Patients with group 1 pulmonary hypertension and high HFpEF probability have a unique metabolome overlapping with clinical HFpEF, characterized by enhanced tryptophan-kynurenine pathway breakdown, lower serotonin, and decreased nitric oxide precursors.
This study stratified group 1 pulmonary hypertension (PH) patients by HFpEF probability and found that those with high probability (n=131) had significant metabolomic changes compared to low probability (n=62), including increased kynurenine metabolites and decreased serotonin, linoleate, arginine, and homoarginine. These changes overlapped with clinical HFpEF (n=240) and were abnormal relative to controls (n=85), suggesting biological overlap between the two conditions.
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Patients with group 1 pulmonary hypertension and high HFpEF probability have a unique metabolome overlapping with clinical HFpEF, characterized by enhanced tryptophan-kynurenine pathway breakdown, lower serotonin, and decreased nitric oxide precursors. The current body of evidence comprises 1 study. EvidenceHub rates the overall confidence at 34/100 (low).
The Claim
Patients with group 1 pulmonary hypertension and high HFpEF probability have a unique metabolome overlapping with clinical HFpEF, characterized by enhanced tryptophan-kynurenine pathway breakdown, lower serotonin, and decreased nitric oxide precursors.
This conclusion is most relevant to: Patients with group 1 pulmonary hypertension (n=193), healthy controls (n=85), and clinical HFpEF subjects (n=240)..
What the Research Shows
The conclusion draws on 1 linked study. Highlights from the cited literature:
- ▸Metabolomic Evidence of Biological Overlap with Heart Failure with Preserved Ejection Fraction in a Subset of Pulmonary Arterial Hypertension. (American journal of respiratory and critical care medicine, 2025) —
How It Works
The proposed biological pathway:
- ▸Enhanced tryptophan-kynurenine pathway breakdown in group 1 PH with high HFpEF probability
- ▸Lower serotonin concentrations
- ▸Deficiency of amino acids (glycine, serine) and precursors (linoleate, arginine, homoarginine)
- ▸Result: Metabolome changes overlap with clinical HFpEF, indicating shared biological pathways
Who Might Benefit
Evidence fit by population:
- ▸Patients with group 1 pulmonary hypertension (n=193), healthy controls (n=85), and clinical HFpEF subjects (n=240).
Recommended Dose
N/A
Limitations & Caveats
Important context when interpreting this evidence:
- ▸Observational study design cannot establish causality
- ▸HFpEF probability was based on a clinical score (HFpEF-ABA) rather than direct hemodynamic or imaging confirmation
- ▸Metabolome changes may be influenced by medications or comorbidities not fully accounted for
Frequently Asked Questions
What is the HFpEF-ABA score?▼
It is a clinical probability score for heart failure with preserved ejection fraction based on age, body mass index, and atrial fibrillation.
What metabolomic changes were most significant in the high HFpEF probability group?▼
Enhanced tryptophan-kynurenine pathway breakdown, lower serotonin, and decreased linoleate, arginine, and homoarginine levels.
Did the metabolome changes originate from the lungs?▼
No, there was no evidence of differential transpulmonary uptake/release for most metabolites, except serotonin and kynurenine, suggesting a nonpulmonary origin.
How many patients were in each group?▼
Group 1 PH with high HFpEF probability: 131; low probability: 62; clinical HFpEF: 240; healthy controls: 85.
References
- 1.Reddy YNV, Asokan AK, Frantz RP, Hemnes A, Hassoun PM, Barnard J, Horn E, Leopold JA, Rischard F, Rosenzweig EB, Hill NS, Erzurum SC, Beck GJ, Finet JE, Grunig G, Jellis CL, Mathai SC, Simpson CE, Tang WHW, Nair KS, Borlaug BA. “Metabolomic Evidence of Biological Overlap with Heart Failure with Preserved Ejection Fraction in a Subset of Pulmonary Arterial Hypertension..” American journal of respiratory and critical care medicine, 2025. PMID: 40504754 DOI: 10.1164/rccm.202501-0034OC