J Sleep Res. (2015) 24, 680–686

Oxygen saturation and atherosclerosis

Minimal nocturnal oxygen saturation predicts future subclinical carotid atherosclerosis: the Wisconsin sleep cohort SVERRIR I. GUNNARSSON1,2, PAUL E. PEPPARD1,2, CLAUDIA E. KORCARZ1,2, JODI H. BARNET1,2, ERIKA W. HAGEN1,2, K. MAE HLA1,2, M A R I P A L T A 1 , 2 , T E R R Y Y O U N G 1 , 2 and J A M E S H . S T E I N 1 , 2 1

Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; and 2Department of Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA

Keywords carotid arteries, epidemiology, sleep apnea Correspondence James H. Stein, MD, School of Medicine and Public Health, University of Wisconsin, 600 Highland Avenue, H4/520 CSC (MC 3248), Madison, WI 53792, USA. Tel.: (608)-265-4188; fax: (608)-263-0405; e-mail: [email protected] Accepted in revised form 26 May 2015; received 12 December 2014 DOI: 10.1111/jsr.12321

SUMMARY

Previous data on the associations between nocturnal oxygen saturation parameters and carotid atherosclerosis are conflicting. We examined the prospective associations of nocturnal oxygen saturation (SaO2) and cardiovascular disease (CVD) risk factors with carotid intima-media thickness (IMT) and plaques. We used data on 689 Wisconsin sleep cohort participants who had baseline overnight polysomnography followed by carotid ultrasonography a mean (SD) of 7.8 (2.5) years later. Far wall common carotid IMT was measured using B-mode ultrasound. Bilateral common, bifurcation and internal carotid artery segments were evaluated for plaque score. Participants (8) were aged 56 years (55% male); 32% had hypertension and mean body mass index (BMI) was 31 (7) kg m2. Mean and minimum nocturnal SaO2 were 95% (2) and 86% (7), respectively. Mean percentage sleep time with SaO2 < 90% was 2% (8). Both mean (odds ratio [OR]: 0.60 lower plaque count per 5% higher mean SaO2, 95% confidence interval [CI]: 0.38–0.96, P = 0.033) and minimum SaO2 (OR: 0.88 lower plaque count per 5% higher minimum SaO2, 95% CI: 0.80–0.97, P = 0.013) predicted carotid plaque score after adjusting for age, sex and BMI. Minimum SaO2 predicted future plaque score after adding adjustment for traditional CVD risk factors (OR: 0.90 lower plaque count per 5% higher minimum SaO2, 95% CI: 0.81–0.99, P = 0.038). Mean SaO2 was not associated with carotid IMT after CVD risk factor adjustment. We conclude that minimum nocturnal SaO2 is an independent predictor of future carotid plaque burden. Other nocturnal SaO2 parameters are not associated with future carotid IMT or plaques after adjusting for traditional CVD risk factors.

INTRODUCTION Obstructive sleep apnea (OSA) is associated with increased risk of cardiovascular disease (CVD), and is characterized by repeated episodes of airway obstruction with a concomitant decrease in oxygen saturation (Campos-Rodriguez et al., 2005; Marin et al., 2005; Somers et al., 2008; Young et al., 2008). Repetitive hypoxic insults may lead to endothelial dysfunction, arterial injury and, eventually, atherosclerosis (Jelic et al., 2008; Kraiczi et al., 2001; Yokoe et al., 2003). OSA is an important public health concern due to its rising prevalence, probably related to the obesity epidemic (Peppard et al., 2000, 2013). Carotid artery intima-media thickness

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(IMT) and carotid artery plaques are established markers of subclinical arterial disease that predict future CVD events (Den Ruijter et al., 2012; Inaba et al., 2012; Stein et al., 2008a). We have shown previously that the apnea–hypopnea index (AHI) is associated with greater future carotid atherosclerosis (Gunnarsson et al., 2014). However, existing data on associations between nocturnal oxygen saturation parameters and carotid atherosclerosis are limited to small crosssectional and case–control studies that have shown conflicting results (Baguet et al., 2005, 2009; Drager et al., 2005, 2010; Minoguchi et al., 2005; Ozdemir et al., 2013; Protogerou et al., 2007; Saletu et al., 2006; Schulz et al., 2005; ova  et al., 2007; Tan et al., 2012). Suzuki et al., 2004; Szabo ª 2015 European Sleep Research Society

Nocturnal oxygen saturation and carotid plaque Also, very few studies have looked at the relationships between oxygen saturation parameters and plaques (Baguet et al., 2005; Saletu et al., 2006; Schulz et al., 2005). Thus, we undertook this study to investigate the prospective associations of baseline nocturnal oxygen saturation parameters with carotid IMT and plaque score using data from the Wisconsin sleep cohort study, a large cohort study of the natural history of OSA in adults. We hypothesized that the severity of oxygen desaturation would predict higher future carotid IMT and carotid plaques and that the associations would persist after adjusting for body mass index (BMI) and other CVD risk factors. METHODS Participants and study procedures The study was approved by the UW Health Sciences Institutional Review Board. All subjects provided free informed consent for participation in all study activities. The design of the parent study, the Wisconsin sleep cohort study (WSCS), begun in 1989, has been reported previously (Peppard et al., 2013). The protocol for the current investigation of nocturnal saturation and subclinical carotid atherosclerosis was added in 2004. Subjects underwent in-laboratory overnight polysomnography from August 2000 to September 2013 (see Fig. 1). Methods for performing and interpreting these polysomnograms have been described elsewhere (Young et al., 1993). Note that between 1988 and 2000, sleep studies were scored using a paper-based system; since 2000, studies have been scored on a computer. All statistical modelling adjusts for the scoring Wisconsin Sleep Cohort Study Participants (n = 1522) Excluded: Not invited or available to participate in Daytime Visit (10/2004-12/2008) or Overnight Visit (9/2009-9/2013 (n = 565) Completed WSCS Visit between 2004-2013 (n = 957) Excluded: Did not complete the IMT protocol (n = 108) Completed IMT Visit (n = 849) Excluded: Incomplete oximetry data (n = 92) Using CPAP at SaO2 visit (n = 47) Incomplete covariate data (n = 21)

Complete IMT and SaO2 Data (n = 689)

Figure 1. Participant flow diagram. ª 2015 European Sleep Research Society

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changes; this removes instrumentation-related influences on sleep-disordered breathing assessments after 2000. The polysomnography variables of interest were mean nocturnal oxygen saturation (mean SaO2), minimum nocturnal oxygen saturation (minimum SaO2), defined as the lowest saturation reached during sleep, and percentage of time spent asleep with oxygen saturation below 90% (TST < 90%). Arterial oxygen saturation (SaO2) was measured using pulse oximetry (Datex-Ohmeda 3900 Pulse Oximeter; Datex-Ohmeda Inc., Madison, WI, USA). All values of SaO2 < 50% were considered to be measurement error and were excluded. Only five subjects had minimum saturation

Minimal nocturnal oxygen saturation predicts future subclinical carotid atherosclerosis: the Wisconsin sleep cohort.

Previous data on the associations between nocturnal oxygen saturation parameters and carotid atherosclerosis are conflicting. We examined the prospect...
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