P < 0.013). E-selectin and interleukin 1 receptor antagonist were more female-specific, whereas IL17A and CHIT1 tended to be male sex-specific for incident HF. CONCLUSIONS: The majority of biomarkers associated with incident HF did not significantly differ between women and men, despite clear differences in biomarkers at baseline.


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