Henry K. Yaggi

Obstructive sleep apnea as a risk factor for type 2 diabetes.

PURPOSE Cross-sectional studies have documented the co-occurrence of obstructive sleep apnea (hereafter, sleep apnea) with glucose intolerance, insulin resistance, and type 2 diabetes mellitus (hereafter, diabetes). It has not been determined, however, whether sleep apnea is independently associated with the subsequent development of diabetes, accounting for established risk factors. METHODS This observational cohort study examined 1233 consecutive patients in the Veteran Affairs Connecticut Healthcare System referred for evaluation of sleep-disordered breathing; 544 study participants were free of preexisting diabetes and completed a full, attended, diagnostic polysomnogram. The study population was divided into quartiles based on severity of sleep apnea as measured by the apnea-hypopnea index. The main outcome was incident diabetes defined as fasting glucose level >126 mg/dL and a corresponding physician diagnosis. Compliance with positive airway pressure therapy, and its impact on the main outcome, also was examined. RESULTS In unadjusted analysis, increasing severity of sleep apnea was associated with an increased risk of diabetes (P for linear trend <.001). After adjusting for age, sex, race, baseline fasting blood glucose, body mass index, and weight change, an independent association was found between sleep apnea and incident diabetes (hazard ratio per quartile 1.43; confidence interval 1.10-1.86). Among patients with more severe sleep apnea (upper 2 quartiles of severity), 60% had evidence of regular positive airway pressure use, and this treatment was associated with an attenuation of the risk of diabetes (log-rank test P=.04). CONCLUSION Sleep apnea increases the risk of developing diabetes, independent of other risk factors. Among patients with more severe sleep apnea, regular positive airway pressure use may attenuate this risk.

Obstructive sleep apnoea and stroke

Many patients with stroke have concomitant sleep apnoea, which can affect recovery potential. Although stroke can lead to the development of sleep-disordered breathing, the current evidence suggests that sleep-disordered breathing may function as a risk factor for stroke. In this review, we focus on the association between obstructive sleep apnoea and stroke reviewing both the epidemiological data with respect to causation and the biological data, which explores pathogenesis. There is convincing evidence to believe that sleep apnoea is a modifiable risk factor for stroke; however, prospective studies are needed to establish the cause-and-effect relationship.

Sleep-disordered breathing and stroke.

Sleep-related breathing disorders are strongly associated with increased risk of stroke independent of known risk factors. The direction of causation favors sleep-disordered breathing leading to stroke rather than the other way around, although definitive proof of this awaits the results of prospective cohort studies. If causal, even a moderately elevated risk of stroke coupled with the high prevalence of sleep-disordered breathing could have significant public health implications. The relationship between sleep-disordered breathing and stroke risk factors is complex, and likely part of the risk for cerebrovascular events is because of higher cardiovascular risk factors in patients with increased RDI. The mechanisms underlying this increased risk of stroke are multi-factorial and include reduction in cerebral blood flow, altered cerebral autoregulation, impaired endothelial function, accelerated atherogenesis, thrombosis, and paradoxic embolism. Because of the effects of sleep-disordered breathing on vascular tone, hypertension is believed to be a major mechanism by which sleep-disordered breathing might influence risk of stroke. Because sleep-related breathing disorders are treatable patients with stroke/TIA should undergo investigation, with a thorough sleep history interview, physical examination, and polysomnography. Treatment of sleep apnea has been shown to improve quality of life, lower blood pressure, improve sleep quality, improve neurocognitive functioning, and decrease symptoms of excessive daytime sleepiness [98]. Further treatment trials are needed to determine whether treatment improves outcome after stroke and whether treatment may serve as secondary prophylaxis and modify the risk of recurrent stroke or death.

Respiratory impairment and mortality in older persons: a novel spirometric approach.

Background The Lambda-Mu-Sigma (LMS) method calculates the lower limit of normal for spirometric measures of pulmonary function as the fifth percentile of the distribution of z scores, suitably accounting for age-related changes in pulmonary function. Extending prior work, and to assess whether the LMS method is clinically valid when evaluating respiratory impairment in the elderly, our current objective was to evaluate the association of LMS-defined respiratory impairment (airflow limitation and restrictive pattern) with all-cause mortality and respiratory symptoms (chronic bronchitis, dyspnea, or wheezing) in older persons. Methods Spirometric data and outcome data on white participants aged 65 to 80 years were obtained from the Third National Health and Nutrition Examination Survey (NHANES-III, n = 1497) and the Cardiovascular Health Study (CHS, n = 3583). Multivariable analyses determined the corresponding associations, adjusting for important covariates. Results In the NHANES-III and CHS populations, respectively, LMS-defined airflow limitation had adjusted hazard ratios (95% confidence interval) of 1.64 (1.28-2.11) and 1.69 (1.48-1.92) for mortality; adjusted odds ratios for respiratory symptoms were 2.71 (1.92-3.83) and 2.63 (2.11-3.27). The LMS-defined restrictive pattern was also significantly associated with mortality (adjusted hazard ratios of 1.98 [1.54-2.53] and 1.68 [1.44-1.95]), as well as with respiratory symptoms (adjusted odds ratios of 1.55 [1.03-2.34] and 1.37 [1.07-1.75]) in NHANES-III and CHS, respectively. Conclusions The LMS-defined airflow limitation and restrictive pattern confers a significantly increased risk of death and likelihood of having respiratory symptoms. These results support the use of LMS-derived spirometric z scores as a basis for evaluating respiratory impairment in older persons.

Polysomnographic phenotypes and their cardiovascular implications in obstructive sleep apnoea

Background Obstructive sleep apnoea (OSA) is a heterogeneous disorder, and improved understanding of physiologic phenotypes and their clinical implications is needed. We aimed to determine whether routine polysomnographic data can be used to identify OSA phenotypes (clusters) and to assess the associations between the phenotypes and cardiovascular outcomes. Methods Cross-sectional and longitudinal analyses of a multisite, observational US Veteran (n=1247) cohort were performed. Principal components-based clustering was used to identify polysomnographic features in OSA’s four pathophysiological domains (sleep architecture disturbance, autonomic dysregulation, breathing disturbance and hypoxia). Using these features, OSA phenotypes were identified by cluster analysis (K-means). Cox survival analysis was used to evaluate longitudinal relationships between clusters and the combined outcome of incident transient ischaemic attack, stroke, acute coronary syndrome or death. Results Seven patient clusters were identified based on distinguishing polysomnographic features: ‘mild’, ‘periodic limb movements of sleep (PLMS)’, ‘NREM and arousal’, ‘REM and hypoxia’, ‘hypopnoea and hypoxia’, ‘arousal and poor sleep’ and ‘combined severe’. In adjusted analyses, the risk (compared with ‘mild’) of the combined outcome (HR (95% CI)) was significantly increased for ‘PLMS’, (2.02 (1.32 to 3.08)), ‘hypopnoea and hypoxia’ (1.74 (1.02 to 2.99)) and ‘combined severe’ (1.69 (1.09 to 2.62)). Conventional apnoea–hypopnoea index (AHI) severity categories of moderate (15≤AHI<30) and severe (AHI ≥30), compared with mild/none category (AHI <15), were not associated with increased risk. Conclusions Among patients referred for OSA evaluation, routine polysomnographic data can identify physiological phenotypes that capture risk of adverse cardiovascular outcomes otherwise missed by conventional OSA severity classification.

The Association between Nocturnal Cardiac Arrhythmias and Sleep-Disordered Breathing: The DREAM Study.

STUDY OBJECTIVES To determine whether sleep-disordered breathing (SDB) is associated with cardiac arrhythmia in a clinic-based population with multiple cardiovascular comorbidities and severe SDB. METHODS This was a cross-sectional analysis of 697 veterans who underwent polysomnography for suspected SDB. SDB was categorized according to the apnea-hypopnea index (AHI): none (AHI < 5), mild (5 ≥ AHI < 15), and moderate-severe (AHI ≥ 15). Nocturnal cardiac arrhythmias consisted of: (1) complex ventricular ectopy, (CVE: non-sustained ventricular tachycardia, bigeminy, trigeminy, or quadrigeminy), (2) combined supraventricular tachycardia, (CST: atrial fibrillation or supraventricular tachycardia), (3) intraventricular conduction delay (ICD), (4) tachyarrhythmias (ventricular and supraventricular), and (5) any cardiac arrhythmia. Unadjusted, adjusted logistic regression, and Cochran-Armitage testing examined the association between SDB and cardiac arrhythmias. Linear regression models explored the association between hypoxia, arousals, and cardiac arrhythmias. RESULTS Compared to those without SDB, patients with moderate-severe SDB had almost three-fold unadjusted odds of any cardiac arrhythmia (2.94; CI 95%, 2.01-4.30; p < 0.0001), two-fold odds of tachyarrhythmias (2.16; CI 95%,1.47-3.18; p = 0.0011), two-fold odds of CVE (2.01; 1.36-2.96; p = 0.003), and two-fold odds of ICD (2.50; 1.58-3.95; p = 0.001). A linear trend was identified between SDB severity and all cardiac arrhythmia subtypes (p value linear trend < 0.0001). After adjusting for age, BMI, gender, and cardiovascular diseases, moderate-severe SDB patients had twice the odds of having nocturnal cardiac arrhythmias (2.24; 1.48-3.39; p = 0.004). Frequency of obstructive respiratory events and hypoxia were strong predictors of arrhythmia risk. CONCLUSIONS SDB is independently associated with nocturnal cardiac arrhythmias. Increasing severity of SDB was associated with an increasing risk for any cardiac arrhythmia.

Observational Study of Obstructive Sleep Apnea in Wake-Up Stroke: The SLEEP TIGHT Study

Background: Wake-up stroke (WUS) accounts for a quarter of all ischemic strokes. Its conspicuous occurrence during sleep suggests that WUS may be associated with obstructive sleep apnea (OSA). We investigated the potential association among WUS, OSA, and measures of sympathetic hyperactivity. Methods: This is a cross-sectional analysis of data from the Sleep Apnea in Transient Ischemic Attack and Stroke (SLEEP TIGHT) study. Ischemic stroke patients were divided into WUS and non-WUS groups. Participants underwent polysomnography and ambulatory blood pressure monitoring. Collected data included demographic, medical, stroke characteristics (including severity by National Institutes of Health Stroke Scale), cholesterol, serum catecholamines, C-reactive protein, interleukin-6, B-type natriuretic peptide, blood pressure, and polysomnographic (apnea-hypopnea index (AHI); measures of hypoxia). Because both stroke and OSA affect men and women to varying degrees, the cohort was considered as a whole and by gender stratification. Results: Among 164 participants, 30.3% had WUS. The mean age was 62.0 ± 11.3 and the mean body mass index was 30.2 ± 7.9 kg/m2. One-hundred-and-five participants (63.6%) were males and 92 participants (56.8%) were Caucasian. Neither AHI nor OSA (AHI ≥5) frequency differed between WUS and non-WUS groups. Men tended to be more likely than women to have WUS (74.0 vs. 59.6%; p = 0.08), but this was not statistically significant. In gender-stratified analyses, men with WUS compared to men with non-WUS had significantly higher rates of severe OSA (AHI >30: 45.0 vs. 17.6%; p = 0.03) and tended toward more 3% oxygen desaturation events (57.0 ± 63.9 vs. 31.8 ± 22.9; p = 0.06). These differences were not seen in women. WUS patients tended to be of the male gender (74.0 vs. 59.6%; p = 0.08). History of stroke, hypertension, diabetes, dyslipidemia, or atrial fibrillation, serum catecholamines, and inflammatory biomarkers was no different between the groups. Low-density lipoprotein (LDL) was significantly higher in WUS (114.5 ± 36.3 vs. 101.4 ± 37.6; p = 0.04). Baseline diastolic blood pressure (DBP) was significantly greater in the WUS group. There was no difference in systolic or ambulatory blood pressure (including nighttime blood pressure) between WUS and non-WUS groups. Conclusions: WUS may be associated with severe OSA with more oxygen desaturation in men but not in women. WUS may be associated with high DBP and increased LDL cholesterol.

Age-Related Differences in Sleep–Wake Symptoms of Adults Undergoing Polysomnography

To evaluate age‐related differences in sleep–wake symptoms.

Reducing cardiovascular risk through treatment of obstructive sleep apnea: 2 methodological approaches

Obstructive sleep apnea (OSA) significantly impacts cardiovascular health, demonstrated by observational investigations showing an independently increased risk of ischemic heart disease, diabetes, hypertension, congestive heart failure, acute coronary syndrome, stroke, cardiovascular mortality, and all-cause mortality. Positive airway pressure (PAP), a medical therapy for sleep apnea, reverses airway obstruction and may help reduce cardiovascular risk. Prior to planning large phase III randomized controlled trials to test the impact of PAP on cardiovascular outcomes, several gaps in knowledge need to be addressed. This article describes 2 independent studies that worked collaboratively to fill these gaps. The populations, design features, and relative benefits/challenges of the 2 studies (SleepTight and BestAIR) are described. Both studies were encouraged to have multidisciplinary teams with expertise in behavioral interventions to improve PAP compliance. Both studies provide key information that will be useful to the research community in future large-scale, event-driven, randomized trials to evaluate the efficacy and/or effectiveness of strategies to identify and treat significant OSA for decreasing risk of major adverse cardiovascular events in high-risk patients.

Prevalence and correlates of obstructive sleep apnoea among patients with and without HIV infection.

In HIV‐uninfected populations, obstructive sleep apnoea (OSA) is commonly associated with cardiovascular disease, metabolic syndrome, and cognitive impairment. These comorbidities are common in HIV‐infected patients, but there are scarce data regarding OSA in HIV‐infected patients. Therefore, we examined the prevalence and correlates of OSA in a cohort of HIV‐infected and uninfected patients.