Key result
Obese HFpEF is linked to higher biomarkers of volume expansion, fibrosis, and systemic inflammation.
Why the study?
Recent evidence points towards a distinct obese phenotype among patients with HFpEF, prompting identification of differentially expressed circulating biomarkers linked to disease severity and outcomes.
Are specific circulating biomarkers differentially expressed in obese HFpEF patients compared to lean HFpEF or obese non-HF patients, and do they correlate with disease severity and mortality?
Observational (n=2,218)
Are specific circulating biomarkers differentially expressed in obese HFpEF patients compared to lean HFpEF or obese non-HF patients, and do they correlate with disease severity and mortality?
p-value: p=<0.001
Obese HFpEF patients exhibit a distinct biomarker profile reflecting volume expansion, myocardial fibrosis, and systemic inflammation, supporting the existence of a specific obese HFpEF phenotype.
Supports obese HFpEF phenotype via biomarkers; hypothesis-generating for targeted trials.
Aims Recent evidence points towards a distinct obese phenotype among patients with heart failure with preserved ejection fraction (HFpEF). We aimed to identify differentially expressed circulating biomarkers in obese HFpEF patients and link them to disease severity and outcomes. Methods and results From the LIFE‐Heart study, 999 patients with HFpEF and 999 patients without heart failure (no‐HF) were selected and 92 circulating serum biomarkers were measured using a proximity extension assay. Elevation of identified biomarkers was validated in 220 patients from the Aldo‐DHF trial with diagnosed HFpEF. HFpEF patients were older and had more comorbidities including coronary artery disease and type 2 diabetes as compared to no‐HF patients ( P < 0.05 for all). After adjusting for covariates, adrenomedullin (ADM), galectin‐9 (Gal‐9), thrombospondin‐2 (THBS‐2), CD4, and tumour necrosis factor‐related apoptosis‐inducing ligand receptor 2 (TRAIL‐R2) were significantly higher in obese HFpEF patients [body mass index (BMI) ≥30 kg/m 2 , n = 464] as compared to lean HFpEF (BMI <30 kg/m 2 , n = 535) and obese no‐HF patients (BMI ≥30 kg/m 2 , n = 387) ( P < 0.001 for both); these findings were verified in the Aldo‐DHF validation cohort ( P < 0.001). Except for CD4 these proteins were associated with increased estimates of left atrial pressure in a linear fashion. Importantly, ADM and CD4 were associated with increased mortality in obese HFpEF patients after adjusting for covariates. Conclusion Obese HFpEF patients exhibit higher circulating biomarkers of volume expansion (ADM), myocardial fibrosis (THBS‐2) and systemic inflammation (Gal‐9, CD4) compared to obese non‐HFpEF or lean HFpEF patients. These findings support the clinical definition of a distinct obese HFpEF phenotype and might merit further investigation.
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Kresoja et al. (2021) conducted an observational in Heart failure with preserved ejection fraction (HFpEF) and obesity (n=2,218). Obesity (BMI ≥30 kg/m2) vs. Lean HFpEF (BMI <30 kg/m2) and obese no-HF patients was evaluated on Differentially expressed circulating biomarkers (ADM, Gal-9, THBS-2, CD4, TRAIL-R2) (p=<0.001). Obese HFpEF patients had significantly higher circulating biomarkers of volume expansion, myocardial fibrosis, and systemic inflammation than lean HFpEF or obese non-HFpEF patients (P<0.001).
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