A 3-year longitudinal study of sleep disordered breathing in the elderly.

Limited and controversial data exist on the natural evolution of sleep disordered breathing (SDB) in untreated individuals. This study examines the evolution of SDB over a 3-yr period in a community-based sample of elderly subjects. From the initial cohort of 854 healthy subjects aged mean ± SD 68.4 ± 0.8 yrs, 519 untreated subjects accepted clinical and instrumental follow-up 3.6 ± 1.6 yrs later. SDB was defined as a respiratory disturbance index (RDI) >15 events · h(-1). At baseline, 202 (39%) subjects had an RDI ≤ 15 events · h(-1) and 317 (61%) had an RDI >15 events · h(-1). 3 yrs later, 280 (54%) subjects were non-SDB and 239 (46%) had SDB. Between evaluations, the RDI decreased from 22.3 ± 16.2 to 16.4 ± 13.0 events · h(-1), with a greater decrease in the number of cases with an RDI >30 events · h(-1) that in those with RDI ≥ 30 events · h(-1). In the non-SDB group, 81% had a stable RDI and 19% increased their RDI by a mean of 13.7 events · h(-1). In the SDB group, the RDI decreased to values ≤ 15 events · h(-1) in 36.6% of cases, 63.4% still having SDB. The RDI changes did not depend on weight changes. In healthy elderly subjects, the prevalence and severity of SDB did not show a tendency toward natural worsening, some cases having improvement or a remission independent of weight changes. These findings also suggest that in the elderly, natural SDB progression is still hypothetical.

At 68 years, unrecognised sleep apnoea is associated with elevated ambulatory blood pressure.

After the age of 65 yrs the specific impact of unrecognised sleep-related breathing disorders (SRBD) on 24-h blood pressure (BP) levels remains under debate. We tested the cross-sectional relationship between the severity of obstructive sleep apnoea/hypopnoea (OSAH) and the increase of BP using ambulatory BP monitoring (ABPM) in the PROOF (PROgnostic indicator OF cardiovascular and cerebrovascular events study)-SYNAPSE (Autonomic Nervous System Activity, Aging and Sleep Apnea/Hypopnea study) cohort. 470 subjects (aged 68 yrs) neither treated for hypertension nor diagnosed for SRBD were included. All subjects underwent ABPM, and unattended at-home polygraphic studies. OSAH was defined by an apnoea/hypopnoea index (AHI) >15 · h(-1). The severity of the sleep apnoea was also quantified as the index of dips in oxyhaemoglobin saturation >3% (ODI). Results are expressed in per protocol analysis. Severe OSAH (AHI >30 · h(-1), 17% of subjects) was associated with a significant 5 mmHg increase in both diurnal and nocturnal systolic BP (SBP), and with a nocturnal 3 mmHg increase in diastolic BP (DBP). Systolic (mean SBP >135 mmHg) or diastolic (mean DBP >80 mmHg) hypertension were more frequently encountered in subjects suffering from moderate (AHI 15-30) or severe OSAH. After adjustment, the independent association between severe OSAH and 24-h systolic hypertension remained significant (OR 2.42, 95% CI 1.1-5.4). The relationship was further reinforced when SRBD severity was expressed using ODI >10 · h(-1). The impact of unrecognised SRBD on BP levels also exists at the age of 68 yrs. The hypoxaemic load appears to be the pathophysiological cornerstone for such a relationship.

Obstructive sleep apnea and the metabolic syndrome in an elderly healthy population: the SYNAPSE cohort.

BACKGROUND: Obstructive sleep apnea syndrome (OSA) has been recently considered as a cause and a component of the metabolic syndrome (MetS), previous studies showing the presence of OSA in about half of middle-aged patients having MetS. To date, no study has considered the association of OSA and MetS in the elderly. In this study we examine the prevalence of MetS and its strength association among healthy elderly OSA subjects. METHODS: A cohort of 806 subjects aged 68.5 years, participants of a 7-year follow-up study, was examined. All subjects underwent clinical evaluation, blood sample measurements, and an at-home polygraphy. OSA was assessed as an apnea/hypopnea index (AHI) >15, and MetS was diagnosed according to the Adult Treatment Panel III. RESULTS: In the total group, 9.8% of cases met criteria for MetS with a prevalence similar in men and women. Of the entire group with Mets, 51.3% were women and 48.7% men. OSA was diagnosed in 55.9% of the sample, and among the OSA group, 12.5% had MetS. Oxyhemoglobin desaturation index (ODI, p < 0.0001) and AHI (p = 0.003) were found significantly higher in subjects with MetS than in those without it. Most of MetS components were significantly associated with AHI and ODI, the relationship stronger with ODI. After adjustment for covariables such as obesity, gender, and presence of diabetes, ODI was independently associated with three MetS components, glycemia (p < 0.0001), hypertension (p = 0.002), and triglyceride levels (p = 0.02). Sleepiness, autonomic arousal index, and sleep duration had no effect on the metabolic parameters. CONCLUSIONS: In elderly subjects, the association between OSA and MetS was stronger for hyperglycemia and hypertension. Among factors explaining this association, hypoxemia appears to be the most important factor without any effect of indices of sleep fragmentation, sleep duration, and sleepiness.

Cognitive function and sleep related breathing disorders in a healthy elderly population: the SYNAPSE study.

STUDY OBJECTIVES: Sleep related breathing disorders (SRBD) are risk factors for cognitive dysfunction in middle-aged subjects, but this association has not been observed in the elderly. We assess the impact of SRBD on cognitive performance in a large cohort of healthy elderly subjects. DESIGN: Cross-sectional study examining the association between subjective memory test, neuropsychological battery testing and SRBD in the elderly. SETTING: Community-based sample in home and research clinical settings. PARTICIPANTS: 827 subjects, 58.5% women, aged 68 y at study entry, participated in the study. All were free of previously diagnosed SRBD, coronary heart disease, and neurological disorders, including stroke and dementia. Clinical interview, neurological assessment, polygraphy, and extensive cognitive testing were conducted for all participants. INTERVENTION: N/A. MEASUREMENT AND RESULTS: SRBD (apnea-hypopnea index [AHI] > 15 events/h) was diagnosed in 445 (53%) subjects, 167 (37%) of them with AHI > 30. Minimal daytime sleepiness was found in the group; 9.2% of the population had an Epworth Sleepiness Scale score > 10. No significant association was found between AHI, nocturnal hypoxemia, and cognitive scores. Comparison of mild vs severe cases showed a trend toward lower cognitive scores with AHI > 30, affecting delayed recall and Stroop test. CONCLUSIONS: The impact of undiagnosed SRBD on cognitive function appeared quite limited in a generally older healthy population, and only slightly affected severe cases. The implication of undiagnosed SRBD on the cognitive impairment in elderly subjects remains hypothetical and needs to be prospectively studied.

Components of arterial stiffness in a population of 65-year-old subjects: PROOF study.

OBJECTIVES: Arterial stiffness increases with age, diabetes and hypertension, and is linked to the occurrence of cardiovascular complications, independently of traditional risk factors. The important influence of age and blood pressure on arterial stiffness and cardiovascular risk complicates analysis of factors involved in increased arterial stiffness. Study of the PROOF cohort supplied further information by analysis of subjects of identical age using a method that eliminates the immediate influence of blood pressure on pulse wave velocity. METHODS: The PROOF cohort comprised 1011 subjects, aged 65 years, from the city of Saint-Etienne (France). All benefited from 24-h ambulatory blood pressure monitoring coupled with measurement of QKD interval. Ambulatory Arterial Stiffness Index and QKD(100-60), were calculated for each recording. Measurements were performed again 2 years later. RESULTS: Height-predicted QKD(100-60) was correlated with pulse pressure and the presence of diabetes. We found no significant influence of sex, current smoking or total serum cholesterol. Ambulatory Arterial Stiffness Index, whether it was height predicted or not, only had a significant relationship with blood pressure. Two years later, although the QKD(100-60) remained stable for the overall population, it was reduced in the normotensive subjects. Over the whole population, there was a correlation between the changes in 24-h systolic blood pressure and QKD(100-60). CONCLUSION: QKD(100-60), an isobaric index of arterial stiffness, is significantly linked to blood pressure and blood sugar levels in a population of 65-year-old subjects. Two years later, the arterial stiffness increased significantly in the normotensive subjects, whereas it remained stable in the hypertensive subjects.

Monitoring of ventilation during the early part of cardiopulmonary exercise testing: the first step to detect central sleep apnoea in chronic heart failure.

BACKGROUND AND PURPOSE: To evaluate the prediction of nocturnal central sleep apnoea (CSA) syndrome from the presence of periodic breathing (PB) on diurnal monitoring of pre-exercise (cardiopulmonary exercise test [CPX]) parameters. CSA syndrome is commonly found in congestive heart failure (CHF) patients and has several prognostic and therapeutic implications but is frequently undiagnosed. Awake PB pattern is sometimes observed during the CPX cardiopulmonary monitoring period of gas exchanges in CHF patients referred to the stress test laboratory for routine peak VO2 determination. PATIENTS AND METHODS: Forty-five consecutive ambulatory patients (2 women/43 men; 60.2+/-11.7 years old) with clinically moderate to severe CHF (New York Heart Association [NYHA] class II/III: 22/23; mean+/-standard deviation left ventricular ejection fraction [LVEF]: 30.5+/-6.6%) underwent a classical maximal CPX test including a 2-min period (pre-test) of gas exchange monitoring and nocturnal ambulatory polygraphic monitoring. PB was defined when a cyclical pattern of VE, VO2, VCO2, was visually noted during the pre-exercise period and/or during the first 4 min of the CPX. CSA syndrome was retained as a central apnoea-plus-hypopnea index (cAHI) equal to or more than 10/h. The sleep study scoring procedure was done independently of the knowledge of the CPX results. Sensitivity, specificity and predictive values were calculated and receiver operating characteristic (ROC) curve analysis was constructed. RESULTS: Peak VO2 reached 16.4+/-5.2 mL kg(-1)min(-1) (55% of the theoretical value adjusted for gender and age). The polygraphy was completed and validated (at least five consecutive hours of sleep) in all cases. CSA syndrome was found in 28 (62%) patients (mean cAHI: 19.3+/-8.6/h). Sensitivity for the prediction of CSA syndrome reached 92.9% (two false-negative patients with a cAHI of nine) and specificity 94.1% with a predictive accuracy of 93.3%. The only false-positive patient suffered a moderate but significant obstructive sleep apnoea syndrome. Using ROC curve analysis, the W value reached 0.99 for the prediction of CSA from the presence of PB. The presence of CSA syndrome, using logistic regression analysis, is associated with a more severe functional status (NYHA: p<0.01, peak VO2: p<0.002), a lower basal and peak end-expiratory CO2 pressure (PETCO2, all p<0.03), a worse LVEF (p<0.01) and age equal to or more than 60 years (p<0.03). CONCLUSIONS: The observation of PB in the preliminary period of the CPX test in CHF patients appeared highly predictive of the presence of CSA syndrome during sleep and could prompt the use of polygraphic monitoring in severe CHF patients.

Pain and emotion as predictive factors of interoception in fibromyalgia.

INTRODUCTION: This study investigated interoception in fibromyalgia (FM), a disorder characterized by chronic pain accompanied by mood deregulation. Based on observations on the relationship between somatosensory processing and pain in FM and considering the affective symptoms of this disorder, we tested in FM three dimensions of interoception: interoceptive accuracy (IA), interoceptive awareness (IAW) and interoceptive sensibility (IS). MATERIALS AND METHODS: Twenty-one female FM patients (Mage = 50.3) and 21 female matched controls (Mage = 46.3) completed a heartbeat tracking task as an assessment of IA, rated confidence in their responses as a measure of IAW and completed the Multidimensional Assessment of Interoceptive Awareness as a measure of IS. Furthermore, they completed self-report scales that, according to a principal component analysis, targeted anxiety, emotional consciousness and pain-related affect and reactions. RESULTS: Multiple regression analyses showed that increased pain-related affect and reactions decrease IA in FM. When the results of each group were examined separately, such effect was found only in FM patients. On its turn, IS was predicted by emotional consciousness and pain-related affect and reactions, but these effects did not differ between FM and controls. Finally, none of the variables we used predicted IAW. DISCUSSION: Pain-related affect and reactions in FM patients can reduce their interoceptive ability. Our results help to better understand the integration between bodily signals and emotional processing in chronic pain.

Obstructive Sleep Apnea in Cardiac Rehabilitation Patients.

STUDY OBJECTIVES: Although regular physical activity improves obstructive sleep apnea (OSA) in the general population, this finding has not been assessed in postmyocardial infarction (MI) patients in a rehabilitation setting (coronary artery disease, CAD). We aimed to determine whether cardiac rehabilitation may benefit post-MI patients in terms of OSA disease and associated autonomic nervous system (ANS) activity. METHODS: Consecutive post-MI patients participating in the ambulatory cardiac rehabilitation program of St-Etienne University Hospital were included in this study. The apnea-hypopnea index calculated from electrocardiogram (ECG)-derived respiration (AHIEDR) was obtained through nocturnal Holter ECG recordings. According to AHIEDR, patients were classified as normal, mild, moderate, or severe OSA (< 5, 5-14, 15-29, ≥ 30, respectively). Physiological performance (peak VO2) was established via cardiopulmonary exercise testing. ANS activity was evaluated through spontaneous baroreflex sensibility as well as heart rate variability analysis. RESULTS: Of the 105 patients with CAD and OSA included (95 men, 55.2 ± 12.4 years), 100 had at least 1 cardiovascular risk factor (98%) and 52 patients (50%) had an ANS dysfunction. Surprisingly, 68 of these patients with OSA (65%) were free of classical diurnal symptoms usually associated with sleep apnea. In response to cardiac rehabilitation, AHIEDR decreased significantly (-9.3 ± 9.5, P < .0001) only in patients with severe OSA, and the decrease was even greater when peak VO2 and baroreflex sensibility improved beyond 20% compared to basal values (-11.6 ± 9.1, P < .001). CONCLUSIONS: Severe OSA in patients with CAD is significantly improved after 2 months of cardiopulmonary rehabilitation. Reviving ANS activity through physical activity might be a target for complementary therapy of OSA in patients with CAD.

Autonomic nervous system activity and decline as prognostic indicators of cardiovascular and cerebrovascular events: the 'PROOF' Study. Study design and population sample. Associations with sleep-related breathing disorders: the 'SYNAPSE' Study.

BACKGROUND: Transversal studies have underlined the association between the decline in autonomic nervous system (ANS) activity and all-cause mortality. However, the predictive value of ANS has never been prospectively assessed in a general population-based cohort. METHOD: The PROOF (PROgnostic indicator OF cardiovascular and cerebrovascular events) cohort study was designed to prospectively assess the predictive value of ANS activity level in the general population, with regard to cardiovascular and cerebrovascular events, and death. This predictive power will be compared with the usual and newly discovered risk factors for the purposes of developing a risk model. RESULTS: A prospective cohort of elderly subjects aged 65 years upon study entry were recruited from the electoral list of the city of Saint-Etienne, France. Three initial 2-year examination programs were scheduled for 7 years (2001-2007), followed by late events monitoring. At each examination, ANS activity was assessed along with clinical and biological cardiovascular risk factors, brain MRI, neuropsychological evaluation, physical activity profile, and sleep-related breathing disorders. The main study outcomes are stroke, myocardial infarction and death from any cause. A cohort consisting of 1,011 subjects aged 65.6 (0.8) years was constituted. CONCLUSION: Despite other selective characteristics, the associations between ANS activity and events will be applicable to other populations.

Serum lipid profile, sleep-disordered breathing and blood pressure in the elderly: a 10-year follow-up of the PROOF-SYNAPSE cohort.

OBJECTIVES: Dyslipidemia, sleep-disordered breathing (SDB) and hypertension are comorbid factors evidenced in adults, but poorly studied in old people. This study aimed to examine the long-term evolution of the serum lipid profile, and its relationships with SDB and blood pressure (BP) in the elderly. METHODS: A ten-year follow-up of the prospective Prognostic Indicator of Cardiovascular and Cerebrovascular Events (PROOF) and the Autonomic Nervous System Activity, Aging and Sleep Apnea/Hypopnea (SYNAPSE) cohort, which initially included 1011 elderly subjects from the general population, and who were untreated by continuous positive airway pressure (CPAP). Serum lipid profile, respiratory polygraphy for SDB and ambulatory blood pressure monitoring were performed. RESULTS: A total of 266 subjects (male/female 150/116; age 66.2 ± 0.8 years) were reassessed after 9.6 ± 0.7 years (age 75.8 ± 1.2 years). The prevalence of high-risk dyslipidemia decreased from 61.3 to 44.4%, and hypertension from 57.9 to 27.4%. The nocturnal oxygen desaturation index increased (mean + 2.3 ± 6.7 events/hour; p < 0.001), while the mean SaO2 and minimal SaO2 decreased. These variations (Δ) of oxygen desaturation worsened whether or not elderly subjects took anti-hypertensive and lipid-lowering treatments, and were not associated with serum lipid variations. The decrease in diurnal diastolic BP was independently associated with aging, and with the lowering of the waist/hip ratio (ΔW/H) and low-density lipoprotein cholesterol (LDL-C)/high-density lipoprotein cholesterol (HDL-C) ratio, while the decrease in diurnal systolic BP only depended on aging and ΔW/H. CONCLUSIONS: The results suggested that the observed worsening of nocturnal oxygen desaturation after 10 years in the elderly was independent of the change in circulating lipids, and not influenced by lipid-lowering treatments. However, the variation in blood pressure remained associated with aging, waist/hip and LDL-C/HDL-C ratios. TRIAL REGISTRY: NCT00759304 and NCT00766584 at clinicaltrials.gov.

Association between severe obstructive sleep apnea and incident arterial hypertension in the older people population.

OBJECTIVES: The impact of sleep-related breathing disorders on the incidence of arterial hypertension (AHT) in the older adults is not well-established. The aim of our study was to test the link between severe obstructive sleep apnea (OSA) and the occurrence of hypertension in older subjects after 3 years. METHODS: 372 normotensive subjects with a mean age of 68.2 years were included in our longitudinal study. All participants had a ventilatory polygraphic recording and an ambulatory blood pressure (BP) monitoring at baseline and after 3 years. Severe OSA was defined by an apnea-hypopnea index (AHI) of ≥ P30 per hour. A new onset of hypertension was defined according to a mean 24-hour value >140mmHg for systolic BP and >85mmHg for diastolic BP or the use of antihypertensive medication. RESULTS: The baseline factors significantly associated with an increased risk for new-onset hypertension were male gender, obesity, diabetes mellitus (DM), dyslipidemia, and OSA. Multiple logistic regression analyses showed that an AHI ≥30 per hour was independently associated with incident hypertension after 3 years (P=.02; odds ratio [OR], 1.8; 95% confidence interval [CI], 1.1-2.8). CONCLUSIONS: The presence of severe OSA is associated with new-onset AHT in normotensive elderly (mean age, 68.2 y) subjects.

Pulse transit time in screening sleep disordered breathing in an elderly population: the PROOF-SYNAPSE study.

STUDY OBJECTIVES: Pulse transit time (PPT) has been introduced as a useful screening tool to diagnose sleep disordered breathing (SDB). Since the prevalence of SDB increases with age, the question is whether PTT could be used to diagnose SDB in the elderly. We assess the effectiveness of PTT for SDB screening in a large healthy elderly population. SETTING: Community-based sample in home and research clinical settings. INTERVENTION: N/A. PARTICIPANTS: Seven hundred eighty volunteers, free of cardiac and neurologic disease, aged 68.6 ± 1.0 years, underwent ambulatory polygraphy to measure the apnea-hypopnea index (AHI). The presence of SDB was defined as an AHI of 15 or greater. The PTT was continuously monitored during the nocturnal study, and the overall autonomic arousal index (AAI) was calculated. RESULTS: SDB was diagnosed in 447 (57.3%) subjects. In these subjects, the Bland-Altman plot for AAI revealed an underestimation with a bias of -8.04 ± 16.55 events per hour (mean ± 95% confidence interval). Receiver operating characteristic curves constructed for an AHI of 15 or greater defined an area under the curve of 0.67 and a cutoff point to AAI 32.3 events per hour, giving a sensitivity of 70.5% and a specificity of 54.7%. For prediction of an AHI of at least 30, the area under the curve was equal to 0.74 for a cutoff point of 56.3 events per hour, giving a better specificity (94.7%) but a lower sensitivity (32.2%). CONCLUSIONS: In a healthy older population, the AAI showed moderate sensitivity for predicting SDB. This data does not allow us to use PTT as a screening tool for the diagnosis of SDB in the elderly. CLINICAL TRIAL REGISTRATION: NCT 00759304 and NCT 00766584.

Obstructive sleep apnoea/hypopnea influences high-density lipoprotein cholesterol in the elderly.

BACKGROUND AND PURPOSE: An association between obstructive sleep apnoea/hypopnea (OSAH) and cardiovascular risk factors such as dyslipidemia has been described in adults and high-risk populations. PATIENTS AND METHODS: We examined this association in a prospective cohort (SYNAPSE study) of 846 elderly (68.5+/-1.1 years) volunteers (41.6% of men). No subject presented with recognized OSAH syndrome, heart disease, or any neurological disorder. Unattended at-home polygraphy was done by all subjects. OSAH severity was defined as moderate (apnoea/hypopnea index: AHI>15/h) or severe (AHI>30/h). High-density lipoprotein cholesterol (HDL-c) was measured by immuno-separation-based homogenous assay. RESULTS: The prevalence of severe cases reached 21.5% (AHI mean+/-SD: 43.5+/-11.9). Using univariate linear regression analysis, AHI (R=-0.172; p<0.0001), oxyhemoglobin desaturation index (ODI) (R=-0.108; p<0.002), mean SaO(2) (R=0.125; p<0.0003) and Nadir SaO(2) (R=0.094; p<0.007) were significantly associated with HDL-c. Multiple regression analysis demonstrated that male gender, BMI, waist to hip ratio, ODI, and AHI represent independent predictors of HDL-c. Logistic regression analysis showed a significant association between severe OSAH and low HDL-c serum levels (p<0.03) after adjustment for gender, BMI, hypertension, glycaemia, waist to hip ratio, alcohol intake and treated dyslipidemia. The association appears more evident in subjects free of lipid-lowering medications and beta-blockers (p<0.007). There was no independent association of OSAH syndrome with low-density lipoprotein (LDL) cholesterol. CONCLUSION: Unrecognized moderate to severe apnoea/hypopnea syndrome was independently associated with low HDL-c serum levels in the present cross-sectional based elderly population. This could explain the deleterious effect of OSAH syndrome on cardiovascular risk.