Obstructive Sleep Apnea and Arterial Hypertension: Implications of Treatment Adherence.

PURPOSE OF REVIEW: This review seeks to present an overview of the recent literature on the importance of CPAP and antihypertensive treatment adherence in blood pressure control of hypertensive patients, especially those with obstructive sleep apnea. RECENT FINDINGS: Although it is unquestionable that a good adherence to CPAP and antihypertensive drugs is crucial to improvements in sleep-related symptoms, blood pressure levels (even the modest reductions of 2-2.5 mmHg achieved by CPAP treatment) and future cardiovascular risk, this adherence decreases over time, despite efforts made toward behavioral intervention and monitoring. Curiously, although taking a drug would seem to be easier than the use of CPAP treatment, based on current information, it seems that the compliance with drug treatment in hypertensive subjects is not better than that achieved with CPAP treatment in OSA patients with hypertension. However, some studies have shown some phenotypes of hypertensive and OSA patients with good adherence and better hypertensive effect, such as those with uncontrolled blood pressure (resistant and refractory hypertension), severe forms of sleep apnea, and more sleep-related symptoms, especially a higher degree of diurnal hypersomnia. The positive effect of antihypertensive drugs and CPAP treatment on blood pressure levels depends on the degree of treatment adherence, especially in forms of uncontrolled hypertension, but this adherence decreases over time. Educational programs and new devices are needed to improve adherence to treatment in these patients, along with fuller understanding of the different patterns and phenotypes of non-adherence.

Differential blood pressure response to continuous positive airway pressure treatment according to the circadian pattern in hypertensive patients with obstructive sleep apnoea.

Continuous positive airway pressure (CPAP) has a heterogeneous effect on blood pressure (BP) in hypertensive patients. However, the effect of CPAP on BP in hypertensive subjects regarding circadian BP pattern has never been explored. This study aimed to assess the effect of CPAP on BP, taking into consideration the circadian BP pattern in untreated hypertensive patients.This study is a post hoc analysis of the Spanish Cohort for the Study of the Effect of CPAP in Hypertension (CEPECTA), a multicentre, randomised trial of CPAP versus sham-CPAP in patients with new-onset systemic hypertension and an apnoea-hypopnoea index >15 events·h-1 We included patients for whom 24-h ambulatory BP monitoring (ABPM) data were available at baseline and 12 weeks after the intervention. Subjects were classified based on the dipping ratio (dipper/non-dipper). We evaluated the effect of CPAP on ABPM parameters after 12 weeks of treatment.Overall, 272 hypertensive subjects were included in the analysis (113 dippers and 159 non-dippers). Baseline clinical and polysomnographic variables were similar between the groups. CPAP treatment in non-dipper patients was associated with reductions in 24-h ambulatory BP variables and night-time ambulatory BP measurements. However, a nonsignificant effect was reported in the dipper group. The differential effects of CPAP between the groups were -2.99 mmHg (95% CI -5.92-- -0.06 mmHg) for the mean 24-h ambulatory BP and -5.35 mmHg (95% CI -9.01- -1.69 mmHg) for the mean night-time ambulatory BP.Our results show a differential effect of CPAP treatment on BP in hypertensive patients depending on the circadian pattern. Only non-dipper patients benefited from CPAP treatment in terms of BP reduction.

Report of the 6th (Virtual) Meeting on the Planetary Protection Knowledge Gaps for Human Missions to Mars on June 1-2, 2022.

This paper reports the sixth in a series of meetings held under the auspices of COSPAR (with space agencies support) to identify, refine and prioritize the knowledge gaps that need to be addressed for planetary protection for crewed missions to Mars, as well as to describe where and how needed data can be obtained. This approach is consistent with current scientific understanding and COSPAR policy, that the presence of a biological hazard in Martian material cannot be ruled out, and appropriate mitigations need to be in place. The workshops in the series were intentionally organized to obtain a diverse set of inputs from subject matter experts across a range of expertise on conduct of a potential future crewed Mars exploration mission, identifying and leveraging precursor ground, cis-lunar crewed and Mars robotic activities that can be used to close knowledge gaps. The knowledge gaps addressed by this meeting series fall into three major themes: 1. Microbial and human health monitoring; 2. Technology and operations for biological contamination control, and; 3. Natural transport of biological contamination on Mars. This report describes the findings of the 2022 meeting, which focused on measures needed to protect the crew and the returning Mars samples during the mission, both on the Martian surface and during the return to Earth. Much of this approach to crewed exploration is well aligned with the Principles and Guidelines for Human Missions to Mars described in section 9.3 of the current (2021) COSPAR policy, in terms of goals and intent. There were three specific recommendations.

Acute Effects of Local Ischemic Hypoxia and Systemic Hypoxemia on Neuromuscular and Cognitive Function.

Rivera, Paola M., Chris E. Proppe, Esther Beltran, and Ethan C. Hill. Acute effects of local ischemic hypoxia and systemic hypoxemia on neuromuscular and cognitive function. High Alt Med Biol. 23:18-25, 2022. Background: The application of blood flow restriction (BFR) induces local ischemic hypoxia within the muscle(s) distal to the restriction device. Systemic hypoxemia via oxygen or barometric pressure manipulation achieves whole-body hypoxia and thus may be a more potent exercise adjunct than BFR. Therefore, the purpose of this study was to examine the acute effects of local ischemic hypoxia versus systemic hypoxemia on maximal voluntary isometric contraction (MVIC) torque, electromyographic amplitude (EMG AMP), EMG mean power frequency (MPF), and cognition. Materials and Methods: Twelve recreationally trained women (mean age ± standard deviation = 21 ± 1.6 years) performed 75 submaximal (1 × 30, 3 × 15) unilateral leg extension muscle actions under normoxia, local ischemic hypoxia, and systemic hypoxemia. Before and immediately after the 75 repetitions, MVIC muscle actions were performed, and surface EMG was simultaneously assessed from the vastus lateralis. Cognitive function was assessed immediately after each exercise using the Automated Neuropsychological Assessment Metrics (ANAM). Separate repeated-measures analyses of variance (ANOVAs) were performed to examine changes in MVIC, reaction time, EMG AMP, and EMG MPF responses during the MVIC muscle actions. Results: There were no significant (p = 0.21-0.953) Condition × Time interactions for MVIC, EMG AMP, or EMG MPF but a significant (p < 0.001-0.005) main effect for the Time collapsed across Condition for MVIC torque (pretest 238.8 ± 19.5, posttest 212.7 ± 20.1 Nm) and EMG MPF (88.5% ± 1.4% of pretest). There were no significant (p = 0.503) differences in reaction time among Conditions. Conclusions: The findings of the present study suggest that all three conditions elicited comparable acute changes in performance as assessed by MVIC torque that were associated with no changes in muscle activation but decrease in action potential conduction velocity. Therefore, the application of local ischemic hypoxia or systemic hypoxemia during low-load resistance exercise can be used to elicit similar acute physiological responses and not adversely affect cognitive function relative to nonhypoxic conditions.

miR-146a-5p modulates cellular senescence and apoptosis in visceral adipose tissue of long-lived Ames dwarf mice and in cultured pre-adipocytes.

MicroRNAs (miRNAs) are potent regulators of multiple biological processes. Previous studies have demonstrated that miR-146a-5p increases in normal mice during aging, while long-living Ames dwarf (df/df) mice maintain youthful levels of this miRNA. The aim of this study was to elucidate the involvement of miR-146a-5p in modulating cellular senescence and apoptosis in visceral adipose tissue of df/df mice and cultured pre-adipocytes. To test the effects of miR-146a-5p overexpression on visceral adipose tissue, wild-type, and df/df mice, were treated with miRNA-negative control-base and df/df were transfected with 4 or 8 µg/g of a miR-146a-5p mimetic, respectively. Effects of miR-146a-5p overexpression were also evaluated in 3T3-L1 cells cultured under high and normal glucose conditions. Treatment with miR-146a-5p mimetic increased cellular senescence and inflammation and decreased pro-apoptotic factors in visceral adipose tissue of df/df mice. The miR-146a-5p mimetic induced similar effects in 3T3-L1 cells cultivated at normal but not high glucose levels. Importantly, 3T3-L1 HG cells in high glucose conditions showed significantly higher expression of miR-146a-5p than 3T3-L1 grown in normal glucose conditions. These results indicate that miR-146a-5p can be a marker for cellular senescence. This miRNA represents one of the significant SASP factors that if not precisely regulated, can accentuate inflammatory responses and stimulate senescence in surrounding non-senescent cells. The role of miR-146a-5p is different in healthy versus stressed cells, suggesting potential effects of this miRNA depend on overall organismal health, aging, and metabolic state.

Impact of Social Determinants of Health on Women's Satisfaction with Their Sexual Life and Its Relationship with the Use of Psychotropic Drugs: A Cross-Sectional Study.

Sexual satisfaction (SS) is defined as an affective response arising from one's subjective evaluation of the positive and negative dimensions associated with one's sexual relationship. It is an important indicator of health. In women, SS has an important personal component consisting of the physical experiences of pleasure and the positive feelings and emotions that they experience in their affective-sexual relationships. The socioeconomic position is determined by income, educational level, and work, and it conditions women's sexual health. We aimed to assess whether social determinants of health (income, education, work, and gender) are associated with women's sexual satisfaction and to identify whether the impact of social determinants on sexual satisfaction differs with psychotropic consumption. We conducted a cross-sectional study designed to assess the association between variables related to the social determinants of health (work, education, income, and gender) and sexual satisfaction in women of reproductive age in La Rioja (Spain). The women in this study ranged in age from 17 to 52 years, with a mean age of 33.4 (Standar Deviation 8.6). Most were Spanish (82.9%), had undertaken non-compulsory specialized education (84%), and worked (72.7%). Regarding their relationships, 87% maintained monogamous relationships, 84.5% had stable relationships, and 65.7% lived with their partners. In total, 12.3% of the women were taking psychotropic drugs prescribed for the treatment of anxiety and/or depression. We observed that SS is significantly lower among women who have only undertaken compulsory education (Student-t = −4.745; p < 0.01), in those who have unstable affective-sexual relationships (Student-t = −2.553; p < 0.01), and in those who take psychotropic drugs (Student-t = −4.180, p < 0.01). We conclude that the social determinants of health such as education, not continuing to study beyond compulsory education, gender, and taking psychoactive drugs have a significant impact on women's degree of satisfaction with their sexual life.

Prevalence of Obstructive Sleep Apnoea and Its Association With Atherosclerotic Plaques in a Cohort of Subjects With Mild-Moderate Cardiovascular Risk.

INTRODUCTION: Classic cardiovascular risk factors do not explain all the cardiovascular events. Obstructive sleep apnoea (OSA) has been proposed as a potential and prevalent cardiovascular risk factor. Our study aimed to describe the prevalence of OSA in a middle-aged cohort with mild-moderate cardiovascular risk and evaluate its association with atherosclerotic disease. METHODS: This is an observational cross-sectional ancillary study of the ILERVAS project which was aimed to study subclinical arterial disease in a cohort with mild-moderate cardiovascular risk. In a sample of consecutive subjects, we performed a sleep study and evaluate OSA prevalence and its association with carotid and femoral atheroma plaques and atherosclerotic burden. RESULTS: Overall, 966 subjects with a median age of 57 years (25-75th percentile; 52-62) and a body mass index (BMI) of 28.5kg/m2 (25.6-31.6) were included. Of these, 72.6% (69.7%-75.3%) had OSA (apnoea-hypopnoea index (AHI)≥5/h); 35.7% (32.8%-38.8%) had mild OSA (AHI 5-14.9/h) and 36.9% (33.9%-39.9%) had moderate/severe OSA (AHI≥15/h). Mean oxygen saturation and the percentage of time with oxygen saturation<90% (CT90) were associated with atherosclerotic burden (eß (95%CI) 0.932 (0.892, 0.974); 1.005 (1.002, 1.009), respectively) and total plaque (OR (95%CI) 0.88 (0.797,0.971); 1.013 (1.004,1.021), respectively). No association with the AHI or oxygen desaturation index was found. CONCLUSIONS: This study confirms a high prevalence of OSA in patients with mild-moderate cardiovascular risk and shows an association between atherosclerotic burden, total and femoral plaque with CT90 and mean oxygen saturation, suggesting the importance of OSA-related hypoxaemia in the induction of atherosclerotic disease.

Prediabetes Is Associated with Increased Prevalence of Sleep-Disordered Breathing.

Type 2 diabetes leads to severe nocturnal hypoxemia, with an increase in apnea events and daytime sleepiness. Hence, we assessed sleep breathing parameters in the prediabetes stage. A cross-sectional study conducted on 966 middle-aged subjects without known pulmonary disease (311 patients with prediabetes and 655 controls with normal glucose metabolism) was conducted. Prediabetes was defined by glycated hemoglobin (HbA1c), and a nonattended overnight home sleep study was performed. Participants with prediabetes (n = 311) displayed a higher apnea−hypopnea index (AHI: 12.7 (6.1;24.3) vs. 9.5 (4.2;19.6) events/h, p < 0.001) and hypopnea index (HI: 8.4 (4.0;14.9) vs. 6.0 (2.7;12.6) events/h, p < 0.001) than controls, without differences in the apnea index. Altogether, the prevalence of obstructive sleep apnea was higher in subjects with prediabetes than in controls (78.1 vs. 69.9%, p = 0.007). Additionally, subjects with prediabetes presented impaired measurements of the median and minimum nocturnal oxygen saturation, the percentage of time spent with oxygen saturations below 90%, and the 4% oxygen desaturation index in comparison with individuals without prediabetes (p < 0.001 for all). After adjusting for age, sex, and the presence of obesity, HbA1c correlated with the HI in the entire population (r = 0.141, p < 0.001), and the presence of prediabetes was independently associated with the AHI (B = 2.20 (0.10 to 4.31), p = 0.040) as well as the HI (B = 1.87 (0.61 to 3.14), p = 0.004) in the multiple linear regression model. We conclude that prediabetes is an independent risk factor for an increased AHI after adjusting for age, sex, and obesity. The enhanced AHI is mainly associated with increments in the hypopnea events.

Effect of CPAP treatment on BP in resistant hypertensive patients according to the BP dipping pattern and the presence of nocturnal hypertension.

High heterogeneity in the blood pressure (BP) response to continuous positive airway pressure (CPAP) exists in patients with resistant hypertension (RH). Only nondipper normotensive and hypertensive patients exhibited BP reductions when treated with CPAP; the baseline BP dipping pattern has been proposed as a predictor of BP response to CPAP but has never been explored in patients with RH. This study aimed to assess the effect of CPAP on BP in subjects with RH with respect to BP dipping pattern or nocturnal hypertension. This is an ancillary study of the SARAH study. RH subjects with an apnea/hypopnea index (AHI) ≥ 15/h and who received CPAP treatment for 1 year were included. Subjects underwent a sleep study and ambulatory BP monitoring (ABPM) at baseline and at the 1-year follow-up. Eighty-nine RH subjects were included. The subjects were mainly male (77.5%) and obese, with a mean age of 66 years (25th-75th percentile; 59.0; 70.0) and an AHI of 32.7/h (25th-75th percentile; 25.0; 54.7). A total of 68.5% of participants were nondippers, and 71.9% had nocturnal hypertension. After 1 year of CPAP, no significant differences in ABPM parameters were observed between dippers and nondippers. According to nighttime BP, subjects with nocturnal normotension did not show significant changes in ABPM parameters, while nocturnal hypertensive subjects achieved a significant reduction in mean nighttime BP of -4.38 mmHg (-7.10 to -1.66). The adjusted difference between groups was 3.04 (-2.25 to 8.34), which was not significant. This study shows that the BP response to CPAP in patients with RH does not differ according to the BP dipping pattern (dipper and nondipper) and suggests a differential response according to the presence of nocturnal hypertension (ClinicalTrials.gov: NCT03002558).

Longitudinal Analysis of Causes of Mortality in Continuous Positive Airway Pressure-treated Patients at the Population Level.

Rationale: Randomized controlled trials do not support a role for continuous positive airway pressure (CPAP) in preventing major cardiovascular events or mortality in patients with obstructive sleep apnea (OSA). However, these trials' setting does not apply to most CPAP-treated patients. Objectives: We aimed to assess the effect of CPAP on mortality in real-world patients. Methods: We performed a population-based longitudinal observational study including all patients with OSA prescribed CPAP during 2011 in Catalonia, Spain, and non-OSA control subjects matched (1:2) by sex, 5-year age group, and region who were followed from 2011 to 2016. Results: A total of 9,317 CPAP-treated patients with OSA and 18,370 control subjects without OSA were included (median age, 67 [57-72] years; 74% male). During a median follow-up of 5.5 years, 2,301 deaths were recorded. After adjustment by a composite of diagnosed comorbidities and previous use of healthcare resources, CPAP-treated patients showed a lower risk of death than control subjects (hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.61-0.74), with the association not being statistically significant in women. Cancer-related deaths were the main drivers of this association (men: HR, 0.44; 95% CI, 0.36-0.54; women: HR, 0.44; 95% CI, 0.28-0.68). No significant associations were found for cardiovascular-related deaths. CPAP-treated women had an increased risk of respiratory-related death (HR, 2.41; 95% CI, 1.37-4.23). Conclusions: CPAP-treated patients had a lower mortality rate than control subjects. This relationship was driven by cancer-related, but not cardiovascular-related, deaths. Results suggest a role for sex when prescribing CPAP, especially considering respiratory-related deaths, and foster a debate on the relationship between OSA and cardiovascular outcomes.

Validation of the Satisfaction, Alertness, Timing, Efficiency and Duration (SATED) Questionnaire for Sleep Health Measurement.

Rationale: Sleep constitutes a fundamental pillar of health in individuals and is an indicator of the health of a population.Objectives: Aiming to develop an easy-to-use tool to measure sleep health, we translated to Spanish, adapted, and validated the Satisfaction, Alertness, Timing, Efficiency and Duration (SATED) questionnaire.Methods: The reliability of the questionnaire was evaluated using a sample of 4,385 participants from the 2015 Catalan Health Survey. Criterion validity, construct validity, and feasibility were assessed in an independent sample of 200 subjects who completed the Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, anxiety scale of the State-Trait Anxiety Inventory, mood scale of the Profile of Mood States, and a 1-week sleep diary.Results: The SATED questionnaire obtained adequate internal consistency (Cronbach's α = 0.77), statistically significant correlations of its five items with the total score (rho = 0.55-0.69), and a suitable goodness of fit in the confirmatory factor analysis (χ2 = 30.93; df = 5; P < 0.001; root mean square error of approximation, 0.049; comparative fit index, 0.99; standardized root mean residual, 0.043). The criterion and construct validity were adequate, with correlations in the expected directions. The feasibility of the questionnaire was satisfactory, being easy and intelligible and requiring approximately 1 minute to complete.Conclusions: This questionnaire is reliable and valid for measuring sleep health in the general population. Encouraging the use of SATED is expected to raise awareness that sleep, like diet and physical activity, is a key modifiable factor for promoting health.

Normotensive patients with obstructive sleep apnoea: changes in 24-h ambulatory blood pressure monitoring with continuous positive airway pressure treatment.

BACKGROUND: Continuous positive airway pressure (CPAP) treatment reduces blood pressure (BP) in obstructive sleep apnoea (OSA) and hypertensive patients, but there is a lack of data about the effects of CPAP on the BP in normotensive patients. OBJECTIVE: The aim of the study was to evaluate BP changes in normotensive OSA individuals receiving CPAP treatment. METHODS: We selected 131 normotensive outpatients with an apnoea/hypopnoea index (AHI) greater than 15 events/hour who required CPAP treatment. All patients underwent a sleep study and 24-h ambulatory BP monitoring (ABPM) at baseline and after 6 months. In addition, the patients were assessed for the presence of baseline masked hypertension, defined as office BP less than 140/90 mmHg and increased BP on 24-h ABPM (mean 24-h BP ≥130/80 mmHg). RESULTS: After 6 months of CPAP treatment, a mild reduction in all 24-h ABPM variables was observed, but only the mean 24-h DBP [-1.39 mmHg, 95% confidence interval (95% CI), -2.50 to -0.27], mean daytime DBP (-1.39 mmHg, 95% CI -2.56 to -0.22) and the mean 24-h ambulatory BP (-1.80 mmHg, 95% CI, -3.16 to -0.44) reached statistical significance. The reduction was primarily due to BP changes in individuals with masked hypertension who displayed a mean BP reduction of -4.78 mmHg (-7.25 to -2.30 mmHg). Consistent with a circadian BP pattern, a reduction in mean nocturnal BP of -4.73 mmHg (-7.39 to -2.06 mmHg) was observed at 6 months in nondippers; in contrast, the mean nocturnal BP in dippers increased by 2.61 mmHg (0.60-4.62 mmHg). CONCLUSION: Our findings suggest that the CPAP effects may be different in normotensive outpatients depending on the presence of undiagnosed masked hypertension and the dipping pattern. Therefore, it is important to consider measuring ABPM in this type of patient.

Resistant/Refractory Hypertension and Sleep Apnoea: Current Knowledge and Future Challenges.

Hypertension is one of the most frequent cardiovascular risk factors. The population of hypertensive patients includes some phenotypes whose blood pressure levels are particularly difficult to control, thus putting them at greater cardiovascular risk. This is especially true of so-called resistant hypertension (RH) and refractory hypertension (RfH). Recent findings suggest that the former may be due to an alteration in the renin-angiotensin-aldosterone axis, while the latter seems to be more closely related to sympathetic hyper-activation. Both these pathophysiological mechanisms are also activated in patients with obstructive sleep apnoea (OSA). It is not surprising, therefore, that the prevalence of OSA in RH and RfH patients is very high (as reflected in several studies) and that treatment with continuous positive airway pressure (CPAP) manages to reduce blood pressure levels in a clinically significant way in both these groups of hypertensive patients. It is therefore necessary to incorporate into the multidimensional treatment of patients with RH and RfH (changes in lifestyle, control of obesity and drug treatment) a study of the possible existence of OSA, as this is a potentially treatable disease. There are many questions that remain to be answered, especially regarding the ideal combination of treatment in patients with RH/RfH and OSA (drugs, renal denervation, CPAP treatment) and patients' varying response to CPAP treatment.

Impact of sleep health on self-perceived health status.

Although sleep habits have long been recognized as a promoter of health, the World Health Organization 2014 report on non-communicable diseases (NCDs) only listed smoking, alcohol intake, diet and physical activity (PA) as key modifiable risk factors that could enhance health and prevent NCDs. Cross-sectional data on 4385 surveys from the 2015 Catalan Health Survey, representative of the 2015 non-institutionalized Catalan population over age 14, were used to assess and compare the independent associations of low PA (International Physical Activity Questionnaire (IPAQ): low activity); poor diet (PREvención con DIeta MEDiterránea questionnaire (PREDIMED): low-adherent); poor sleep health (Satisfaction, Alertness, Timing, Efficiency and Duration scale (SATED): <8); smoking status; and, alcohol intake (high-risk drinker based on standard drink units) with having a poor self-perceived health status. Logistic regression models adjusted by age, gender, education level and number of comorbidities showed that poor sleep health had the strongest independent association with poor self-perceived health status (OR = 1.70; 95%CI: 1.37-2.12), followed by poor diet (OR = 1.37; 95%CI: 1.10-1.72) and low PA (OR = 1.31; 95%CI: 1.01-1.69). This suggests that sleep habits should be included among the important modifiable health risk factors and be considered a key component of a healthy lifestyle.

Prevalence, Characteristics, and Association of Obstructive Sleep Apnea with Blood Pressure Control in Patients with Resistant Hypertension.

Rationale: Obstructive sleep apnea (OSA) is associated with poor blood pressure (BP) control and resistant hypertension (RH). Nevertheless, studies assessing its prevalence, characteristics, and association with BP control in patients with RH are limited.Objectives: The aim of this multicenter study was to assess the prevalence of OSA in a large cohort of subjects with RH and to evaluate the association of OSA with BP control.Methods: We recruited consecutive subjects with RH from three countries. A formal sleep test and blood pressure measurements, including 24-hour ambulatory blood pressure monitoring, were performed in all participants.Results: In total, 284 subjects with RH were included in the final analysis. Of these, 83.5% (95% confidence interval [CI], 78.7-87.3%) had OSA (apnea-hypopnea index ≥ 5 events/h); 31.7% (95% CI, 26.5-37.3%) had mild OSA, 25.7% (95% CI, 21-31.1%) had moderate OSA, and 26.1% (95% CI, 21.3-31.5%) had severe OSA. Patients with severe OSA had higher BP values than subjects with mild to moderate or no OSA. A greater effect was observed on the average nighttime BP, with an adjusted effect of 5.72 mm Hg (95% CI, 1.08-10.35 mm Hg) in severe OSA compared with participants without OSA. A dose-response association between the severity of OSA and BP values was observed. The prevalence of severe OSA was slightly higher in uncontrolled participants (adjusted odds ratio, 1.69; 95% CI, 0.97-2.99) but was not statistically significant.Conclusions: The present study confirms the high prevalence of OSA in participants with RH. Furthermore, it shows a dose-response association between OSA severity and BP measurements, especially in the nighttime.Clinical trial registered with www.clinicaltrials.gov (NCT03002558).

Characterization of glycoside residues of porcine zona pellucida and ooplasm during follicular development and atresia.

The glycoside residues (glycoconjugates, GC) of the zona pellucida (ZP) glycoproteins are important during the first phases of fecundation. Our aim in this work was to determine the lectin affinity pattern of porcine ZP in order to analyze the changes that take place during: (a) preantral folliculogenesis, (b) the follicular atresia process, and (c) antral growth. Several prepubertal and adult pig ovaries and different sized antral follicles were used. Conventional carbohydrate histochemical techniques and peroxidase and digoxigenin (DIG) lectins were used to reveal the acid groups and the glycosidic residues of the ZP. It was seen that the ZP forms in the preantral follicles throughout their growth period. In primordial and primary follicles, ZP in the process of formation showed neutral GC. SBA, RCA-I, MAA, WGA lectins, and AAA after methylation-saponification (MS) were positive in the ZP of primordial and primary follicles. The affinity for SBA, RCA-I, MAA, and WGA increased in the multilaminar-primary follicles and new affinities for UEA-I and LFA were observed. After MS, AAA, SNA, PNA, and SBA reactivity was observed. The ZP of antral follicle oocytes of different sizes showed the same lectin pattern as multilaminar-primary follicles. The oocyte ooplasm and the follicular fluid of large antral follicles showed less affinity for WGA and LFA lectins and less intensive staining with AB (pH 2.5). Atresia did not change the antral or preantral follicle oocyte ZP lectin pattern. In conclusion, the follicles showed substantial changes in their ZP glycosidic composition as they developed, especially, during the change from primary to multilaminar-primary follicles. The ZP glycosidic composition showed no significant change during the growth of antral follicles and follicular atresia in our study.

Rationale and Methodology of the SARAH Trial: Long-Term Cardiovascular Outcomes in Patients With Resistant Hypertension and Obstructive Sleep Apnea.

INTRODUCTION: Patients with resistant hypertension (RH) have a high risk of developing cardiovascular events; therefore, new therapeutic approaches to better control blood pressure may be useful in improving cardiovascular outcomes. The prevalence of obstructive sleep apnea (OSA) is very high among patients with RH. Continuous positive airway pressure (CPAP) has been shown to be an effective treatment for reducing blood pressure in patients with RH. Nevertheless, the long-term effect of CPAP treatment on cardiovascular outcomes has not been explored. The main objective of the SARAH study is to assess the impact of OSA and its treatment on cardiovascular outcomes (morbidity and mortality) in patients with RH. METHODS: This study is a multi-center, prospective, observational cohort study. A total of 1371 patients with RH will be enrolled in the study and followed once a year for five years. At inclusion, ambulatory blood pressure monitoring (ABPM) and a sleep study will be performed in all subjects. Socio-demographic, clinical and cardiovascular variables will be collected at baseline and follow-up. Subsequently, subjects with OSA will be managed according to local standard practice. Based on the OSA diagnosis and its treatment, three cohorts of subjects with RH will be defined: non-OSA, treated OSA and non-treated OSA. CONCLUSIONS: This study will contribute to elucidating the long-term impact of OSA treatments on blood pressure control and cardiovascular outcomes in patients with RH. These results will contribute to improve the cardiovascular prognosis of patients with RH.