Comprehensive biomarker profiling in patients with obstructive sleep apnea

TY - JOUR

T1 - Comprehensive biomarker profiling in patients with obstructive sleep apnea

AU - Maeder, Micha T.

AU - Strobel, Werner

AU - Christ, Michael

AU - Todd, John

AU - Estis, Joel

AU - Wildi, Karin

AU - Thalmann, Gregor

AU - Hilti, Jonas

AU - Brutsche, Martin

AU - Twerenbold, Raphael

AU - Rickli, Hans

AU - Mueller, Christian

N1 - Publisher Copyright: © 2014 The Canadian Society of Clinical Chemists.

PY - 2015/3/1

Y1 - 2015/3/1

N2 - Objectives: The pathophysiological links between obstructive sleep apnea syndrome (OSAS) and cardiovascular mortality are incompletely understood. We aimed to contribute to a better characterization by using comprehensive biomarker profiling quantifying hemodynamic cardiac stress, cardiomyocyte injury, inflammation, endothelial function, matrix turnover and metabolism. Design and methods: In 65 patients with moderate or severe OSAS [apnea-hypopnea index (AHI) 39. ±. 20/h] and 33 patients with no or mild OSAS (AHI 8. +. 4/h), B-type natriuretic peptide (BNP), N-terminal-pro-BNP (NT-proBNP), high-sensitivity cardiac troponin I (hs-cTnI), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), and insulin were measured before and after sleep. In a subgroup measurements were repeated in a second night with continuous positive airway pressure (CPAP). Results: Patients with moderate/severe OSAS had higher insulin before sleep [median (interquartile range), 36.4 (21.9-52.1) vs. 20.8 (10.6-32.8). mU/mL; p. =. 0.006], higher IL-6 after sleep [1.00 (0.73-1.58) vs. 0.72 (0.48-0.94). pg/mL; p. =. 0.005], and larger relative overnight reduction in BNP [-. 9 (-. 35-0) vs. -. 3 (-. 21-13)%; p. =. 0.04] than those with mild/no OSAS. Insulin before sleep was the only independent predictor of moderate/severe OSAS. Insulin before and IL-6 after sleep were independent predictors of severe OSAS, and when combined provided high diagnostic accuracy for severe OSAS (area under the receiver operator characteristic curve 0.80; 95%-confidence interval 0.69-0.91). In contrast, there were no significant differences in NT-proBNP, hs-cTnI, VEGF, and MMP-9 between moderate/severe and mild/no OSAS. Short-term CPAP had no impact on biomarker concentrations before and after sleep. Conclusions: Significant OSAS is characterized by a distinct biomarker profile including high insulin before and high IL-6 after sleep.

AB - Objectives: The pathophysiological links between obstructive sleep apnea syndrome (OSAS) and cardiovascular mortality are incompletely understood. We aimed to contribute to a better characterization by using comprehensive biomarker profiling quantifying hemodynamic cardiac stress, cardiomyocyte injury, inflammation, endothelial function, matrix turnover and metabolism. Design and methods: In 65 patients with moderate or severe OSAS [apnea-hypopnea index (AHI) 39. ±. 20/h] and 33 patients with no or mild OSAS (AHI 8. +. 4/h), B-type natriuretic peptide (BNP), N-terminal-pro-BNP (NT-proBNP), high-sensitivity cardiac troponin I (hs-cTnI), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), and insulin were measured before and after sleep. In a subgroup measurements were repeated in a second night with continuous positive airway pressure (CPAP). Results: Patients with moderate/severe OSAS had higher insulin before sleep [median (interquartile range), 36.4 (21.9-52.1) vs. 20.8 (10.6-32.8). mU/mL; p. =. 0.006], higher IL-6 after sleep [1.00 (0.73-1.58) vs. 0.72 (0.48-0.94). pg/mL; p. =. 0.005], and larger relative overnight reduction in BNP [-. 9 (-. 35-0) vs. -. 3 (-. 21-13)%; p. =. 0.04] than those with mild/no OSAS. Insulin before sleep was the only independent predictor of moderate/severe OSAS. Insulin before and IL-6 after sleep were independent predictors of severe OSAS, and when combined provided high diagnostic accuracy for severe OSAS (area under the receiver operator characteristic curve 0.80; 95%-confidence interval 0.69-0.91). In contrast, there were no significant differences in NT-proBNP, hs-cTnI, VEGF, and MMP-9 between moderate/severe and mild/no OSAS. Short-term CPAP had no impact on biomarker concentrations before and after sleep. Conclusions: Significant OSAS is characterized by a distinct biomarker profile including high insulin before and high IL-6 after sleep.

KW - Biomarkers

KW - Diurnal changes

KW - Multimarker

KW - Obstructive sleep apnea syndrome

UR - http://www.scopus.com/inward/record.url?scp=84924588719&partnerID=8YFLogxK

U2 - 10.1016/j.clinbiochem.2014.09.005

DO - 10.1016/j.clinbiochem.2014.09.005

M3 - SCORING: Journal article

C2 - 25218814

AN - SCOPUS:84924588719

VL - 48

SP - 340

EP - 346

JO - CLIN BIOCHEM

JF - CLIN BIOCHEM

SN - 0009-9120

IS - 4-5

ER -