Obstructive sleep apnoea treatment and blood pressure: which phenotypes predict a response? A systematic review and meta-analysis.

The treatment for obstructive sleep apnoea (OSA) with continuous positive airway pressure (CPAP) or mandibular advancement devices (MADs) is associated with blood pressure (BP) reduction; however, the overall effect is modest. The aim of this systematic review and meta-analysis of randomised controlled trials (RCTs) comparing the effect of such treatments on BP was to identify subgroups of patients who respond best to treatment.The article search was performed in three different databases with specific search terms and selection criteria. From 2289 articles, we included 68 RCTs that compared CPAP or MADs with either passive or active treatment. When all the studies were pooled together, CPAP and MADs were associated with a mean BP reduction of -2.09 (95% CI -2.78- -1.40) mmHg for systolic BP and -1.92 (95% CI -2.40- -1.43) mmHg for diastolic BP and -1.27 (95% CI -2.34- -0.20) mmHg for systolic BP and -1.11 (95% CI -1.82- -0.41) mmHg for diastolic BP, respectively. The subgroups of patients who showed a greater response were those aged <60 years (systolic BP -2.93 mmHg), with uncontrolled BP at baseline (systolic BP -4.14 mmHg) and with severe oxygen desaturations (minimum arterial oxygen saturation measured by pulse oximetry <77%) at baseline (24-h systolic BP -7.57 mmHg).Although this meta-analysis shows that the expected reduction of BP by CPAP/MADs is modest, it identifies specific characteristics that may predict a pronounced benefit from CPAP in terms of BP control. These findings should be interpreted with caution; however, they are particularly important in identifying potential phenotypes associated with BP reduction in patients treated for OSA.

Menopause and Sleep Apnea.

Obstructive sleep apnea (OSA) is a chronic and common adult disorder characterized by recurrent episodes of upper-airway obstruction and reopening during sleep. OSA is associated with intermittent hypoxia, sympathetic overactivity, oxidative stress and high cardiovascular mortality and morbidity. It is known to be more common in men than women, partly due to differences in anatomy and functional respiratory components. There are also gender differences in reported symptoms, leading to potential under-diagnosis in females. This gender difference tends to decrease after menopause, demonstrating a role of menopausal status itself in OSA phenotypes. Aging, fat mass distribution, sex hormones and upper-airway collapsibility are postulated to play a major role in these findings. This review focuses on the most recent studies exploring gender differences in the prevalence, pathogenesis and clinical features of OSA. It discusses the role of menopause in this, and explore the underlying pathophysiological mechanisms.

Heart failure and sleep related breathing disorders: Data from PROMISES (Progetto Multicentrico Italiano Sonno e Scompenso Cardiaco) study.

BACKGROUND: In heart failure (HF) sleep problems and sleep-related breathing disorders are frequently reported and are associated with poor prognosis. However, only few large clinical studies have investigated this issue in heart failure through breathing pattern analysis by polysomnography. METHODS AND RESULTS: 370 HF patients, with either moderate-severe reduced ejection fraction or with clinical decompensation, consecutively referred to 10 participating cardiology centers, have been enrolled in the PROMISES Study, an Italian project aimed at generating a large, multidisciplinary database of anthropometric, clinical, echocardiographic and sleep data, the last derived from overnight unattended cardio-respiratory polysomnography in HF patients. Obstructive sleep apnea was the most frequent form of sleep related breathing disorders observed in our cohort (35.4% with an AHI cutoff of 15). The possible determinants of sleep related breathing disorders were analyzed through stepwise logistic regression analysis and two multivariate models showing that a markedly reduced left ventricular ejection fraction was the most important factor associated with central sleep apneas (OR = 7.7 for AHI cutoff = 15 and LVEF ≤ 35%) together with male gender and increasing age. Conventional risk factors for obstructive sleep apnea did not identify HF patients affected by this condition. Conversely, a greater neck circumference was associated with an increased risk for central apneas. CONCLUSIONS: Our paper offers a deeper insight into the features of SRBD and its determinants in HF patients, leading in turn to a better clinical management of these comorbid patients.

Impact of obstructive sleep apnea on cardiac organ damage in patients with acute ischemic stroke.

BACKGROUND AND PURPOSE: Both obstructive sleep apnea (OSA) and cardiac organ damage have a crucial role in acute ischemic stroke. Our aim is to explore the relationship between OSA and cardiac organ damage in acute stroke patients. METHODS: A total of 130 consecutive patients with acute ischemic stroke were enrolled. Patients underwent full multichannel 24-h polysomnography for evaluation of OSA and echocardiography to evaluate left ventricle (LV) mass index (LV mass/BSA, LV mass/height), thickness of interventricular septum (IVS) and posterior wall (LVPW), LV ejection fraction and left atrium enlargement. Information on occurrence of arterial hypertension and its treatment before stroke was obtained from patients' history. RESULTS: 61.9% (70) of patients, mostly men (67.1%), with acute stroke had OSA (AHI > 10). Patients with acute stroke and OSA showed a significant increase (P < 0.05) of LV mass index, IVS and LVPW thickness and a significant left atrial enlargement as compared with patients without OSA. LV ejection fraction was not significantly different in stroke patients with and without OSA and was within normal limits. No relationship was found among cardiac alterations, occurrence of OSA and history of hypertension. CONCLUSION: Acute stroke patients with OSA had higher LV mass and showed greater left atrial enlargement than patients without OSA. This study confirms the high prevalence of OSA in stroke patients, suggesting also an association between OSA and cardiac target organ damage. Our finding of structural LV abnormalities in acute stroke patients with OSA suggests a potential role of OSA as contributing factor in determining both cerebrovascular and cardiac damage, even in absence of clear link with a history of blood pressure elevation.

Effect of continuous positive airway pressure in hypertensive patients with obstructive sleep apnea and high urinary metanephrines.

OBJECTIVE: Some cases of pseudopheochromocytoma have been described among hypertensive patients with obstructive sleep apnea (OSA). This study examined whether a pathological rise of urinary metanephrines is a common feature in hypertensive OSA patients and, in such a case, whether the ventilation treatment during sleep (continuous or biphasic positive airway pressure) may normalize high metanephrines levels. METHODS: Patients with endocrine diseases, drug abuse, therapy with TCA and cardiovascular events in the previous 6 months were excluded. Thirty-four hypertensive patients with OSA (BMI 40.6 ±â€Š8.7 kg/m(2)) performed three 24-h urine collections for metanephrine assessment, before and after 1 month of ventilation therapy. RESULTS: Urinary normetanephrine (uNMT) was above the normal limit in 21 of 34 of the patients. In the 16 to 21 patients with high uNMT who were compliant to ventilation treatment, uNMT decreased in 13 by 26% and normalized in six of 13. uNMT levels were associated with apnea hypopnea index (AHI) (r = 0.799, P < 0.0001) and minimal SaO2 (r = -0.700, P < 0.01). The ventilation therapy-induced changes in AHI were associated with those in uNMT (r = 0.689, P < 0.005). In the multivariate analysis with uNMT changes as dependent variable and changes in AHI, BMI, SBP as independent variables, only AHI changes were independently associated with uNMT changes (ß = 0.738, P < 0.01). CONCLUSION: Two-thirds of OSA hypertensive patients have uNMT values above the normal limit. The early identification of these patients is important as ventilation therapy can correct the pathological sympathoadrenal activation. Patients who do not normalize uNMT with ventilation therapy deserve a strict follow-up as this lack of normalization may indicate insufficient ventilation therapy or resistance of sympathetic hyperactivity to this treatment, not excluding an early stage of a chromaffin tumor.

Heart failure and sleep disorders.

Awareness of the importance of sleep-related disorders in patients with cardiovascular diseases is growing. In particular, sleep-disordered breathing, short sleep time, and low sleep quality are frequently reported by patients with heart failure (HF). Sleep-disordered breathing, which includes obstructive sleep apnoea (OSA) and central sleep apnoea (CSA), is common in patients with HF and has been suggested to increase the morbidity and mortality in these patients. Both OSA and CSA are associated with increased sympathetic activation, vagal withdrawal, altered haemodynamic loading conditions, and hypoxaemia. Moreover, OSA is strongly associated with arterial hypertension, the most common risk factor for cardiac hypertrophy and failure. Intrathoracic pressure changes are also associated with OSA, contributing to haemodynamic alterations and potentially affecting overexpression of genes involved in ventricular remodelling. HF treatment can decrease the severity of both OSA and CSA. Indeed, furosemide and spironolactone administration, exercise training, cardiac resynchronization therapy, and eventually heart transplantation have shown a positive effect on OSA and CSA in patients with HF. At present, whether CSA should be treated and, if so, which is the optimal therapy is still debated. By contrast, more evidence is available on the beneficial effects of OSA treatment in patients with HF.

Obstructive sleep apnea syndrome as a cause of resistant hypertension.

Evidence has consistently supported the association of obstructive sleep apnea syndrome (OSAS) with an increased prevalence of hypertension. It has also been shown that the severity of OSAS is directly correlated with the degree of blood pressure (BP) elevation and that hypertension occurring in subjects with OSAS is more likely to be severe, resistant to antihypertensive treatment and associated with alterations in day-to-night BP changes. Proposed mechanisms for the pathogenesis of OSAS-related hypertension include the activation of the sympathetic nervous system, alterations in autonomic cardiovascular (CV) modulation, the activation of the renin-angiotensin-aldosterone system, endothelial dysfunction, systemic and vascular inflammation, oxidative stress, metabolic abnormalities, arterial stiffness and alterations in cardiac function and structure. Given the adverse prognostic implications of OSAS-related hypertension for CV morbidity and mortality, the confirmation of resistant hypertension by using ambulatory BP monitoring (ABPM) and the identification of alterations in day-to-night BP changes is of the utmost importance to implement more aggressive strategies for achieving BP control. In turn, the proper identification and implementation of specific treatment strategies for OSAS (that is, continuous positive airway pressure) in subjects with resistant hypertension may promote BP control and optimize CV protection. The present paper will review the evidence supporting the association of OSAS with resistant hypertension and the proposed mechanisms for this association. It will also address the role of ABPM in the confirmation of resistant hypertension in subjects with OSAS and whether the proper identification and management of OSAS in subjects with resistant hypertension will improve BP control.

Glucose tolerance and weight loss in obese women with obstructive sleep apnea.

BACKGROUND: The association of obstructive sleep apnea (OSA) with glucose intolerance and the beneficial effect of lifestyle intervention have been poorly investigated in women particularly before menopausal status. The study explored 1) whether OSA is associated with impaired glucose homeostasis in obese non diabetic premenopausal and menopausal women and 2) the effects of a 3- month lifestyle intervention on glucose homeostasis in OSA women. DESIGN AND METHODS: We consecutively recruited 98 obese women (39 premenopausal) from those referred for a weight loss intervention. Ambulatory nocturnal polysomnography, body composition, oral glucose tolerance test, insulin sensitivity and ß cell function were assessed before and after intervention. RESULTS: 41% of premenopausal and 64% of menopausal women had OSA which was associated with worse glucose homeostasis before menopausal status. Mean and minimal nocturnal oxygen saturation (SaO2) was associated with neck/height ratio (NHR), independently of total and central obesity. Mean and minimal nocturnal SaO2 and NHR were correlated with insulin sensitivity and fasting glucose. In multivariate analyses, nocturnal mean SaO2 was negatively and independently correlated with fasting glucose (p<0.0001) and NHR with insulin sensitivity (p<0.0001). In OSA women, the intervention induced a 5% weight reduction and a significant increase in minimal nocturnal SaO2, insulin sensitivity and ß cell function. Changes in fasting glucose and insulin sensitivity were associated with those in minimal nocturnal SaO2 (p<0.05) and not with weight loss. CONCLUSIONS: In obese women, glucose homeostasis worsens due to nocturnal hypoxia and increased neck circumference through mechanisms partially independent of obesity. OSA is more clearly associated with glucose intolerance in premenopausal than in menopausal women. In OSA women, the improvement of nocturnal hypoxia induced by lifestyle modifications is associated with that of glucose homeostasis.

Sleep-wake disturbances in patients with amyotrophic lateral sclerosis.

OBJECTIVE: To evaluate the frequency, severity and determinants of sleep disturbances in patients with amyotrophic lateral sclerosis (ALS). METHODS: Information about night-time complaints was collected using a standardised questionnaire, the Pittsburgh Sleep Quality Index (PSQI), and the Epworth Sleepiness Scale (ESS) in a group of 100 patients with ALS and in 100 control subjects matched for age and sex. Functional disability was assessed using the ALS Functional Rating Scale-Revised (ALSFRS-R). Sleep was studied by overnight polysomnography in 12 patients. RESULTS: Fifty-nine patients with ALS and 36 controls reported sleep disturbances. The mean global PSQI score of patients with ALS was significantly higher than the control participants (6.82 ± 4.0 vs. 4.86 ± 3.2), and three of the seven components of PSQI in patients with ALS were significantly different from controls: 'sleep latency,' 'habitual sleep efficiency' and 'sleep disturbances.' The most commonly reported night-time complaints by patients with ALS were nocturia (54%), sleep fragmentation (48%) and nocturnal cramps (45%). Poor sleep was associated with decreased ALSFRS-R score, highest depression and ESS score. After a multivariate analysis, patients' disability and daytime somnolence remained significantly associated with sleep quality. Polysomnographic studies showed decreased sleep efficiency and fragmented sleep architecture. CONCLUSION: This study demonstrated that patients with ALS have a significant poor quality of sleep, and this correlated with the severity of ALS and daytime somnolence. Increased awareness for sleep-wake problems in patients with ALS is important, as effective intervention could lead to a better management of these patients.