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Objectives: Blood pressure (BP) variability (BPV) can be assessed using office (OBP), home (HBP), or ambulatory BP (ABP) measurements. This analysis investigated the association and agreement between OBP, HBP, and ABP measurements for BPV assessment at baseline and 10 weeks after initiating antihypertensive drug therapy., Methods: Untreated hypertensive patients with elevated BPV were randomized to receive an angiotensin-converting enzyme inhibitor (ramipril) or a calcium channel blocker (nifedipine GITS) in a 10-week, open-label, blinded-end point study. BPV was assessed using standard deviation (SD) and coefficient of variation (CV) (reading-to-reading analyses)., Results: Data from 146 participants from three research centers (Athens/Greece; Milan/Italy; Shanghai/China) were analyzed [mean age 53 ± 10 (SD) years, male individuals 60%, baseline systolic OBP, HBP, and 24 h ABP 144 ± 9, 138 ± 10, and 143 ± 10 mmHg, respectively]. Post-treatment minus pre-treatment systolic CV difference was: OBP: 0.3%, P  = 0.28; HBP: -0.2%, P  = 0.20; 24 h ABP: 1.1%, P  < 0.001. Home and ambulatory (not office) BPV indices presented weak-to-moderate correlation, both before and during treatment (range of coefficients 0.04-0.33). The correlation coefficient between systolic HBP and awake ABP CV was 0.21 and 0.28 before and during treatment, respectively ( P  < 0.05/< 0.001, respectively). Home and ambulatory (not office) BPV indices presented slight-to-fair agreement (range 64-73%) in detecting participants with high systolic BPV (top quartile of respective distributions) both before and during treatment (kappa range 0.04-0.27)., Conclusion: These data showed a weak-to-moderate association between out-of-office (but not office) BPV indices both before and during BP-lowering treatment, with reasonable agreement in detecting individuals with high BPV. Out-of-office BP measurements provide more similar and consistent BPV information than office measurements., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Air pollution and obstructive sleep apnea (OSA) are both linked with cardiovascular co-morbidities and share similar pathophysiological mechanisms. A causal association between the two has been postulated. However, the results of the studies on this topic are conflicting mainly because of the lack of adjustment for important confounders such as seasonality and temperature. We aimed to evaluate if such an association exists in a highly polluted area like Lombardy region (Italy) when accounting for all confounders., Methods: Data of adult patients seen at the Sleep Disorder Centre in Milan from 2010 to 2020 were analysed and the main polygraphic data were retrieved. Air pollutant concentrations of the following pollutants NO 2 , O 3 , PM 2.5 , and PM 10 were collected through monitoring stations., Results: A total of 3493 patients were included: males (2358, 67.5%) mean age 60.1 (SD = 14.3) years, BMI 29.2 (6.2) kg/m 2 , mean AHI 16.5 (18.1) events/h. After adjusting for all confounders, in the multivariable analysis, the only associations that remained significant were long-term exposure to O 3 with indexes of OSA severity (AHI and ODI) but only in spring. Furthermore, a positive association was seen between long-term exposure to PM 10 and ODI but in springtime only., Conclusion: The findings of the current study does not support an association between fine particulate matter and OSA severity., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

High blood pressure is the leading cause of death and disability globally and an important treatable risk factor for cardiovascular, cerebrovascular and chronic kidney diseases. Digital technology, including mobile health solutions and digital therapy, is expanding rapidly in clinical medicine and has the potential to improve the quality of care and effectiveness of drug treatment by making medical interventions timely, tailored to hypertensive patients' needs and by improving treatment adherence. Thus, the systematic application of digital technologies could support diagnosis and awareness of hypertension and its complications, ultimately leading to improved BP control at the population level. The progressive implementation of digital medicine in the national health systems must be accompanied by the supervision and guidance of health authorities and scientific societies to ensure the correct use of these new technologies with consequent maximization of the potential benefits. The role of scientific societies in relation to the rapid adoption of digital technologies, therefore, should encompass the entire spectrum of activities pertaining to their institutional role: information, training, promotion of research, scientific collaboration and advice, evaluation and validation of technological tools, and collaboration with regulatory and health authorities., (© 2023. The Author(s).)

Introduction: The number of Italian citizens unaware of their risk of cardiovascular disease it is still very high., Aim: This study aimed to translate and preliminarily validate a brief Italian version of the Perception of Risk of Heart Disease Scale (PRHDS)., Methods: PRHDS was culturally adapted to the Italian context. Then, the scale was administered to 772 healthy adults. By randomly dividing the sample into two subsamples, we tested the scale dimensionality through Exploratory Factor Analysis (EFA) followed by Confirmatory Factor Analysis (CFA). Finally, we evaluated internal consistency., Results: Psychometric properties of the scale were appropriate. EFA and CFA evidenced a unidimensional structure of a brief version of the scale, composed of six items. Internal consistency was adequate., Conclusions: Italian version of the brief PRHDS is a promising self-report questionnaire to measure cardiovascular risk perception among Italian adults., (© 2023. The Author(s).)

Background and Aim: Continuous Positive Airway Pressure (CPAP) is the most effective therapy for symptomatic obstructive sleep apnoea (OSA). However, uncertainty remains about the effectiveness of CPAP in improving OSA-related metabolic dysregulation. This meta-analysis of randomized controlled trials (RCTs) aimed to investigate whether CPAP, compared to other control treatments, could improve glucose or lipid metabolism in OSA patients., Methods: Relevant articles were searched in three different databases (MEDLINE, EMBASE and Web of Science) from inception to 6th Feb 2022 through specific search terms and selection criteria., Results: From a total of 5553 articles, 31 RCTs were included. CPAP modestly improved insulin sensitivity as determined by mean fasting plasma insulin and Homeostasis Model Assessment of Insulin Resistance reduction of 1.33mU/L and 0.287, respectively. In subgroup analyses pre-diabetic/type 2 diabetic patients as well as those with sleepy OSA showed a greater response to CPAP. Regarding lipid metabolism, CPAP was associated with a mean total cholesterol reduction of 0.064mmol/L. In subgroup analyses, the benefit was higher in patients that showed more severe OSA and oxygen desaturations at the baseline sleep study as well as in younger and obese subjects. Neither glycated haemoglobin nor triglycerides, HDL- and LDL-cholesterol were reduced by CPAP., Conclusion: CPAP treatment may improve insulin sensitivity and total cholesterol levels in OSA patients but with low effect size. Our results suggest that CPAP does not substantially improve metabolic derangements in an unselected OSA population, but the effect may be higher in specific subgroups of OSA patients., (Copyright © 2023 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction: Variable D-dimer trends during hospitalization reportedly result in distinct in-hospital mortality. In this multinational case series from the first and second waves, we show the universality of such D-dimer trends., Methods: We reviewed 405 patients with COVID-19 during the first wave admitted to three institutions in the United States, Italy, and Colombia, and 111 patients admitted to the U.S. site during the second wave and 55 patients during the third wave. D-dimer was serially followed during hospitalization., Results: During the first wave, 66 (15%) patients had a persistently-low pattern, 33 (8%) had early-peaking, 70 (16%) had mid-peaking, 94 (22%) had fluctuating, 30 (7%) had late-peaking, and 112 (26%) had a persistently-high pattern. During the second and third waves, similar patterns were observed. D-dimer patterns were significantly different in terms of in-hospital mortality similarly in all waves. Patterns were then classified into low-risk patterns (persistently-low and early-peaking), where no deaths were observed in both waves, high-risk patterns (mid-peaking and fluctuating), and malignant patterns (late-peaking and persistently-high). Overall, D-dimer trends were associated with an increased risk for in-hospital mortality in the first wave (overall: HR: 1.73) and stayed the same during the second (HR: 1.67, p < 0.001) and the third (HR: 4.4, p = 0.001) waves., Conclusion: D-dimer behavior during COVID-19 hospitalization yielded universal categories with distinct mortality risks that persisted throughout all studied waves of infection. Monitoring D-dimer behavior may be useful in the management of these patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ronderos Botero, Omar, Pengo, Haider, Latif, Parati, Pengo, Cañas Arboleda, Díaz, Villaquirán-Torres, Contreras and Chilimuri.)

Background: Electrical stimulation has recently been introduced to treat patients with Obstructive sleep apnoea There are, however, few data on the effects of transcutaneous submental electrical stimulation (TES) on the cardiovascular system. We studied the effect of TES on cardiorespiratory variables in healthy volunteers during head-down-tilt (HDT) induced baroreceptor loading. Method: Cardiorespiratory parameters (blood pressure, heart rate, respiratory rate, tidal volume, airflow/minute ventilation, oxygen saturation, and end-tidal CO2/O2 concentration) were recorded seated, supine, and during head-down-tilt (50) under normoxic, hypercapnic (FiCO 2 5%) and poikilocapnic hypoxic (FiO 2 12%) conditions. Blood pressure (BP) was measured non-invasively and continuously (Finapres). Gas conditions were applied in random order. All participants were studied twice on different days, once without and once with TES. Results: We studied 13 healthy subjects (age 29 (12) years, six female, body mass index (BMI) 23.23 (1.6) kg·m -2 ). A three-way ANOVA indicated that BP decreased significantly with TES (systolic: p = 4.93E-06, diastolic: p = 3.48E-09, mean: p = 3.88E-08). Change in gas condition (systolic: p = 0.0402, diastolic: p = 0.0033, mean: p = 0.0034) and different postures (systolic: 8.49E-08, diastolic: p = 6.91E-04, mean: p = 5.47E-05) similarly impacted on BP control. When tested for interaction, there were no significant associations between the three different factors electrical stimulation, gas condition, or posture, except for an effect on minute ventilation (gas condition/posture p = 0.0369). Conclusion: Transcutaneous electrical stimulation has a substantial impact on the blood pressure. Similarly, postural changes and variations in inspired gas impact on blood pressure control. Finally, there was an interaction between posture and inspired gases that affects minute ventilation. These observations have implications on our understanding of integrated cardiorespiratory control, and may prove beneficial for patients with SDB who are assessed for treatment with electrical stimulation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Alsharifi, Kaltsakas, Pengo, Parati, Serna-Pascual, Rafferty and Steier.)

Background and Objective: Obstructive sleep apnea (OSA) is associated with heart derangements detected at echocardiography as higher left ventricular mass index (LVMI), higher left ventricular end-diastolic diameter, lower left ventricular ejection fraction (LVEF), and impaired diastolic function. However, the currently used parameter to define OSA diagnosis and severity, the apnea/hypopnea index (AHI), poorly predicts cardiovascular damage, cardiovascular events, and mortality. Our study aimed to assess if other polygraphic indices of OSA presence and severity, in addition to AHI, might better predict echocardiographic cardiac remodeling., Methods and Results: We enrolled two cohorts of individuals referred for suspected OSA to the outpatient facilities of the IRCCS Istituto Auxologico Italiano, Milano, and of the Clinica Medica 3, Padova. All patients underwent home sleep apnea testing and echocardiography. Based on the AHI the cohort was divided into no-OSA (AHI<15 events/hour) and moderate-severe OSA (AHI≥15 events/hour). We recruited 162 patients and found that compared to patients with no-OSA, those with moderate-severe OSA showed higher LV remodeling [left ventricular end-diastolic volume (LVEDV) 48.4 ± 11.5 ml/m2 vs. 54.1 ± 14.0 ml/m2, respectively, p = 0.005] and lower LVEF (65.3 ± 5.8% vs. 61.6 ± 7.8%, respectively, p = 0.002), whereas we could not find any difference in LVMI and early and late ventricular filling velocity ratio (E/A). At multivariate linear regression analysis two polygraphic hypoxic burden-related markers were independent predictors of LVEDV and E/A, i.e., the percentage of time with O2 saturation below 90% (β = 0.222) and ODI (β = -0.422), respectively., Conclusions: Our study shows that nocturnal hypoxia-related indexes were associated with left ventricular remodeling and diastolic dysfunction in OSA patients., Competing Interests: Declaration of competing interest Authors have no financial or non-financial conflicts of interest to declare., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Pulmonary vascular diseases (PVDs), defined as arterial or chronic thromboembolic pulmonary hypertension, are associated with autonomic cardiovascular dysregulation. Resting heart rate variability (HRV) is commonly used to assess autonomic function. Hypoxia is associated with sympathetic overactivation and patients with PVD might be particularly vulnerable to hypoxia-induced autonomic dysregulation. In a randomised crossover trial, 17 stable patients with PVD (resting PaO 2 ≥ 7.3 kPa) were exposed to ambient air (FiO 2 = 21%) and normobaric hypoxia (FiO 2 = 15%) in random order. Indices of resting HRV were derived from two nonoverlapping 5-10-min three-lead electrocardiography segments. We found a significant increase in all time- and frequency-domain HRV measures in response to normobaric hypoxia. There was a significant increase in root mean squared sum difference of RR intervals (RMSSD; 33.49 (27.14) vs. 20.76 (25.19) ms; p < 0.01) and RR50 count divided by the total number of all RR intervals (pRR50; 2.75 (7.81) vs. 2.24 (3.39) ms; p = 0.03) values in normobaric hypoxia compared to ambient air. Both high-frequency (HF; 431.40 (661.56) vs. 183.70 (251.25) ms 2 ; p < 0.01) and low-frequency (LF; 558.60 (746.10) vs. 203.90 (425.63) ms 2 ; p = 0.02) values were significantly higher in normobaric hypoxia compared to normoxia. These results suggest a parasympathetic dominance during acute exposure to normobaric hypoxia in PVD.

Many modifiable and non-modifiable risk factors have been associated with hypertension. However, current screening programs are still failing in identifying individuals at higher risk of hypertension. Given the major impact of high blood pressure on cardiovascular events and mortality, there is an urgent need to find new strategies to improve hypertension detection. We aimed to explore whether a machine learning (ML) algorithm can help identifying individuals predictors of hypertension. We analysed the data set generated by the questionnaires administered during the World Hypertension Day from 2015 to 2019. A total of 20206 individuals have been included for analysis. We tested five ML algorithms, exploiting different balancing techniques. Moreover, we computed the performance of the medical protocol currently adopted in the screening programs. Results show that a gain of sensitivity reflects in a loss of specificity, bringing to a scenario where there is not an algorithm and a configuration which properly outperforms against the others. However, Random Forest provides interesting performances (0.818 sensitivity - 0.629 specificity) compared with medical protocols (0.906 sensitivity - 0.230 specificity). Detection of hypertension at a population level still remains challenging and a machine learning approach could help in making screening programs more precise and cost effective, when based on accurate data collection. More studies are needed to identify new features to be acquired and to further improve the performances of ML models., (© 2022. The Author(s).)

The majority of the current international obstructive sleep apnea (OSA) guidelines base the recommendation to treat OSA with continuous positive airway pressure (CPAP) on the presence of symptoms (principally, albeit not exclusively on daytime hypersomnolence). In nonsleepy patients, even with severe OSA, controversies remain, as clear evidence supporting CPAP treatment of this subgroup of OSA patients is lacking. However, given the nonnegligible proportion of non-sleepy OSA patients, clinicians often face a serious dilemma since CPAP treatment in these patients may prove to be not cost-effective. Here, we propose a simple three-step-based algorithm that attempts to better phenotype non-sleepy OSA patients prior to reaching a CPAP treatment decision while also considering a series of clinically relevant elements in the process that may improve with CPAP therapy. Such algorithm focuses on the presence of several OSA symptoms that are susceptible to benefit from treatment and also relies on OSA phenotypes that need to be considered in an effort to achieve optimal cardiovascular prevention. Here, we attempt to establish a framework for clinicians who are evaluating severe nonsleepy OSA patients in their practices. However, the algorithm proposal needs to be extensively validated before being systematically implemented in clinical settings., (© The Author(s) 2022. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Competing Interests: Conflict of interest: none declared.

Coronavirus disease 2019 (COVID-19) is a newly recognized infectious disease which can lead to acute respiratory distress syndrome requiring ventilatory support and intensive care unit admission. The aim of our study is to evaluate the performance of two non-invasive respiratory function indices (the ROX index and the SatO2/FiO2 ratio), as compared to the traditional PaO2/FiO2 ratio, in predicting a clinically relevant composite outcome (death or intubation) in hospitalized patients for COVID-19 pneumonia. Four hospital centers in Northern Italy conducted an observational retrospective cohort study during the first wave of COVID-19 pandemic. Four hundred and fifty-six patients with COVID-19 pneumonia admitted to medical or sub-intensive wards were enrolled. Clinical, laboratory, and respiratory parameters, for the calculation of different indices, were measured at hospital admission. In medical wards (Verona and Padua) the PaO2/FiO2 ratio, ROX index and SatO2/FiO2 ratio were able to predict intubation or death with good accuracy (AUROC for the PaO2/FiO2 ratio, ROX index and SatO2/FiO2 ratio of 75%, 75% and 74%, respectively). Regarding sub-intensive wards (Milan and Mantua), none of the three respiratory function indices was significantly associated with the composite outcome. In patients admitted to medical wards for COVID-19 pneumonia, the ROX index and the SatO2/FiO2 ratio demonstrated not only good performance in predicting intubation or death, but their accuracy was comparable to that of the PaO2/FiO2 ratio. In this setting, where repeated arterial blood gas tests are not always feasible, they could be considered a reliable alternative to the invasive PaO2/FiO2 ratio., (© 2022. The Author(s).)

This article describes a user-centred approach taken by a group of five procurers to set specifications for the procurement of value-based research and development services for IT-supported integrated hypertension management. The approach considered the unmet needs of patients and health systems of the involved regions. The procurers established a framework for requirements and a solution design consisting of nine building blocks, divided into three domains: service delivery, devices and integration, and health care organisation. The approach included the development of questionnaires, capturing patients' and professionals' views on possible system functionalities, and a template collecting information about the organisation of healthcare, professionals involved and existing IT systems at the procurers' premises. A total of 28 patients diagnosed with hypertension and 26 professionals were interviewed. The interviewees identified 98 functional requirements, grouped in the nine building blocks. A total of nine use cases and their corresponding process models were defined by the procurers' working group. As result, a digitally enabled integrated approach to hypertension has been designed to allow citizens to learn how to prevent the development of hypertension and lead a healthy lifestyle, and to receive comprehensive, individualised treatment in close collaboration with healthcare professionals.

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 0.13̶-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., Competing Interests: Conflicts of interest The authors do not have any conflicts of interest to disclose., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Vitamin D deficiency has been suggested to favor a poorer outcome of Coronavirus disease-19 (COVID-19). We aimed to assess if 25-hydroxyvitamin-D (25OHD) levels are associated with interleukin 6 (IL-6) levels and with disease severity and mortality in COVID-19., Methods: We prospectively studied 103 in-patients admitted to a Northern-Italian hospital (age 66.1 ± 14.1 years, 70 males) for severely-symptomatic COVID-19. Fifty-two subjects with SARS-CoV-2 infection but mild COVID-19 symptoms (mildly-symptomatic COVID-19 patients) and 206 subjects without SARS-CoV-2 infection were controls. We measured 25OHD and IL-6 levels at admission and focused on respiratory outcome during hospitalization., Results: Severely-symptomatic COVID-19 patients had lower 25OHD levels (18.2 ± 11.4 ng/mL) than mildly-symptomatic COVID-19 patients and non-SARS-CoV-2-infected controls (30.3 ± 8.5 ng/mL and 25.4 ± 9.4 ng/mL, respectively, p < 0.0001 for both comparisons). 25OHD and IL-6 levels were respectively lower and higher in severely-symptomatic COVID-19 patients admitted to intensive care Unit [(ICU), 14.4 ± 8.6 ng/mL and 43.0 (19.0-56.0) pg/mL, respectively], than in those not requiring ICU admission [22.4 ± 1.4 ng/mL, p = 0.0001 and 16.0 (8.0-32.0) pg/mL, p = 0.0002, respectively]. Similar differences were found when comparing COVID-19 patients who died in hospital [13.2 ± 6.4 ng/mL and 45.0 (28.0-99.0) pg/mL] with survivors [19.3 ± 12.0 ng/mL, p = 0.035 and 21.0 (10.5-45.9) pg/mL, p = 0.018, respectively). 25OHD levels inversely correlated with: i) IL-6 levels (ρ - 0.284, p = 0.004); ii) the subsequent need of the ICU admission [relative risk, RR 0.99, 95% confidence interval (95%CI) 0.98-1.00, p = 0.011] regardless of age, gender, presence of at least 1 comorbidity among obesity, diabetes, arterial hypertension, creatinine, IL-6 and lactate dehydrogenase levels, neutrophil cells, lymphocytes and platelets count; iii) mortality (RR 0.97, 95%CI, 0.95-0.99, p = 0.011) regardless of age, gender, presence of diabetes, IL-6 and C-reactive protein and lactate dehydrogenase levels, neutrophil cells, lymphocytes and platelets count., Conclusion: In our COVID-19 patients, low 25OHD levels were inversely correlated with high IL-6 levels and were independent predictors of COVID-19 severity and mortality.

Cardiovascular (CV) diseases are burdened by high mortality and morbidity, being responsible for half of the deaths in Europe. Although hypertension is recognized as the most important CV risk factor, hypertension awareness, and blood pressure (BP) control are still unsatisfactory. In 2017 and 2018, respectively >10 000 and >5000 individuals took part in the May Measurement Month (MMM) campaign in Italy, of whom 30.6% and 26.3% were found to have high BP, respectively. To raise public awareness on the importance of hypertension and to collect BP data on a nation-wide scale in Italy. In the frame of the MMM campaign, an opportunistic cross-sectional survey of volunteers aged ≥18 years was carried out in May 2019. BP measurement, the definition of hypertension, and statistical analysis followed the standard MMM protocol. Screening was conducted in multiple sites by health personnel. Among the 10 182 people screened (females: 52.3%, mean age 58 ± 16years) mean BP was 127/78 mmHg, and 3171 (31.1%) participants had arterial hypertension, of whom 62.1% were aware of being hypertensive. Diabetes, body mass index >25 kg/m 2 were associated with higher BP and previous myocardial infarction with lower BP. For the third consecutive year we collected a nation-wide snapshot of BP control in a large sample of individuals. The high participation, with some yearly fluctuations likely due to the limitations of the sampling technique, confirms the power of this kind of health campaign in reaching a significant number of people to raise awareness on health topics., (Published on behalf of the European Society of Cardiology. © The Author(s) 2021.)

The authors hypothesized that the cytokine storm described in COVID-19 patients may lead to consistent cell-based tissue factor (TF)-mediated activation of coagulation, procoagulant microvesicles (MVs) release, and massive platelet activation. COVID-19 patients have higher levels of TF + platelets, TF + granulocytes, and TF + MVs than healthy subjects and coronary artery disease patients. Plasma MV-associated thrombin generation is present in prophylactic anticoagulated patients. A sustained platelet activation in terms of P-selectin expression and platelet-leukocyte aggregate formation, and altered nitric oxide/prostacyclin synthesis are also observed. COVID-19 plasma, added to the blood of healthy subjects, induces platelet activation similar to that observed in vivo. This effect was blunted by pre-incubation with tocilizumab, aspirin, or a P2Y 12 inhibitor., Competing Interests: This work was supported by a grant from Italian Ministry of Health (Ricerca Corrente Reti 2020- RCR-2020-23670065, to Prof. Camera). The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2021 The Authors.)

Hypertension is a major contributor to fatal/nonfatal cardiovascular diseases, and timely identification and appropriate management of factors affecting hypertension and its control are mandatory public health issues. By inducing neurohormonal alterations and metabolic impairment, sleep disorders have an impact on a variety of cardiovascular risk factors, including hypertension, and ultimately increase the risk of cardiovascular events. There is evidence that qualitative and quantitative sleep disorders are associated with resistant hypertension and with impaired circadian blood pressure variations. However, sleep disturbances are often unrecognized, or heterogeneity exists in their management by non-specialists in the field. This document by the Italian Society of Hypertension summarizes the updated evidence linking sleep disorders to hypertension and cardiovascular diseases, the major underlying mechanisms, and the possible management strategies. A simplified, evidence-based diagnostic and therapeutic algorithm for comorbid hypertension and common sleep disorders, namely obstructive sleep apnoea and insomnia, is proposed.

Purpose: Electrical stimulation of the upper airway dilator muscles is an emerging treatment for obstructive sleep apnea (OSA). Invasive hypoglossal nerve stimulation (HNS) has been accepted as treatment alternative to continuous positive airway pressure (CPAP) for selected patients, while transcutaneous electrical stimulation (TES) of the upper airway is being investigated as non-invasive alternative., Methods: A meta-analysis (CRD42017074674) on the effects of both HNS and TES on the apnea-hypopnea index (AHI) and the Epworth Sleepiness Scale (ESS) in OSA was conducted including published evidence up to May 2018. Random-effects models were used. Heterogeneity and between-study variance were assessed by I 2 and τ 2 , respectively., Results: Of 41 identified clinical trials, 20 interventional trials (n = 895) could be pooled in a meta-analysis (15 HNS [n = 808], 5 TES [n = 87]). Middle-aged (mean ± SD 56.9 ± 5.5 years) and overweight (body mass index 29.1 ± 1.5 kg/m 2 ) patients with severe OSA (AHI 37.5 ± 7.0/h) were followed-up for 6.9 ± 4.0 months (HNS) and 0.2 ± 0.4 months (TES), respectively. The AHI improved by - 24.9 h -1 [95%CI - 28.5, - 21.2] in HNS (χ 2 79%, I 2 82%) and by - 16.5 h -1 [95%CI - 25.1, - 7.8] in TES (χ 2 7%, I 2 43%; both p < 0.001). The ESS was reduced by - 5.0 (95%CI - 5.9, - 4.1) (p < 0.001)., Conclusion: Both invasive and transcutaneous electrical stimulation reduce OSA severity by a clinically relevant margin. HNS results in a clinically relevant improvement of symptoms. While HNS represents an invasive treatment for selected patients with moderate to severe OSA, TES should be further investigated as potential non-invasive approach for OSA.

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 Spo 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 Spo 2 81.2 versus 77.8 versus 77.5% for low, moderate, and high cardioembolic risk, respectively, P <0.05)., Conclusions: These results support the potential role of OSA-related hypoxia in the risk for cardioembolic complications such as stroke in patients with AF.

Millions of people worldwide live at high altitude, being chronically exposed to hypobaric hypoxia. Hypertension is a major cardiovascular risk factor but data on its prevalence and determinants in highlanders are limited, and systematic studies with ambulatory blood pressure monitoring are not available. Aim of this study was to assess the prevalence of clinic and ambulatory hypertension and the associated factors in a sample of Andean highlanders. Hypertension prevalence and phenotypes were assessed with office and ambulatory blood pressure measurement in a sample of adults living in Cerro de Pasco, Peru (altitude 4340 m). Basic clinical data, blood oxygen saturation, hematocrit, and Qinghai Chronic Mountain Sickness score were obtained. Participants were classified according to the presence of excessive erythrocytosis and chronic mountain sickness diagnosis. Data of 289 participants (143 women, 146 men, mean age 38.3 years) were analyzed. Office hypertension was present in 20 (7%) participants, while ambulatory hypertension was found in 58 (20%) participants. Masked hypertension was common (15%), and white coat hypertension was rare (2%). Among participants with ambulatory hypertension, the most prevalent phenotypes included isolated nocturnal hypertension, isolated diastolic hypertension, and systodiastolic hypertension. Ambulatory hypertension was associated with male gender, age, overweight/obesity, 24-hour heart rate, and excessive erythrocytosis. Prevalence of hypertension among Andean highlanders may be significantly underestimated when based on conventional blood pressure measurements, due to the high prevalence of masked hypertension. In highlanders, ambulatory hypertension may be independently associated with excessive erythrocytosis.

: Managing hypertension in syncope patients requires the accurate balancing of hypotensive and cardiovascular risks. On the basis of the available literature, this study analyses the complex inter-relationship between these clinical problems and presents an algorithm strategy to guide hypertension management in patients affected by syncope episodes. A SBP target of 120 mmHg is recommended in patients with a low syncope risk and a high cardiovascular risk. In patients with a high syncope risk and a low cardiovascular risk, and in older (70+) frail individuals, a less intensive treatment is advisable, targeting SBP of 140 mmHg. SBP values up to 160 mmHg can be tolerated in severe frailty or disability.Patients with hypertension and syncope may benefit from team-based care by a 'Blood Pressure Team' including experts on hypertension and syncope and a geriatrician. The team should carry out a multidimensional assessment to balance syncope and cardiovascular risk and develop therapeutic strategies customized to individuals' frailty and functional status.

Hypertension is one of the primary risk factors for heart disease and stroke, the leading causes of death worldwide. Current evidence supports the treatment of high blood pressure (BP) values in order to obtain a substantial reduction of cardiovascular burden. Sleep plays an important role in maintaining nocturnal BP control and nocturnal hypertension which, in turn, can be affected by the presence of sleep disorders. Whilst respiratory disturbances have been extensively studied and their causal role in the development of nocturnal hypertension has been demonstrated in both cross sectional and prospective studies, less is known about the impact of other sleep disorders such as insomnia. In this review, we aim to describe the role of sleep disorders in the development of nocturnal and diurnal hypertension. Furthermore, we aim to discuss the potential impact of the treatment of such sleep disorders on BP values as an adjunct treatment for patients with hypertension., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jtd-cus-2020-014). The series “5th Clinical Update Sleep” was commissioned by the editorial office without any funding or sponsorship. GP reports personal fees from Omron Healthcare, personal fees from Sanofi, outside the submitted work. The other authors have no other conflicts of interest to declare., (2020 Journal of Thoracic Disease. All rights reserved.)

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., Competing Interests: Conflict of interest: M.F. Pengo has nothing to disclose. Conflict of interest: D. Soranna has nothing to disclose. Conflict of interest: A. Giontella has nothing to disclose. Conflict of interest: E. Perger has nothing to disclose. Conflict of interest: P. Mattaliano has nothing to disclose. Conflict of interest: E.I. Schwarz has nothing to disclose. Conflict of interest: C. Lombardi has nothing to disclose. Conflict of interest: G. Bilo has nothing to disclose. Conflict of interest: A. Zambon has nothing to disclose. Conflict of interest: J. Steier has nothing to disclose. Conflict of interest: G. Parati has nothing to disclose. Conflict of interest: P. Minuz has nothing to disclose. Conflict of interest: C. Fava has nothing to disclose., (Copyright ©ERS 2020.)

Background and Aim: Considering the amount of novel knowledge generated in the last five years, a team of experienced hypertensionlogists was assembled to furnish updated clinical practice guidelines for the management of primary aldosteronism., Methods: To identify the most relevant studies, the authors utilized a systematic literature review in international databases by applying the PICO strategy, and then they were required to make use of only those meeting predefined quality criteria. For studies of diagnostic tests, only those that fulfilled the Standards for Reporting of Diagnostic Accuracy recommendations were considered., Results: Each section was jointly prepared by at least two co-authors, who provided Class of Recommendation and Level of Evidence following the American Heart Association methodology. The guidelines were sponsored by the Italian Society of Arterial Hypertension and underwent two rounds of revision, eventually reexamined by an External Committee. They were presented and thoroughly discussed in two face-to-face meetings with all co-authors and then presented on occasion of the 36th Italian Society of Arterial Hypertension meeting in order to gather further feedbacks by all members. The text amended according to these feedbacks was subjected to a further peer review., Conclusions: After this process, substantial updated information was generated, which could simplify the diagnosis of primary aldosteronism and assist practicing physicians in optimizing treatment and follow-up of patients with one of the most common curable causes of arterial hypertension., Competing Interests: None., (© 2020 The Authors.)

Background: Excessive daytime sleepiness (EDS) is a contributing factor to road traffic accidents. It is commonly assessed using self-administered questionnaires. These assessments are important information when discussing with the Driver and Vehicle Licensing Agency (DVLA) about fitness-to-drive. We hypothesised that patients may be confounded in their assessments after being informed about these potential implications., Patients and Methods: This was a prospective single-centre study. Patients attending clinics for sleep-disordered breathing were asked to fill in the Epworth Sleepiness Scale (ESS) and the Stanford Sleepiness Scale (SSS). Following their consultation, patients were informed about EDS in the context of driving and that the DVLA might request information based on their self-assessed sleepiness. They were then asked to complete the same questionnaires again. Parameters recorded included age, gender, body mass index (BMI), driving licence holder, and collar size. An ESS score above 10 points was defined as EDS., Results: One hundred twenty-two subjects were studied (age 59.4 years (15.2); 72 males; BMI 32.1 kg/m 2 (8.3), driving licence held for 25.2 years (20.6) (n = 94); collar size 42.7 cm (5.0)). There was no difference in the ESS [8 (8) vs 8 (8) points; p = 0.289] or the SSS [2 (2) vs 2 (2) points; p = 0.320] between the two occasions, although seven patients (5.7%) changed their scores from "sleepy" to "non-sleepy" and four patients (3.3%) from "non-sleepy" to "sleepy"., Conclusion: Providing patients with information about the risk of driving in the context of sleepiness does not significantly change how they score their symptoms using self-administered questionnaires; only about 9.0% of the patients had inconsistent results.

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., (Copyright © 2019. Published by Elsevier B.V.)

Background Obstructive sleep apnoea (OSA) is an independent risk factor of hypertension and cardiovascular diseases. Recurrent episodes of upper airways collapse during sleep causing blood oxygen desaturation, hypercapnia, and micro-arousals, are known to activate the sympathetic nervous system (SNS). However, whether changes in the renin-angiotensin-aldosterone system and endothelial activation also occur remains contentious. Methods Based on routine use of drug-induced sleep endoscopy (DISE) for the work-up of OSA patients in our centre, we designed a prospective study to investigate the haemodynamic and humoral changes occurring during the apnoeic episodes reproduced in vivo in the course of DISE. Specifically, plasma aldosterone concentration and renin activity, C-terminal fragment of proendothelin-1, as a marker of endothelial damage, and free plasma catecholamines, will be measured at fixed times during DISE. The activity of catechol-O-methyltransferase (COMT), a key catecholamine-inactivating enzyme that has been scantly investigated thus far owing to the lack of commercially available kits, will be also determined by a newly developed high performance liquid chromatography method, which is herein described. Results and conclusions The aim of this study is to provide novel information on the haemodynamic, hormonal, and SNS changes, and also on COMT activity modification concomitantly occurring during apnoea, thus contributing substantively to the understanding of the pathophysiology of OSA.