CLINICAL REVIEW Systematic review on noninvasive assessment of subclinical cardiovascular disease in obstructive sleep apnea: new kid on the block! Shozab S. Ali a, b , Ebenezer T. Oni a , Haider J. Warraich c , Michael J. Blaha e , Roger S. Blumenthal e , Adil Karim a , Sameer Shaharyar a , Omar Jamal a , Jonathan Fialkow f , Ricardo Cury f , Matthew J. Budoff g , Arthur S. Agatston a , Khurram Nasir a, d, e, h, * a Center for Prevention and Wellness Research, Baptist Health Medical Group, Miami FL, USA b University of Manchester School of Medicine, Manchester, United Kingdom c Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA d Department of Epidemiology, Robert Stempel College of Public Health, Florida International University, Miami, FL, USA e Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Johns Hopkins University, Baltimore, MD, USA f Baptist Hospital of Miami and Baptist Cardiac & Vascular Institute, Miami, FL, USA g Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, CA, USA h Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA article info Article history: Received 11 September 2013 Received in revised form 24 January 2014 Accepted 24 January 2014 Available online xxx Keywords: Obstructive sleep apnea Atherosclerosis Endothelial dysfunction Cardiovascular disease Coronary artery calcium Intima media thickness Flow-mediated dilation Pulse wave velocity summary Patients with obstructive sleep apnea (OSA) have a high burden of cardiovascular disease (CVD) but a causal relationship between OSA and atherosclerotic CVD remains unclear. We systematically reviewed the literature analyzing the relationship. A review of the Medline database for studies noninvasively evaluating subclinical CVD in OSA was conducted. A total of fifty-two studies were included in this review. Across the studies the prevalence of atherosclerosis, as assessed by coronary artery calcification, ca- rotid intima-media thickness, brachial artery flow-mediated dilation and pulse wave velocity was higher in patients with OSA and correlated with increasing severity and duration of OSA. This study shows OSA is an independent predictor of subclinical CVD as CVD is more likely to occur in patients with long standing and severe OSA. Further research is however necessary to identify specific OSA populations that would benefit from aggressive screening. Ó 2014 Elsevier Ltd. All rights reserved. Introduction Obstructive sleep apnea (OSA) is a clinical disorder character- ized by alternating episodes of apnea and hypopnea. OSA is defined as an apnea/hypopnea index (AHI) of 5 events/h. The burden is enormous as it affects about 4% of middle-aged men and 2% of middle-aged women [1,2]. OSA affects an estimated 15 million adult Americans [3]. It is estimated that 93% of women and 82% of men with moderate to severe sleep apnea syndrome have not been clinically diagnosed [4]. The prevalence of OSA is slated to increase considerably in concert with the global obesity pandemic. This disorder is associated with high rates of morbidity and mortality [5]. Moderate to severe sleep apnea has been described as an in- dependent predictor of mortality [6] and it is well established that these patients have an increased risk of cardiovascular disease (CVD) and cardiovascular death [5,7e9]. However, whether early accelerated atherosclerosis and endothelial dysfunction are the primary drivers of this phenomenon remains to be clearly estab- lished [10]. Early recognition of atherosclerotic changes in these patients may significantly impact risk stratification and subsequent risk factor reduction in these patients. Traditional risk stratification has * Corresponding author. Center for Prevention and Wellness Research, Baptist Health Medical Group, 1691 Michigan Avenue, Suite 500, Miami Beach, FL 33139, USA. E-mail addresses: KhurramN@baptisthealth.net, knasir1@jhmi.edu (K. Nasir). Contents lists available at ScienceDirect Sleep Medicine Reviews journal homepage: www.elsevier.com/locate/smrv 1087-0792/$ e see front matter Ó 2014 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.smrv.2014.01.004 Sleep Medicine Reviews xxx (2014) 1e13 Please cite this article in press as: Ali SS, et al., Systematic review on noninvasive assessment of subclinical cardiovascular disease in obstructive sleep apnea: new kid on the block!, Sleep Medicine Reviews (2014), http://dx.doi.org/10.1016/j.smrv.2014.01.004