Association of Serum YKL-40 With the Presence and Severity of Obstructive Sleep Apnea Syndrome Wei Li, MD,1† Zhen Yu, MD,2† Chengcheng Jiang, MD1* Lab Med Summer 2014;45:220-225 DOI: 10.1309/LMS98AKCXRSL2XOR
ABSTRACT Objective: This study examined the association of serum YKL-40 concentrations with the presence and severity of obstructive sleep apnea syndrome (OSAS). Methods: A total of 156 patients with OSAS and 110 healthy subjects were enrolled in this study. Results: OSAS patients had significantly higher serum YKL-40 levels compared with healthy controls. Multivariable logistic regression analysis indicated that serum YKL-40 levels were an independent determinant of the presence of OSAS. Serum YKL-40 levels were
Obstructive sleep apnea syndrome (OSAS) is a common disorder characterized by recurrent episodes of complete or partial obstruction of the upper airway during sleep, along
Abbreviations OSAS, obstructive sleep apnea syndrome; BMI, body mass index; CRP, C-reactive protein; HOMA-IR, homeostasis model assessment of insulin resistance; AHI, apnea-hypopnea index; ICAM-1, intercellular adhesion molecule-1; VCAM-1, vascular cell adhesion molecule-1; IL-6, interleukin-6; MCP-1, monocyte chemoattractant protein-1; PSG, polysomnography; FPG, fasting plasma glucose; TG, triglycerides; TC, total cholesterol; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; OR, odds ratio; CI, confidence intervals; SBP, systolic blood pressure; DBP, diastolic blood pressure; TST, total sleep time; ODI, xygen desaturation index; ESS, Epworth Sleepiness Scale; TNF-α, tumor necrosis factor-α; CAD, coronary artery disease; CPAP, continuous positive airway pressure. Department of Respiration, Chinese Medicine Hospital of Chongqing, Chongqing; 2Department of Respiration, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China 1
†
These two authors contributed equally to this article
*To whom correspondence should be addressed. E-mail: [email protected]
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significantly elevated in severe OSAS patients compared with mild and moderate OSAS patients. Spearman correlation analysis revealed that serum YKL-40 levels were correlated with the severity of OSAS. Simple linear regression analysis showed that the serum levels of YKL40 were correlated with body mass index (BMI), homeostasis model assessment of insulin resistance (HOMA-IR), C-reactive protein (CRP), and apnea-hypopnea index (AHI) in patients with OSAS. Conclusion: Elevated serum YKL-40 levels are associated with the presence and severity of OSAS. Keywords: YKL-40, inflammation, obstructive sleep apnea syndrome, severity
with decreased oxygen saturation and sleep fragmentation.1 It has been estimated that 3% to 7% of adult men and 2% to 5% of adult women are affected by OSAS.2 OSAS patients are at increased risk for cardiovascular and cerebrovascular conditions including atherosclerosis, hypertension, coronary heart disease, and stroke.3 The exact mechanism of OSAS remains unclear. Recent evidence suggests that low-grade systemic inflammation may play an important role in the pathophysiology of OSAS. A variety of inflammatory markers, including intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), interleukin-6 (IL-6), IL-8, IL-1β, and monocyte chemoattractant protein-1 (MCP-1) are elevated in patients with OSAS.4 YKL-40, also known as human cartilage glycoprotein 39, is a 40 kDa plasma protein without glycolytic properties.5 YKL-40 is secreted by activated macrophages, neutrophils, chondrocytes, vascular smooth muscle cells, and cancer cells.6 YKL-40 appears to be involved in inflammation, cell migration, reorganization, and tissue remodeling.7 Increased levels of circulating YKL-40 have been observed in patients with endothelial dysfunction, atherosclerosis, diabetes, and coronary artery disease.8 Inflammation is
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associated with the mechanism of OSAS. Therefore, YKL40 is hypothesized to be involved in the pathophysiology of OSAS. Although there have been studies on the association of YKL-40 with obesity, atherosclerosis, diabetes, and coronary artery disease,8 to our knowledge no investigation on the association between YKL-40 and OSAS has been performed. We measured serum levels of YKL-40 in patients with OSAS to assess its role in the pathophysiology of OSAS.
Materials and Methods Patients One hundred fifty-six newly diagnosed male patients with OSAS were enrolled in the study. The diagnosis of OSAS was established on the basis of clinical and polysomnographic criteria. Patients with a history of cerebrovascular or cardiovascular events, respiratory disease, kidney disease, malignancy, and hormonal disease were excluded. The control participants were 110 healthy male subjects who underwent medical check-ups in our hospital and were matched to the study subjects by age and body mass index (BMI). The study protocol was approved by our hospital research ethics committee. All participants gave their informed consent before they were enrolled in the study.
Sleep Study Polysomnography (PSG) monitoring was performed on all patients using the Compumedics P-series Sleep System (Compumedics Sleep, Melbourne, Australia). Polysomnographic recordings were obtained by standard techniques. Apnea was defined as the cessation of breathing for at least 10 seconds, and hypopnea was defined as a 50% decrease in nasal airflow with at least a 4% decrease in oxygen saturation. The ApneaHypopnea Index (AHI) was calculated as the sum of the total respiratory events of apnea and hypopnea per hour of sleep. Subjects with AHI
ABSTRACT Objective: This study examined the association of serum YKL-40 concentrations with the presence and severity of obstructive sleep apnea syndrome (OSAS). Methods: A total of 156 patients with OSAS and 110 healthy subjects were enrolled in this study. Results: OSAS patients had significantly higher serum YKL-40 levels compared with healthy controls. Multivariable logistic regression analysis indicated that serum YKL-40 levels were an independent determinant of the presence of OSAS. Serum YKL-40 levels were
Obstructive sleep apnea syndrome (OSAS) is a common disorder characterized by recurrent episodes of complete or partial obstruction of the upper airway during sleep, along
Abbreviations OSAS, obstructive sleep apnea syndrome; BMI, body mass index; CRP, C-reactive protein; HOMA-IR, homeostasis model assessment of insulin resistance; AHI, apnea-hypopnea index; ICAM-1, intercellular adhesion molecule-1; VCAM-1, vascular cell adhesion molecule-1; IL-6, interleukin-6; MCP-1, monocyte chemoattractant protein-1; PSG, polysomnography; FPG, fasting plasma glucose; TG, triglycerides; TC, total cholesterol; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; OR, odds ratio; CI, confidence intervals; SBP, systolic blood pressure; DBP, diastolic blood pressure; TST, total sleep time; ODI, xygen desaturation index; ESS, Epworth Sleepiness Scale; TNF-α, tumor necrosis factor-α; CAD, coronary artery disease; CPAP, continuous positive airway pressure. Department of Respiration, Chinese Medicine Hospital of Chongqing, Chongqing; 2Department of Respiration, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China 1
†
These two authors contributed equally to this article
*To whom correspondence should be addressed. E-mail: [email protected]
220
Lab Medicine Summer 2014 | Volume 45, Number 3
significantly elevated in severe OSAS patients compared with mild and moderate OSAS patients. Spearman correlation analysis revealed that serum YKL-40 levels were correlated with the severity of OSAS. Simple linear regression analysis showed that the serum levels of YKL40 were correlated with body mass index (BMI), homeostasis model assessment of insulin resistance (HOMA-IR), C-reactive protein (CRP), and apnea-hypopnea index (AHI) in patients with OSAS. Conclusion: Elevated serum YKL-40 levels are associated with the presence and severity of OSAS. Keywords: YKL-40, inflammation, obstructive sleep apnea syndrome, severity
with decreased oxygen saturation and sleep fragmentation.1 It has been estimated that 3% to 7% of adult men and 2% to 5% of adult women are affected by OSAS.2 OSAS patients are at increased risk for cardiovascular and cerebrovascular conditions including atherosclerosis, hypertension, coronary heart disease, and stroke.3 The exact mechanism of OSAS remains unclear. Recent evidence suggests that low-grade systemic inflammation may play an important role in the pathophysiology of OSAS. A variety of inflammatory markers, including intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), interleukin-6 (IL-6), IL-8, IL-1β, and monocyte chemoattractant protein-1 (MCP-1) are elevated in patients with OSAS.4 YKL-40, also known as human cartilage glycoprotein 39, is a 40 kDa plasma protein without glycolytic properties.5 YKL-40 is secreted by activated macrophages, neutrophils, chondrocytes, vascular smooth muscle cells, and cancer cells.6 YKL-40 appears to be involved in inflammation, cell migration, reorganization, and tissue remodeling.7 Increased levels of circulating YKL-40 have been observed in patients with endothelial dysfunction, atherosclerosis, diabetes, and coronary artery disease.8 Inflammation is
www.labmedicine.com
Science
associated with the mechanism of OSAS. Therefore, YKL40 is hypothesized to be involved in the pathophysiology of OSAS. Although there have been studies on the association of YKL-40 with obesity, atherosclerosis, diabetes, and coronary artery disease,8 to our knowledge no investigation on the association between YKL-40 and OSAS has been performed. We measured serum levels of YKL-40 in patients with OSAS to assess its role in the pathophysiology of OSAS.
Materials and Methods Patients One hundred fifty-six newly diagnosed male patients with OSAS were enrolled in the study. The diagnosis of OSAS was established on the basis of clinical and polysomnographic criteria. Patients with a history of cerebrovascular or cardiovascular events, respiratory disease, kidney disease, malignancy, and hormonal disease were excluded. The control participants were 110 healthy male subjects who underwent medical check-ups in our hospital and were matched to the study subjects by age and body mass index (BMI). The study protocol was approved by our hospital research ethics committee. All participants gave their informed consent before they were enrolled in the study.
Sleep Study Polysomnography (PSG) monitoring was performed on all patients using the Compumedics P-series Sleep System (Compumedics Sleep, Melbourne, Australia). Polysomnographic recordings were obtained by standard techniques. Apnea was defined as the cessation of breathing for at least 10 seconds, and hypopnea was defined as a 50% decrease in nasal airflow with at least a 4% decrease in oxygen saturation. The ApneaHypopnea Index (AHI) was calculated as the sum of the total respiratory events of apnea and hypopnea per hour of sleep. Subjects with AHI
