Sleep Medicine 16 (2015) 652–658
Contents lists available at ScienceDirect
Sleep Medicine j o u r n a l h o m e p a g e : w w w. e l s e v i e r. c o m / l o c a t e / s l e e p
Original Article
Nocturia is an independent predictive factor of prevalent hypertension in obstructive sleep apnea patients Marie Destors a,b,*, Renaud Tamisier a,c, Marc Sapene d, Yves Grillet e, Jean-Philippe Baguet f, Philippe Richard g, Janie Girey-Rannaud h, Sonia Dias-Domingos a,c, Francis Martin i, Bruno Stach j, Bruno Housset k, Patrick Levy a,c, Jean-Louis Pepin a,c a
HP2 Laboratory, INSERM U 1042, University Grenoble Alpes, Grenoble, France Service de Pneumologie, CHU Grenoble, Grenoble, France c Pôle Locomotion, Rééducation et Physiologie, CHU Grenoble, Grenoble, France d Unité Sommeil et Vigilance, Polyclinique Bordeaux Caudéran, Bordeaux, France e Pneumologie, Cabinet Médical, Valence, France f Unité d’Hypertension artérielle, Clinique de cardiologie, CHU de Grenoble, Grenoble, France g Pneumologie, Cabinet Médical, St-Omer, France h Pneumologie, Cabinet Médical, Grenoble, France i Unité des pathologies du sommeil, Centre hospitalier de Compiègne, Compiègne, France j Pneumologie, Cabinet Médical Saint Michel, Valenciennes, France k Service de Pneumologie, Centre Hospitalier Intercommunal Créteil, Créteil, France b
A R T I C L E
I N F O
Article history: Received 8 May 2014 Received in revised form 14 October 2014 Accepted 25 October 2014 Available online 29 January 2015 Keywords: Obstructive sleep apnea Hypertension Nocturia Cardiovascular risk
A B S T R A C T
Objective: The aim of this study was to determine whether nocturia is an independent predictor for prevalent hypertension in obstructive sleep apnea (OSA). Methods: We analyzed data from a national prospective clinical cohort of OSA patients participating in the French national prospective registry. Anthropometric data, comorbidities, OSA severity, and number of voids/night were included in multivariate analyses to determine the independent variables associated with prevalent hypertension. Results: A total of 22,674 OSA patients were included, of which 11,332 were hypertensive. The prevalence of hypertension among OSA patients was about 1.3 times higher in patients suffering from nocturia at 61.45% versus 46.52% in hypertensive and non-hypertensive OSA patients (p < 0.001). There was a significant positive relationship between hypertension and the severity of nocturia beyond two voids/ night: two voids/night versus none: odds ratio (OR) = 1.270 (95% confidence interval (CI) = 1.175; 1.372), three voids/night versus none: OR = 1.422 (95% CI = 1.293; 1.565), and four voids/night versus none: OR = 1.575 (95% CI = 1.394; 1.781). The strength of the association was enhanced in patients over 64 years of age. Conclusions: Nocturia is a strong independent predictor of prevalent hypertension in OSA. This association exhibited a “dose–response” relationship beyond two voids/night. The resolution of nocturia after continuous positive airway pressure (CPAP) treatment might be an important outcome to consider for the response of hypertension to CPAP. © 2014 Elsevier B.V. All rights reserved.
1. Introduction Nocturia is defined as waking at night one or more times in order to void before returning to sleep [1]. This is a common complaint with a prevalence that increases with age (27% in men 60 years of age) [2] and is the most frequent cause of nocturnal wakening in the general US population (75.5%)
* Corresponding author. Laboratoire EFCR, CHU de Grenoble, CS 10217, 38043 Grenoble Cedex 09, France. Tel.: +33 4 76 76 55 16; fax: +33 4 76 76 55 86. E-mail address: [email protected] (M. Destors). http://dx.doi.org/10.1016/j.sleep.2014.10.019 1389-9457/© 2014 Elsevier B.V. All rights reserved.
[3]. Thus, nocturia is associated with a poorer quality of life mainly explained by sleep loss and daytime sleepiness [4–6], with an increased prevalence of depressive symptoms [7–9], and a risk of falls and fractures in older patients [9]. In addition, data from the National Health and Nutrition Examination Survey III have shown nocturia to be a major predictor of mortality [10]. This increased mortality rate is certainly due to the association between nocturia and cardiovascular morbidities, such as diabetes, cardiac disease [11], stroke, and hypertension. The prevalence of hypertension in patients with nocturia is 10% higher [12,13] with a non-dipping pattern during sleep in ambulatory blood pressure monitoring (ABPM) [13]. Interestingly, nocturia is a common
M. Destors et al./Sleep Medicine 16 (2015) 652–658
symptom of sleep apnea syndrome (SAS); however, the association between nocturia and cardiovascular disease remained even after adjustment for SAS and other confounding factors [14]. In this context, we sought to determine whether nocturia is one of the features that predicts the occurrence of hypertension in obstructive sleep apnea (OSA). To accomplish this aim, we performed a cross-sectional analysis of a large national cohort of patients with OSA that contains information on anthropometrics, comorbidities, OSA, and nocturia severity. We hypothesized that nocturia was independently associated with prevalent hypertension in OSA patients with a “dose–response”-type relationship. 2. Methods 2.1. Study population and data source We report a cross-sectional analysis of data from a prospective national cohort, using the research database of the “Observatoire Sommeil de la Fédération de Pneumologie” (OSFP) (www.osfp.fr; date of consultation: 6 May 2013). The OSFP is a high-quality standardized web-based report, administered by the French Federation of Pneumology. It contains anonymized longitudinal data from patients complaining of sleep disorders, completed and validated by more than 500 respiratory physicians in private practice, general hospitals, and university hospitals. Periodic quality control checks are performed to ensure up-to-standard data recording. Ethical committee approval for setting up the database was obtained from “Le Comité consultatif sur le traitement de l’information en matière de recherche en santé” (CCTIRS n° 09.521) and authorization from the “Commission Nationale Informatique et Liberté” (CNIL), the French information technology and personal data protection authority. The OSFP Independent Scientific Advisory Committee approved data use for this study. All patients included in the database gave written informed consent. 2.2. Data collection and outcome Patients, over 18 years of age, who had a baseline medical visit reported in the OSFP database were screened for the following:
• • •
Diagnosis of obstructive sleep apnea syndrome (OSAS) [apnea/ hypopnea index (AHI) ≥ 15 events/h or oxygen desaturation index (ODI) ≥ 10 events/h] Number of voids/night Valid clinical blood pressure (BP) measurements
Patients were excluded from the studied population if they had central sleep apnea syndrome or obesity hypoventilation syndrome. Patients’ visits and clinical information collected in the OSFP include diagnoses, symptoms, procedures (ie, respiratory polygraphy or polysomnography), and the prescriptions issued at the first visit. Anthropometric data, Epworth Sleepiness Scale (ESS) [15], Pichot fatigue scale, and the Pichot depression scale [16,17] scores were also recorded. Nocturia was defined as waking at night one or more times to void. For each subject, the number of voids/night was specified. Hypertension was defined as systolic blood pressure (SBP)/diastolic blood pressure (DBP) > 140/90 mmHg or as hypertension selfreported by the patient and confirmed by the patient’s respiratory physician. 2.3. Statistical analysis Data were analyzed using Statistical Analysis System (SAS®) software version 9.1.3 (SAS Institute, Cary, NC, USA). Continuous data
653
were expressed as mean (SD) or median (IQR) and categorical data as percentage. Univariate conditional logistic regression models were used to compare all the variables between hypertensive and nonhypertensive OSA patients. When the log-linearity of a continuous variable was not respected, the variable was converted to categorical data (with quartiles). Variables which were associated with the risk of being hypertensive in univariate analysis (p < 0.05) were included in a multivariable conditional logistic regression model (backward selection). In this model testing nocturia and hypertension, covariables were age, sex, body mass index(BMI), alcohol consumption, AHI (total test and 24/h–34/h vs. < 24/h, 34/h–50/h vs. < 24/h, ≥ 50/h vs. < 24/h), chronic obstructive pulmonary disease (COPD), myocardial infarction, coronary heart disease, heart failure, arrhythmias, stroke, gastroesophageal reflux, diabetes (total and type 1 vs. 0, type 2 vs. 0), hypercholesterolemia, hypertriglyceridemia, and depression. Colinearity between variables was verified by Pearson’s coefficient, Spearman’s coefficient, or Cramer’s V2. The variables with >15% of missing data were not included in the logistic regression. These missing values (
Contents lists available at ScienceDirect
Sleep Medicine j o u r n a l h o m e p a g e : w w w. e l s e v i e r. c o m / l o c a t e / s l e e p
Original Article
Nocturia is an independent predictive factor of prevalent hypertension in obstructive sleep apnea patients Marie Destors a,b,*, Renaud Tamisier a,c, Marc Sapene d, Yves Grillet e, Jean-Philippe Baguet f, Philippe Richard g, Janie Girey-Rannaud h, Sonia Dias-Domingos a,c, Francis Martin i, Bruno Stach j, Bruno Housset k, Patrick Levy a,c, Jean-Louis Pepin a,c a
HP2 Laboratory, INSERM U 1042, University Grenoble Alpes, Grenoble, France Service de Pneumologie, CHU Grenoble, Grenoble, France c Pôle Locomotion, Rééducation et Physiologie, CHU Grenoble, Grenoble, France d Unité Sommeil et Vigilance, Polyclinique Bordeaux Caudéran, Bordeaux, France e Pneumologie, Cabinet Médical, Valence, France f Unité d’Hypertension artérielle, Clinique de cardiologie, CHU de Grenoble, Grenoble, France g Pneumologie, Cabinet Médical, St-Omer, France h Pneumologie, Cabinet Médical, Grenoble, France i Unité des pathologies du sommeil, Centre hospitalier de Compiègne, Compiègne, France j Pneumologie, Cabinet Médical Saint Michel, Valenciennes, France k Service de Pneumologie, Centre Hospitalier Intercommunal Créteil, Créteil, France b
A R T I C L E
I N F O
Article history: Received 8 May 2014 Received in revised form 14 October 2014 Accepted 25 October 2014 Available online 29 January 2015 Keywords: Obstructive sleep apnea Hypertension Nocturia Cardiovascular risk
A B S T R A C T
Objective: The aim of this study was to determine whether nocturia is an independent predictor for prevalent hypertension in obstructive sleep apnea (OSA). Methods: We analyzed data from a national prospective clinical cohort of OSA patients participating in the French national prospective registry. Anthropometric data, comorbidities, OSA severity, and number of voids/night were included in multivariate analyses to determine the independent variables associated with prevalent hypertension. Results: A total of 22,674 OSA patients were included, of which 11,332 were hypertensive. The prevalence of hypertension among OSA patients was about 1.3 times higher in patients suffering from nocturia at 61.45% versus 46.52% in hypertensive and non-hypertensive OSA patients (p < 0.001). There was a significant positive relationship between hypertension and the severity of nocturia beyond two voids/ night: two voids/night versus none: odds ratio (OR) = 1.270 (95% confidence interval (CI) = 1.175; 1.372), three voids/night versus none: OR = 1.422 (95% CI = 1.293; 1.565), and four voids/night versus none: OR = 1.575 (95% CI = 1.394; 1.781). The strength of the association was enhanced in patients over 64 years of age. Conclusions: Nocturia is a strong independent predictor of prevalent hypertension in OSA. This association exhibited a “dose–response” relationship beyond two voids/night. The resolution of nocturia after continuous positive airway pressure (CPAP) treatment might be an important outcome to consider for the response of hypertension to CPAP. © 2014 Elsevier B.V. All rights reserved.
1. Introduction Nocturia is defined as waking at night one or more times in order to void before returning to sleep [1]. This is a common complaint with a prevalence that increases with age (27% in men 60 years of age) [2] and is the most frequent cause of nocturnal wakening in the general US population (75.5%)
* Corresponding author. Laboratoire EFCR, CHU de Grenoble, CS 10217, 38043 Grenoble Cedex 09, France. Tel.: +33 4 76 76 55 16; fax: +33 4 76 76 55 86. E-mail address: [email protected] (M. Destors). http://dx.doi.org/10.1016/j.sleep.2014.10.019 1389-9457/© 2014 Elsevier B.V. All rights reserved.
[3]. Thus, nocturia is associated with a poorer quality of life mainly explained by sleep loss and daytime sleepiness [4–6], with an increased prevalence of depressive symptoms [7–9], and a risk of falls and fractures in older patients [9]. In addition, data from the National Health and Nutrition Examination Survey III have shown nocturia to be a major predictor of mortality [10]. This increased mortality rate is certainly due to the association between nocturia and cardiovascular morbidities, such as diabetes, cardiac disease [11], stroke, and hypertension. The prevalence of hypertension in patients with nocturia is 10% higher [12,13] with a non-dipping pattern during sleep in ambulatory blood pressure monitoring (ABPM) [13]. Interestingly, nocturia is a common
M. Destors et al./Sleep Medicine 16 (2015) 652–658
symptom of sleep apnea syndrome (SAS); however, the association between nocturia and cardiovascular disease remained even after adjustment for SAS and other confounding factors [14]. In this context, we sought to determine whether nocturia is one of the features that predicts the occurrence of hypertension in obstructive sleep apnea (OSA). To accomplish this aim, we performed a cross-sectional analysis of a large national cohort of patients with OSA that contains information on anthropometrics, comorbidities, OSA, and nocturia severity. We hypothesized that nocturia was independently associated with prevalent hypertension in OSA patients with a “dose–response”-type relationship. 2. Methods 2.1. Study population and data source We report a cross-sectional analysis of data from a prospective national cohort, using the research database of the “Observatoire Sommeil de la Fédération de Pneumologie” (OSFP) (www.osfp.fr; date of consultation: 6 May 2013). The OSFP is a high-quality standardized web-based report, administered by the French Federation of Pneumology. It contains anonymized longitudinal data from patients complaining of sleep disorders, completed and validated by more than 500 respiratory physicians in private practice, general hospitals, and university hospitals. Periodic quality control checks are performed to ensure up-to-standard data recording. Ethical committee approval for setting up the database was obtained from “Le Comité consultatif sur le traitement de l’information en matière de recherche en santé” (CCTIRS n° 09.521) and authorization from the “Commission Nationale Informatique et Liberté” (CNIL), the French information technology and personal data protection authority. The OSFP Independent Scientific Advisory Committee approved data use for this study. All patients included in the database gave written informed consent. 2.2. Data collection and outcome Patients, over 18 years of age, who had a baseline medical visit reported in the OSFP database were screened for the following:
• • •
Diagnosis of obstructive sleep apnea syndrome (OSAS) [apnea/ hypopnea index (AHI) ≥ 15 events/h or oxygen desaturation index (ODI) ≥ 10 events/h] Number of voids/night Valid clinical blood pressure (BP) measurements
Patients were excluded from the studied population if they had central sleep apnea syndrome or obesity hypoventilation syndrome. Patients’ visits and clinical information collected in the OSFP include diagnoses, symptoms, procedures (ie, respiratory polygraphy or polysomnography), and the prescriptions issued at the first visit. Anthropometric data, Epworth Sleepiness Scale (ESS) [15], Pichot fatigue scale, and the Pichot depression scale [16,17] scores were also recorded. Nocturia was defined as waking at night one or more times to void. For each subject, the number of voids/night was specified. Hypertension was defined as systolic blood pressure (SBP)/diastolic blood pressure (DBP) > 140/90 mmHg or as hypertension selfreported by the patient and confirmed by the patient’s respiratory physician. 2.3. Statistical analysis Data were analyzed using Statistical Analysis System (SAS®) software version 9.1.3 (SAS Institute, Cary, NC, USA). Continuous data
653
were expressed as mean (SD) or median (IQR) and categorical data as percentage. Univariate conditional logistic regression models were used to compare all the variables between hypertensive and nonhypertensive OSA patients. When the log-linearity of a continuous variable was not respected, the variable was converted to categorical data (with quartiles). Variables which were associated with the risk of being hypertensive in univariate analysis (p < 0.05) were included in a multivariable conditional logistic regression model (backward selection). In this model testing nocturia and hypertension, covariables were age, sex, body mass index(BMI), alcohol consumption, AHI (total test and 24/h–34/h vs. < 24/h, 34/h–50/h vs. < 24/h, ≥ 50/h vs. < 24/h), chronic obstructive pulmonary disease (COPD), myocardial infarction, coronary heart disease, heart failure, arrhythmias, stroke, gastroesophageal reflux, diabetes (total and type 1 vs. 0, type 2 vs. 0), hypercholesterolemia, hypertriglyceridemia, and depression. Colinearity between variables was verified by Pearson’s coefficient, Spearman’s coefficient, or Cramer’s V2. The variables with >15% of missing data were not included in the logistic regression. These missing values (
