Lower Plasma Melatonin Levels Predict Worse Long-Term Survival in Pulmonary Arterial Hypertension
Open accessAbstract
Exogenous melatonin has been reported to be beneficial in the treatment of pulmonary hypertension (PH) in animal models. Multiple mechanisms are involved, with melatonin exerting anti-oxidant and anti-inflammatory effects, as well as inducing vasodilation and cardio-protection. However, endogenous levels of melatonin in treatment-naïve patients with PH and their clinical significance are still unknown. Plasma levels of endogenous melatonin were measured by liquid chromatography-tandem mass spectrometry in PH patients (n = 64, 43 pulmonary arterial hypertension (PAH) and 21 chronic thromboembolic PH (CTEPH)) and healthy controls (n = 111). Melatonin levels were higher in PH, PAH, and CTEPH patients when compared with controls (Median 118.7 (IQR 108.2–139.9), 118.9 (109.3–147.7), 118.3 (106.8–130.1) versus 108.0 (102.3–115.2) pM, respectively, p all <0.001). The mortality was 26% (11/43) in the PAH subgroup during a long-term follow-up of 42 (IQR: 32–58) months. Kaplan–Meier analysis showed that, in the PAH subgroup, patients with melatonin levels in the 1st quartile (<109.3 pM) had a worse survival than those in quartile 2–4 (Mean survival times were 46 (95% CI: 30–65) versus 68 (58–77) months, Log-rank, p = 0.026) with an increased hazard ratio of 3.5 (95% CI: 1.1–11.6, p = 0.038). Endogenous melatonin was increased in treatment-naïve patients with PH, and lower levels of melatonin were associated with worse long-term survival in patient with PAH.
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Low endogenous melatonin correlated with decreased long-term survival in patients with pulmonary hypertension.
“Cai et al. [124] correlated low levels of endogenous melatonin to decreased long-term survival in patients with pulmonary hypertension.”
From Is Melatonin the “Next Vitamin D”?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements (2022) · cites this paper as [124]
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- Authors
- Cai, Z., Klein, T., Geenen, L. W., Tu, L., Tian, S., van den Bosch, A. E., de Rijke, Y. B., Reiss, I. K. M., Boersma, E., Duncker, D. J., Boomars, K. A., Guignabert, C., & Merkus, D.
- Affiliations
- Erasmus MC (NL)
- Department of Clinical Chemistry, Erasmus MC, University Medical Center Rotterdam, 3000 CB Rotterdam, The Netherlands
- Inserm (FR)
- Department of Cardiology, Erasmus MC, University Medical Center Rotterdam, 3000 CA Rotterdam, The Netherlands
- Corresponding author
- Merkus, Daphne
- ORCID
- Venue
- Journal of Clinical Medicine
- Publisher
- MDPI AG
- Published
- 2020-04-25
- Volume
- 9
- Issue
- 5
- Pages
- 1248
- ISSN
- 2077-0383 (ISSN-L)
- PMC
- PMC7287676
- OpenAlex
- W3019381868
- Cited by
- 17
- References
- 46
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 3 · 2023: 2 · 2022: 2 · 2021: 3 · 2020: 1 · 2018: 1
- FWCI
- 1.13
- Type
- journal article
- Language
- en
- Open access
- gold
- dx.doi.org
- Licence
- Locations
- Journal of Clinical Medicine (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion, other-oa)
- HAL (submittedVersion, other-oa)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, other-oa)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- China Scholarship Council (201606230252)
- CardioVascular Research Initiative Netherlands: an initiative with support of the Dutch Heart Foundation (CVON2014-11, RECONNECT)
- Deutsches Zentrum für Herz-Kreislaufforschung (DZHK81Z0600207)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Pulmonary Hypertension Research and Treatments
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Physiology › Obstructive Sleep Apnea Research
- Keywords
- melatonin, pulmonary arterial hypertension, chronic thromboembolic pulmonary hypertension, plasma melatonin levels, endogenous melatonin, long-term survival, mortality, prognostic factors, treatment-naive patients
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