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Inflammation in patients with obstructive sleep apnea and coronary artery disease

Robust correlations between inflammation markers and obstructive sleep apnea severity, and the impact of CPAP

Inflammation bei Patienten mit obstruktiver Schlafapnoe und koronarer Herzerkrankung

Robuste Korrelationen zwischen Inflammationsmarkern und dem Schweregrad der obstruktiven Schlafapnoe sowie Einfluss der CPAP-Therapie

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Abstract

Background and objective

Obstructive sleep apnea (OSA) and coronary artery disease (CAD) are known to be associated with activation of inflammatory pathways. Treatment of OSA is hypothesized to lead to a reduction in inflammation. This study investigated the association between OSA and inflammation in CAD patients, and determined the effect of one night of continuous positive airway pressure (CPAP) therapy.

Materials and methods

Patients with stable CAD and moderate–severe OSA underwent overnight polysomnography (PSG) one night, and again during CPAP the following night. Cardiac stress and inflammation markers were determined in the morning after each PSG.

Results

Included were 23 patients with OSA (74% male; age 63 ± 10 years; ejection fraction 50 ± 8%). During CPAP, the most remarkable decreases from baseline were observed in the apnea–hypopnea index (AHI; from 35 ± 21 to 11 ± 11/h; p < 0.001), high-sensitivity C‑reactive protein (hs-CRP; 0.396 ± 0.428 to 0.308 ± 0.299 mg/dL; p = 0.006), and creatine kinase-MB (CKMB; 1.818 ± 1.014 to 1.551 ± 0.819 U/L; p = 0.018). After adjusting for age, gender, obesity, and heart failure severity as relevant confounders, there was a significant correlation between baseline AHI and myoglobin (r = 0.650; p = 0.002). Likewise, there were correlations between mean desaturation and CKMB (r = 0.606, p = 0.007), and between time spent with O2 saturation <90% (T < 90%) and interleukin 6 (r = 0.525, p = 0.013).

Conclusion

Among CAD patients there are clear correlations between surrogate measures of OSA severity, such as T < 90%, mean desaturation, and AHI, and inflammation, even after adjustment for obesity and the severity of heart failure as crucial confounding factors. Effective treatment of OSA with CPAP decreased cardiac stress and inflammation.

Zusammenfassung

Hintergrund und Ziel der Arbeit

Sowohl die obstruktive Schlafapnoe (OSA) als auch die koronare Herzkrankheit (KHK) sind bekanntermaßen mit einer Aktivierung inflammatorischer Wege assoziiert. Eine Therapie der OSA führt mutmaßlich zu einer Verminderung der Entzündung. In dieser Studie wurde die Assoziation von OSA und KHK in Bezug auf die Entzündung und die Effekte einer einmaligen nächtlichen Überdrucktherapie (CPAP) untersucht.

Material und Methoden

Patienten mit stabiler KHK und moderater bis schwerer OSA unterzogen sich einer Nacht mit diagnostischer Polysomnographie (PSG) und einer PSG während der Therapie mit Überdruckbeatmung („continuous positive airway pressure“, CPAP) in der Folgenacht. Marker für kardiale Belastung und Entzündung wurden jeweils am Morgen nach der PSG bestimmt.

Ergebnisse

23 Patienten (74 % männlich; 63 ± 10 Jahre alt; Ejektionsfraktion: 50 ± 8 %) zeigten eine obstruktive Schlafapnoe. Unter CPAP wies der Apnoe-Hypopnoe-Index (AHI) einen signifikanten Abfall auf (AHI; von 35 ± 21 auf 11 ± 11/h; p < 0,001). Außerdem zeigte sich ein signifikanter Abfall im hochsensitiven CRP (hs-CRP; von 0,396 ± 0,428 auf 0,308 ± 0,299 mg/dl; p = 0,006) und in der Kreatininkinase-MB (CKMB; von 1,818 ± 1,014 auf 1,551 ± 0,819 U/l; p = 0,018). Es ergab sich – in einem multivariaten Modell nach Adjustierung für Alter, Geschlecht, Adipositas und Schwere der Herzinsuffizienz als wichtige Störfaktoren – eine signifikante Korrelation zwischen dem Ausgangs-AHI und Myoglobin (r = 0,650; p = 0,002). Darüber hinaus zeigten sich Korrelationen zwischen der mittleren Sauerstoffentsättigung und dem CKMB-Wert (r = 0,606; p = 0,007) sowie zwischen der Zeit mit einer Sauerstoffsättigung unter 90 % (T < 90 %) und Interleukin-6 (r = 0,525; p = 0,013).

Schlussfolgerungen

Bei Patienten mit KHK ergaben sich robuste Korrelationen zwischen Surrogatmarkern der Schwere der OSA, wie z. B. T < 90 %, mittlere Sauerstoffentsättigung und AHI, sowie Inflammationsmarkern, selbst nach Adjustierung für Adipositas und Schwere der Herzinsuffizienz als entscheidende Störfaktoren. Eine effektive Therapie der OSA mit CPAP vermindert kardialen Stress und Entzündung.

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Authors and Affiliations

  1. Clinic for Cardiology, Herz- und Diabeteszentrum Nordrhein-Westfalen, Ruhr-Universität Bochum, Georgstraße 11, 32545, Bad Oeynhausen, Germany

    Jens Spießhöfer, Heidi Schmalgemeier, Florian Schindhelm, Thomas Bitter, Henrik Fox, Anke Türoff, Dieter Horstkotte & Olaf Oldenburg MD

  2. Department of Cardiology, Royal Brompton Hospital, London, UK

    Simon Pearse

  3. National Heart and Lung Institute, Imperial College London, London, UK

    Simon Pearse

  4. Accident and Emergency Department, Asklepios Klinik Wandsbek, Hamburg, Germany

    Anke Türoff

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  1. Jens Spießhöfer
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  9. Olaf Oldenburg MD
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Correspondence to Olaf Oldenburg MD.

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Conflict of interest

T. Bitter, H. Fox, and O. Oldenburg received honoraria for speaking at symposia and financial support for attending symposia by ResMed Germany Inc., Novartis, and Bayer; H. Fox received financial support for educational programs by Novartis. F. Schindhelm received financial support for attending a symposium by Itamar. J. Spießhöfer, H. Schmalgemeier, S. Pearse, A. Türoff, and D. Horstkotte declare that they have no competing interests.

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.

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J. Spießhöfer and H. Schmalgemeier share first authorship

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Spießhöfer, J., Schmalgemeier, H., Schindhelm, F. et al. Inflammation in patients with obstructive sleep apnea and coronary artery disease. Somnologie 21, 257–264 (2017). https://doi.org/10.1007/s11818-017-0111-y

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