Factors Associated With Increased Carotid Intima-Media Thickness in Obstructive Sleep Apnea/Hypopnea Syndrome Teng-Yeow Tan, MD,*w Chia-Wei Liou, MD,*w Michael Friedman, MD, FACS,zy Hsin-Ching Lin, MD, FACS,w8 Hsueh-Wen Chang, PhD,z and Meng-Chih Lin, MDw# Background: Obstructive sleep apnea/hypopnea syndrome (OSAHS) is strongly associated with the increase of cardiovascular and cere- brovascular disorders. Carotid intima-media thickness (IMT) is used as a surrogate marker for subclinical or early atherosclerosis. Knowledge regarding early atherosclerosis in patients with OSAHS is scarce, and factors predicting carotid IMT have not been well studied. Objective: To compare IMT in patients with OSAHS versus controls and explore the factors associated with increased IMT in OSAHS. Methods: One hundred fifty-six OSAHS patients and 35 controls without history of vascular events, hypertension, and diabetes mellitus who underwent polysomnography were consecutively enrolled. Carotid IMT was measured using B-mode ultrasonography. Body mass index, waist circumference, hip circumference, waist-to-hip circumference ratio, Epworth Sleepiness Scale, and polysomnographic variables including arousal index, apnea/hypopnea index, mean oxygen satu- ration, and lowest oxygen saturation were assessed. Fasting plasma glucose, blood lipid profile, and high-sensitivity C-reactive protein were measured. Results: Average carotid IMT of OSAHS patients was significantly thicker than controls (0.66 vs. 0.58mm, P = 0.002) and multivariable logistic regression analysis revealed that arousal index [odds ratio (OR), 0.77; confidence interval (CI), 0.63-0.95; P = 0.01] and lowest oxygen saturation (OR, 1.91; CI, 1.24-2.95; P = 0.003) were significantly associated with OSAHS patients. Among the OSAHS patients, age (OR, 1.16; CI, 1.10-1.22; P <0.0001), fasting plasma glucose (OR, 1.05; CI, 1.01-1.10; P =0.04), low-density lipoprotein cholesterol (OR, 1.03; CI, 1.02-1.05; P <0.0001), and high-sensitivity C-reactive protein (OR, 1.48; CI, 1.13-1.95; P =0.005) were significantly associated with patients with IMTZ0.65 mm. Conclusions: IMT was thicker in OSAHS patients without history of vascular events, hypertension, and diabetes mellitus. This study demonstrates that early atherosclerosis exists in this group of patients. Key Words: atherosclerosis, intima-media thickness, obstructive sleep apnea/hypopnea syndrome (The Neurologist 2012;18:277–281) O bstructive sleep apnea/hypopnea syndrome (OSAHS) is a disorder in which loss of pharyngeal dilator muscle tone during sleep causes recurrent pharyngeal collapse and tempo- rary cessation of breathing. Such apneas cause repetitive hypoxia and carbon dioxide retention, and provoke awakenings that restore pharyngeal dilator muscle tone and airflow. Solid evidence is emerging that the apneic or hypopneic events that occur during sleep lead to hemodynamic changes, including elevated sympathetic tone, decreased stroke volume, lower cardiac output, increased heart rate, worsened systemic hyper- tension, and changes in circulating hormones that regulate blood pressure, fluid volume, vasoconstriction, and vaso- dilatation. This ultimately results in an increased risk of hyper- tension, coronary artery disease, stroke, and death in untreated OSAHS patients. 1–3 Stroke incidence among OSAHS patients is increased independent from other known vascular and metabolic factors. 4,5 Potential mechanisms include hypoxemia-induced increases in sympathetic activity, blood pressure, and platelet aggregation, and apnea-related cardiac arrhythmia, diminished endothelial vasodilatory capacity, and altered cerebral hemody- namics. 2,6–10 Among the potential mechanisms for increased stroke risk, increase in sympathetic activity, hypertension, increased platelet aggregation, and endothelial inflammation further contribute to the progression of atherosclerosis process. Carotid intima-media thickness (IMT) is frequently used as a surrogate marker for subclinical or early atherosclerosis in epidemiological and interventional studies. Previous reports also have demonstrated that increased carotid IMT is associated with OSAHS 11–14 and that carotid IMT, as evaluated by noninvasive and reproducible B-mode ultrasound, correlates well with anatomic measurements and is furthermore recognized as a significant independent predictor for cardiovascular outcome. 15 Knowledge regarding early atherosclerosis in the Asian population with OSAHS is scarce, and factors predicting car- otid IMT have not been well studied. This study was designed to compare the carotid IMT of OSAHS patients versus controls in Taiwan and to explore the findings that were associated with OSAHS patients with increased IMT. SUBJECTS AND METHODS Study Design This study was carried out at a tertiary referral medical center serving an area with 3 million inhabitants. Institutional review board approval was obtained from the Chang Gung Memorial Hospital Ethical Committee. Received for publication January 18, 2011; accepted June 27, 2012. From the *Department of Neurology, Division of Cerebrovascular Disease; 8Department of Otolaryngology, Sleep Center; #Department of Internal Medicine, Sleep Center, Division of Pulmonary and Critical Care Medicine, Kaohsiung Chang Gung Memorial Hospital; wChang Gung University College of Medicine; zDepartment of Biological Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan; zDepartment of Otolaryngology and Bronchoesophagology, Rush University Medical Center; and yDepartment of Otolaryngology, Advanced Center for Specialty Care, Advocate Illinois Masonic Medical Center, Chicago, IL. Supported by grant CMRPG880271 from the Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan. The authors declare no conflict of interest. Reprints: Hsin-Ching Lin, MD, Department of Otolaryngology, Sleep Center, Kaohsiung Chang Gung Memorial Hospital, 123, Ta-Pei Rd., Niao-Sung District, Kaohsiung City 833, Taiwan. E-mail: enthclin@ aol.com. Copyright r 2012 by Lippincott Williams & Wilkins ISSN: 1074-7931/12/1805-0277 DOI: 10.1097/NRL.0b013e3182675344 ORIGINAL ARTICLE The Neurologist  Volume 18, Number 5, September 2012 www.theneurologist.org | 277