Pre- and post-diagnosis signalling lipid profiles in heart failure with preserved ejection fraction: a prospective...

Heart failure with preserved ejection fraction (HFpEF) is a prevalent syndrome with limited diagnostic and therapeutic options. Dyslipidaemia is a common comorbidity, and signalling lipids, bioactive molecules regulating key pathophysiological processes, are implicated in HFpEF, though their relationships remain unclear.

Plasma samples from the PREVEND cohort were analysed, including 172 control samples, 125 PreDx-HFpEF samples (before diagnosis), and 30 PostDx-HFpEF samples (after diagnosis, paired with PreDx-HFpEF). A total of 261 signalling lipids were profiled via LC-MS/MS. Additionally, sums and ratios of specific signalling lipid targets were calculated. Cox proportional hazards and logistic regression models were performed to identify relationships between signalling lipids and HFpEF progression.

PreDx-HFpEF individuals showed elevated non-esterified oxylipins (derived from DHA, AA, EPA) and specific lysophospholipids, compared with controls, and these signalling lipids emerged as potential predictors of incident HFpEF. In contrast, the PostDx-HFpEF subgroup demonstrated an attenuation of non-esterified oxylipins and lysophospholipids compared with control and PreDx-HFpEF samples, although findings are exploratory given the limited sample size. Among 103 detected non-esterified oxylipins, 44 showed significant associations with HFpEF-related outcomes. Together with 18 additional signalling lipids, this yielded 62 significant signalling lipids, 68% of which were independent of high-density lipoprotein (HDL).

Selected signalling lipids provide predictive information prior to HFpEF diagnosis, whereas post-diagnostic lipid alterations reflect disease-associated metabolic changes and should be interpreted cautiously. These findings highlight the potential relevance of signalling lipids in HFpEF.

This study was funded by Netherlands Heart Foundation, Chinese Scholarship Council, and Dutch Research Council.