Morning Larks and Night Owls: Considering Chronotype in Evaluation of Patients with Pulmonary Hypertension.

Abstract

Background: Pulmonary hypertension (PH) is a systemic illness with increasingly subtle disease manifestations including sleep disruption. Patients with PH are at increased risk for disturbances in circadian biology, although to date there is no data on "morningness" or "eveningness" in pulmonary vascular disease.

Research questions: Our group studied circadian rhythms in PH patients based upon chronotype analysis, to explore whether there is a link between circadian parameters and physiologic risk-stratifying factors to inform novel treatment strategies in patients with PH?

Study design and methods: We serially recruited participants from July 2022 to March 2024, administering in clinic the Munich Chronotype Questionnaire (MCTQ). We then compared free-day sleep measurements in PH and bed-partner controls (BPCs), investigating associations with survival predictors. In exploratory analysis we looked for associations between known single nucleotide polymorphism (SNP) variants of core clock genes and cardiopulmonary hemodynamics. Finally, we performed circadian analysis of time-stamped heart rate (HR) variation from a PH cohort compared to controls.

Results: In this pilot study, we recruited 103 patients with PH and 38 bed-partner controls (BPCs) aged 20 to 86 years. Compared to BPCs patients with PH had longer sleep duration and less social jet lag (SJL), with no clear difference in chronotype. Within the PH cohort, sleep duration was associated with worse functional class, while SJL was associated with a low risk for disease progression, and more severe signs of right ventricular dysfunction. However, a later chronotype was associated with a decrease in mean pulmonary artery pressure (mPAP). In an independent cohort of PH patients there was a relationship between functionally distinct core clock gene SNP variants and relevant hemodynamic parameters. PH patients exhibited a distinct delayed phase shift in circadian HR variation.

Interpretation: PH in adults is associated with significant changes in sleep duration and SJL, corroborated by both genomic and physiologic data. Dependence between circadian variables, SNP data and disease characteristics suggests that findings may directly relate to disease pathogenesis via derangement in the molecular core clock.