J.-C. Barthelemy

Predicting sleep apnoea syndrome from heart period: a time-frequency wavelet analysis

Heart rate fluctuations are a typical finding during obstructive sleep apnoea, characterised by bradycardia during the apnoeic phase and tachycardia at the restoration of ventilation. In this study, a time-frequency domain analysis of the nocturnal heart rate variability (HRV) was evaluated as the single diagnostic marker for obstructive sleep apnoea syndrome (OSAS). The predictive accuracy of time-frequency HRV variables (wavelet (Wv) decomposition parameters from level 2 (Wv2) to level 256 (Wv256)) obtained from nocturnal electrocardiogram Holter monitoring were analysed in 147 consecutive patients aged 53.8±11.2 yrs referred for possible OSAS. OSAS was diagnosed in 66 patients (44.9%) according to an apnoea/hypopnoea index ≥10. Using receiver-operating characteristic curves analysis, the most powerful predictor variable was Wv32 (W 0.758, p<0.0001), followed by Wv16 (W 0.729, p<0.0001) and Wv64 (W 0.700, p<0.0001). Classification and Regression Trees methodology generated a decision tree for OSAS prediction including all levels of Wv coefficients, from Wv2 to Wv256 with a sensitivity reaching 92.4% and a specificity of 90.1% (percentage of agreement 91.2%) with this nonparametric analysis. Time-frequency parameters calculated using wavelet transform and extracted from the nocturnal heart period analysis appeared as powerful tools for obstructive sleep apnoea syndrome diagnosis.

Sex differences in obstructive sleep apnoea in an elderly French population

Obstructive sleep apnoea (OSA) affects females and males differently, and increases in prevalence with age. The aim of the present study was to characterise clinical, anthropometric and polygraphic sex differences in a large elderly OSA population. A total of 641 subjects aged 68 yrs were examined. Measurements of fat mass, using dual-energy X-ray absorptiometry (DEXA) and polygraphy, were obtained in all subjects. An apnoea/hypopnoea index (AHI) of >15 events·h−1 identified the presence of OSA. OSA was diagnosed in 57% of the sample, 34% having a mild form and 23% having an AHI of >30 events·h−1. Females with OSA exhibited a lower AHI, less severe hypoxaemia and greater peripheral fat mass, and frequently reported anxiety and depression. Comparison of females with and without OSA did not reveal significant differences in clinical, anthropometric and DEXA data. After adjustment for body mass index, hypertension, diabetes, smoking, anxiety and depression, logistic regression analysis revealed that the presence of hypertension was significantly associated with OSA risk in females (OR 1.52, p = 0.04). In a general community healthy population, the prevalence of undiagnosed OSA in females increases with age, with a risk similar to that in males. In females, the clinical spectrum, anthropometric data and fat distribution appear to be more sex-related than OSA-dependent. The occurrence of OSA contributes to hypertensive risk in elderly females.

Birth prematurity determines prolonged autonomic nervous system immaturity.

Because of its multiple involvement in physiological processes, autonomic nervous system (ANS) activity, a key regulator of homeostatic control, demonstrates a progressive increase during pregnancy. The profile of its maturation, mainly in the parasympathetic arm, in premature or full term infants, may help us to better understand its pathophysiological role. We prospectively evaluated ANS maturity in a group of 23 premature (PREM) infants at their theoretical term age and in 8 full term (FT) newborns. All recordings were registered close to the theoretical full term period (from 38 to 41 weeks) for the PREM group and during the first week of life for the FT newborns. Polygraphic recordings, EEG monitoring associated with visual clinical control, and Holter ECG, were performed simultaneously. ANS indices were then calculated during quiet sleep periods, using Wavelet transform of RR (beat to beat) intervals. High frequency components were found to be significantly lower in the PREM than in the FT group (p<0.05). Furthermore, at theoretical full term age, the greater the prematurity, the lower was parasympathetic activity. Because it is easy, monitoring of parasympathetic activity may help us to understand autonomic maturation and its clinical prognostic implications.

Sympathetic overactivity due to sleep fragmentation is associated with elevated diurnal systolic blood pressure in healthy elderly subjects: the PROOF-SYNAPSE study

AIMS Sleep fragmentation is a landmark of sleep disorders, because microarousals are systematically associated with sympathetic surges (i.e., sympathetic arousals). However, the impact of sympathetic sleep fragmentation on blood pressure (BP) remains understudied. We assessed the relationships between 24 h ambulatory BP monitoring, the autonomic arousal index (AAI) derived from pulse transit time, and heart rate variability indices. We hypothesized that repeated sympathetic arousals during sleep are associated with elevated BP in a large population of elderly volunteers. METHODS AND RESULTS Volunteer subjects (n = 780, 57.4% women) with a mean age of 68.7 years and free of known sleep-disordered breathing, coronary heart diseases, and neurological disorders underwent polygraphy, 24 h ECG Holter monitoring, and 24 h ambulatory BP monitoring. Multivariate regressions showed that sleep fragmentation, expressed by AAI, was associated with elevated diurnal (P = 0.008) and 24 h (P = 0.005) systolic BP and higher risk for 24 h [odds ratio (OR): 1.70 (1.04-2.80), P = 0.036] systolic hypertension, independently of confounders such as sleep-disordered breathing, body mass index, sex, diabetes, hypercholesterolaemia, and self-reported sleep duration and quality. Increased AAI was associated with higher nocturnal and diurnal low-frequency power (P < 0.001) and low-to-high-frequency ratio (P < 0.001), suggesting nocturnal and diurnal sympathetic overactivity. CONCLUSION In healthy elderly subjects, repetitive sympathetic arousals during sleep are associated with elevated systolic BP and higher risk of hypertension, after controlling for confounders. Sympathetic overactivity is the proposed underlying mechanism. CLINICAL TRIAL REGISTRATION NCT00766584 and NCT00759304.

Influence of exercise training on cardiac baroreflex sensitivity in patients with COPD

Decreased spontaneous cardiac baroreflex sensitivity (BRS), which could lead to the onset of cardiovascular events, has been demonstrated in chronic obstructive pulmonary disease patients. This study evaluates the effects of an exercise training programme on BRS. Twenty-one chronic obstructive pulmonary disease patients (mean±sd age 62±9 yrs; forced expiratory volume in one second 43.6±18.1% of the predicted value) with mild hypoxaemia (arterial oxygen tension 8.96±1.18 kPa) were compared to 18 healthy age-matched subjects. BRS was calculated as the slope of the baroreflex sequences between spontaneous changes in systolic blood pressure and subsequent consecutive relative risk deviation length, and was measured in the supine position and following head-up tilt for sympathetic stimulation. Pulmonary function test results and blood gas levels, measured only in patients, did not change after the training programme. Exercise training increased the maximal sustained workload (16.5%) and peak oxygen consumption (20.5%). Before training, BRS was lower in patients than in controls (2.7±1.5 versus 7.8±4.9 ms·mmHg−1) and tilting induced a smaller reduction in BRS (13 versus 34%). After training, BRS increased to 3.4±2.6 ms·mmHg−1 in patients but remained lower than in controls. The response to the tilt test remained unchanged after training. It is concluded that, in chronic obstructive pulmonary disease patients, exercise training is associated with a gain in spontaneous baroreflex sensitivity, reflecting cardiovascular benefits.

Metabolic Syndrome and Short-Term and Long-Term Heart Rate Variability in Elderly Free of Clinical Cardiovascular Disease: The PROOF Study

OBJECTIVE Autonomic nervous system (ANS) activity decrease has been associated with a higher risk of sudden cardiovascular and cerebrovascular disease. Thus, we explored the relationship between ANS control of the cardiovascular system and metabolic syndrome. METHODS We analyzed the relationship with both short-term and long-term heart rate variability (HRV) and metabolic syndrome in the cross-sectional PROgnostic indicator OF cardiovascular and cerebrovascular events (PROOF) cohort study of 1,011 elderly subjects recruited amongst the inhabitants of the city of Saint Etienne, France, aged 65.6 ± 0.8 years at the inclusion date. Physical examination included measurements of height, weight, systolic and diastolic blood pressure, waist circumference, and biological parameters. HRV variables were measured over 5-min, nighttime, and 24-h periods using Holter monitoring. RESULTS After adjustment for current type 2 diabetes, depression, and smoking, we found that metabolic syndrome status, high-density lipoprotein cholesterol (HDL-C), and waist circumference were significantly (p < 0.05) associated with total power, very-low frequency, low-frequency/high-frequency (LF/HF) ratio, and normalized LF. HDL-C and metabolic syndrome status were significantly associated with decreased long-term HRV variables. Both nighttime and 24-h HRV showed closer associations with metabolic syndrome than did short-term HRV (5-min). Metabolic syndrome severity was associated with a decrease in both the long-term and short-term HRV variables. CONCLUSIONS ANS control alteration of the cardiovascular system was more pronounced when evaluated by long-term than short-term HRV recordings, particularly in women.

Analysis of the interbeat interval increment to detect obstructive sleep apnoea/hypopnoea

The prevalence of obstructive sleep apnoea/hypopnoea syndrome (OSAHS) is underestimated and its diagnosis is costly and restricted to specialised sleep laboratories. The frequency component of interbeat interval increment (III) has been proposed as a simple and inexpensive diagnostic tool in OSAHS. In a set of 150 patients with clinically suspected sleep-related breathing disorder, the actual predictive accuracy of the power spectral density of the III of the very low frequencies (%VLFI) was analysed by comparing with the apnoea/hypopnoea index (AHI), as assessed by synchronised polysomnography. OSAHS was defined in 100 patients according to an AHI ≥15 events·h−1. Receiver operator characteristic curves built for %VLFI confirmed that this variable was able to separate OSAHS positive from OSAHS negative with statistical significance. Using an appropriate threshold (>4%), %VLFI demonstrated a positive predictive value of 80%. Misclassification of false-positive subjects occurred when the patient presented significant sleep discontinuity and sleep fragmentation (sleep fragmentation index ≥50 events·h−1) related to insomnia or periodic limb movements. A power spectral density of the interbeat interval increment of very low frequencies >4% allowed correct classification of obstructive sleep apnoea/hypopnoea syndrome when the clinical history suggested sleep-related breathing disorders and when moderate-to-severe cases are considered. Higher power spectral density of the interbeat interval increment of very low frequencies may also indicate disrupted sleep in the absence of clear clinical symptoms of sleep apnoea/hypopnoea syndrome.

Association between C-reactive protein and unrecognised sleep-disordered breathing in the elderly

Elevated levels of C-reactive protein (CRP) have been reported in patients with sleep-disordered breathing (SDB) and may represent an inflammatory marker of cardiovascular risk. However, the association of CRP with SBD in presumed healthy elderly subjects is unknown. In total, 851 (58.5% females) 68-yr-old subjects, who were free of any known cardiac or sleep disorders, were prospectively examined. Subjects underwent unattended polygraphy, and the apnoea/hypopnoea index (AHI) and oxyhaemoglobin desaturation index (ODI) were assessed. Elevated levels of CRP were found on the morning after the sleep study in patients with more severe SDB. A significant correlation was found between CRP levels, time spent at night with arterial oxygen saturation <90% and ODI. No association was found between CRP levels and AHI. After adjustments for body mass index, smoking status, hypertension, diabetes and dyslipidaemia, a significant association remained between CRP levels and ODI >10 events·h−1. CRP levels were frequently increased in a large sample of elderly subjects free of major cardiovascular disease. CRP levels were not correlated with the AHI and the indices of sleep fragmentation; the ODI >10 events·h−1 was the strongest predictor of raised CRP level. The present results suggest that, in the elderly, intermittent hypoxaemia may underlie inflammatory processes leading to cardiovascular morbidity.

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.

Is tidal expiratory flow limitation predictive of sleep-related disorders in the elderly?

Sleep-related disorders represent an important health burden and their prevalence increases with age. In patients with snoring or sleepiness, the presence of expiratory flow limitation (EFL), determined via the negative expiratory pressure (NEP) method, is related to the apnoea/hypopnoea index (AHI). In this study, we examined whether EFL can be used to predict obstructive sleep apnoea syndrome (OSAS) in healthy asymptomatic older subjects. A group of 72-yr-old subjects (n = 448, 44% males) with a mean body mass index of 25.5±3.8 kg·m−2 were examined. All subjects underwent spirometry, NEP (-5 cmH2O, sitting position) and ventilatory polygraphy (VP). Spirometry was within normal values in 88% of the group and EFL was present in 143 (32%) subjects with a higher prevalence in females (89 out of 249 versus 54 out of 199 in females and males, respectively). VP showed an AHI<15 h−1 in 238 subjects (53%) and OSAS with an AHI ≥15 h−1 in 47%. EFL was found in 15% of subjects with OSAS. Consequently, EFL had low sensitivity and specificity in the prediction of OSAS (31.4% and 67.7%, respectively). We conclude that the prevalence of EFL is elevated in healthy older subjects and cannot be used to predict the presence of sleep-related disorders in an older population.