Key result
In patients with heart failure with preserved ejection fraction, female sex was associated with differential expression of 9 circulating proteins but was not significantly associated with cardiovascular death or hospitalization compared to male sex (adjusted HR 1.48).
Why the study?
Many patients with HFpEF are women, but studies focusing on sex differences in circulating proteins in HFpEF are scarce.
Observational (n=392)
Yes
Hazard Ratio: 1.48 (95% CI 0.83–2.63)
Absolute Event Rate: 16.4% vs 13.4%
p-value: p=0.18
In patients with HFpEF, significant sex differences exist in circulating proteins related to lipid metabolism, transcriptional regulation, and extracellular matrix organization, though sex itself was not associated with 1-year cardiovascular outcomes.
Sex-specific protein differences in HFpEF are hypothesis-generating; leaves open relevance to outcomes and should not yet change practice.
BACKGROUND: Many patients with heart failure with preserved ejection fraction (HFpEF) are women. Exploring mechanisms underlying the sex differences may improve our understanding of the pathophysiology of HFpEF. Studies focusing on sex differences in circulating proteins in HFpEF patients are scarce. METHODS: A total of 415 proteins were analyzed in 392 HFpEF patients included in The Metabolic Road to Diastolic Heart Failure: Diastolic Heart Failure study (MEDIA-DHF). Sex differences in these proteins were assessed using adjusted logistic regression analyses. The associations between candidate proteins and cardiovascular (CV) death or CV hospitalization (with sex interaction) were assessed using Cox regression models. RESULTS: We found 9 proteins to be differentially expressed between female and male patients. Women expressed more LPL and PLIN1, which are markers of lipid metabolism; more LHB, IGFBP3, and IL1RL2 as markers of transcriptional regulation; and more Ep-CAM as marker of hemostasis. Women expressed less MMP-3, which is a marker associated with extracellular matrix organization; less NRP1, which is associated with developmental processes; and less ACE2, which is related to metabolism. Sex was not associated with the study outcomes (adj. HR 1.48, 95% CI 0.83-2.63), p = 0.18. CONCLUSION: In chronic HFpEF, assessing sex differences in a wide range of circulating proteins led to the identification of 9 proteins that were differentially expressed between female and male patients. These findings may help further investigations into potential pathophysiological processes contributing to HFpEF.
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Stienen et al. (2020) conducted an observational in Heart failure with preserved ejection fraction (HFpEF) (n=392). Female sex vs. Male sex was evaluated on Composite of cardiovascular death and/or cardiovascular hospitalizations (HR 1.48, 95% CI 0.83-2.63, p=0.18). In patients with heart failure with preserved ejection fraction, female sex was associated with differential expression of 9 circulating proteins but was not significantly associated with cardiovascular death or hospitalization compared to male sex (adjusted HR 1.48).
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