Incident Coronary Calcium Score in Patients With OSA With and Without Excessive Sleepiness: Brazilian Longitudinal Study of Adult Health.

BACKGROUND: Uncertainty exists about the impact of OSA and its phenotypes on cardiovascular disease. RESEARCH QUESTION: Are OSA and clinical features such as daytime sleepiness associated with incident subclinical coronary atherosclerosis? STUDY DESIGN AND METHODS: In this prospective community-based cohort study, we administered a sleepiness questionnaire, actigraphy, and home sleep studies at baseline. Coronary artery calcium (CAC; 64-slice multidetector CT scan imaging) was measured at two different time points throughout the study (baseline, between 2010 and 2014, and follow-up, between 2016 and 2018). Incidence of subclinical atherosclerosis was defined as baseline CAC of 0 followed by CAC of > 0 at a 5-year follow-up visit. The association of incident CAC outcome was assessed using logistic regression. Stratified analyses based on excessive daytime sleepiness (EDS) were performed. RESULTS: We analyzed 1,956 participants with available CAC scores at baseline (mean age, 49 ± 8 years; 57.9% female; 32.4% with OSA). In covariate-adjusted analyses (n = 1,247; mean follow-up, 5.1 ± 0.9 years), we found a significant association between OSA and incidence of subclinical atherosclerosis (OR, 1.26; 95% CI, 1.06-1.48), with stronger effects among those reporting EDS (OR, 1.66; 95% CI, 1.30-2.12; P = .028 for interaction). Interestingly, EDS per se was not associated with any CAC outcome. An exploratory analysis of the square root of CAC progression (baseline CAC > 0 followed by a numerical increase in scores at follow-up; n = 319) showed a positive association for both OSA (ß = 1.084; 95% CI, 0.032-2.136; P = .043) and OSA with EDS (ß = 1.651; 95% CI, 0.208-3.094; P = .025). INTERPRETATION: OSA, particularly with EDS, predicts the incidence and progression of CAC. These results support biological plausibility for the increased cardiovascular risk observed among patients with OSA with excessive sleepiness.

Gender Modulated the Association of Sleep Apnea and Sleep Duration with Arterial Stiffness: The ELSA-Brasil Study.

Increased arterial stiffness is independently associated with cardiovascular risk. Obstructive sleep apnea (OSA) and sleep duration (SDUR) may contribute to increased arterial stiffness, but it is unclear whether this association is modulated by gender. We aimed to evaluate the potential impact of gender in modulating the association of OSA and SDUR with arterial stiffness. Participants from the ELSA-Brasil study performed sleep assessments with portable polygraph to define OSA severity and SDUR by 1-week wrist actigraphy. Pulse wave velocity (PWV) was measured using a standard technique without access to the sleep data. We studied 1863 participants (42.2% male, age: 49±8 years, respiratory disturbance index (RDI): 9.9 (4.5-19.4) events/h, SDUR: 6.5 (5.9-7.1) hours, mean PWV: 7.3 ± 1.2 m/s). We found that men had higher PWV, higher frequency of diabetes, and higher blood pressure when compared to women. The regression analysis showed an independent association between increased RDI and PWV in men (ß: 0.007; 95% CI: 0.001-0.012), but not in women. In contrast, an independent association between SDUR and increased arterial stiffness was observed only in women (ß: 0.068; 95% CI: 0.002-0.134). In conclusion, the association of sleep disorders with arterial stiffness showed a distinct gender pattern depending on the sleep variable studied.

Excessive daytime sleepiness, but not sleep apnea, sleep duration or insomnia, was associated with poor adherence to anti-hypertensive treatment: The ELSA-Brasil study.

Hypertension is the leading risk factor for cardiovascular mortality. Poor adherence may partially explain this scenario. Beyond traditional factors, it is conceivable that sleep conditions such as Obstructive Sleep Apnea (OSA), Sleep Duration (SDUR), sleepiness and insomnia may contribute to impair adherence but the evidence is scanty. Consecutive participants with hypertension from the ELSA-Brasil study performed a home sleep monitoring and 7-days actigraphy to determine OSA (apnea-hypopnea index ≥15 events/hour) and SDUR, respectively. Excessive daytime sleepiness (EDS) and insomnia were evaluated by Epworth Sleepiness Scale (ESS) and Clinical Interview Scheduled Revised (CIS-R), respectively. The 4-itens Morisky questionnaire was used to evaluate adherence to anti-hypertensive therapy. A total of 411 patients were including in the analysis (mean age: 54 ± 8 years, 47% men). Medium/low adherence to anti-hypertensive therapy was observed in 62%. Compared to the high adherence group, the participants with medium/low adherence had lower frequencies of Whites (64.1 vs. 47.8%), high-degree education (50.6 vs. 40%), and monthly per-capita income ($1021.90 vs. $805.20). In contrast, we observed higher frequency of EDS (35.9 vs. 46.1%). No differences were observed for OSA, short SDUR (<6 h) and insomnia. Logistic regression analysis showed that race other than White (OR: 1.80; 95% IC:1.15-2.82), lower monthly income (OR: 1.74; 95% IC:1.01-3.0) and EDS (OR: 1.63; 95% IC:1.05-2.53) were independently associated with medium/low adherence to the anti-hypertensive treatment. Interestingly, EDS mediated the abdominal obesity-adherence outcome. In conclusion, among sleep-related parameters, EDS, but not OSA, short SDUR or insomnia, were associated to impaired adherence to anti-hypertensive therapy.

Sleep irregularity and the association with hypertension and blood pressure levels: the ELSA-Brasil study.

OBJECTIVE: To evaluate the associations of sleep irregularity with hypertension (HTN) and blood pressure (BP) levels. METHODS: Adult participants from the ELSA-Brasil performed a clinical evaluation including objective sleep duration (actigraphy), insomnia, and a sleep study for defining obstructive sleep apnoea (OSA). To quantify sleep irregularity, we used two parameters obtained through actigraphy: 7-day standard deviation (SD) of sleep duration and 7-day SD of sleep-onset timing. A multivariate analysis was used to determine the independent associations of sleep irregularity with HTN and SBP/DBP values. RESULTS: We studied 1720 participants (age 49 ±â€Š8 years; 43.4% men) and 27% fulfilled the HTN diagnosis. After adjustments for age, gender, race, BMI, excessive alcohol consumption, physical activity intensity, urinary sodium excretion, insomnia, objective sleep duration and OSA (apnoea-hypopnoea index ≥15 events/h), we found that the continuous analysis of 7-day SD of sleep duration was modestly associated with prevalent HTN. However, 7-day SD of sleep duration more than 90 min was independently associated with SBP [ ß : 1.55; 95% confidence interval (CI) 0.23-2.88] and DBP ( ß : 1.07; 95% CI 0.12-2.01). Stratification analysis excluding participants with OSA revealed that a 7-day SD of sleep duration greater than 90 min was associated with a 48% higher chance of having HTN (OR: 1.48; 95% CI: 1.05-2.07). No significant associations were observed for the SD of sleep-onset timing. CONCLUSION: Objective measurement of sleep irregularity, evaluated by SD of sleep duration for 1 week, was associated with HTN and higher BP levels, especially in participants without OSA.

Association between objective sleep measures and cognitive performance: a cross-sectional analysis in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) study.

Sleep disturbances often co-exist, which challenges our understanding of their potential impact on cognition. We explored the cross-sectional associations of insomnia and objective measures of sleep with cognitive performance in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) study stratified by middle-aged and older adults. Participants aged ≥55 years underwent cognitive evaluations, polygraphy for 1 night, and actigraphy for 7 days. Insomnia was evaluated using the Clinical Interview Scheduled Revised. Obstructive sleep apnea (OSA) and short sleep duration (SSD) were defined by an apnea-hypopnea index (AHI) of ≥15 events/h and <6 h/ night, respectively. In 703 participants (mean [SD] age 62 [6] years, 44% men), cognition was evaluated using a 10-word list, verbal fluency, and trail-making tests. The frequencies of insomnia, SSD, and OSA were 11%, 24%, and 33%, respectively. In all, 4% had comorbid OSA and insomnia, and 11% had both OSA and SSD. Higher wake after sleep onset (ß = -0.004, 95% confidence interval [CI] -0.008, -0.001) and the number of awakenings (ß = -0.006, 95% CI -0.012, -0.001) were associated with worse verbal fluency performance. Compared to those without insomnia, older participants with insomnia had worse global performance (ß = -0.354, 95% CI -0.671, -0.038). Insomnia was an effect modifier in the associations between AHI and executive function performance (p for the interaction between insomnia and AHI = 0.004) and between oxygen saturation <90% and memory performance (p for the interaction between insomnia and oxygen saturation = 0.02). Although some associations between sleep measures and cognition were significant, they should be considered with caution due to the large sample size and multiple testing performed in this study.

The Cardiovascular Impact of Obstructive Sleep Apnea in Women: Current Knowledge and Future Perspectives.

Overall, cardiovascular diseases have many sex-related differences in prevalence, clinical presentation, and outcomes. A considerable amount of evidence suggests that obstructive sleep apnea (OSA) increases the risk for several cardiovascular diseases. Only recently, the sex-related differences in cardiovascular outcomes gained interest in the literature. In this review, the authors discuss the current evidence addressing the cardiovascular impact of OSA in women. Particular attention is devoted to hypertension, target-organ damage, heart failure, atrial fibrillation, and cardiovascular events (including mortality). A research agenda is proposed to increase the understanding of the relevance of OSA in women from the Cardiology perspective.

Self-reported versus actigraphy-assessed sleep duration in the ELSA-Brasil study: analysis of the short/long sleep duration reclassification.

PURPOSE: This study was aimed to determine the magnitude and predictors of self-reported short/long sleep duration (SDUR) reclassifications using objective measurements. METHODS: Adult participants from the ELSA-Brasil study performed self-reported SDUR, 7-day wrist actigraphy, and a portable sleep study. We explored two strategies of defining self-reported SDUR reclassification: (1) short and long SDUR defined by <6 and ≥8h, respectively; (2) reclassification using a large spectrum of SDUR categories (<5, 5-6, 7-8, 8-9, and >9 h). RESULTS: Data from 2036 participants were used in the final analysis (43% males; age: 49±8 years). Self-reported SDUR were poorly correlated (r=0.263) and presented a low agreement with actigraphy-based total sleep time. 58% of participants who self-reported short SDUR were reclassified into the reference (6-7.99 h) or long SDUR groups using actigraphy data. 88% of participants that self-reported long SDUR were reclassified into the reference and short SDUR. The variables independently associated with higher likelihood of self-reported short SDUR reclassification included insomnia (3.5-fold), female (2.5-fold), higher sleep efficiency (1.35-fold), lowest O2 saturation (1.07-fold), higher wake after sleep onset (1.08-fold), and the higher number of awakening (1.05-fold). The presence of hypertension was associated with a 3.4-fold higher chance of self-reported long SDUR reclassification. Analysis of five self-reported SDUR categories revealed that the more extreme is the SDUR, the greater the self-reported SDUR reclassification. CONCLUSION: In adults, we observed a significant rate of short/long SDUR reclassifications when comparing self-reported with objective data. These results underscore the need to reappraise subjective data use for future investigations addressing SDUR.

Obstructive Sleep Apnea, Sleep Duration, and Associated Mediators With Carotid Intima-Media Thickness: The ELSA-Brasil Study.

[Figure: see text].

Obstructive sleep apnea is associated with lower adiponectin and higher cholesterol levels independently of traditional factors and other sleep disorders in middle-aged adults: the ELSA-Brasil cohort.

PURPOSE: Obstructive sleep apnea (OSA) may contribute to metabolic and inflammatory deregulation but previous studies failed to consider sleep duration, sleep fragmentation, insomnia, and daytime sleepiness as potential confounders. METHODS: Consecutive non-diabetic middle-aged participants from the ELSA-Brasil cohort were invited to perform a clinical evaluation, home sleep study for 1 night, and wrist actigraphy for 7 days. OSA was defined by an apnea-hypopnea index ≥ 15 events/h. Participants were stratified according to the presence of OSA measuring the following markers: fasting glucose, glucose tolerance test, homeostatic model assessment of insulin resistance (HOMA-IR) index, fasting insulin, insulin after 2 h of glucose load, glycated hemoglobin, total cholesterol and their fractions, triglycerides, C-reactive protein, TNF-alpha, interleukin-6, interleukin-10, leptin, adiponectin, E-selectin, ADMA, MCP-1, TGF, apolipoprotein B, fibrinogen, and lipoprotein(a). Differences between groups were identified by chi-square test and ANOVA. RESULTS: We studied 708 participants (mean age: 46 ± 5 years, men: 44%, BMI 26.1 ± 4.1 kg/m2). Compared to no OSA, participants with OSA presented higher levels while fasting and after 2 h glucose load of insulin, HOMA-IR, cholesterol, triglycerides, and C-reactive protein (all p < 0.001). After linear regression analysis adjusting for traditional risk factors plus sleep duration, fragmentation, insomnia, and daytime sleepiness, OSA was negatively associated with adiponectin (ß = - 0.271 CI 95% - 0.456 - 0.085) and positively associated with cholesterol (ß = 9.707 CI 95% 2.737 16.678). Sex-stratification revealed that these associations were significant for men but not women. CONCLUSIONS: In non-diabetic middle-age adults, men with OSA presented with lower adiponectin and higher cholesterol levels independently of sleep duration, sleep fragmentation, insomnia, and daytime sleepiness.

Association of Sodium with Obstructive Sleep Apnea. The ELSA-Brasil Study.

Rationale: Excessive sodium may have a role in the pathogenesis of obstructive sleep apnea (OSA) for patients with hypervolemic conditions, but it is unclear whether this is valid for all patients with OSA, including those with no significant comorbidities.Objectives: To test the association of urinary sodium and OSA in a large sample of participants from the ELSA-Brasil (Estudo Longitudinal de Saúde do Adulto-Brasil) Study. In addition, we stratified the analysis participants according to the presence of hypertension.Methods: In this cross-sectional study, OSA was defined by an apnea-hypopnea index ≥15 events/h. A validated 12-hour urine collection as representative of the 24-hour period was obtained from all participants to measure sodium excretion. We performed a logistic regression analysis to test the association of urinary sodium excretion with OSA (dependent variable) adjusting for age, sex, race and income, glomerular filtration rate, diabetes, physical activity, and antihypertensive classes related to sodium excretion. To address potential residual factors that may influence sodium excretion, we performed additional analysis replacing sodium excretion for salt intake (food frequency questionnaire) using the same models.Results: We studied 1,946 participants (age 49 ± 8 yr; 43.4% men). A third of them had OSA. Compared with those with no OSA, participants with OSA presented with higher sodium excretion (1.66 [1.19-2.29] vs. 1.99 [1.44-2.69] g/12 h; P < 0.001). After adjustments for confounding factors, we found no overall significant associations of sodium excretion with OSA (odds ratio [OR], 1.09; 95% confidence interval [CI], 0.97-1.23; P = 0.150). Regardless of the OSA status, the sodium excretion was higher in hypertensive than in normotensive participants (1.93 [1.35-2.64] vs. 1.71 [1.22-2.37] g/12 h). An independent association of sodium excretion with OSA was observed in patients with hypertension only (OR, 1.326; 95% CI, 1.067-1.648; P = 0.011), but the interaction of urinary sodium with hypertension was not significant (P = 0.37). The analysis of salt intake revealed consistent findings.Conclusions: The potential role of sodium in the pathogenesis of OSA seems to be modest and limited for those with higher salt intake and, consequently, higher fluid retention such as observed in patients with hypertension.

Pragmatic Validation of Home Portable Sleep Monitor for diagnosing Obstructive Sleep Apnea in a non-referred population: The ELSA-Brasil study.

OBJECTIVE: Polygraphy (PG) is an attractive alternative for diagnosing obstructive sleep apnea (OSA) in patients with high pre-test probability. However, several patients may not present typical symptoms. In this scenario, it is unclear the performance of PG for diagnosing OSA in non-referred populations to sleep laboratories. METHODS: Data from participants of the ELSA-Brasil cohort were used for this analysis. We performed an overnight home PG (Embletta GoldTM) synchronized with a wrist actigraphy (Actiwatch model 2TM). The validation strategy comprised three scorings from each participant: 1) Original scoring (PG): Routine scoring using data from the exclamation button mark to define "analysis start" and "analysis stop"; 2) Scoring using actigraphy data (PG+actigraphy): total sleep time defined by the actigraphy data; 3) Scoring using diaries (PG+diary): "analysis start" and "analysis stop" based on the diaries. Bland-Altman plots were generated to assess the agreements (Kappa) between each scoring strategy. RESULTS: A total of 300 participants were included in the final analysis (45% males, mean age: 48±8 years). The frequency of OSA using the PG score was 27.3%. Despite small differences in the OSA severity index, we obtained a high concordance of AHI comparing the PG vs. PG+actigraphy (Kappa: 0.95) as well as PG+diary vs. PG+actigraphy (Kappa: 0.96). No significant changes in the OSA classification (mild, moderate and severe) were observed in the 3 protocols. CONCLUSION: Using a pragmatic approach to address OSA at home, our results suggest that PG is a useful tool for OSA diagnosis even in subjects not referred to sleep studies.

Accuracy of global and/or regional anthropometric measurements of adiposity in screening sleep apnea: the ELSA-Brasil cohort.

OBJECTIVE: Adiposity is a well-established risk factor for obstructive sleep apnea (OSA) but the existence of a preferable anthropometric measurement is not established or whether the combination of measurements may improve the accuracy to detect OSA. This study aimed to compare the accuracies of body mass index (BMI), several surrogate markers of body fat (in isolation or combined) and validated questionnaires for screening OSA. METHODS: A total of 2059 participants from the ELSA-Brasil study given anthropometric measurements using standard procedures and a home sleep study. OSA was defined by an apnea-hypopnea index ≥15 events/hour. RESULTS: The frequency of OSA was 32.3%. Compared with the non-OSA group, all anthropometric measurements were higher in the OSA group. Age and gender-adjusted BMI afforded the highest accuracy to detect OSA [AUC = 0.760 (0.739-0.781)], followed by waist [AUC = 0.753 (0.732-0.775)] and neck [AUC = 0.733 (0.711-0.755)] circumferences, waist-to-hip ratio [AUC = 0.722 (0.699-0.745)] and body shape index [AUC = 0.680 (0.656-0.704)]. The combination of two or more anthropometric measurements did not improve the accuracy of BMI in predicting OSA. The adjusted BMI had similar predictive performance to the NoSAS score [AUC = 0.748 (0.727-0.770)] but a better accuracy than the Berlin Questionnaire [AUC = 0.676 (0.653-0.699)]. CONCLUSIONS: Despite one's intuition, surrogate markers of regional adiposity are not better than BMI in screening OSA. Combining measurements of global and/or regional adiposity did not have additional value in detecting OSA. The merely fair accuracy range of BMI and sleep questionnaires underscore the need for additional tools to improve OSA underdiagnosis.

OSA, Short Sleep Duration, and Their Interactions With Sleepiness and Cardiometabolic Risk Factors in Adults: The ELSA-Brasil Study.

BACKGROUND: OSA and short sleep duration (SSD) are frequently associated with daytime symptoms and cardiometabolic deregulation. However, the vast majority of studies addressing OSA have not evaluated SSD, and vice versa. Our aim was to evaluate the association of OSA, SSD, and their interactions with sleepiness and cardiometabolic risk factors in a large cohort of adults. METHODS: Consecutive subjects from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) participated in clinical evaluations, sleep questionnaires, home sleep monitoring, and actigraphy. OSA was defined as an apnea-hypopnea index ≥ 15 events/hour. SSD was defined by a mean sleep duration < 6 h. RESULTS: Data from 2,064 participants were used in the final analysis (42.8% male; mean age, 49 ± 8 years). The overall frequency of OSA and SSD were 32.9% and 27.2%, respectively. Following an adjustment for multiple confounding factors, excessive daytime sleepiness was independently associated with SSD (OR, 1.448; 95% CI, 1.172-1.790) but not with OSA (OR, 1.107; 95% CI, 0.888-1.380). The SSD interaction with OSA was not significant. Prevalent obesity (OR, 3.894; 95% CI, 3.077-4.928), hypertension (OR, 1.314; 95% CI, 1.035-1.667), and dyslipidemia (OR, 1.251; 95% CI, 1.006-1.555) were independently associated with OSA but not with SSD. Similarly, the interactions of OSA with SSD were not significant. An additional analysis using < 5 h for SSD or continuous sleep duration did not change the lack of association with the cardiometabolic risk factors. CONCLUSIONS: Objective SSD but not OSA was independently associated with daytime sleepiness. By contrast, OSA, but not SSD, was independently associated with obesity, hypertension, and dyslipidemia.