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Aims: Exercise oscillatory ventilation (EOV) is a pivotal cardiopulmonary exercise test parameter for the prognostic evaluation of patients with chronic heart failure (HF). It has been described in patients with HF with reduced ejection fraction (50%, HFpEF), but no data are available for patients with HF with mid-range ejection fraction (40–49%, HFmrEF). The aim of the study was to evaluate the prognostic role of EOV in HFmrEF patients. Methods and results: We analysed 1239 patients with HFmrEF and 4482 patients with HFrEF, enrolled in the MECKI score database, with a 2-year follow-up. The study endpoint was the composite of cardiovascular death, urgent heart transplant, and ventricular assist device implantation. We identified EOV in 968 cases (16% and 17% of cases in HFmrEF and HFrEF,. respectively). HFrEF EOV+ patients were significantly older, and their parameters suggested a more severe HF than HFrEF EOV− patients. A similar behaviour was found in HFmrEF EOV+ vs. EOV− patients. Kaplan–Meier analysis, irrespective of ejection fraction, showed that EOV is associated with a worse survival, and that patients with HFrEF and HFmrEF EOV+ had a significantly worse outcome than the EOV− of the same ejection fraction groups. EOV-associated survival differences in HFmrEF patients started after 18 months of follow-up. Conclusion: Exercise oscillatory ventilation has a similar prevalence and ominous prognostic value in both HFmrEF and HFrEF patients, indicating a group of patients in need of a more intensive follow-up and a more aggressive therapy. In HFmrEF, the survival curves between EOV+ and EOV− patients diverged only after 18 months.

Background The higher cardiovascular variability and the increased prevalence of arrhythmias in patients with obstructive sleep apneas may contribute to their higher rate of fatal events during sleep. In this regard, the use of beta blockers (BB) is debated because they may induce bradyarrhythmias and alter the pattern of heart rate changes induced by apneas. Thus, the aim of our study is to quantify peri‐apneic heart‐rate swings and prevalence of nocturnal bradyarrhythmias in BB‐treated and BB‐naïve patients with obstructive sleep apnea. Methods and Results Our real‐life, retrospective, cohort study analyzed data from patients with obstructive sleep apnea after a basal cardiorespiratory polysomnography. Among 228 eligible participants, we enrolled 78 BB‐treated and 88 BB‐naïve patients excluding those treated with antiarrhythmic drugs or pacemakers, or with uninterpretable ECG traces during polysomnography. In each patient, type and frequency of arrhythmias were identified and peri‐apneic changes of RR intervals were evaluated for each apnea. BB‐treated patients were older and with more comorbidities than BB‐naïve patients, but had similar obstructive sleep apnea severity, similar frequency of arrhythmic episodes, and similar prevalence of bradyarrhythmias. Apnea‐induced heart‐rate swings, unadjusted for age, showed lower RR interval changes in BB‐treated (133.5±63.8 ms) than BB‐naïve patients (171.3±87.7 ms, P =0.01), lower RR interval increases during apneas (58.5±28.5 versus 74.6±40.2 ms, P =0.01), and lower RR interval decreases after apneas (75.0±42.4 versus 96.7±55.5 ms, P Conclusions BB appear to be safe in patients with obstructive sleep apnea because they are not associated with worse episodes of nocturnal bradyarrhythmias and even seem protective in terms of apnea‐induced changes of heart rate.

Background Despite considerable progress, it remains unclear why some patients admitted for COVID-19 develop adverse outcomes while others recover spontaneously. Clues may lie with the predisposition to hypoxemia or unexpected absence of dyspnea (‘silent hypoxemia’) in some patients who later develop respiratory failure. Using a recently-validated breath-holding technique, we sought to test the hypothesis that gas exchange and ventilatory control deficits observed at admission are associated with subsequent adverse COVID-19 outcomes (composite primary outcome: non-invasive ventilatory support, intensive care admission, or death). Methods Patients with COVID-19 (N = 50) performed breath-holds to obtain measurements reflecting the predisposition to oxygen desaturation (mean desaturation after 20-s) and reduced chemosensitivity to hypoxic-hypercapnia (including maximal breath-hold duration). Associations with the primary composite outcome were modeled adjusting for baseline oxygen saturation, obesity, sex, age, and prior cardiovascular disease. Healthy controls (N = 23) provided a normative comparison. Results The adverse composite outcome (observed in N = 11/50) was associated with breath-holding measures at admission (likelihood ratio test, p = 0.020); specifically, greater mean desaturation (12-fold greater odds of adverse composite outcome with 4% compared with 2% desaturation, p = 0.002) and greater maximal breath-holding duration (2.7-fold greater odds per 10-s increase, p = 0.036). COVID-19 patients who did not develop the adverse composite outcome had similar mean desaturation to healthy controls. Conclusions Breath-holding offers a novel method to identify patients with high risk of respiratory failure in COVID-19. Greater breath-hold induced desaturation (gas exchange deficit) and greater breath-holding tolerance (ventilatory control deficit) may be independent harbingers of progression to severe disease.

Background and Purpose: An accurate determination of the cardioembolic risk in patients with atrial fibrillation (AF) is crucial to prevent consequences like stroke. Obstructive sleep apnea (OSA) is a known risk factor for both AF and stroke. We aim to explore a possible association between OSA and an increased cardioembolic risk in patients with AF. Methods: We assessed data from the ESADA (European Sleep Apnea Database) cohort where patients with known AF and OSA were included. Parameters of OSA severity and related hypoxia like lowest Sp o 2 and 4% oxygen desaturation index were analyzed. Patients were stratified according to their cardioembolic risk estimated with the CHA 2 DS 2 -VASc score. Results: From the initial cohort of 14 646 patients, a final set of 363 patients were included in the analysis. Indices of hypoxia during sleep were associated with increased CHA 2 DS 2 -VASc score (4% oxygen desaturation index 17.9 versus 29.6 versus 30.5 events/hour and the lowest Sp o 2 81.2 versus 77.8 versus 77.5% for low, moderate, and high cardioembolic risk, respectively, P Conclusions: These results support the potential role of OSA-related hypoxia in the risk for cardioembolic complications such as stroke in patients with AF.

Introduction Positive airway pressure (PAP) treatment modifies blood pressure (BP) in patients with obstructive sleep apnea (OSA). We aimed to explore which factors that influence the BP response to PAP therapy in the European Sleep Apnea Database (ESADA). Methods A total of 2662 OSA patients with PAP therapy ≥90 days were included in the analysis (74% male, age 55±11 years, body mass index 32.3±6.1 kg/m2, 47% hypertensives, apnea-hypopnea index 40±24 events/h, treatment duration 1.0±1.1 years, PAP compliance 5.2±1.9 h/day). Anthropometric data, co-medications and office BP were assessed at baseline and follow-up visit. Results Systolic and diastolic BP were modestly reduced after PAP therapy compared to baseline (133±17 vs. 134±17 mmHg, 78±11 vs. 81±11 mmHg, p2 kg at follow up (−2.0 [−3.7 to −0.4], p=0.016), and use of auto-adjusted PAP (−1.3 [−2.5 to −0.02], p=0.046) were associated with a reduction of systolic BP at follow-up. Conclusions BP reduction following PAP treatment in patients with moderate to severe OSA was modest. We identified several predictors of a favorable BP response including the use of auto adjusted PAP. Our findings suggest that weight reduction strategies in addition to PAP treatment should be considered to obtain adequate BP control in OSA patients. Funding Acknowledgement Type of funding source: Other. Main funding source(s): European Respiratory Society funded Clinical Research Collaboration (2015-2020)

Summary: Allergic rhinitis (AR) is a common disease affecting up to 40% of the general population worldwide. In the Coronavirus 2019 (COVID-19) pandemic era, many observational studies analysing the effect of asthma and chronic obstructive pulmonary disease on the risk of developing COVID-19 were conducted, while data on AR are limited.In this paper, we review the risk of developing SARS-Cov-2 infection carried by AR patients, the outcomes of those with COVID-19 disease, and the COVID-19 influence on the allergic and nasal symptoms and the psychological status of AR patients, in both adult and paediatric populations.AR patients seem to be protected from COVID 19 infection. Even if data about the influence of AR on the severity of COVID-19 disease are still not conclusive, it seems that being an AR patient does not increase the risk of poor COVID-19 prognoses. The clinical manifestation of AR can be distinguished by COVID-19 symptoms. Treating AR adequately is also strongly recommended, especially during pandemic.

Introduction and Aim: Obstructive sleep apnea (OSA) is associated with a higher cardiovascular risk and abnormal autonomic control can play a role in this context. Thus, heart rate variability (HRV) changes induced by sleep may help to understand the autonomic derangement in OSA. Methods: From the ESADA database, we selected 84 polysomnographies with 10-min ECG segments both pre- and post-dormitum in male patients who underwent a diagnostic sleep study at Sleep Disorder Centre of the Antwerp. Patients were classified as moderate, mild or severe OSA based on the Apnea-Hypopnea Index (AHI). We estimated HRV indices of vagal tone (pNN50+ and RMSSD), of sympatho/vagal balance (short term DFA), and vagal/sympatho balance (SampEn), comparing pre- vs post-dormitum (Wilcoxon paired test). Results and Conclusions: From pre- to post-dormitum, the vagal tone increases significantly in moderate and mild OSA only; the sympatho/vagal balance increases similarly in the three groups, see table (data are expressed as median and interquartile range). Our data suggest that in severe OSA we observe a lower increase of vagal indices in post-dormitum associated with a relative sympathetic overactivity, potentially leading, in turn, to a higher risk of cardiovascular events.

In response to chronic hypobaric hypoxia, residents at altitude develop physiological adaptations. Despite these adaptations, chronic mountain sickness (CMS) can be observed in 5-33% of individuals residing at high altitude. CMS frequently triggers cardiorespiratory diseases such as pulmonary hypertension and right or left heart failure. Ambient hypoxia further amplifies sleep-related disorders so that sleep disturbance is an important feature of CMS. Our aim was to characterize nocturnal hypoxemia and the associated sleep and ambulatory (A) blood pressure (BP) changes in highlanders. Methods: Cardiorespiratory sleep and 24h ABP monitoring studies were performed in highlanders living in Puno (3800m) and La Rinconada (5100m), Peru. Subjects were divided in groups according to CMS severity scale. Results: 77 males were evaluated (age 43 [34-49] yr, BMI 25 [23-27] kg/m2). Subjects with CMS showed higher 24 h and daytime systolic and diastolic BP than those with no CMS. Highlanders with CMS were characterized by a lower nocturnal oxygen saturation (SpO2) mean, nocturnal SpO2 nadir and a higher oxygen desaturation index than those with no CMS. No difference was found in terms of apnea-hypopnea index. Altitude (β -4.3, p=0.02) and CMS class (β -0.5, p=0.01) were significant predictors of a lower nocturnal SpO2. Conclusions: At altitude lower mean nocturnal SpO2 and frequent desaturations might be implicated in CMS pathogenesis. Moreover, CMS subjects showed higher ABP, which might contribute to their reported worse cardiovascular prognosis as compared with no-CMS highlanders. Further pathophysiological and therapeutic intervention studies are needed for a better management of CMS.

[No Abstract Available]

Background and aim: Obstructive sleep apnea (OSA) is an independent risk factor for dyslipidemia. The current study examined the effects of positive airway pressure (PAP) treatment on lipid status in the European Sleep Apnea Database (ESADA). Methods: The prospective cohort study enrolled 1564 OSA subjects (74% male, mean age 54 ± 11y, body mass index (BMI) 32.7 ± 6.6 kg/m2 and apnea-hypopnea index (AHI) 40.3 ± 24.4 n/h) undergoing PAP therapy for at least three months (mean 377.6 ± 419.5 days). Baseline and follow-up total cholesterol (TC) from nine centers were analyzed. Repeated measures and logistic regression tests (adjusted for age, sex, weight changes, lipid lowering medication, PAP compliance, and treatment duration) were used to compare changes in TC concentration. Incident risk for a coronary heart disease event (CHD) was used to compute a Framingham CHD risk score (estimated from age, BMI, blood pressure, and TC). Results: Adjusted means of TC decreased from 194.2 mg/dl to 189.3 mg/dl during follow-up (p = 0.019). A clinically significant (10%) reduction of TC at PAP follow-up was observed in 422 patients (27%). Duration of PAP therapy was identified as independent predictor for TC reduction, which implies an approximately 10% risk reduction for incident CHD events (from 26.7% to 24.1% in men and from 11.2% to 10.1% in women, p < 0.001 respectively). Conclusion: This observational study demonstrates a reduction of TC after long-term PAP treatment. The close association between TC concentration and cardiovascular (CV) mortality suggests that identification and treatment of OSA may have a beneficial effect on overall CV risk due to this mechanism. This possibility needs to be evaluated in prospective randomized studies. © 2020 Elsevier B.V., ResMed Foundation European Respiratory Society, ERS European Respiratory Society, ERS European Respiratory Society, ERS, The ESADA network has received support from the European Union COST action B26 and the European Respiratory Society (ERS) funded Clinical Research Collaboration (CRC). Unrestricted seeding grants from the ResMed Foundation and the Philips Respironics Foundation for establishment of the database in 2007 and 2011 are gratefully acknowledged. The ESADA network has a scientific collaboration with Bayer AG., Nonfinancial support was provided by the European Sleep Research Society (ESRS) and the European Respiratory Society (ERS) in terms of logistics for communication, meetings and data presentations for the ESADA collaborators., Dr. Verbraecken reports grants and personal fees from ResMed, Bioprojet, Jazz Pharmaceutics; personal fees from Philips, Sanofi, Agfa-Gevaert, grants from AirLiquide; personal fees from Springer, Westfalen Medical, SomnoMed, Vivisol, Total Care, Medidis, Fisher & Paykel, Wave Medical, OSG, Mediq Tefa, NightBalance, Heinen & Löwenstein, AstraZen, Accuramed, Bekaert Deslee Academy and UCB Pharma, outside the submitted work. Dr. Hedner reports grants from ResMed, Philips Respironics, and the European Respiratory Society all related to maintenance of database on behalf of the ESADA group during the conduct of the study. Dr. Grote reports grants from Bayer, Resmed, Respironics/Philips, and from the European Respiratory Society during the conduct of the study; non-financial support and other from Itamar Medical, Resmed, Philips, and Astra Zeneca, outside the submitted work. In addition, Dr. Grote has a patent on sleep apnea therapy licensed. The remaining co-authors have no conflict of interest to declare.

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 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.

[No Abstract Available]

The increasing number of patients with heart failure HF and comorbidities is due to aging population and increase of life expectancy of patients with cardiovascular disease. Encouraging results derived by recent trials may suggest some comorbidities as new targets for new drugs, highlighting the need for a better understanding of the comorbidities’ effects in HF patients and the need of a multidisciplinary approach for the management of chronic HF with comorbidities. We report a brief review about main cardiovascular and non-cardiovascular comorbidities in HF patients in order to update physicians and researchers engaged in the HF research or in “fight against heart failure.”

STUDY OBJECTIVES: The association of mild obstructive sleep apnea (OSA) with important clinical outcomes remains unclear. We aimed to investigate the association between mild OSA and systemic arterial hypertension (SAH) in the European Sleep Apnea Database cohort. METHODS: In a multicenter sample of 4,732 participants, we analyzed the risk of mild OSA (subclassified into 2 groups: mild(AHI 5

Obstructive sleep apnoea (OSA) is a common disorder, in which loss of pharyngeal dilator muscle tone during sleep causes recurrent collapse of the upper airway and temporary cessation of breathing. Repeated apneas and hypopneas lead to cycles of intermittent hypoxia/hypercapnia, increased negative intrathoracic pressure and arousals from sleep. These consequences of OSA are associated with a cascade of cardiovascular and neurohumoral consequences, including sympathetic nervous system hyperactivity, raised heart rate variability, increases in blood pressure, myocardial wall stress, oxidative stress, systemic inflammation, platelet aggregation and impaired vascular endothelial function, which contribute, in turn, to increased cardiovascular risk and, in particular, to the development of chronic systemic arterial hypertension and arrhythmias, especially atrial fibrillation (AF). Given that the prevalence of OSA is modified by age and gender, OSA-related cardiovascular diseases may also be affected by the same factors. This review focuses on the potential role of OSA in systemic arterial hypertension and AF, and discusses the most interesting studies on age and gender as predisposing factors.

Summary Hypertension and blunted blood pressure (BP) dipping during nighttime sleep are associated with increased cardiovascular risk. Chronic insomnia and restless legs syndrome (RLS) may affect the 24-h BP profile. We systematically reviewed the association of insomnia and RLS with BP values during nighttime sleep and the relative BP dipping pattern. We searched relevant articles in any language with selection criteria including enrolment of subjects with insomnia or RLS and with obstructive sleep apnea comorbidity assessment. Of the 872 studies originally retrieved, seven were selected. Four studies enrolled subjects with insomnia. One study relied on sleep diaries to classify nighttime sleep BP, whereas three relied only on clock time. At meta-analysis, subjects with insomnia displayed an attenuated dipping of systolic BP (−2.00%; 95% confidence interval (CI): −3.61 - −0.39%) and diastolic BP (−1.58%; 95% CI: −2.66 −0.49%) during nighttime sleep compared to controls. Three studies enrolled subjects with RLS. One study relied on polysomnography to classify nighttime sleep BP, whereas two relied only on clock time. Subjects with RLS showed increases in nighttime sleep systolic BP (5.61 mm Hg, 95% CI 0.13–11.09 mm Hg) compared to controls. In conclusion, the limited available data suggest that insomnia and RLS are both associated with altered BP control during nighttime sleep. There is need for more clinical studies to confirm these findings, specifically focusing on measurements of BP during objectively defined sleep, on causal roles of leg movements during sleep and alterations in sleep architecture, and on implications for cardiovascular risk. Prospero acknowledgement of number CRD42020217947.

Aims Risk stratification in heart failure (HF) is crucial for clinical and therapeutic management. A multiparametric approach is the best method to stratify prognosis. In 2012, the Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score was proposed to assess the risk of cardiovascular mortality and urgent heart transplantation. The aim of the present study was to compare the prognostic accuracy of MECKI score to that of HF Survival Score (HFSS) and Seattle HF Model (SHFM) in a large, multicentre cohort of HF patients with reduced ejection fraction. Methods and results We collected data on 6112 HF patients and compared the prognostic accuracy of MECKI score, HFSS, and SHFM at 2- and 4-year follow-up for the combined endpoint of cardiovascular death, urgent cardiac transplantation, or ventricular assist device implantation. Patients were followed up for a median of 3.67 years, and 931 cardiovascular deaths, 160 urgent heart transplantations, and 12 ventricular assist device implantations were recorded. At 2-year follow-up, the prognostic accuracy of MECKI score was significantly superior [area under the curve (AUC) 0.781] to that of SHFM (AUC 0.739) and HFSS (AUC 0.723), and this relationship was also confirmed at 4 years (AUC 0.764, 0.725, and 0.720, respectively). Conclusion In this cohort, the prognostic accuracy of the MECKI score was superior to that of HFSS and SHFM at 2- and 4-year follow-up in HF patients in stable clinical condition. The MECKI score may be useful to improve resource allocation and patient outcome, but prospective evaluation is needed.

Treatment of obstructive sleep apnoea (OSA) has been shown to reduce blood pressure (BP). However, the effect size is modest and treatment of OSA is not recommended as the only treatment target when treating hypertension. The aim of this systematic review and meta-analysis was to identify potential predictors for BP response in patients with OSA undergoing CPAP treatment. A systematic search was conducted in three databases (MEDLINE, Embase and Web of Science) between January 1st 1960 to December 31st 2017 using terms exploring three domains (obstructive sleep apnoea, CPAP, clinical trial) Out of 2445 articles, 59 RCTs were included (n=7,329 subjects) comparing CPAP with control groups. CPAP was associated with a net reduction in systolic BP of -2.12 (95% CI -2.82 to -1.42) mmHg and in diastolic BP of -1.97 (95% CI -2.46 to -1.48) mmHg, favouring treatment of OSA using CPAP (both p-values Younger patients (

Background: Acute exposure to high altitude (>2500 m) is known to induce a rise in blood pressure (BP) and the appearance of sleep related breathing alterations, in particular central sleep apneas and periodic breathing. Little information is available on whether this is the case in humans also for acute exposure to moderate altitude (between 1500 and 2500 m). Aim of this study was to evaluate the effects of acute exposure of healthy volunteers to moderate altitude on conventional and ambulatory BP as well as on the frequency and severity of breathing alterations during sleep. Methods: Forty-four healthy lowlanders underwent 24-hour ambulatory BP monitoring and nocturnal cardio-respiratory sleep study at sea level and during acute (1–2 days after arrival) exposure to moderate altitude (2035 m, Sestriere, Italy). The key variables investigated included average systolic and diastolic BP and heart rate over daytime, night-time and 24 h, the frequency of obstructive and central apneas/hypopnoeas and the behaviour of oxygen saturation during sleep. Results: Compared to sea level, during moderate altitude exposure mean systolic/diastolic BP increased significantly during daytime (respectively from 125.6 ± 10.9 to 130.6 ± 12.3, p = 0.0032 and from 78.8 ± 6.7 to 81.8 ± 7.7 mmHg, p = 0.0048) and during night-time (respectively from 102.4 ± 12.4 to 107.4 ± 12.7, p = 0.0028, and from 62.0 ± 8.2 to 65.8 ± 8.2 mmHg, p = 0.0014), with no change in nocturnal BP dipping. BP increase was more evident in participants aged over 40 years. Apnea-hypopnea index (AHI) increased from 1.60 (0.40–2.90) to 5.4 (2.90–10.60), p < 0.0001), mainly because of increasing frequency of hypopneas and central apneas, in particular in males aged over 40 years. No association was found between size of BP changes and AHI. Conclusion: Our results indicate that in healthy subjects even exposure to moderate altitude may induce significant, although mild, changes in ambulatory BP and in respiratory patterns during sleep with gender and age-related differences. Further studies are needed to explore the clinical relevance of these findings

Background: Adherence to inhaled drugs is linked to patients’ satisfaction with their device, and an incorrect use can negatively affect the outcomes of asthma treatment. We speculated that this is particularly true in elderly asthmatic subjects. Aim: We performed a national pre-post interventional multicentre study, enrolling moderate-to-severe asthmatic subjects aged ≥65 ​years treated with fixed inhaled combination drugs by dry powder inhaler (DPI) or pressurized metered dose inhaler (pMDI). Adherence and critical errors were evaluated by means of validated questionnaires at first visit (V1) and after 3–6 months (V2). At V1, subjects underwent intensive training on the correct use of their device by physical demonstration. Results: A total of 411 asthmatics (F/M: 238/173, mean age±SD: 72 ​± ​5 ​years) participated to the study. At V1, 50% of the study subjects showed an Asthma Control Test (ACT) score ≤19 despite GINA step 3 and 4 treatment, and 40% had experienced at least one severe asthma exacerbation in the previous year. Poor adherence to treatment was recorded in 43% of subjects, and at least one error in using the device was registered in 56% of subjects. At V2, available for 318 patients, both the percentage of individuals with poor adherence and with at least one critical error significantly decreased (from 46% to 25%, and from 49% to 25%, respectively; p ​

European-Respiratory-Society (ERS) International Congress -- SEP 28-OCT 02, 2019 -- Madrid, SPAIN, Riha, Renata/0000-0001-8983-9985, WOS: 000507372405424, [No abstract available], European Respiratory Soc

Cardiovascular disease (CVD) is the leading cause of mortality and morbidity in women.Some authors highlighted that the female risk profile consists of traditional and emerging risk factors. Despite the lower prevalence of type 2 diabetes, years of life lost owing to the disease for women are substantially higher compared with men. In addition, pregnancy complicated by gestational diabetes represents a risk factor for CVD. Women with gestational diabetes have a higher prevalence of coronary artery disease that occur at a younger age and are independent of T2DM.Hypertension is an important cardiovascular risk factor in women. Estrogens and progesterone, known to have an impact on blood pressure levels, have also been proposed to be protective against sleep-disordered breathing. It is very difficult to understand whereas obstructive sleep apnea in women is independently associated with hypertension or if many confounders acting at different stages of the woman lifespan mediate this relation.The cardioprotective effect of physical activity in women of all ages is well known. Women are generally more physically inactive than men. During and after menopause, most women tend to reduce their physical activity levels and together with the reduction in basal metabolic rate, women experience loss of skeletal muscle mass with a negative change in the ratio of fat-to-lean mass.In conclusion, sex differences in the cardiovascular system are because of dissimilarities in gene expression and sex hormones; these result in variations in prevalence and presentation of CVD and associated conditions, such as diabetes, hypertension and vascular and cardiac remodeling.Changes in lifestyle and increase in physical activity could help in prevention of cardiovascular disease in women.

Purpose of Review: Obstructive sleep apnea (OSA) and hypertension are two phenomena deeply linked together and, although a causal relationship has been suggested, a recent meta-analysis showed only a very modest effect of OSA treatment on blood pressure (BP). However, a vast number of randomized controlled trials published so far share some limitations, mainly of methodological nature: neither OSA nor BP is always assessed in a standardized way. Moreover, compliance with OSA treatment is often sub-optimal making the results of these trials difficult to interpret. Recent Findings: Recent studies have shown that antihypertensive drugs can reduce BP more than OSA treatment, showing a better compliance profile and very few side effects. Summary: Considering the importance of reducing the overall cardiovascular risk of OSA patients, a more careful management of patient’s antihypertensive medication could allow a better BP control also in this condition. In addition, greater efforts should be made to improve patient’s acceptance of OSA treatment with the aim of improving their compliance.

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.

Background: Mild obstructive sleep apnoea (OSA) is highly prevalent, however its association with important clinical outcomes like arterial hypertension remains unknown. Aims and Objectives: To investigate the association between mild OSA and arterial hypertension in the European Sleep Apnoea Database (ESADA) cohort after adjusting for relevant confounding factors. Methods: A multicentric sample of 4974 adults from the ESADA cohort who showed simple snoring or mild OSA at cardiorespiratory polygraphy was studied. We compared the predictive value of mild OSA (AHI 5- Results: Arterial hypertension prevalence was 37% in mild OSA patients (n=2457) compared to 20% in non-apnoeic snorers (n=2517, p Conclusions: Mild OSA was associated with an independent 43% risk increase for arterial hypertension in this large, multicentric clinical patient cohort.

Autonomic nervous system (ANS) has been extensively explored in obstructive sleep apnea (OSA). Autonomic alterations in these patients have been described by means of several methods, evaluating ANS function both directly with microneurography and indirectly through baroreflex sensitivity (BRS, by the sequence method or the cross-spectral approach), heart rate variability analysis (HRV, both in the time and frequency domain) during sleep and wake, or conventional laboratory tests, including cold pressor test, hand grip test or measurement of urinary cathecolamine excretion. Several studies in OSA patients have shown ANS alterations, in particular sympathetic overactivity, both acutely during apnea events and chronically during the daytime, being both also involved in cardiovascular consequences of sleep disordered breathing. The association between OSA and sympathetic dysregulation suggests a dose response relationship between OSA severity and the degree of sympathetic overactivity and this association seems to be reversible as the treatment of OSA is implemented. Additionally ANS is involved in regulating visceral and humoral functions to maintain the body homeostasis and in reaction and adaptation to external and internal stressor stimuli. However, the vast majority of studies have focussed on cardiovascular alterations, which are easier to measure, somewhat neglecting the other functions regulated by ANS. More evidence is therefore needed to better characterize the impact that sleep disorder breathing may have on ANS both in the short and long term.

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 2.7), 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.

Background Acute exposure to high‐altitude hypobaric hypoxia induces a blood pressure rise in hypertensive humans, both at rest and during exercise. It is unclear whether this phenomenon reflects specific blood pressure hyperreactivity or rather an upward shift of blood pressure levels. We aimed at evaluating the extent and rate of blood pressure rise during exercise in hypertensive subjects acutely exposed to high altitude, and how these alterations can be counterbalanced by antihypertensive treatment. Methods and Results Fifty‐five subjects with mild hypertension, double‐blindly randomized to placebo or to a fixed‐dose combination of an angiotensin‐receptor blocker (telmisartan 80 mg) and a calcium‐channel blocker (nifedipine slow release 30 mg), performed a cardiopulmonary exercise test at sea level and after the first night's stay at 3260 m altitude. High‐altitude exposure caused both an 8 mm Hg upward shift ( P P P P Conclusions In hypertensive subjects exposed to high altitude, we observed a hypoxia‐driven upward shift and steepening of the blood pressure response to exercise. The effect of the combination of telmisartan/nifedipine slow release outweighed these changes and was associated with better muscle oxygen delivery. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 01830530.

Background Recent advances in wearable technology make continuous cardiorespiratory monitoring possible, with potential applications in assessment of cardiopulmonary patients, healthy subjects and athletes. The aim of the present study was to qualitatively and quantitatively evaluate a new wearable device (Learn Inspire Free Entertain = L.I.F.E.) by embedding in a compression shirt a 12‑lead ECG system and 5 respiratory sensors. Methods Thirty cardiorespiratory patients and ten healthy subjects were studied for 24 h during their usual life activities. In 8 healthy subjects, simultaneous measurements of the device and of an ergo-spirometer were performed during different levels of ventilation in five different body positions. The quality of ECG signals in terms of measurability of heart rate, P wave, QRS complex and ST segment, was analyzed by four expert cardiologists/respiratory physiologists using an arbitrary 1–5 scale. The sum of the respiratory signals was used to calculate the respiratory rate, inspiratory time and relative changes of tidal volume. These parameters were compared to ergo-spirometer measurements. Results Median quality value was >3 for heart rate, QRS complex, ST segment and P wave (except in L3, aVL, aVF, V1 and V2 leads). Median quality of respiratory traces was >4 in patients and between 3 and 4 in healthy subjects. The respiratory monitoring of respiratory rate and inspiratory time was accurate in all body positions. Tidal volumes were underestimated due to a high level of ventilation. Conclusions The L.I.F.E. device provides an accurate continuous monitoring of cardiorespiratory signals during the 24 h both in normal subjects and cardiorespiratory patients.

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. 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.

BACKGROUND Increasing left ventricular assist device (LVAD) pump speed according to the patient's activity is a fascinating hypothesis. This study analyzed the short-term effects of LVAD speed increase on cardiopulmonary exercise test (CPET) performance, muscle oxygenation (near-infrared spectroscopy), diffusion capacity of the lung for carbon monoxide (D lco ) and nitric oxide (D lno ), and sleep quality. METHODS We analyzed CPET, D lco and D lno , and sleep in 33 patients supported with the Jarvik 2000 (Jarvik Heart Inc., New York, NY). After a maximal CPET (n = 28), patients underwent 2 maximal CPETs with LVAD speed randomly set at 3 or increased from 3 to 5 during effort (n = 15). Then, at LVAD speed randomly set at 2 or 4, we performed (1) constant workload CPETs assessing O2 kinetics, cardiac output (CO), and muscle oxygenation (n = 15); (2) resting D lco and D lno (n = 18); and (3) nocturnal cardiorespiratory monitoring ( n = 29). RESULTS The progressive pump speed increase raised peak volume of oxygen consumption (12.5 ± 2.5 ml/min/kg vs 11.7 ± 2.8 ml/min/kg at speed 3; p = 0.001). During constant workload, from speed 2 to 4, CO increased (at rest: 3.18 ± 0.76 liters/min vs 3.69 ± 0.75 liters/min, p = 0.015; during exercise: 5.91 ± 1.31 liters/min vs 6.69 ± 0.99 liters/min, p = 0.014), and system efficiency (τ = 65.8 ± 15.1 seconds vs 49.9 ± 14.8 seconds, p = 0.002) and muscle oxygenation improved. At speed 4, D lco decreased, and obstructive apneas increased despite a significant apnea/hypopnea index and a reduction of central apneas. CONCLUSIONS Short-term LVAD speed increase improves exercise performance, CO, O2 kinetics, and muscle oxygenation. However, it deteriorates lung diffusion and increases obstructive apneas, likely due to an increase of intrathoracic fluids . Self-adjusting LVAD speed is a fascinating but possibly unsafe option, probably requiring a monitoring of intrathoracic fluids.

Objective:Acute exposure to high/moderate altitude (HMA) induces increase in ambulatory blood pressure (BP), which may be particularly pronounced during the night, leading to reduced nocturnal BP dipping. Occurrence of central sleep apneas (CSA) is also typical for HMA exposure. Aim of this study wa

Background: Hypertension and severe obstructive sleep apnea (OSA)may independently contribute to left ventricular diastolic dysfunction. However, scanty data is available on this issue in hypertensives withmild.moderate OSA. Methods and results:Weperformed polysomnography, echocardiography and 24 h ambulatory blood pressure monitoring in 115 treated essential hypertensives with suspicion of OSA. After exclusion of severe/treated OSA and/or cardiovascular disease patients, mild.moderate OSA (5 ≥ apnoea/hypopnoea index b 30 events·h-1) was diagnosed in 47.3% of the remaining 91 patients, while 52.7% were free of OSA. Transmitral early (E) and late (A) peak flow velocities were assessed in 69 patients, and mitral annular velocity (E′) in 53. Compared to non- OSA, mild.moderate OSA heart rate was higher (p =0.031) while E/A was lower (p = 0.001) without differences in 24 h mean systolic and diastolic blood pressures (125.36 ± 12.46/76.46 ± 6.97 vs 128.63 ± 11.50/77.70 ± 7.72 mm Hg, respectively, NS). Patients with E′ > 10 cm/s and E/A > 0.8 showed a lower mean SpO2 than subjects with normal diastolic function (p = 0.004; p > 0.001). In a logistic regression model age, mean SpO2, daytime heart rate and nocturnal diastolic blood pressure fall were associated with altered relaxation pattern, independently from BMI and gender. Conclusions: In controlled hypertensives mild.moderate OSA may be associated with early diastolic dysfunction, independently from age, gender andmean blood pressure and in the absence of concentric left ventricular hypertrophy. Moreover nocturnal hypoxia may be a key factor in determining early diastolic dysfunction, under the synergic effects of hypertension and mild.moderate OSA.

BACKGROUND OSA is associated with an increased risk of cardiovascular morbidity. A driver of this is metabolic dysfunction and in particular type 2 diabetes mellitus (T2DM). Prior studies identifying a link between OSA and T2DM have excluded subjects with undiagnosed T2DM, and there is a lack of population-level data on the interaction between OSA and glycemic control among patients with diabetes. We assessed the relationship between OSA severity and T2DM prevalence and control in a large multinational population. METHODS We performed a cross-sectional analysis of 6,616 participants in the European Sleep Apnea Cohort (ESADA) study, using multivariate regression analysis to assess T2DM prevalence according to OSA severity, as measured by the oxyhemoglobin desaturation index. Patients with diabetes were identified by previous history and medication prescription, and by screening for undiagnosed diabetes with glycosylated hemoglobin (HbA1c) measurement. The relationship of OSA severity with glycemic control was assessed in diabetic subjects. RESULTS T2DM prevalence increased with OSA severity, from 6.6% in subjects without OSA to 28.9% in those with severe OSA. Despite adjustment for obesity and other confounding factors, in comparison with subjects free of OSA, patients with mild, moderate, or severe disease had an OR (95% CI) of 1.33 (1.04-1.72), 1.73 (1.33-2.25), and 1.87 (1.45-2.42) ( P P CONCLUSIONS Increasing OSA severity is associated with increased likelihood of concomitant T2DM and worse diabetic control in patients with T2DM.

Obstructive sleep apnea syndrome (OSAS), combining nighttime occurring intermittent obstruction of upper airways with daytime somnolence, is associated with impairment in important mechanisms of cardiovascular regulation, in particular with neural and reflex mechanisms involved in blood pressure (BP) control. The resultant sympathetic activation and the associated metabolic and humoral responses lead to important autonomic and hemodynamic changes (vasoconstriction, fluid retention, elevated blood pressure and blood pressure variability, elevated heart rate, and reduced heart rate variability), which are not only present during the apneic episodes occurring at night but also during daytime wakefulness. The presence of all these conditions, the magnitude of which is directly associated to the severity of OSAS, not only promotes future development of hypertension but also makes hypertension occurring in OSAS more severe and resistant to antihypertensive treatment and associated with profound alterations in day-to-night BP changes. The evidence mentioned above highlights the relevance of OSAS as a risk condition not only for arterial hypertension but also for other cardiovascular diseases. This chapter is aimed at reviewing: 1. The effects of OSAS on different mechanisms involved in integrated cardiovascular modulation (2) The resultant autonomic and hemodynamic responses to these alterations 2. The epidemiological evidence supporting the association of elevated BP with OSAS 3. The prognostic significance of OSAS-related hypertension 4. The diagnostic approach to OSAS-related hypertension 5. Finally, the role of pharmacological and non-pharmacological strategies on OSAS-related hypertension with emphasis on CPAP (i.e., which is known to be effective in reducing the sympathetic nervous system overdrive; a major contributing mechanism for OSAS-related alterations in BP regulation) and whether it may promote achievement of BP control and stabilization of BP levels for improving cardiovascular morbidity and mortality in OSAS patients

This randomized, double-blind, placebo-controlled study was designed to explore the effects of exposure to very high altitude hypoxia on vascular wall properties and to clarify the role of renin–angiotensin–aldosterone system inhibition on these vascular changes. Forty-seven healthy subjects were included in this study: 22 randomized to telmisartan (age, 40.3±10.8 years; 7 women) and 25 to placebo (age, 39.3±9.8 years; 7 women). Tests were performed at sea level, pre- and post-treatment, during acute exposure to 3400 and 5400-m altitude (Mt. Everest Base Camp), and after 2 weeks, at 5400 m. The effects of hypobaric hypoxia on mechanical properties of large arteries were assessed by applanation tonometry, measuring carotid–femoral pulse wave velocity, analyzing arterial pulse waveforms, and evaluating subendocardial oxygen supply/demand index. No differences in hemodynamic changes during acute and prolonged exposure to 5400-m altitude were found between telmisartan and placebo groups. Aortic pulse wave velocity significantly increased with altitude ( P P P P P Clinical Trial Registration— URL: https://www.clinicaltrialsregister.eu/ . Unique identifier: 2008-000540-14.

INTRODUCTION: Slow breathing training (SBT) has been proposed as a new nonpharmacologic treatment in patients with chronic heart failure (CHF). OBJECTIVES: The aim of this study was to assess the effects of SBT on exercise capacity, hemodynamic parameters, and sleep respiratory patterns in a relatively large sample of CHF patients. PATIENTS AND METHODS: A crossover open study was conducted. Patients completed, in a random order, 10- to 12-week SBT, with 2 15-minute sessions of device-guided SBT each day, reaching 6 breaths/min, and a 10- to 12-week follow-up under standard care. Clinical data collection, polysomnography, echocardiography, 6-minute walk test (6MWT), and laboratory tests were performed. RESULTS: A total of 96 patients (74 men, 22 women) in New York Heart Association classes I-III, with an average age of 65 years and an ejection fraction (EF) of 31%, completed the study. Home-based SBT was safe. After training, EF and 6MWT distance improved (EF: 31.3% ±7.3% vs 32.3% ±7.7%; P = 0.030; 6MWT: 449.9 ±122.7 m vs 468.3 ±121.9 m; P

Blood pressure (BP) is characterized by marked fl uctuations occurring within the 24 h as a result of complex interactions between behavioral, environmental, humoral, and neural central or refl ex infl uences. Signifi cant BP variations also occur over more prolonged periods of time (i.e. between days, weeks, months, seasons and even years), not as a random phenomenon but as a result of several interacting factors yet not completely identifi ed. Depending on the method and time interval considered for measurement, the clinical signifi cance and prognostic implications of different types of BP variability (BPV) may substantially differ. Either in the short or in the long term, BPV has been associated with development, progression and severity of cardiac, vascular and renal organ damage and with an increased risk of cardiovascular events and mortality, independently adding to cardiovascular risk, over and above the contribution of elevated mean BP levels. The present paper provides a review on the main methods currently employed for assessment of BPV as well as on the mechanisms, clinical interpretation and prognostic signifi cance of different types of BPV, addressing the question on whether BPV should be a target for antihypertensive treatment for the current prevention of cardiovascular disease.

High-altitude tourism is increasingly frequent, involving also subjects with manifest or subclinical coronary artery disease. Little is known, however, on the effects of altitude exposure on factors affecting coronary perfusion. The aim of our study was to assess myocardial oxygen supply/demand ratio in healthy subjects during acute exposure at high altitude and to evaluate the effect of acetazolamide on this parameter. Forty-four subjects (21 men, age range: 24–59 years) were randomized to double-blind acetazolamide 250 mg bid or placebo. Subendocardial viability ratio and oxygen supply/demand ratio were estimated on carotid artery by means of a validated PulsePen tonometer, at sea level, before and after treatment, and after acute and more prolonged exposure to high altitude (4559 m). On arrival at high altitude, subendocardial viability ratio was reduced in both placebo (from 1.63±0.15 to 1.18±0.17; P P P P P P

Background: Little is known about the effects of cardiovascular drugs at high altitude. Objective: To assess 24-h blood pressure (BP) and heart rate (HR) during short-term altitude exposure in healthy normotensive persons treated with carvedilol or nebivolol. Methods: Participants were randomized in double-blind to placebo, nebivolol 5 mg once daily or carvedilol 25 mg b.i.d. Tests were performed at sea level (baseline and after 2 weeks treatment) and on second to third day at altitude (Monte Rosa, 4559 m), still on treatment. Data collection included conventional BP, 24-h ambulatory BP monitoring (ABPM), oxygen saturation (SpO2), Lake Louise Score and adverse symptoms score. Results: Twenty-four participants had complete data (36.4 ± 12.8 years, 14 men). Both beta-blockers reduced 24-h BP at sea level. At altitude 24-h BP increased in all groups, mainly due to increased night-time BP. Twenty-four-hour SBP at altitude was lower with carvedilol (116.4 ± 2.1 mmHg) than with placebo (125.8 ± 2.2 mmHg; P < 0.05) and intermediate with nebivolol (120.7 ± 2.1 mmHg; NS vs. others). Rate of nondipping increased at altitude and was lower with nebivolol than with placebo (33 vs. 71%; P = 0.065). Side effects score was higher with carvedilol than with placebo (P = 0.04), and intermediate with nebivolol. SpO2 at altitude was higher with placebo (86.1 ± 1.2%) than with nebivolol (81.7 ± 1.1%; P = 0.07) or carvedilol (81.1 ± 1.1%; P = 0.04). Conclusions: Both carvedilol and nebivolol partly counteract the increase in BP at altitude in healthy normotensive individuals but are associated with a lower SpO2. Carvedilol seems more potent in this regard, whereas nebivolol more effectively prevents the shift to a nondipping BP profile and is better tolerated. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.