880 Exp Physiol 93.7 pp 880–891 Experimental Physiology Overnight variability in transcutaneous carbon dioxide predicts vascular impairment in women Jenni Aittokallio 1 , Olli Polo 1,2 , Jukka Hiissa 3 , Arho Virkki 3 , Jyri Toikka 4,5 , Olli Raitakari 5 , Tarja Saaresranta 1,6 and Tero Aittokallio 1,3,7 1 Sleep Research Unit, Department of Physiology and 3 Biomathematics Research Group, Department of Mathematics, University of Turku, Finland Departments of 2 Pulmonary Diseases and 4 Clinical Physiology and Nuclear Medicine, Tampere University Hospital, Tampere, Finland Departments of 5 Clinical Physiology and Nuclear Medicine and 6 Pulmonary Diseases, Turku University Central Hospital, Turku, Finland 7 Systems Biology Unit, Institut Pasteur, Paris, France While there are a number of studies demonstrating association between arterial oxyhaemoglobin saturation events during sleep and markers of vascular impairment, the contribution of peripheral carbon dioxide to the development of atherosclerosis is poorly understood. We used ultrasound imaging to measure carotid artery intima–media thickness (IMT), as well as flow-mediated dilatation (FMD) and nitroglycerin-mediated dilatation (NMD) of brachial artery, in 103 generally healthy 46-year-old (±2 years) women. Characteristic event patterns were extracted from their overnight recordings of arterial oxyhaemoglobin saturation ( S aO 2 ), end-tidal partial pressure of carbon dioxide ( P ET,CO 2 ) and transcutaneous partial pressure of carbon dioxide ( P TC,CO 2 ). Importance of the event patterns was evaluated through predictive modelling of classes of the ultrasound measurements while controlling for potential confounders. Prediction accuracy was assessed with cross-validation and reported as the area under the receiver operating characteristic curve (AUC). Overnight P TC,CO 2 patterns predicted each of the ultrasound measurements with high accuracy (IMT, AUC = 0.70; FMD, AUC = 0.75; and NMD, AUC = 0.81; all with P < 0.001). Adding the S aO 2 or P ET,CO 2 patterns into the models did not significantly increase their predictive powers (AUC = 0.72, AUC = 0.77 and AUC = 0.83, respectively). The most important patterns reflected overnight variability in P TC,CO 2 . These results suggest a novel link between overnight carbon dioxide events and early signs of vascular impairment in middle-aged women. Non-invasive P TC,CO 2 measurements combined with non-linear modelling techniques could be used to reveal potential markers of vascular impairment present in relatively healthy subjects. (Received 9 November 2007; accepted after revision 18 February 2008; first published online 22 February 2008) Corresponding author J. Aittokallio: Sleep Research Unit, University of Turku, Dentalia, Lemmink¨ aisenkatu 2, FI-20520 Turku, Finland. Email: jemato@utu.fi Current evidence supports an independent association between obstructive sleep apnoea (OSA) and increased cardiovascular risk as assessed with multiple measurement techniques (Foster et al. 2007; McNicholas & Bonsigore, 2007). Several studies have shown that OSA patients have increased carotid artery intima–media thickness (IMT; Drager et al. 2005; Schulz et al. 2005), which is an established marker of subclinical atherosclerosis (Salonen & Salonen, 1990). The IMT correlates with conventional This paper has online supplemental material. vascular risk factors, as well as predicting the likelihood of cardiovascular and cerebrovascular events (Bots et al. 1997). The severity and duration of hypoxaemia during OSA events are related to IMT thickening (Suzuki et al. 2004; Minoguchi et al. 2005). Arterial endothelial dysfunction is another key early event in atherosclerosis (Celermajer et al. 1992). Endothelial dysfunction is related to many known risk factors for vascular diseases, including smoking (Celermajer et al. 1992), visceral obesity (Chudek & Wiecek, 2006), hypertension (Panza et al. 1990), hypercholesterolaemia (Celermajer et al. 1992), diabetes DOI: 10.1113/expphysiol.2007.041277 C  2008 The Authors. Journal compilation C  2008 The Physiological Society