Sleep apnea predicts cardiovascular death in patients with Marfan syndrome: a cohort study

Nele Gessler; Peter Wohlmuth; Omar Anwar; Eike Sebastian Debus; Christian Eickholt; Melanie A Gunawardene; Samer Hakmi; Kathrin Heitmann; Meike Rybczynski; Helke Schueler; Sara Sheikhzadeh; Eike Tigges; Gunther H Wiest; Stephan Willems; Ekaterina Adam; Yskert von Kodolitsch

doi:10.1007/s13167-022-00291-4

Sleep apnea predicts cardiovascular death in patients with Marfan syndrome: a cohort study

EPMA J. 2022 Jul 29;13(3):451-460. doi: 10.1007/s13167-022-00291-4. eCollection 2022 Sep.

Authors

Nele Gessler^{1

2

3}, Peter Wohlmuth³, Omar Anwar^{1

2}, Eike Sebastian Debus^{2

4}, Christian Eickholt^{1

2}, Melanie A Gunawardene^{1

2}, Samer Hakmi^{1

2}, Kathrin Heitmann^{1

3}, Meike Rybczynski^{2

4}, Helke Schueler^{2

4}, Sara Sheikhzadeh^{5

6}, Eike Tigges^{1

2}, Gunther H Wiest⁷, Stephan Willems^{1

2}, Ekaterina Adam⁴, Yskert von Kodolitsch^{2

4}

Affiliations

¹ Department of Cardiology and Internal Intensive Care Medicine, Asklepios Clinic St. Georg, Semmelweis University, Campus Hamburg, Lohmuehlenstrasse 5, 20099 Hamburg, Germany.
² DZHK (German Center for Cardiovascular Research), Partner Site Hamburg/Kiel/Luebeck, Berlin, Germany.
³ Asklepios Proresearch, Research Institute, Hamburg, Germany.
⁴ University Heart Center Hamburg Eppendorf, Hamburg, Germany.
⁵ Emergency Department, Asklepios Clinic St. Georg, Semmelweis University, Campus Hamburg, Hamburg, Germany.
⁶ Emergency Department, Asklepios Clinic Harburg, Semmelweis University, Campus Hamburg, Hamburg, Germany.
⁷ Department of Pneumology and Sleep Medicine, Asklepios Clinic Harburg, Semmelweis University, Campus Hamburg, Hamburg, Germany.

Abstract

Background: Surgical replacement of the aortic root is the only intervention that can prevent aortic dissection and cardiovascular death in Marfan syndrome (MFS). However, in some individuals, MFS also causes sleep apnea. If sleep apnea predicts cardiovascular death, a new target for predictive, preventive, and personalized medicine (PPPM) may emerge for those individuals with MFS who have sleep apnea.

Methods: This is an investigator-initiated study with long-term follow-up data of 105 individuals with MFS. All individuals were screened for sleep apnea regardless of symptoms. Cardiovascular death served as a primary endpoint, and aortic events as a secondary outcome.

Results: Sleep apnea with an apnea-hypopnea index (AHI) > 5/h was observed in 21.0% (22/105) with mild sleep apnea in 13% (14/105) and moderate to severe sleep apnea in 7.6% (8/105). After a median follow-up of 7.76 years (interquartile range: 6.84, 8.41), 10% (10/105) had died, with cardiovascular cause of death in 80% (8/10). After adjusting for age and body mass index (BMI), the AHI score emerged as an independent risk factor for cardiovascular death (hazard ratio 1.712, 95% confidence interval [1.061-2.761], p = 0.0276). The secondary outcome of aortic events occurred in 33% (35/105). There was no effect of the AHI score on aortic events after adjusting for age and BMI (hazard ratio 0.965, 95% confidence interval [0.617-1.509]), possibly due to a high number of patients with prior aortic surgery.

Interpretation: Sleep apnea is emerging as an independent predictor of cardiovascular death in MFS. It seems mandatory to screen all individuals with MFS for sleep apnea and to include these individuals, with both MFS and sleep apnea, in further studies to evaluate the impact of preventive measures with regard to cardiovascular death.

Supplementary information: The online version contains supplementary material available at 10.1007/s13167-022-00291-4.

Keywords: Aortic rupture; Cardiovascular death; Connective tissue deficits; Marfan syndrome; Mortality; Predictive preventive personalized medicine; Sleep apnea.