Anna Randby

A Norwegian population‐based study on the risk and prevalence of obstructive sleep apnea The Akershus Sleep Apnea Project (ASAP)

The Berlin Questionnaire (BQ) is a widely used screening tool for obstructive sleep apnea (OSA), but its performance in the general population setting is unknown. The prevalence of OSA in middle‐aged adults is not known in Norway. Accordingly, the aims of the current study were to evaluate the utility of the BQ for OSA screening in the general population and to estimate the prevalence of OSA in Norway. The study population consisted of 29 258 subjects (aged 30–65 years, 50% female) who received the BQ by mail. Of these, 16 302 (55.7%) responded. Five‐hundred and eighteen subjects were included in the clinical sample and underwent in‐hospital polysomnography. Screening properties and prevalence were estimated by a statistical model that adjusted for bias in the sampling procedure. Among the 16 302 respondents, 24.3% (95% confidence interval (CI) = 23.6–25.0%) were classified by the BQ to be at high‐risk of having OSA. Defining OSA as an apnea–hypopnea index (AHI) ≥5, the positive predictive value of the BQ was estimated to be 61.3%, the negative predictive value 66.2%, the sensitivity 37.2% and the specificity 84.0%. Estimated prevalences of OSA were 16% for AHI ≥ 5 and 8% for AHI ≥ 15. In conclusion, the BQ classified one out of four middle‐aged Norwegians to be at high‐risk of having OSA, but the screening properties of the BQ were suboptimal. The estimated prevalence of OSA was comparable to previous estimates from general populations in the USA, Australia and Europe.

Impaired endothelial function in persons with obstructive sleep apnoea: impact of obesity

Objective Obstructive sleep apnoea (OSA) and obesity are both associated with endothelial dysfunction, which precedes the development of atherosclerosis. As obesity is highly prevalent in OSA, we wanted to test the hypothesis that OSA is associated with endothelial dysfunction independently of obesity. Design Cross-sectional, population-based study. Setting Norwegian university hospital. Patients Seventy-one subjects (median age 44 years, 35% female) were recruited from a population-based study in Norway. Participants were categorised as obese (body mass index (BMI) ≥30 kg/m2), non-obese (BMI<30 kg/m2) with OSA (apnoea–hypopnoea index (AHI)≥10), or non-obese without OSA (AHI<5). Interventions None. Main outcome measures Endothelial function measured by brachial artery ultrasound and expressed as percentage of flow-mediated dilation (FMD%). Results When non-obese subjects without OSA were used as the reference (FMD% (mean±SD) 10.1±6.3), endothelial function was found to be impaired in subjects with OSA (FMD% 6.4±3.2) (p=0.003). FMD% did not differ between obese (6.0±3.4) and non-obese (6.7±3.1) OSA subjects (p=0.3). By univariate linear regression analysis, AHI, BMI, gender and baseline brachial artery diameter were significantly associated with FMD%. When these variables were entered into a multivariate model, only AHI was significantly associated with FMD%. Conclusions OSA is associated with endothelial dysfunction independently of obesity and conventional risk factors.

Obstructive Sleep Apnea Is Associated With Increased High-Sensitivity Cardiac Troponin T Levels

BACKGROUND Obstructive sleep apnea (OSA) is associated with increased cardiovascular risk. Stress imposed on the myocardium by repeated severe hypoxemia and/or BP surges during sleep may result in subclinical myocardial injury. A high-sensitivity cardiac troponin T (hs-cTnT) assay has been developed. We hypothesized that the severity of OSA, as assessed by the apnea-hypopnea index (AHI), is associated with circulating levels of hs-cTnT in the general population. METHODS Five hundred five subjects drawn from the general population (age range, 30-65 years; 45% women) underwent in-hospital polysomnography and had morning blood samples drawn. Oversampling of subjects at high risk of OSA was performed. RESULTS Overall, hs-cTnT was detectable (≥ 3 ng/L) in 216 subjects (42.8%). After categorizing subjects according to AHI cutoffs that correspond to no, mild to moderate, and severe OSA, the proportion of subjects with detectable hs-cTnT levels increased with increasing severity of OSA (P for trend < .001). Multivariate logistic regression with detectable hs-cTnT as the dependent variable was used to further assess the association between OSA and troponin T. After adjustment for significant univariate predictors of detectable hs-cTnT, the association between AHI and hs-cTnT was no longer statistically significant. CONCLUSIONS The prevalence of detectable hs-cTnT increases in proportion to OSA severity, but this association is likely to be caused by a clustering of cardiovascular risk factors among subjects with OSA.

Cardiac arrhythmias in obstructive sleep apnea (from the Akershus Sleep Apnea Project).

Increased prevalence of cardiac arrhythmias has been reported in patients with severe obstructive sleep apnea (OSA), but this may not be generalizable to patients from the general population with a milder form of the condition. The aim of this study was to assess the association between cardiac arrhythmias and OSA of mainly mild and moderate severity. In total, 486 subjects (mean age 49 years, 55% men) recruited from a population-based study in Norway underwent polysomnography for OSA assessment and Holter recordings for arrhythmia assessment. Of these, 271 patients were diagnosed with OSA (apnea-hypopnea index [AHI] ≥5, median AHI 16.8, quartiles 1 to 3 8.9 to 32.6). Mean nadir oxygen saturations were 82% and 89% in patients with and without OSA, respectively. Ventricular premature complexes (≥5/hour) were more prevalent in subjects with OSA compared to subjects without OSA (median AHI 1.4, quartiles 1 to 3 0.5 to 3.0) during the night (12.2% vs 4.7%, p = 0.005) and day (14% vs 5.1%, p = 0.002). In multivariate analysis after adjusting for relevant confounders, AHI was independently associated with an increased prevalence of ventricular premature complexes at night (odds ratio per 1-U increase of log-transformed AHI 1.5, 95% confidence interval 1.1 to 2.0, p = 0.008) and during the day (odds ratio 1.37, 95% confidence interval 1.0 to 1.8, p = 0.035). In conclusion, the prevalence of ventricular premature complexes is increased in middle-aged patients with mainly mild or moderate OSA, suggesting an association between OSA and ventricular arrhythmias even in mild OSA.

Prevalence of cardiovascular risk factors and concentration of C-reactive protein in Type D personality persons without cardiovascular disease

Background: Type D personality is associated with poor cardiovascular outcome in patients with coronary or peripheral arterial disease. Whether Type D personality is associated with cardiovascular risk in persons without overt cardiovascular disease remains unknown. We hypothesized that Type D personality is associated with higher prevalence of traditional cardiovascular risk factors and higher concentration of C-reactive protein. Design: Cross-sectional study. Methods: Type D personality was assessed in 453 participants without cardiovascular disease derived from an epidemiological study of obstructive sleep apnoea. An evaluation of obesity, lipid status, diabetes, blood pressure, heart rate, smoking, leisure-time physical activity and high-sensitivity C-reactive protein was performed. Results: Smoking (43% vs. 21%, P < 0.001) and low leisure-time physical activity (<3 hours/week, 57% vs. 40%, P = 0.003) were more prevalent, and heart rate (mean (standard deviation), 75 (10) vs. 71 (9), P = 0.001) and body mass index was higher (29.8 (6.0) vs. 28.4 (4.5) kg/m2, P = 0.009) in Type D compared to non-Type D participants. The total number of risk factors was significantly higher in Type D than non-Type D participants (3.4 (1.3) vs. 3.0 (1.2), P = 0.004). The concentration of C-reactive protein was higher in participants with Type D personality (median, interquartile range 1.6, 0.7–3.4 vs. 1.1, 0.6–2.6, P = 0.047), although not statistically significant after adjustment for possible mediating factors. Conclusions: Among participants at high risk of cardiovascular disease, presence of Type D personality was associated with elevated body mass index and unhealthy behaviour such as smoking and low physical activity, which may have mediated the elevated concentration of C-reactive protein.

Severity of obstructive sleep apnea is associated with cardiac troponin I concentrations in a community-based sample: data from the Akershus Sleep Apnea Project.

OBJECTIVES Previous community-based studies have failed to demonstrate an independent association between OSA and circulating cardiac troponin concentrations, a marker of myocardial injury. However, these studies have used troponin assays with modest analytic sensitivity to detect low-level, chronic increments in troponin levels. Using a highly sensitive troponin I (hs-TnI) assay, we tested the hypothesis that the severity of OSA is associated with myocardial injury independently of comorbidities. DESIGN Cross-sectional study. SETTING Community-based. PARTICIPANTS 514 subjects (54% men, age 48 ± 11 y [mean ± SD]). INTERVENTIONS N/A. MEASUREMENTS AND RESULTS hs-TnI concentrations were measured in fasting morning blood samples and 318 participants (62%) had hs-TnI concentration above the limit of detection ([LoD] 1.2 ng/L). The severity of OSA, expressed as the apnea-hypopnea index (AHI) and nocturnal hypoxemia, was assessed by in-hospital polysomnography. After adjustment for age, gender, estimated creatinine clearance, history of coronary artery disease and hypertension, smoking, diabetes mellitus, systolic blood pressure, heart rate, body mass index, left ventricular hypertrophy, and cholesterol ratio in multivariate linear regression models, higher AHI (standardized β = 0.12, P = 0.006), lower mean SpO2 (β = -0.13, P = 0.012) and higher percentage of total sleep time with SpO2 < 90% (β = 0.12, P = 0.011) were all associated with higher hs-TnI levels in separate models. Additional analyses with hs-TnI categorized in tertiles or using a different strategy for persons with hs-TnI levels below the LoD did not change the results. CONCLUSION Increased obstructive sleep apnea (OSA) severity is independently associated with higher concentrations of hs-TnI, suggesting that frequent apneas or hypoxemia in OSA may cause low-grade myocardial injury.

Sex-Dependent Impact of OSA on Digital Vascular Function

BACKGROUND Indexes of associations between OSA and impaired vascular function are mainly based on small, clinic-based studies of conduit artery function in men with severe sleep apnea. Larger population-based studies show no independent associations or associations in women only. Sex differences in OSA-related mortality may exist, and sex differences in vascular function in subjects with OSA need to be explored. We, therefore, assessed whether OSA is associated with digital vascular function in a large population-based sample and whether this association is influenced by sex. METHODS From a population-based cohort of 30,000 subjects aged 30 to 65 years, we examined 479 subjects (mean age, 48 years; 43% women). Oversampling of subjects at high risk of OSA was performed. Sleep apnea was assessed by inhospital polysomnography. Endothelial function was assessed by digital peripheral arterial tonometry and was expressed as the reactive hyperemia index (RHI). RESULTS OSA was diagnosed in 266 subjects (55.5%). The RHI was significantly lower in subjects with severe OSA than in those without OSA (P = .002). In the multivariate model for RHI, a significant interaction between OSA and sex was found. In sex-specific multivariate linear regression models, adjusting for conventional cardiovascular risk factors, OSA was an independent predictor of a low RHI in women (P = .006) but not in men. The association between OSA and low RHI in women was independent of postmenopausal status. CONCLUSIONS In a large population-based sample of middle-aged subjects, OSA was independently associated with impaired digital vascular function in women only.

Circulating cytokine concentrations are not associated with major depressive disorder in a community-based cohort

OBJECTIVE The objective was to test the hypotheses that cytokine levels are elevated in community-residing persons at high risk for obstructive sleep apnea with major depressive disorder (MDD) compared to nondepressive persons and that cytokine levels show stronger correlations with somatic than psychological symptoms of depression. METHOD A case-control study within the cross-sectional Akershus Sleep Apnea Project was performed. Two controls matched for age, gender, metabolic syndrome and obstructive sleep apnea were drawn for each case of MDD. RESULTS Group comparisons revealed no significant difference in the levels of 17 cytokines [interleukin-1β, -2,-4, -5, -6, -7, -8, -10, -12(p70), -13 and -17; tumor necrosis factor-α; interferon-γ; granulocyte colony-stimulating factor; granulocyte-monocyte colony-stimulating factor; macrophage chemoattractant protein-1 and monocyte inhibitory protein-1β] between persons with (n=34) and without MDD (n=68). There was no association between cytokines levels and MDD in multivariate regression analyses. The concentration of interleukin-4 was significantly more positively correlated with psychological than somatic symptoms (r=0.046 vs. -0.143, respectively, P=0.024), while no different correlations were observed for other cytokines. CONCLUSION The cytokine levels were not elevated in MDD, and cytokine levels were not more strongly associated with somatic than psychological symptoms of depression. The depression-specific effect on inflammation may be weak in community-based samples with prevalent somatic comorbidity.

Major depressive disorder, anxiety disorders, and cardiac biomarkers in subjects at high risk of obstructive sleep apnea.

Objective: Cardiac biomarkers may be valuable when exploring potential mechanisms for the association between cardiovascular disease and psychiatric disorders. In subjects at increased risk for obstructive sleep apnea, we examined whether major depressive disorder (MDD), anxiety disorders, or the combination of these was associated with circulating C-reactive protein (CRP), cardiac troponin T (cTnT), or heart rate variability (HRV). Methods: From the Akershus Sleep Apnea Project, 290 participants were assessed for MDD or any anxiety disorder by a physician using the Structured Clinical Interview for DSM-IV. Fasting blood samples were analyzed with high-sensitivity assays for CRP, cTnT, and HRV calculated from a Holter recording. Age, sex, hypertension, diabetes, hyperlipidemia, obesity, smoking, apnea-hypopnea index, and previous cardiovascular disease were adjusted for. Results: The CRP levels (median [interquartile range], mg/L) were higher in depressive (2.7 [1.1-5.8]) versus nondepressive (1.3 [0.7-3.1], p = .02) and in anxious (2.8 [0.9-5.2]) versus nonanxious (1.3 [0.7-3.1], p = .01). MDD was independently associated with CRP (unstandardized &bgr; = 0.387, p = .04), but anxiety was not (unstandardized &bgr; = 0.298, p = .09). The CRP level was highest in subjects with comorbid MDD and anxiety (3.4 [1.1-7.8]). The unadjusted and adjusted odds ratios (95% confidence interval) for having measurable cTnT (>3 ng/L) were 0.49 (0.24-1.07) and 0.92 (0.31-2.67) for MDD versus nondepressive and 0.38 (0.18-0.80) and 0.61 (0.30-2.05) for anxiety versus nonanxiety, respectively. HRV did not vary between groups. Conclusions: Although CRP was increased both in MDD and anxiety disorders, patients with comorbid MDD and anxiety may be particularly prone to increased systemic inflammation. Neither MDD nor anxiety disorders were associated with low-level myocardial damage or HRV.ASAP = Akershus Sleep Apnea Project; BMI = body mass index; BQ = Berlin Questionnaire; CRP = C-reactive protein; cTnT = cardiac troponin T; CVD = cardiovascular disease; GAD = generalized anxiety disorder; HF = power in the high-frequency spectrum; HRV = heart rate variability; LF = power in the low-frequency spectrum; MDD = major depressive disorder; OCD = obsessive-compulsive disorder; OSA = obstructive sleep apnea; PD = panic disorder; PTSD = posttraumatic stress disorder; SCID = Structured Clinical Interview for DSM-IV; SDNN = standard deviation of NN-intervals.

Type D personality is associated with increased prevalence of ventricular arrhythmias in community-residing persons without coronary heart disease

Background Type D personality may be a risk factor for poor outcome in patients with cardiovascular disease. The biological mechanisms underlying this association are poorly understood. The objective of the study was to test the hypotheses that Type D personality is associated with biological markers for sympathetic dysregulation. Design Cross-sectional community-based study. Methods Type D personality was evaluated by DS-14 in 450 persons (46% men), aged between 30 and 65 years. From a Holter-recording, (mean length 18.3 hours), long-term heart rate, ventricular arrhythmias, and heart rate variability (HRV) were registered as markers of sympathetic dysregulation. Traditional cardiovascular risk factors, apnoea–hypopnoea index, medication, and anxiety symptoms were adjusted for. Results Type D persons had higher long-term averaged heart rate (74 vs. 71 beats/min, p = 0.003), but this difference was attenuated and not significant in the multivariate model (p = 0.078)). There was an increased prevalence of complex ventricular ectopy (bigeminy, trigeminy, or non-sustained ventricular tachycardia; 14 vs. 6%, p = 0.005 in multivariate model). HRV indices did not differ significantly between those with or without Type D personality. Anxiety symptoms did not confound these associations. Conclusions Type D personality is independently associated with a higher likelihood of ventricular arrhythmias, which may be implicated in the increased cardiovascular risk observed in persons with Type D personality.