Association of sleep problems with neuroendocrine hormones and coagulation factors in patients with acute myocardial infarction

Roland von Känel, Mary Princip, Jean-Paul Schmid, Jürgen Barth, Hansjörg Znoj, Ulrich Schnyder, Rebecca E Meister-Langraf, Roland von Känel, Mary Princip, Jean-Paul Schmid, Jürgen Barth, Hansjörg Znoj, Ulrich Schnyder, Rebecca E Meister-Langraf

Abstract

Background: Obstructive sleep apnea (OSA) and insomnia are frequent sleep problems that are associated with poor prognosis in patients with coronary heart disease. The mechanisms linking poor sleep with an increased cardiovascular risk are incompletely understood. We examined whether a high risk of OSA as well as insomnia symptoms are associated with neuroendocrine hormones and coagulation factors in patients admitted with acute myocardial infarction.

Methods: We assessed 190 patients (mean age 60 years, 83% men) in terms of OSA risk (STOP screening tool for the assessment of high vs. low OSA risk) and severity of insomnia symptoms (Jenkins Sleep Scale for the assessment of subjective sleep difficulties) within 48 h of an acute coronary intervention. Circulating concentrations of epinephrine, norepinephrine, cortisol, fibrinogen, D-dimer, and von Willebrand factor were measured the next morning. The association of OSA risk and insomnia symptoms with neuroendocrine hormones and coagulation factors was computed using multivariate models adjusting for demographic factors, health behaviors, somatic and psychiatric comorbidities, cardiac disease-related variables, and OSA risk in the model for insomnia symptoms, respectively, for insomnia symptoms in the model for OSA risk.

Results: High OSA risk was identified in 41% of patients and clinically relevant insomnia symptoms were reported by 27% of patients. Compared to those with low OSA risk, patients with high OSA risk had lower levels of epinephrine (p = 0.015), norepinephrine (p = 0.049) and cortisol (p = 0.001). More severe insomnia symptoms were associated with higher levels of fibrinogen (p = 0.037), driven by difficulties initiating sleep, and with lower levels of norepinephrine (p = 0.024), driven by difficulties maintaining sleep.

Conclusions: In patients with acute myocardial infarction, sleep problems are associated with neuroendocrine hormones and coagulation activity. The pattern of these relationships is not uniform for patients with a high risk of OSA and those with insomnia symptoms, and whether they contribute to adverse cardiovascular outcomes needs to be established.

Trial registration: ClinicalTrials.gov NCT01781247 .

Keywords: Acute coronary syndrome; Biomarker; Blood coagulation; HPA axis; Insomnia; Sleep apnea; Sympathetic nervous system.

Conflict of interest statement

Ethics approval and consent to participate

The study protocol was approved by the ethics committee of the State of Bern, Switzerland (KEK-Nr. 170/12). All patients were informed and gave signed consent.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Risk of obstructive sleep apnea and mean values of neuroendocrine measures. The bar graphs illustrate the significant differences in epinephrine (p = 0.015), norepinephrine (p = 0.049) and cortisol (p = 0.001) levels between subjects with high (n = 77) vs. low (n = 113) risk of obstructive sleep apnea (OSA), expressed as geometric mean values with 95% confidence interval. Adjustments were made for age, sex, education, Charlson comorbidity index, positive history of hypertension/high cholesterol/depression, body mass index, smoking, alcohol consumption, physical activity, previous myocardial infarction (MI), ST-segment MI, number of stenotic coronary arteries, Global Registry of Acute Coronary Events risk score, acute distress, and sleep difficulties
Fig. 2
Fig. 2
Sleep difficulties and mean values of neuroendocrine and coagulation measures. The bar graphs illustrate the significant differences in norepinephrine (p = 0.010) and fibrinogen (p = 0.003) levels between subjects with poor sleep (i.e., sleep difficulties on more than 7 days in the previous 4 weeks; n = 52) and those with good sleep (n = 138), expressed as geometric mean values with 95% confidence interval. Adjustments were made for age, sex, education, Charlson comorbidity index, positive history of hypertension/high cholesterol/depression, body mass index, smoking, alcohol consumption, physical activity, previous myocardial infarction (MI), ST-segment MI, number of stenotic coronary arteries, Global Registry of Acute Coronary Events risk score, acute distress, and risk of obstructive sleep apnea

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