Cluster analysis identifies a pathophysiologically distinct subpopulation with increased serum leptin levels and severe
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SLEEP BREATHING PHYSIOLOGY AND DISORDERS • ORIGINAL ARTICLE
Cluster analysis identifies a pathophysiologically distinct subpopulation with increased serum leptin levels and severe obstructive sleep apnea Yutaka Kozu 1 & Yusuke Kurosawa 1 & Shiho Yamada 1 & Asami Fukuda 1 & Mari Hikichi 1 & Hisato Hiranuma 1 & Toshiki Akahoshi 1 & Yasuhiro Gon 1 Received: 20 March 2020 / Revised: 27 July 2020 / Accepted: 1 August 2020 # The Author(s) 2020
Abstract Purpose To investigate the different pathophysiologies of obstructive sleep apnea (OSA) phenotypes using cluster analysis. Differences between leptin/adiponectin levels in the resulting OSA phenotypes were also examined. Methods In total, 1057 OSA patients were selected, and a retrospective survey of clinical records, polysomnography results, and blood gas data was conducted. Patients were grouped into four clusters by their OSA severity, PaCO2, body mass index (BMI), and sleepiness. A k-means cluster analysis was performed, resulting in a division into four subpopulations. The Tukey or GamesHowell tests were used for intergroup comparisons. Results Among the 20 clinical OSA items, four common factors (Epworth Sleepiness Scale [ESS], BMI, Apnea-Hypopnea Index [AHI], and PaCO2) were extracted by principal component analysis, and a cluster analysis was performed using the k-means method, resulting in four distinct phenotypes. The Clusters 1 (middle age, symptomatic severe OSA) and 4 (young, obese, symptomatic very severe OSA) exhibited high leptin levels. C-reactive protein levels were also elevated in Cluster 4, indicating a different pathophysiological background. No apparent differences between clusters were observed regarding adiponectin/leptin ratios and adiponectin levels. Classification into groups based on phenotype showed that Epworth Sleepiness Scale [ESS] score and disease severity were not correlated, suggesting that sleepiness is affected by multiple elements. Conclusions The existence of multiple clinical phenotypes suggests that different pathophysiological backgrounds exist such as systemic inflammation and metabolic disorder. This classification may be used to determine the efficacy of continuous positive airway pressure treatment that cannot be determined by the AHI. Keywords Obstructive sleep apnea . Phenotypes . Cluster analysis . Leptin . Blood gas analysis
Introduction The prevalence of obstructive sleep apnea (OSA) was reported 20 years ago by Young and colleagues, affecting up to 9% of men and 4% of women [1–4]. Although there have been no major epidemiological studies in Japan, OSA prevalence rates in men in their 40s and 50s are 23.4% and 30.6%, respectively
* Yutaka Kozu [email protected] 1
Division of Respiratory Disease, Nihon University School of Medicine, 30-1 Ohyaguchi-Kamicho, Itabashiku, Tokyo 173-8610, Japan
[2]. The OSA prevalence in Japan is comparable with that in Europe and the USA. OSA substantially complicates cardiovascular diseases and they are important factors in determining the OSA prognosis. Repeated nocturnal hypo
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