Thomas B. Rice

The influence of abdominal visceral fat on inflammatory pathways and mortality risk in obstructive lung disease

BACKGROUND Low-grade systemic inflammation, particularly elevated IL-6, predicts mortality in chronic obstructive pulmonary disease (COPD). Although altered body composition, especially increased visceral fat (VF) mass, could be a significant contributor to low-grade systemic inflammation, this remains unexplored in COPD. OBJECTIVE The objective was to investigate COPD-specific effects on VF and plasma adipocytokines and their predictive value for mortality. DESIGN Within the Health, Aging, and Body Composition (Health ABC) Study, an observational study in community-dwelling older persons, we used propensity scores to match n = 729 persons with normal lung function to n = 243 persons with obstructive lung disease (OLD; defined as the ratio of forced expiratory volume in 1 s to forced vital capacity < lower limit of normal). Matching was based on age, sex, race, clinic site, BMI, and smoking status. Within this well-balanced match, we compared computed tomography-acquired visceral fat area (VFA) and plasma adipocytokines, analyzed independent associations of VFA and OLD status on plasma adipocytokines, and studied their predictive value for 9.4-y mortality. RESULTS Whereas whole-body fat mass was comparable between groups, persons with OLD had increased VFA and higher plasma IL-6, adiponectin, and plasminogen activator inhibitor 1 (PAI-1). Both OLD status and VFA were independently positively associated with IL-6. Adiponectin was positively associated with OLD status but negatively associated with VFA. PAI-1 was no longer associated with OLD status after VFA was accounted for. Participants with OLD had increased risk of all-cause, respiratory, and cardiovascular mortality, of which IL-6 was identified as an independent predictor. CONCLUSION Our data suggest that excessive abdominal visceral fat contributes to increased plasma IL-6, which, in turn, is strongly associated with all-cause and cause-specific mortality in older persons with OLD.

Evaluation of a Single-Channel Portable Monitor for the Diagnosis of Obstructive Sleep Apnea

STUDY OBJECTIVE To validate the ApneaLINK (AL) as an accurate tool for determining the presence of obstructive sleep apnea (OSA) in an at-risk sleep clinic population in a home test environment. METHODS Consecutive participants referred with the suspicion of OSA were evaluated in the home with the AL portable monitor (AL Home), followed by simultaneous data collection with diagnostic polysomnography (PSG) and AL in the sleep laboratory (AL Lab). Prevalence, sensitivity, specificity, and ROC curves were calculated for PSG vs. AL Lab, PSG vs. AL Home, and AL Lab vs. AL Home test. Pearson correlations and Bland-Altman plots were constructed. RESULTS Fifty-three (55% female) participants completed the entire study. The mean age of the population was 45.1 ± 11.3 years, and body mass index was 35.9 ± 9.1 kg/m(2). The prevalence of an apnea hypopnea index (AHI) ≥ 15 in the cohort was 35.9%. The results demonstrated a high sensitivity and specificity of the AL respiratory disturbance index (RDI-AL) compared with the AHI from the PSG. The AL Lab had the highest sensitivity and specificity at RDI-AL values ≥ 20 events/h (sensitivity 100%, specificity 92.5%). The AL Home was most sensitive and specific at an RDI-AL ≥ 20 events/h (sensitivity 76.9%, specificity 92.5%). The Pearson correlations for PSG vs. AL Lab and PSG vs. AL Home were ρ = 0.88 and ρ = 0.82, respectively. The Bland-Altman Plots demonstrated good agreement between the methodologies. CONCLUSION The AL home test is an accurate alternative to PSG in sleep clinic populations at risk for moderate and severe OSA. TRIAL REGISTRATION clinicaltrials.gov ID: NCT00354614.

Snoring, daytime sleepiness, and incident cardiovascular disease in the health, aging, and body composition study.

OBJECTIVES To examine the association between snoring and incident cardiovascular disease (CVD). DESIGN SETTINGS AND PARTICIPANTS This is a prospective study in which community dwelling older adults were evaluated at baseline, and followed up for an average of 9.9 years. MEASUREMENTS Data on snoring, daytime sleepiness, as well as demographic and clinical characteristics of study participants was collected at baseline, and participants were followed up every six months for an average of 9.9 years. Based on snoring and sleepiness status, 4 groups of participants were created: (1) No Snoring, No Sleepiness; (2) No Snoring, Sleepiness; (3) Snoring, No Sleepiness; (4) Snoring, Sleepiness. Incident CVD was defined as a diagnosis of myocardial infarction, angina pectoris, or congestive heart failure that resulted in overnight hospitalization during the follow-up period. Cox proportional hazard was used to estimate the risk of incident cardiovascular disease during follow-up by baseline snoring and sleepiness status. RESULTS A total of 2,320 participants with a mean age of 73.6 (2.9) years at baseline were included in the analysis. Fifty-two percent were women, and 58% were white. A total of 543 participants developed CVD events during the follow-up period. Participants who reported snoring associated with daytime sleepiness had significantly increased hazard ratio for CVD events (HR = 1.46 [1.03-2.08], P = 0.035) after adjusting for demographic and clinical confounding factors. CONCLUSION The results suggest that self-reported snoring and daytime sleepiness status are associated with an increased risk of future cardiovascular disease among older adults.

Pulmonary symptoms and diagnoses are associated with HIV in the MACS and WIHS cohorts

BackgroundSeveral lung diseases are increasingly recognized as comorbidities with HIV; however, few data exist related to the spectrum of respiratory symptoms, diagnostic testing, and diagnoses in the current HIV era. The objective of the study is to determine the impact of HIV on prevalence and incidence of respiratory disease in the current era of effective antiretroviral treatment.MethodsA pulmonary-specific questionnaire was administered yearly for three years to participants in the Multicenter AIDS Cohort Study (MACS) and Women’s Interagency HIV Study (WIHS). Adjusted prevalence ratios for respiratory symptoms, testing, or diagnoses and adjusted incidence rate ratios for diagnoses in HIV-infected compared to HIV-uninfected participants were determined. Risk factors for outcomes in HIV-infected individuals were modeled.ResultsBaseline pulmonary questionnaires were completed by 907 HIV-infected and 989 HIV-uninfected participants in the MACS cohort and by 1405 HIV-infected and 571 HIV-uninfected participants in the WIHS cohort. In MACS, dyspnea, cough, wheezing, sleep apnea, and incident chronic obstructive pulmonary disease (COPD) were more common in HIV-infected participants. In WIHS, wheezing and sleep apnea were more common in HIV-infected participants. Smoking (MACS and WIHS) and greater body mass index (WIHS) were associated with more respiratory symptoms and diagnoses. While sputum studies, bronchoscopies, and chest computed tomography scans were more likely to be performed in HIV-infected participants, pulmonary function tests were no more common in HIV-infected individuals. Respiratory symptoms in HIV-infected individuals were associated with history of pneumonia, cardiovascular disease, or use of HAART. A diagnosis of asthma or COPD was associated with previous pneumonia.ConclusionsIn these two cohorts, HIV is an independent risk factor for several respiratory symptoms and pulmonary diseases including COPD and sleep apnea. Despite a higher prevalence of chronic respiratory symptoms, testing for non-infectious respiratory diseases may be underutilized in the HIV-infected population.

The Effect of Changes in Cardiorespiratory Fitness and Weight on Obstructive Sleep Apnea Severity in Overweight Adults with Type 2 Diabetes

STUDY OBJECTIVES To examine the effect of changes in cardiorespiratory fitness on obstructive sleep apnea (OSA) severity prior to and following adjustment for changes in weight over the course of a 4-y weight loss intervention. METHODS As secondary analyses of a randomized controlled trial, 263 overweight/obese adults with type 2 diabetes and OSA participated in an intensive lifestyle intervention or education control condition. Measures of OSA severity, cardiorespiratory fitness, and body weight were obtained at baseline, year 1, and year 4. Change in the apnea-hypopnea index (AHI) served as the primary outcome. The percentage change in fitness (submaximal metabolic equivalents [METs]) and change in weight (kg) were the primary independent variables. Primary analyses collapsed intervention conditions with statistical adjustment for treatment group and baseline METs, weight, and AHI among other relevant covariates. RESULTS At baseline, greater METs were associated with lower AHI (B [SE] = -1.48 [0.71], P = 0.038), but this relationship no longer existed (B [SE] = -0.24 [0.73], P = 0.75) after adjustment for weight (B [SE] = 0.31 [0.07], P < 0.0001). Fitness significantly increased at year 1 (+16.53 ± 28.71% relative to baseline), but returned to near-baseline levels by year 4 (+1.81 ± 24.48%). In mixed-model analyses of AHI change over time without consideration of weight change, increased fitness at year 1 (B [SE] = -0.15 [0.04], P < 0.0001), but not at year 4 (B [SE] = 0.04 [0.05], P = 0.48), was associated with AHI reduction. However, with weight change in the model, greater weight loss was associated with AHI reduction at years 1 and 4 (B [SE] = 0.81 [0.16] and 0.60 [0.16], both P < 0.0001), rendering the association between fitness and AHI change at year 1 nonsignificant (B [SE] = -0.04 [0.04], P = 0.31). CONCLUSIONS Among overweight/obese adults with type 2 diabetes, fitness change did not influence OSA severity change when weight change was taken into account. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov identification number NCT00194259.

Sleep apnea is related to the atherogenic phenotype, lipoprotein subclass B.

STUDY OBJECTIVES Sleep apnea has been implicated as an independent risk factor for atherosclerotic coronary artery disease (CAD). An association between the severity of sleep apnea and total cholesterol levels has previously been reported. However, the association with small dense low density lipoprotein (LDL) cholesterol concentration (subclass B), one of the strongest predictors of atherosclerosis, is unknown. We examined the relationship between sleep apnea and LDL subclass B, considering body size. METHODS This is a cross-sectional observational cohort of participants enrolled in a cardiovascular health study. Sleep apnea was assessed with a validated portable monitor. Lipid panels included total cholesterol, triglycerides, high density lipoprotein cholesterol, LDL cholesterol, and LDL subclasses A, B, and A/B. Sleep apnea was analyzed categorically using the apnea hypopnea index (AHI). RESULTS A total of 519 participants were evaluated. Mean age was 58.7 ± 7.4 years; BMI was 29.6 ± 5.7; 65% were female; 59% were Caucasian, and 37% were African American. Among participants with abnormal waist circumference by ATP III criteria, moderate to severe sleep apnea (AHI ≥ 25) was not independently associated with LDL subclass B. In contrast, among participants with normal waist circumference, moderate to severe sleep apnea was associated with 4.5-fold odds of having LDL subclass B. CONCLUSIONS Sleep apnea is independently associated with an atherogenic phenotype (LDL subclass B) in non-obese individuals. The association between sleep apnea and LDL subclass B in those with normal waist circumference may account, in part, for the increased risk of atherosclerosis and subsequent vascular events.

A nuisance or nemesis: the adverse effects of snoring.

mized rabbits that were anesthetized and mechanically ventilated. Furthermore, the negative intrapleural pressure swings that accompany apneas and hypopneas were eliminated. Lastly, unlike other models of vibratory injury, this more ecologically valid model resulted in reduced endothelial dysfunction in the absence of histologic evidence that endothelial architecture was disrupted. In the carefully controlled experiments by Cho et al. reported in this issue of SLEEP, the external vibration from the speaker that was delivered to the right carotid artery (vRCA) at a level commensurate with snoring was different from the much lower level of vibration measured in the left carotid artery (vLCA). 1 These vibrations resulted in differential effects on the vRCA vs. the vLCA in both biochemical outcomes and functional measures of endothelial function. They showed that acetylcholine (ACH) stimulated cyclic guanosine monophosphate (cGMP) was reduced in the vRCA. This effect was eliminated with the addition of sodium nitroprusside, a nitric oxide (NO) donor, establishing reduced NO bioavailability as a putative mechanism. Then, they demonstrated reduced ex vivo ACH stimulated vasorelaxation of the vRCA in comparison to the vLCA and the unvibrated control animals. In total, these findings suggest that a single 6-hour period of vibration led to impaired endothelial function, in the absence of the usual perturbations of OSA. Consequently, it is possible that snoring represents its own vascular risk in the non-apneic, as well as an additional vascular insult in those with OSA and snoring.

Sleep and insulin-like growth factors in the cardiovascular health study

STUDY OBJECTIVES Sleep and sleep disordered breathing (obstructive sleep apnea [OSA]) are known to affect the growth hormone/insulin-like growth factor (GH/IGF) axis. There are few relevant population studies in this area, particularly in the elderly. We conducted this study to investigate the relationship between sleep (architecture and OSA) and circulating IGF-I (insulin-like growth factor-1), IGFBP-1 (insulin-like growth factor binding protein-1), and IGFBP-3 (insulin-like growth factor binding protein-3) levels in an elderly population. DESIGN SETTING Cross-sectional analysis of participants from the year 9 visit of the Cardiovascular Health Study (CHS) who were enrolled in the Sleep Heart Health Study (SHHS). PATIENTS OR PARTICIPANTS 1,233 elderly participants from the CHS and SHHS. MEASUREMENTS AND RESULTS The mean age of males (n = 526) and females (n = 697) was 77 years. The mean value of IGF-I (ng/mL) in males was 112.4 vs. 97.1 in females (p < 0.01). Mean IGFBP-1 and IGFBP-3 levels were higher in females than males (p < 0.01). As expected, slow wave sleep was better preserved in females compared to males (22% total sleep time vs. 9% total sleep time, p < 0.01). Furthermore, as expected, OSA (apneahypopnea index [AHI] ≥ 5/h) was more prevalent in males compared to females (60% vs. 46%, p < 0.01). Multivariable linear regression was used to determine the relationship between objective sleep parameters and circulating IGF-I, IGFBP-1, and IGFBP-3 levels, with adjustment for age, sex, race, BMI, diabetes, estrogen use, progestin use, and physical activity. We did not detect a significant association between slow wave sleep (SWS) (per 5 min) and IGF-I, IGFBP-1, and IGFBP-3 levels (ng/mL). We found no significant linear association between OSA (AHI ≥ 5/h) and IGF-I, IGFBP-1, and IGFBP-3 levels. Gender-stratification of the entire cohort did not alter these findings. Sensitivity analyses excluding diabetics revealed that moderate OSA (AHI ≥ 5 and < 15) is inversely associated with IGFBP-3 levels in women. Conclusions The relationship between SWS and GH/IGF system is not significant in the elderly. Furthermore, OSA does not appear to adversely influence the GH/IGF axis, as reported in younger individuals. Whether our study findings are due to diminished GH/IGF-I axis activity in elderly needs further investigation by replication in other large population based elderly cohorts.

Update in Sleep Medicine 2011

Although it is unclear why all respiratory events in obstructive sleep apnea (OSA) are not terminated with a recognizable cortical arousal, it has been hypothesized that events terminated without arousal may lead to more stable breathing. Jordan and colleagues attempted to define the physiologic parameters immediately related to stable breathing, including airflow, genioglossus and tensor palatini muscle activity, and airway resistance, after respiratory events terminated with or without cortical arousal (1). They hypothesized that respiratory events terminated without cortical arousal would produce less hyperventilation and less secondary events due to higher pharyngeal dilator activity compared with events with arousal. Sixteen patients with mild to severeOSA already treated with continuous positive airway pressure (CPAP) were studied. Using a sudden drop in CPAP pressure to subtherapeutic levels, they found that respiratory events terminated without arousal led to less hyperventilation and less secondary events (primarily hypopneas) compared with events terminated with arousal. This reduction in inspiredminute ventilation and subsequent events was not accounted for by differences in residual pharyngeal dilator activity. Specifically, secondary events were marked by less flow limitation and greater pharyngeal dilator activity relative to the initial event whether cortical arousal was present or not. These findings question the notion of arousal predisposing patients to further obstructive events.