Covassin, Naima

Abstract Introduction Voluntary sleep curtailment decreases insulin sensitivity. However, molecular mechanisms underlying impaired insulin signaling are not completely understood. To gain molecular insights, we examined the transcription of known cellular insulin-signaling regulators in adipose tissue obtained from subjects undergoing experimental sleep restriction. Methods Nineteen healthy subjects (males: 11; age: 19 - 36 years; BMI: 24.5 ± 3.6 kg/m2) underwent a normal (9 hours/night) and a restricted sleep (4 hours/night) sequence in a random order. Each inpatient stay included a screen visit followed by 4 days of acclimation and 9 days of experimental phase consisting of a controlled sleep opportunity. Eucaloric diet was provided to ensure weight maintenance. Abdominal fat sample was obtained at the screen and end of the experimental phase. mRNA was quantified by RT-PCR. Fasting morning blood draws were obtained at the end of acclimation and experimental phases. Mixed models were used for analysis. Results mRNA expression did not differ in normal and restricted sleep condition for SOCS3 [changes in normal Vs. restricted sleep, 0.02 (0.11, -0.01) Vs. 0.01 (0.12, -0.07), p=0.33], PTEN [-0.22 (0.18, -0.39) Vs. -0.10 (0.21, -0.20), p=0.22], PTB1B [-0.003 (0.04, -0.07) Vs. -0.01 (0.06, -0.06), p=0.74] and Cav-1 [-2.45 (0.78, -8.39) Vs. -6.31 (1.68, -8.29), p=0.34]. Further, transcription of insulin-receptor also did not change [0.01 (0.07, -0.06) Vs. -0.03 (0.09, -0.07), p=0.92]. However, within group analysis show significant decreases in Cav-1 mRNA only during sleep restriction (normal: p=0.09; restricted: p=0.003). Importantly, restricting sleep duration was associated with lowering of insulin (0.6 ± 1.9 Vs. -1.6 ± 1.7 uIU/ml; p=0.003), no change in glucose (-1.5 ± 3.8 Vs. -3.7 ± 4.12 mg/dl, p=0.06) and improvement in HOMA-IR index (0.12 ± 0.44 Vs -0.42 ± 0.43, p=0.002). Conclusion Chronic sleep restriction does not alter the transcription of cell-signaling regulators in abdominal adipose tissue. Moreover, restricting sleep duration without increasing calorie intake did not seem to decrease insulin sensitivity as determined by HOMA-IR. Support NIH grants HL114676, Mayo Clinic CCaTS UL1 TR002377; AHA grant 13POST16420009 to NC

Background Dietary habits are critical determinants of health and especially of cardiometabolic risk status. Previous studies have examined the relationship between breakfast consumption and indices of obesity, with conflicting findings. Such discrepancy may be owed to the use of surrogate measures of adiposity such as body mass index. Furthermore, it is unknown whether frequency of breakfast consumption is associated with different patterns of regional body fat distribution. Objective In this study, we aimed at investigating the association between frequency of breakfast consumption and body fat distribution. Methods We compiled data from 184 individuals (64% males, mean age 35.8±12.6 years, ranging from 18 to 63 years old) who participated in research studies performed in the Mayo Clinic Cardiovascular/Sleep Laboratory from 2005 to 2019 and underwent whole body dual‐energy X‐ray absorptiometry (DXA) for body composition. Breakfast eating habits were assessed by questionnaire and frequency of consumption was determined as number of times per week (range 0 to 7). Responses were recoded as low frequency (0 to 2 times/week), middle frequency (3 to 4 times/week), and high frequency (5 to 7 times/week). Measures of height and weight were collected to compute body mass index (BMI, kg/m 2 ). Total body fat percentage, fat mass, and lean mass were obtained from DXA. Regions of interest were manually adjusted with the DXA software to quantify abdominal fat and lower body fat. Abdominal fat/total body fat and lower body fat/total body fat ratios were calculated. Results Low frequency of breakfast consumption was reported by 14% of the subjects (n=26), while 18% (n=34) reported middle‐frequency of consumption. The proportion of men/women (p=0.1) and BMI values (p=0.78) were similar across breakfast eating categories. Compared to those who had breakfast with high‐frequency, those who ate it less frequently were younger (p=0.038). In age, sex, and BMI‐adjusted analysis, low‐frequency of breakfast consumption was significantly associated with greater abdominal fat mass (standardized beta=0.11, 95% CI 0.09‐ 1.29, p=0.024) and higher abdominal fat/total body fat ratio (standardized beta=0.16, 95% CI 0.003–0.024, p=0.013). Total body fat percentage (p=0.26), fat mass (p=0.26), and lean mass (p=0.22) were not associated with frequency of breakfast consumption. Similarly, no relations were seen with lower body fat (p=0.85) or lower body fat/total body fat ratio (p=0.51). Conclusion Our study showed that infrequent breakfast consumption is selectively associated with greater abdominal fat mass. As accumulation of fat in the abdominal depot is a more robust predictor of adverse outcomes than total adiposity, these findings suggest that abdominal fat may mediate the increased cardiometabolic risk previously observed in conjunction with infrequent breakfast consumption.

Background Psychological stress and insufficient sleep are both associated with an increased risk of developing hypertension. While the underlying mechanisms are not well defined, it has been postulated that this may be facilitated by modulation of baroreflex control of sympathetic activity. Short periods (<5 min) of mental stress attenuate sympathetic baroreflex sensitivity (sBRS), but it is currently unclear whether this holds true for longer bouts of stress. As such, we sought to examine the effect of 10 min of mental stress on sBRS. Additionally, we evaluated the impact of experimental sleep restriction on baroreflex control of blood pressure during mental stress. We hypothesized that mental stress would attenuate sBRS, and that prolonged exposure to restricted sleep would result in a greater reduction in sBRS during mental stress. Methods Fourteen healthy adults (10M/4F, 25±1 yrs) underwent 10 min of mental stress consisting of a 5‐min mental arithmetic task, followed immediately by a 5‐min Stroop color‐word conflict test. Heart rate (electrocardiography), blood pressure (finger photoplethysmography), and muscle sympathetic nerve activity (microneurography of the common peroneal nerve) were continuously measured to determine sBRS at baseline and during mental stress. A subset of participants (n=9) completed the mental stress protocol under both experimental sleep restriction (4 hr/night) and control sleep conditions (8–9 hr/night) while inpatient at a hospital‐based clinical research unit. Subjects underwent a 3‐night acclimation period, followed by 9 or 14 nights of either sleep restriction or control sleep. Data from Day 2/1 or Day 13/15 (during control sleep only) were used to assess the effect of mental stress alone, and data from Day 13/15 (under both conditions) were used to assess the effect of sleep restriction. Results Acute mental stress resulted in a marked blunting of sBRS from baseline (−2.7±0.5 to −1.5±0.4 bursts·100hb −1 ·mmHg −1 , p=0.04). Examining the mental stress interventions individually revealed a significant decrease in sBRS during the initial 5 min of stress (mental arithmetic, p=0.03), but not during the subsequent 5 min of testing (Stroop test, p=0.75). Mental stress also reduced baroreflex function following sleep restriction (main effect of condition, p<0.01); however, the reduction in sBRS was not significantly different in restricted sleep compared to control (main effect of visit, p=0.78). There was no significant interaction effect between sleep restriction and mental stress (p=0.81). Conclusions These data provide further support that, in young healthy individuals, sBRS is attenuated early in mental stress but quickly returns to baseline values. In contrast, prolonged sleep restriction does not appear to alter sympathetic control of blood pressure. Support or Funding Information NIH HL114024 (VKS), NIH HL114676 (VKS), NIH HL083947 (MJJ), FAER Medical Student Anesthesia Research Fellowship (NMP)

Sleep apnea is very common in patients with cardiovascular disease, especially in patients with hypertension. Over the last few decades a number of discoveries have helped support a causal relationship between the two and even resistant hypertension. The role neurogenic mechanisms play has gathered more attention in the recent past due to their immediate bedside utility. Several innovative discoveries in pathogenesis including those exploring the role of baroreflex gain, cardiovascular variability, chemoreceptor reflex activation and the sympathetic nervous system have emerged. In this review, we discuss the epidemiology of sleep apnea and hypertension and the pathogenic mechanisms contributing to neurogenic hypertension. Furthermore, recent management strategies in addition to continuous positive airway pressure (CPAP), such as upper airway stimulation and renal denervation that target these pathogenic mechanisms, are also discussed.

Due to frequent abnormal breathing events and their effects on sleep architecture, patients with obstructive sleep apnea (OSA) exhibit decreased amounts of slow wave sleep (SWS). Reduced SWS has been linked to hypertension in community-based studies. We sought to investigate whether SWS percentage modifies the association between OSA and prevalent hypertension. We studied 7107 patients with OSA and 1118 primary snorers who underwent in-laboratory polysomnography. Patients were classified into quartiles of percent SWS. Hypertension was defined based either on clinic blood pressure measures or on physician diagnosis. Multivariable logistic regression model showed a significant interaction effect of OSA and SWS on prevalent hypertension ( P =0.002). Decreased SWS was associated with higher odds for hypertension in OSA but not in primary snoring, with patients with OSA exhibiting <0.1% SWS (OR, 1.44 [95% CI, 1.21–1.70]; P =0.001) and those with 0.1% to 4.8% SWS (OR, 1.20 [95% CI, 1.03–1.40]; P =0.02) being more likely to have hypertension compared with those with >11.1% SWS. In analysis stratified by OSA severity, significant associations between percent SWS and blood pressure emerged only in moderate and severe OSA. Effect modifications by sex ( P =0.040) and age ( P =0.007) were also only evident in OSA, indicating that decreased SWS was associated with hypertension only in men and in patients <60 years old. Decreased SWS is associated with a dose-dependent increase in odds of prevalent hypertension in patients with OSA. The effects of SWS are likely to be modulated by OSA severity. SWS may be implicated in the heightened risk of cardiovascular diseases exhibited by patients with OSA.

Hypertension is a major determinant of cardiovascular morbidity and mortality and is highly prevalent in the general population. While the relationship between sleep apnea and increased blood pressure has been well documented, less recognized is emerging evidence linking sleep-related movement disorders such as restless legs syndrome/periodic limb movements of sleep and sleep-related bruxism with blood pressure (BP) dysregulation and hypertension. There is also recent literature linking narcolepsy-cataplexy with elevated BP and altered pressor responses, and there are data suggesting abnormal BP control in rapid eye movement sleep behavior disorder. It is thought that neural circulatory mechanisms, sympathetic activation in particular, comprise the predominant mediator underlying elevated BP in these neurological sleep disorders. There is very limited evidence that treating these sleep disorders may be beneficial in lowering BP primarily because this question has received very little attention. In this review, we discuss the potential pathophysiologic mechanisms underlying elevated BP in restless legs syndrome/periodic limb movements of sleep, sleep-related bruxism, narcolepsy-cataplexy, and rapid eye movement sleep behavior disorder. We also examine the relationship between these sleep disorders and elevated BP and the impact of treatment of these conditions on BP control. Last, we discuss gaps in the literature evaluating the associations between these sleep disorders and elevated BP and identify areas for further research.

SummaryWe aimed at assessing cardiac autonomic function by heart rate variability during sleep in patients with obstructive sleep apnea and periodic limb movements during sleep, and to compare it with that of patients with obstructive sleep apnea only, periodic limb movements during sleep only, and controls. We also aimed at investigating the interaction effect between apnea–hypopnea index and periodic limb movement index on heart rate variability. Four groups of patients (n = 42 each, total = 168) were identified based on the presence/absence of obstructive sleep apnea and periodic limb movements during sleep: + obstructive sleep apnea/− periodic limb movements during sleep (5 ≤ apnea–hypopnea index < 30 events per hr), − obstructive sleep apnea/+ periodic limb movements during sleep (periodic limb movement index > 15 events per hr), + obstructive sleep apnea/+ periodic limb movements during sleep, − obstructive sleep apnea/− periodic limb movements during sleep (controls). All groups were matched for age, sex and body mass index. Time‐ and frequency‐domain heart rate variability measures were calculated over 5‐min periods of stable stage 2 non‐rapid eye movement sleep. In patients with both obstructive sleep apnea and periodic limb movements during sleep, LFnu and LF/HF ratio were higher than in those with obstructive sleep apnea only, periodic limb movements during sleep only, and controls, while HFnu was the lowest among the four groups. LFnu, HFnu and LF/HF ratio were significantly and independently associated with minimal oxygen saturation in the + obstructive sleep apnea/+ periodic limb movements during sleep group. There was a significant interaction effect between apnea–hypopnea index and periodic limb movement index on LF/HF ratio (p = 0.038) in patients with obstructive sleep apnea. Patients with elevated apnea–hypopnea index and elevated periodic limb movement index exhibited higher sympathovagal balance compared with those with high apnea–hypopnea index and low periodic limb movement index, and compared with those with low apnea–hypopnea index (regardless of periodic limb movement index). Increased sympathetic activation and decreased parasympathetic control appear to be related to the severity of oxygen desaturation. Apnea–hypopnea index and periodic limb movement index had interactive effects on increased sympathovagal balance in patients with obstructive sleep apnea.