High Risk for Obstructive Sleep Apnea in Relation to Hypertension Among Southeast Asian Young Adults: Role of Obesity as an Effect Modifier

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1 Original Article High Risk for Obstructive Sleep Apnea in Relation to Hypertension Among Southeast Asian Young Adults: Role of Obesity as an Effect Modifier Wipawan C. Pensuksan, 1 Xiaoli Chen, 2 Vitool Lohsoonthorn, 3 Somrat Lertmaharit, 3,4 Bizu Gelaye, 2 and Michelle A. Williams 2 background Obstructive sleep apnea (OSA) has been linked to hypertension among middle-aged and older adults in Western countries. Few studies have focused on young adults, especially those in Southeast Asian countries undergoing epidemiologic transitions and experiencing elevated noncommunicable disease burden. We investigated associations of high risk for OSA with hypertension among Asian young adults. methods A total of 2,911 college students in Thailand participated in this study. The high risk for OSA was assessed using the Berlin Questionnaire. Blood pressure (BP) and anthropometric measurements were taken by trained research staff. Elevated BP and hypertension were defined as BP 120/80 mm Hg and 140/90 mm Hg, respectively. Multivariable logistic regression models were fit to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of elevated BP and hypertension. Stratified analyses were conducted to examine whether observed associations varied by weight status. results High risk for OSA was significantly associated with elevated BP (OR = 2.38; 95% CI = ) and hypertension (OR = 2.55; 95% CI = ) after adjustment for demographic and lifestyle factors. When body mass index was further controlled for, observed associations were greatly attenuated. The associations were only evident among overweight and obese students. conclusions The high risk for OSA among overweight and obese young adults is associated with elevated BP and hypertension. Enhanced efforts directed toward screening and diagnosing OSA and weight control among young adults could be one strategy for improving cardiovascular health. Keywords: blood pressure; college student; high risk; hypertension; obstructive sleep apnea; Thailand; weight status. doi: /ajh/hpt194 Hypertension is a major risk factor of cardiovascular diseases and mortality worldwide. 1 The National Health and Nutrition Examination Survey showed that the prevalence of hypertension was 6.8% among US adults aged years, 30.4% for those aged years, and 66.7% for those aged 60 years. 2 It has been reported that the prevalence of hypertension in Asia is similar to that in Western countries, but the awareness of hypertension is much lower than in Western countries. 3 Obstructive sleep apnea (OSA) is an increasingly common disorder in the general population, affecting 15 million US adults. 4 OSA is characterized by recurrent episodes of cessation of respiratory airflow caused by upper airway inspiratory collapse during sleep, with a consequent decrease in oxygen saturation. 4 OSA is highly prevalent in Western countries. 5,6 A recent systematic review has highlighted the lack of data on the OSA prevalence in Asia. 7 A growing body of evidence has shown that OSA is associated with adverse health outcomes, including hypertension. 5,8,9 Epidemiologic studies have documented associations of OSA with hypertension in both general and clinic-based populations. 5,8,10 14 Gus et al. reported that the risk for OSA assessed by the Berlin Questionnaire was significantly associated with resistant hypertension in a case control study in Brazil. 10 Another study by Drager et al. found that the Berlin Questionnaire was a good screening tool for the risk of OSA in the presence of hypertension in clinical populations. 15 It has been reported that successful treatment of OSA with continuous positive airway pressure (CPAP) can reduce blood pressure (BP) levels or lower the risk of hypertension. 14,16 Although OSA has been linked to hypertension in epidemiologic studies, most studies have been conducted among middle-aged and older adults in Western countries. 5,8,10,12 The associations of OSA with elevated BP Correspondence: Xiaoli Chen (xchen@hsph.harvard.edu). Initially submitted June 29, 2013; date of first revision July 29, 2013; accepted for publication September 19, 2013; online publication October 16, School of Nursing, Walailak University, Nakhon Si Thammarat, Thailand; 2 Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts; 3 Department of Preventive and Social Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; 4 College of Public Health Sciences, Chulalongkorn University, Bangkok, Thailand. American Journal of Hypertension, Ltd All rights reserved. For Permissions, please journals.permissions@oup.com American Journal of Hypertension 27(2) February

2 Pensuksan et al. and hypertension among young adults have not gained enough attention. Furthermore, the association between OSA and hypertension is complex. OSA and obesity often coexist and share multiple pathophysiological mechanisms, 17 and epidemiologic studies support associations between obesity and hypertension as well as the association between OSA and obesity. 4,12,18,19 As such, it is possible that part of the association between OSA and hypertension is related to the presence of obesity. Investigators of the Sleep Heart Health Study reported that adjustment for body mass index (BMI) diminished the strength of the association between OSA evaluated by the apnea-hypopnea index (AHI) and hypertension of adults aged 40 years. 8 However, most previous studies on the association between OSA and hypertension have adjusted for BMI, waist circumference (WC), or waistto-hip ratio (WHR), 5,8,10 13,20 a covariable considered to be in the causal pathway of OSA and hypertension. To our knowledge, few studies have assessed obesity as an effect modifier of the association between OSA and hypertension. This is an important concept given the rise in obesity worldwide, especially in Asian countries undergoing epidemiologic transitions and experiencing elevated noncommunicable disease burden. 21 This study aimed to examine associations of high risk for OSA with hypertension among young adults in Thailand. We tested whether the association between high risk for OSA and hypertension would be moderated by obesity, which usually coexists with OSA. METHODS Study population This cross-sectional study was conducted between December 2010 and February 2011 at 7 colleges in Thailand. The study procedures have been described elsewhere. 22 A total of 3,000 full-time undergraduate students participated in the study. Students with incomplete questionnaires and missing data for high risk for OSA were excluded (n = 89). Students excluded from our analyses were similar to the total population with regard to their demographic and lifestyle characteristics. The final analyzed sample included 2,911 (97.0%) college students (n = 964 men and 1,947 women) with complete information on demographic and lifestyle factors, high risk for OSA, BP, and anthropometric measurements. All the completed questionnaires were anonymous, and no personal identifiers were collected. All study procedures were approved by the institutional review boards of the Faculty of Medicine Chulalongkorn University and Walailak University in Thailand and the University of Washington in the United States. The Harvard School of Public Health Office of Human Research Administration granted approval to use the anonymous dataset for analysis. Measures Recruitment flyers were posted on each campus to invite college students to participate in the study. Students who expressed an interest in participating were asked to meet in a 230 American Journal of Hypertension 27(2) February 2014 large classroom or an auditorium where they were informed of the purpose of the study. Students who consented to participate were invited to complete a self-administered questionnaire survey regarding demographic information, lifestyle factors, and the Berlin Questionnaire. Measurements of BP, height, weight, WC, and hip circumference were taken by 3 trained research nurses following the same research instructions in all research sites after the questionnaire was completed. The Microlife BP 3AQ1 is a fully automatic, digital BP measuring device (Microlife AG, Espenstrasse Widnau, Switzerland). 23 A fan shape wide range (M-L size) cuff was used for the arm circumference ranging cm. Systolic and diastolic BP values were taken in a seated position after participants had rested for at least 5 minutes. All the BP and anthropometric measurements were taken twice, either in the late morning or afternoon, and the averages of these measurements were used in the data analyses. Elevated BP and hypertension. Elevated BP was defined as systolic BP 120 mm Hg or diastolic BP 80 mm Hg, without an upper limit. Participants with elevated BP can have prehypertension or hypertension, which was defined as BP 140/90 mm Hg. 1 High systolic BP was defined as systolic BP 140 mm Hg, and high diastolic BP was defined as diastolic BP 90 mm Hg. Isolated systolic hypertension (ISH) was defined as systolic BP 140 mm Hg and diastolic BP <90 mm Hg. Isolated diastolic hypertension (IDH) was defined as systolic BP <140 mm Hg and diastolic BP 90 mm Hg. 24 Risk factor for OSA. The Berlin Questionnaire was used for the assessment of high risk for OSA. The Berlin Questionnaire has been validated and widely used in previous studies. 25,26 The questionnaire is divided into 3 sections. Section 1 is about snoring behavior. Section 2 is about individuals feelings of fatigue, tiredness, and daytime sleepiness, and section 3 ascertains the presence of obesity or hypertension. In sections 1 and 2, high risk for OSA is considered when there is a persistent symptom (>3 4 times/week). In section 3, high risk for OSA is defined when there is a history of hypertension or BMI 30 kg/m 2. Individuals are considered as having a high risk for OSA if they are qualified as high risk in 2 or 3 sections. Covariables. Demographic information was collected for age, sex, and education level. Lifestyle factors investigated were moderate or vigorous physical activity participation, cigarette smoking history, alcohol consumption, and use of energy drinks. 22 Students were asked whether they consumed >1 stimulant or energy drink per week every month during the current academic semester/quarter. Lifestyle factors were summarized and categorized as dichotomous variables (no vs. yes). Measured weight and height were used to calculate BMI and to define normal weight (BMI <25 kg/m 2 ), overweight (BMI of kg/m 2 ), and obesity (BMI 30 kg/m 2 ). Central obesity was defined using the new International Diabetes Federation criteria for Asians: WC 90cm for men and WC 80cm for women. 27 WHR was calculated and

3 Sleep Apnea and Hypertension in Young Adults categorized by quartile distribution. Central obesity was also defined by the upper quartile of WHR ( Q3 = 0.831). Statistical analysis The exposure variable was high risk for OSA; the major outcome variables were elevated BP and hypertension. Unpaired t tests and χ 2 tests were conducted to evaluate the differences in covariables on either a continuous or discrete scale across the high risk for OSA status. Linear regression analyses were conducted to evaluate the associations of high risk for OSA with systolic BP and diastolic BP, with and without adjustment for covariables. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated using the logistic regression models to assess associations of high risk for OSA with elevated BP, hypertension, high systolic BP, high diastolic BP, ISH, and IDH. Potential confounders included age, sex, education, physical activity participation, alcohol consumption, use of energy drinks, and cigarette smoking. Potential effect modifier was obesity evaluated by BMI, WC, and WHR. Stratified analyses were conducted to examine whether observed associations varied by sex and obesity status. To address the concern that the Berlin Questionnaire was used to determine high risk for OSA, which might bias the association between high risk for OSA and hypertension/obesity, sensitivity analyses were conducted by restricting the definition of high risk for OSA to those with high risk in section 1 (snoring behavior) and section 2 (fatigue, tiredness, and daytime sleepiness) but not section 3 (history of hypertension or obesity). All tests were performed using Statistical Analysis Software (SAS version 9.3; SAS Institute, Cary, NC). The significance level was set at P < 0.05 for 2-sided analyses. RESULTS Of 2,911 college students, 33.1 % were men. The average age was 20.3 years (SD = 1.3). Overall, 6.3% of students had high risk for OSA, 12.9% had elevated BP, 4.6% had hypertension, 3.1% had high systolic BP, 2.7% had high diastolic BP, 1.9% had ISH, 1.4% had IDH, 9.6% were overweight (BMI of kg/m 2 ), and 4.5% were obese (BMI 30 kg/ m 2 ). Based on the International Diabetes Federation criteria, 12.3% of students were centrally obese. Factors related to high risk for OSA were male sex, older age, alcohol consumption, cigarette smoking, and the use of energy drinks. Students with high risk for OSA had higher BMI, WC, hip circumference, and WHR, higher systolic and diastolic BP values, and higher percentages of general and central obesity and hypertension than those without having high risk for OSA (Table 1). High risk for OSA was linearly and significantly related to systolic and diastolic BP values with and without adjustment for demographic and lifestyle factors (Table 2). For example, high risk for OSA was associated with higher systolic BP (β = 4.67; SE = 0.80; P < 0.001) and diastolic BP (β = 2.30; SE = 0.59; P < 0.001), after adjustment for sex, age, education, physical activity participation, alcohol consumption, use of energy drinks, and cigarette smoking. However, the associations became nonsignificant after BMI and/or WHR were further adjusted for, suggesting that these associations might be explained by obesity status. As shown in Table 3, high risk for OSA was strongly associated with elevated BP, hypertension, high systolic and diastolic BP, ISH, and IDH with adjustment for demographic and lifestyle factors. Students with high risk for OSA were more than 2 times as likely to have an elevated BP (OR = 2.38; 95% CI = ), hypertension (OR = 2.55; 95% CI = ), ISH (OR = 3.03; 95% CI = ), and IDH (OR = 2.78; 95% CI = ). When BMI was further controlled for, these associations were greatly attenuated (elevated BP: OR = 1.19, 95% CI = ; hypertension: OR = 1.12, 95% CI = ). Further adjustment for WHR did not change these estimates substantially. Because the obesity-adjusted estimates may be subject to overadjustment for the association between high risk for OSA and hypertension, we further conducted stratified analysis to examine whether the observed associations might vary by obesity status. Associations of high risk for OSA with elevated BP and hypertension were robust and evident for both men and women (Table 4). However, the associations were only evident among overweight and obese students with BMI 25 kg/m 2 and those with central obesity as measured by WC and WHR. Sensitivity analyses, completed after restricting the definition of high risk for OSA to those with snoring behavior and daytime sleepiness but not history of hypertension or obesity, showed similar but attenuated results. For example, high risk for OSA was associated with higher systolic BP (β = 4.17; SE = 1.18; P < 0.001) and diastolic BP (β = 1.71; SE = 0.79; P = 0.03) (Supplementary Table S1). The corresponding values in our primary analysis were β = 8.16 (SE = 0.94; P < 0.001) for systolic BP and β = 4.11 (SE = 0.63; P < 0.001) for diastolic BP (Table 2). Similarly, logistic regression analyses, conducted after restricting the high risk of OSA, yielded similar results for elevated BP and hypertension (Supplementary Table S2) as those reported in our primary analysis (Table 3). Discussion In this study, we found that 6.3% of college students had high risk for OSA, 12.9% had elevated BP, and 4.5% had hypertension. High risk for OSA was significantly associated with elevated BP and hypertension independent of demographic and lifestyle factors. The associations were only evident among overweight and obese college students. These results indicate that high risk for OSA may be related to elevated BP and hypertension and that weight control and early detection and treatment of OSA may be important modalities for preventing the development of hypertension among healthy young adults. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure, released almost a decade ago, recognized OSA as one of the 9 possible identifiable causes of hypertension. 1 The association between OSA and hypertension has been demonstrated in epidemiologic studies primarily American Journal of Hypertension 27(2) February

4 Pensuksan et al. Table 1. Characteristics of 2,911 college students in Thailand, according to high risk for obstructive sleep apnea status High risk for obstructive sleep apnea Variable Total (n = 2,911) No (n = 2,728) Yes (n = 183) P value a Age, y, mean (SD) 20.3 (1.3) 20.3 (1.3) 20.6 (1.5) Male sex, % <0.001 Physical activity participation, % Alcohol consumption, % <0.001 Cigarette smoking, % <0.001 Use of energy drinks, % BMI, kg/m 2, mean (SD) 21.6 (3.8) 21.4 (3.4) 25.9 (6.1) <0.001 Weight status, % Normal weight (BMI <25 kg/m 2 ) <0.001 Overweight (BMI = kg/m 2 ) Obese (BMI 30 kg/m 2 ) Central obesity b, % <0.001 Waist circumference, cm, mean (SD) 73.2 (9.4) 72.6 (8.5) 83.3 (14.3) <0.001 Hip circumference, cm, mean (SD) 91.2 (7.7) 90.7 (7.1) 98.7 (11.3) <0.001 Waist-to-hip ratio, mean (SD) 0.80 (0.05) 0.80 (0.05) 0.84 (0.06) <0.001 Systolic BP, mm Hg, mean (SD) (12.4) (12.1) (14.5) <0.001 Diastolic BP, mm Hg, mean (SD) 71.6 (8.4) 71.3 (8.2) 75.5 (9.4) <0.001 Elevated blood pressure c, % <0.001 Hypertension d, % <0.001 High systolic BP e, % <0.001 High diastolic BP f, % <0.001 Isolated systolic hypertension g, % <0.001 Isolated diastolic hypertension h, % <0.001 Abbreviations: BMI, body mass index; BP, blood pressure. a Unpaired t test for continuous variables; χ 2 test for categorical variables. b International Diabetes Federation definition of central obesity in Asia was used: waist circumference 90 cm for men and waist circumference 80 cm for women. c Elevated BP was defined as systolic BP 120 mm Hg or diastolic BP 80 mm Hg. d Hypertension was defined as systolic BP 140 mm Hg or diastolic BP 90 mm Hg. e High systolic BP was defined as systolic BP 140 mm Hg. f High diastolic BP was defined as diastolic BP 90 mm Hg. g Isolated systolic hypertension was defined as systolic BP 140 mm Hg and diastolic BP <90 mm Hg. h Isolated diastolic hypertension was defined as systolic BP <140 mm Hg and diastolic BP 90 mm Hg. Table 2. Linear regression analyses: association between high risk for obstructive sleep apnea and blood pressure among 2,911 college students in Thailand Systolic BP, mm Hg Diastolic BP, mm Hg Model β (SE) P value β (SE) P value Model 1: Unadjusted 8.16 (0.94) < (0.63) <0.001 Model 2: Adjusted for demographic 4.79 (0.80) < (0.59) <0.001 factors a Model 3: Model 2 + lifestyle factors b 4.67 (0.80) < (0.59) <0.001 Model 4: Model 3 + BMI 0.02 (0.81) (0.62) 0.96 Model 5: Model 3 + BMI + WHR 0.01 (0.81) (0.62) 0.95 Abbreviations: BMI, body mass index; BP, blood pressure; WHR, waist-to-hip ratio. a Demographic factors were age, sex, and education level. b Lifestyle factors were physical activity participation, alcohol consumption, use of energy drinks, and cigarette smoking. 232 American Journal of Hypertension 27(2) February 2014

5 Sleep Apnea and Hypertension in Young Adults Table 3. Logistic regression analyses: association between high risk for obstructive sleep apnea and hypertension among 2,911 college students in Thailand Elevated BP a Hypertension b High SBP c High DBP d ISH e IDH f Model OR (95% CI) OR (95% CI) OR (95% CI) OR (95% CI) OR (95% CI) OR (95% CI) Model 1: Unadjusted 3.17 ( ) 4.02 ( ) 3.86 ( ) 3.08 ( ) 4.89 ( ) 3.73 ( ) Model 2: Adjusted for 2.45 ( ) 2.67 ( ) 2.38 ( ) 2.08 ( ) 3.09 ( ) 2.91 ( ) demographic factors g Model 3: Model ( ) 2.55 ( ) 2.26 ( ) 1.93 ( ) 3.03 ( ) 2.78 ( ) lifestyle factors h Model 4: Model 3+ BMI Model 5: Model 3+ BMI+ WHR 1.19 ( ) 1.12 ( ) 0.94 ( ) 0.74 ( ) 1.75 ( ) 1.57 ( ) 1.19 ( ) 1.12 ( ) 0.93 ( ) 0.74 ( ) 1.74 ( ) 1.58 ( ) Abbreviations: BMI, body mass index; BP, blood pressure; CI, confidence interval; DBP, diastolic blood pressure; IDH, isolated diastolic hypertension; ISH, isolated systolic hypertension; OR, odds ratio; SBP, systolic blood pressure; WHR, waist-to-hip ratio. a Elevated BP defined as SBP 120 mmhg or DBP 80 mmhg. b Hypertension defined as SBP 140 mm Hg or DBP 90 mm Hg. c High SBP: SBP 140 mm Hg. d High DBP: DBP 140 mm Hg. e Definition of ISH: SBP 140 mm Hg and DBP <90 mm Hg f Definition of IDH: SBP <140 mm Hg and DBP 90 mm Hg. g Demographic factors were age, sex, and education level. h Lifestyle factors were physical activity participation, alcohol drinking, use of energy drinks, and cigarette smoking. Table 4. Stratified analysis for the association between high risk for obstructive sleep apnea and elevated blood pressure/hypertension among 2,911 college students in Thailand, according to sex and obesity status Elevated BP a Hypertension b Variable OR (95% CI) c OR (95% CI) c Sex Male 1.88 ( ) 2.38 ( ) Female 2.91 ( ) 3.27 ( ) P value for interaction Obesity status BMI <25 kg/m ( ) 1.23 ( ) BMI 25 kg/m ( ) 1.94 ( ) P value for interaction Central obesity status (based on WC) d No 1.07 ( ) 1.17 ( ) Yes 2.93 ( ) 1.84 ( ) P value for interaction Central obesity (based on WHR) WHR < Q ( ) 1.57 ( ) WHR Q ( ) 2.78 ( ) P value for interaction Abbreviations: BMI, body mass index; BP, blood pressure; CI, confidence interval; OR, odds ratio; WC, waist circumference; WHR, waistto-hip ratio. a Elevated BP was defined as systolic BP 120 mm Hg or diastolic BP 80 mm Hg. b Hypertension was defined as systolic BP 140 mm Hg or diastolic BP 90 mm Hg. c Age, sex, education, physical activity participation, alcohol consumption, use of energy drinks, and cigarette smoking were adjusted for. Sex was not adjusted for in the stratified analysis by sex. d International Diabetes Federation definition of central obesity in Asia: waist circumference 90 cm for men and waist circumference 80 cm for women. American Journal of Hypertension 27(2) February

6 Pensuksan et al. focused on middle-aged and old adults. 5,8,10,13 For example, the Wisconsin Sleep Cohort Study of healthy, communitybased, middle-aged adults has reported a dose response association between AHI and hypertension independent of obesity and other covariables. 5 A case control study of 120 hypertensive and 120 normotensive participants aged years in a clinic-based setting in Malaysia reported that persons with OSA (AHI 5) were more likely to have hypertension than those without OSA; adjustments for covariables including BMI decreased the magnitude of the association substantially. 28 Given the scarcity of population-based epidemiologic studies conducted among young adults, our study provide strong evidence that high risk for OSA is associated with elevated BP and hypertension in healthy Asian young adults. Emerging evidence suggest rapid acquisition of noncommunicable disease risk factors among youths in countries undergoing epidemiologic and demographic transitions. 21 The potential causal association between OSA and hypertension may involve both an independent role of OSA in the BP elevation and the obesity hypertension association. 1 Hypertension in normal weight and obese individuals might be mediated by different mechanisms. 29 A longitudinal study of 1,889 participants conducted in Spain reported that the association between OSA and hypertension remained statistically significant after adjustment for change in BMI during the follow-up (median = 12.2 years). 14 Cross-sectional analyses of 6,132 participants in the Sleep Heart Health Study showed that the association between OSA and hypertension was significant only among individuals with obesity (BMI 30 kg/m 2 ) (OR = 1.54; 95% CI = ). 8 Longitudinal analyses of 2,470 participants from the Sleep Heart Health Study showed that the OSA hypertension association was attenuated and not statistically significant after adjustment for baseline BMI, indicating that much of the relationship was accounted for by obesity. 6 In our study, the associations of high risk for OSA with elevated BP and hypertension were robust and evident for both men and women. However, the associations were only evident among students with BMI 25 kg/m 2 and those with central obesity as measured by WC (WC 90 cm for men and WC 80 cm for women) and WHR (WHR Q3 (0.831)), similar to the findings in the Sleep Heart Health Study. Further research is needed to examine whether the OSA hypertension association may vary by different populations, racial/ethnic groups, and OSA definition. Possible mechanisms for the association between OSA and hypertension in obese individuals include increased sympathetic activity, sleep disturbance, elevated angiotensin level, oxidative stress, systemic inflammation, endothelial dysfunction, renal dysfunction, and increased arterial stiffness. 4,30,31 Poorer sleep quality and shorter sleep duration due to OSA may play a reinforcing role in the fatigue and daytime sleepiness, which may elevate BP. 32 Untreated OSA has been shown to increase the risk of hypertension and cardiovascular events. 4 Effective treatment of OSA including continuous positive airway pressure has been reported to lower the BP level and the risk of hypertension, 4,33 35 suggesting a potential causal association between OSA and hypertension. Given that OSA is a risk factor for hypertension and cardiovascular disease and that continuous positive airway pressure treatment for OSA is highly effective and essentially safe, 36 individuals with high risk for OSA should be screened and treated to reduce BP level and related cardiovascular risk. Our study has strengths. First, this is a large, population-based, cross-sectional study of college students in Thailand. Second, the Berlin Questionnaire is a validated instrument that has been used widely to identify individuals who are at risk for OSA. 10,15,25,26 The measure of internal reliability, Cronbach s alpha coefficient, was 0.84, indicating good reliability in our study population. Third, we used several robust statistical approaches and different definitions of hypertension to evaluate the associations between high risk for OSA and hypertension. We also conducted stratified analyses to test effect modification of obesity for the association between high risk for OSA and hypertension. Our study has limitations. First, we did not use random sampling but instead considered subjects who were willing to participate in the study, so it was a convenient sample. 22 Hence, our findings may be subject to volunteer bias. Second, our study only included full-time Thai college students and did not include students taking classes in correspondence, extension, or night school programs. Thus, the results might not be generalized to those students and other racial/ethnic groups. Third, because this was a cross-sectional study, we were unable to determine the causal association between high risk for OSA and hypertension. Fourth, our study population was mainly recruited from female-dominated academic fields (e.g., arts, liberal arts, medicine, nursing), and may not be representative in the young adult population of Thailand. Fifth, we did not include participants information on medical history or health conditions, pregnancy for women, medication use, or sleep time, which could affect BP levels. In addition, we only used the Berlin Questionnaire to define high risk for OSA. Although polysomnography is the gold-standard test for the diagnosis of OSA in clinical settings, 13 it is expensive and time consuming and is not available in the general population. A systematic review has shown that the Berlin Questionnaire has a higher sensitivity and specificity (as high as 97%) in predicting OSA. 37 A study by Sharma et al. reported that the Berlin Questionnaire had a sensitivity of 86%, specificity of 95%, and positive and negative predictive values of 96% and 82%, respectively. 38 Some investigators have reported a lower sensitivity for screening OSA among health-care workers. 39 It is possible that the Berlin Questionnaire might have a high proportion of false negatives, hence, the prevalence of high risk for OSA may have been underestimated in our study population. The Berlin Questionnaire may identify individuals at high risk for OSA and thus can avoid expensive polysomnography studies, especially in resource-limited settings. Future prospective studies using overnight polysomnography are warranted to thoroughly elucidate bidirectional associations between OSA and hypertension among college students and other young adults. 234 American Journal of Hypertension 27(2) February 2014

7 Sleep Apnea and Hypertension in Young Adults In conclusion, we found that high risk for OSA was significantly associated with elevated BP and hypertension independent of demographic and lifestyle factors among young adults. The observed associations were only evident among overweight and obese college students. Further prospective studies on the longitudinal association between OSA and changes in BP and hypertension incidence will help elucidate the true nature and magnitude of the association among young adults. If our cross-sectional findings are confirmed in prospective studies, enhanced efforts directed toward weight control, as well as early detection through screening and diagnosing OSA among young adults, particularly those with other cardiovascular risk factors, could be one strategy for improving cardiovascular health. SUPPLEMENTARY MATERIAL Supplementary materials are available at American Journal of Hypertension ( Acknowledgments This work was supported by awards from the National Institutes of Health (National Institute on Minority Health and Health Disparities: T37-MD001449; and National Center for Research Resources and the National Center for Advancing Translational Sciences: 8UL1TR ). DISCLOSURE The authors declared no conflict of interest. References 1. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, Jones DW, Materson BJ, Oparil S, Wright JT Jr, Roccella EJ. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA 2003; 289: Yoon SS, Burt V, Louis T, Carroll MD. Hypertension among adults in the United States, NCHS Data Brief 2012; 107: Kim JS, Song WH, Shin C, Park CG, Seo HS, Shim WJ, Oh DJ, Ryu SH, Rho YM. 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