Covassin, Naima

Background Obstructive sleep apnea (OSA) increases the risk for metabolic and cardiovascular disease. Telomere shortening has been linked to hypertension, diabetes mellitus, and cardiovascular diseases such as stroke and myocardial infarction. Because these conditions are highly prevalent in sleep apnea, we hypothesized that telomere length (TL) would be reduced in patients with OSA. Methods Genomic DNA was isolated from circulating leukocytes in 176 subjects (42.8 ± 13.8 years, 22.7 % women) who had undergone overnight polysomnographic evaluation. Of these individuals, 92 subjects had an Apnea Hypopnea Index (AHI) >5 events/hour and were classified as OSA patients. TL was measured using a quantitative PCR where a telomere to single copy gene ratio is determined and represented as number of base pairs (bp). The effect of OSA on TL was determined by comparing a control group (no OSA) (AHI<5, n=92) with patients with mild OSA (≥ 5 AHI <15, n=25), and those with moderate to severe OSA (AHI ≥15, n=59) in unadjusted and age‐adjusted models. Results Compared to control subjects, mild and moderate to severe OSA subjects were older: 48.9 ± 11.2 vs. 36.0 ± 11.2 years (p<0.001) and 50.8 ± 13.1 vs. 36.0 ± 11.2 years (p<0.001), respectively. Statistical models examining the effects of OSA severity on TL showed a J‐shaped curve : longer TL in moderate to severe OSA (4867 ± 221 bp) and controls (4820 ± 160 bp), and the shortest TL in mild OSA (4742 ± 155 bp). The mean TL in moderate to severe OSA was significantly longer than in mild OSA (p=0.0048). These effects were more pronounced after adjustment for age, when we observed significant differences in mean TL between moderate to severe OSA and mild OSA (p=0.0036) and between moderate to severe OSA and the control group (p=0.0379) (). However, the mean TL between control subjects and subjects with mild OSA was not different. Conclusion Moderate to severe OSA patients had longer TL compared with mild OSA and control group. This association was independent of age. Even though OSA is associated with increased cardiovascular risk, telomere lengthening in subjects with moderate to severe OSA suggests the presence of protective compensatory mechanisms to prevent telomere shortening in OSA. On the other hand, the existence of longer telomere in subjects with moderate and severe OSA may also indicate triggering of molecular mechanisms which may contribute to cancer development. Further studies are needed to explain the role of hypoxia in telomere dynamics in OSA, and the interactions between telomere length and increased longevity reported in older patients with OSA. Support or Funding Information NIH R01 grant (#HL65176); Singh P. is supported by AHA scientist development grant (11SDG7260046). Becari C. is supported by grant from CNPq‐Brazil (# 203802/2014‐4).

Cardiovascular health disparities are present in several minority racial and ethnic groups including African Americans, who exhibit an increased risk of hypertension compared to non-Hispanic Whites. Somali Americans, a subgroup of African Americans of East African origins, exhibit high rates of diabetes and obesity, conditions often comorbid with impaired blood pressure (BP) regulation. Importantly, it remains unknown whether the disparate cardiovascular risk profile, namely poor nocturnal BP regulation, manifested in African Americans can be applied to Somali Americans. We therefore examined 24-hour BP patterns in Somali Americans compared to White control participants. We hypothesized that Somali Americans would present with heightened nocturnal BP and heart rate (HR). We utilized ambulatory blood pressure monitoring (ABPM) to quantify 24-hour BP patterns in 25 Somali (10 female, 15 male; age: 34 ± 3 years; BMI: 27 ± 1 kg/m2) and 25 White (13 female, 12 male; age: 38 ± 3 years; BMI: 27 ± 1 kg/m2) individuals. Each ABPM recorded a BP reading every 20 minutes throughout the 24-hour period. Subjects were instructed to abstain from caffeine, alcohol, and vigorous exercise during the recording period. From the 24-hour recording, an ambulatory arterial stiffness index (AASI) was calculated as 1 minus the regression slope of systolic (SAP) and diastolic (DAP) arterial pressure. SAP, DAP, and HR obtained between 12:00am and 6:00am were averaged to compute nocturnal means. BP and HR dipping was determined as the percent change between daytime and nocturnal BP and HR. Statistical analysis included independent samples t-tests to determine differences in BP and HR between racial groups (i.e., Somali vs. White). Nocturnal SAP (105 ± 2 vs. 106 ± 3 mmHg, p = 0.364) and DAP (60 ± 1 vs. 58 ± 2 mmHg, p = 0.093) were not different between Somali and White participants. In contrast, nocturnal HR was significantly higher in Somalis compared to Whites (72 ± 2 vs. 64 ± 2 beats/minute, p = 0.009). Similarly, SAP (12 ± 2% vs. 12 ± 1%, p = 0.437) and DAP (18 ± 2% vs. 21 ± 2%, p = 0.127) dipping were comparable between groups, while Somali individuals exhibited blunted HR dipping (11 ± 2% vs. 19 ± 2%, p = 0.008) compared to Whites. AASI (0.32 ± 0.03 vs. 0.24 ± 0.03 a.u., p = 0.031) was higher in Somali compared to White individuals. These findings suggest Somali Americans present with impaired nocturnal cardiovascular regulation and increased arterial stiffness, which may place this racial minority at increased cardiovascular risk. Future work to investigate the mechanistic relationships of cardiovascular dysfunction in Somali Americans is warranted. Research grant from Sleep Number to Mayo Clinic for studies of sleep and cardiovascular risk in Somali Americans, and by NIH R01-HL160619, T32-DK007013, T32-HL007111, and T32-HL105355. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Hypertension is commonly observed with obstructive sleep apnea (OSA), partly due to dysregulation of sympathetic activity. As OSA is considered male-dominant, potential sex differences in the sympathetic regulation of BP have yet to be explored. Hemodynamic responses to an orthostatic challenge have implications for cardiovascular risk and are sympathetically-modulated. Therefore, we tested the hypothesis that females with OSA have differential BP and HR responses to orthostasis relative to males with OSA. 160 individuals not taking antihypertensive medications completed an overnight polysomnography to identify OSA (apnea-hypopnea index ≥5 events/hr). Orthostatic responses were quantified as the changes (Δ) in BP and HR (assessed via brachial cuff) from rest (10min supine) to 60sec post-standing. Females with (n=17, 42±14yrs, 30.7±6.0kg/m2) and without (n=43, 39±12yrs, 27.6±5.7kg/m2) OSA were compared to males with (n=60, 45±11yrs, 31.4±3.8kg/m2) and without (n=40, 39±13yrs, 27.4±3.1kg/m2) OSA using a one-way ANOVA. There were no between-group differences in age (p>0.05 for post-hoc comparisons) and BMI was lower in both females, and males, without OSA relative to males with OSA (p<0.05 for both). ΔSBP did not differ between females with (1±8mmHg) and without (2±8mmHg) OSA nor between males with (4±8mmHg) and without OSA (5±12mmHg, ANOVA p=0.37). Females with OSA had a blunted ΔDBP relative to females without OSA (5±7 vs. 10±6mmHg, p<0.05), whereas males with and without OSA demonstrated similar responses (9±8 vs. 10±6mmHg, p=0.95). ΔHR did not differ between females with (8±8beats/min) and without OSA (9±11beats/min) nor between males with (13±10beats/min) and without OSA (12±10beats/min, ANOVA p=0.06). ΔDBP was not associated with the apnea-hypopnea index (Spearman's r=-0.19, p=0.47; Spearman’s r=0.23, p=0.08) nor nadir SpO2 (Spearman's r=0.27, p=0.29; Spearman’s r=0.06, p=0.64) in females or males with OSA. These data suggest that OSA influences the DBP response to orthostasis in females to a greater extent than males. As DBP is associated with sympathetic activation, this finding could indicate greater sympathetic dysregulation in females, relative to males, with OSA. This work was supported by the National Institutes of Health T32-HL007111 (JMB), HL134808 (NC), HL065176 (PS and VKS), and HL134885 (VKS). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Obstructive sleep apnea (OSA) is a highly prevalent sleep disorder and an established risk factor for cardiovascular diseases, including hypertension. The pathogenesis of elevated blood pressure (BP) in OSA is multifactorial, including sympathetic overdrive, vascular aberrations, oxidative stress, inflammation, and metabolic dysregulation. Among the mechanisms potentially involved in OSA-induced hypertension, the role of the gut microbiome is gaining increasing attention. Perturbations in the diversity, composition, and function of the gut microbiota have been causally linked to numerous disorders, and robust evidence has identified gut dysbiosis as a determinant of BP elevation in various populations. In this brief review, we summarize the current body of literature on the implications of altered gut microbiota for hypertension risk in OSA. Data from both preclinical models of OSA and patient populations are presented, and potential mechanistic pathways are highlighted, along with therapeutic considerations. Available evidence suggests that gut dysbiosis may promote the development of hypertension in OSA and may thus be a target for interventions aimed at attenuating the adverse consequences of OSA in relation to cardiovascular risk.

Objective: Sleep fragmentation determined by repetitive arousals from sleep in obstructive sleep apnea (OSA) is associated with hypertension. We aimed to quantify the independent association of arousals during rapid eye movement (REM)/non-rapid eye movement (NREM) sleep with prevalent hypertension. Methods: We included adults with 4 h of total sleep time and at least 30 min of REM sleep obtained from overnight in-laboratory polysomnography. Logistic regression models were fitted to explore the association between arousals during REM/NREM sleep and prevalent hypertension. All models controlled for OSA metrics and arousals during NREM/REM sleep, either by statistical adjustment or by stratification. Results: The sample comprised of 11 643 patients, of which 10 055 were OSA patients. Fully adjusted models demonstrated significant dose-relationships between arousal index during REM sleep (AI-REM) and prevalent hypertension (P trend = 0.002). The higher relative odds of prevalent hypertension were most evident with AI-REM > 40 events/h. In OSA patients with arousal index during NREM sleep (AI-NREM) <15 events/h, every10-unit increase in the AI-REM was associated with 18% higher odds of hypertension (odds ratio, 1.18; 95% confidence interval, 1.11–1.27) in OSA. On the contrary, AI-NREM was not a significant predictor of hypertension in any of the models. Conclusions: Our findings indicate that arousals during REM sleep are associated with prevalent hypertension. This is clinically relevant because treatment of OSA is often limited to the first half of the sleep period leaving most of sleep fragmentation during REM sleep untreated.

Importance Evidence regarding the nature and prevalence of 24-hour activity pattern phenotypes in older adults, especially those related to depression symptoms and cognition, is needed to guide the development of targeted mechanism research and behavioral interventions. Objectives To identify subgroups of older adults with similar 24-hour activity rhythm characteristics and characterize associated depression symptoms and cognitive performance. Design, Setting, and Participants From January to March 2022, a cross-sectional analysis of the 2011-2014 National Health and Nutrition Examination and Survey (NHANES) accelerometer study was conducted. The NHANES used a multistage probability sample that was designed to be representative of noninstitutionalized adults in the US. The main analysis included participants 65 years or older who had accelerometer and depression measures weighted to represent approximately 32 million older adults. Exposures Latent profile analysis identified subgroups with similar 24-hour activity pattern characteristics as measured using extended-cosine and nonparametric methods. Main Outcomes and Measures Covariate-adjusted sample-weighted regressions assessed associations of subgroup membership with (1) depression symptoms defined as 9-Item Patient Health Questionnaire (PHQ-9) scores of 10 or greater (PHQ-9) and (2) having at least psychometric mild cognitive impairment (p-MCI) defined as scoring less than 1 SD below the mean on a composite cognitive performance score. Results The actual clustering sample size was 1800 (weighted: mean [SD] age, 72.9 [7.3] years; 57% female participants). Clustering identified 4 subgroups: (1) 677 earlier rising/robust (37.6%), (2) 587 shorter active period/less modelable (32.6%), (3) 177 shorter active period/very weak (9.8%), and (4) 359 later settling/very weak (20.0%). The prevalence of a PHQ-9 score of 10 or greater differed significantly across groups (cluster 1, 3.5%; cluster 2, 4.7%; cluster 3, 7.5%; cluster 4, 9.0%; χ 2  P = .004). The prevalence of having at least p-MCI differed significantly across groups (cluster 1, 7.2%; cluster 2, 12.0%; cluster 3, 21.0%; cluster 4, 18.0%; χ 2  P &amp;lt; .001). Five of 9 depression symptoms differed significantly across subgroups. Conclusions and Relevance In this cross-sectional study, findings indicate that approximately 1 in 5 older adults in the US may be classified in a subgroup with weak activity patterns and later settling, and approximately 1 in 10 may be classified in a subgroup with weak patterns and shorter active duration. Future research is needed to investigate the biologic processes related to these behavioral phenotypes, including why earlier and robust activity patterns appear protective, and whether modifying disrupted patterns improves outcomes.

Introduction: Growing evidence suggests that aberrant sleep architecture is linked to heightened risk of cardiovascular disease independently of sleep apnea. Rapid Eye Movement (REM) sleep is characterized by increased sympathetic activity and blood pressure (BP) compared to non-REM sleep stages. However, whether REM sleep is associated with BP across the 24 hours has not been investigated. Hypothesis: We hypothesized that increased REM sleep would be associated with higher ambulatory BP. Methods: We recruited 137 individuals (58% men, aged 39±14 years, office systolic/diastolic BP [SBP/DBP] 125±14/77±11 mmHg) who completed overnight polysomnography followed by 24-h ambulatory BP monitoring. Sleep was scored according to standard criteria. 24-h, daytime, and nighttime averages were calculated for SBP, DBP and heart rate. REM sleep duration was computed as percentage of total sleep time and used to group participants into tertiles as follows: T1 (REM% ≤18.8), T2 (REM% 18.9-24), and T3 (REM% ≥24.1). Results: Sex ratio, body mass index, and apnea-hypopnea index were similar across REM tertiles, but age increased with increasing tertiles (p=0.029). 24-h SBP (T1 vs T2 vs T3: 121±12 vs 117±7 vs 124±12 mmHg, p=0.015) and DBP (72±7 vs 70±6 vs 76±8 mmHg, p<0.001) differed across REM sleep tertiles, with significantly higher values in those in the highest tertile. Results were consistent when considering daytime SBP (T1 vs T2 vs T3: 126±12 vs 122±8 vs 132±14 mmHg, p<0.001) and DBP (77±7 vs 76±6 vs 83±9 mmHg, p<0.001), and nighttime DBP (65±9 vs 61±7 vs 65±8 mmHg, p=0.047). No differences were noted on nighttime SBP or any heart rate measures. A significant interaction was found between hypertension status and REM sleep in multiple regression analysis, with the observed associations being significant only among hypertensives (n=69). In those with hypertension, REM sleep duration was associated with 24-h mean BP independently of age, sex, body mass index, apnea-hypopnea index and antihypertensive medications (standardized beta 0.22, p=0.041). Conclusions: Longer REM sleep duration is independently associated with elevated ambulatory BP in individuals with hypertension. REM sleep may be a novel cardiovascular risk indicator in this population.

Background: The epicardial adipose tissue (EAT) has been identified as a sensitive marker of cardiometabolic risk. Recent evidence suggests efficacy of long-term statin therapy in reducing the EAT in patients with coronary artery disease. Whether the volume of EAT changes in patients with atrial fibrillation (AF) treated with a statin for a short time period is currently unknown. Methods: A population of AF patients undergoing pulmonary vein isolation was randomized to receive either 80 mg/day of atorvastatin (n=51, 44 males, age 55±10 years) or placebo (n=51, 41 males, age 56±10) for a 3 month period. EAT volume was assessed by cardiac computed tomography at baseline and after 3-month follow-up. Results: Patients randomized to statin treatment exhibited significant decreases in EAT volume (baseline vs follow-up: 105.8 ± 52.95 vs 103.05 ± 52.55 cm3, p = 0.05), C-reactive protein (2.97 ± 4.3 mg/L vs 2.03 ± 2.2 mg/L, p < 0.05), total cholesterol (182.5 ± 36.9 vs 129.3 ± 40.6 mg/dL, p < 0.001), and low density lipoprotein-cholesterol (111.88 ± 28 vs 61 ± 32.6 mg/dL, p < 0.001) at follow-up, while the body mass index did not vary (29.42 ± 5.2 vs 29.11 ± 4.8 kg/m2, p = 0.28). No changes were seen in the placebo group. Conclusions: Short-term high-dose statin therapy significantly reduced the volume of EAT in AF patients. EAT volume modulation might be an important mechanism by which statins may influence cardiovascular risk.

Excessive daytime sleepiness (EDS) is classically viewed as a consequence of insufficient sleep or a symptom of sleep disorders. Epidemiological and clinical evidence have shown that patients reporting EDS in tandem with sleep disorders (e.g., obstructive sleep apnoea) are at greater cardiovascular risk than non-sleepy patients. While this may simply be attributable to EDS being present in patients with a more severe condition, treatment of sleep disorders does not consistently alleviate EDS, indicating potential aetiological differences. Moreover, not all patients with sleep disorders report EDS, and daytime sleepiness may be present even in the absence of any identifiable sleep disorder; thus, EDS could represent an independent pathophysiology. The purpose of this review is twofold: first, to highlight evidence that EDS increases cardiovascular risk in the presence of sleep disorders such as obstructive sleep apnoea, narcolepsy and idiopathic hypersomnia and second, to propose the notion that EDS may also increase cardiovascular risk in the absence of known sleep disorders, as supported by some epidemiological and observational data. We further highlight preliminary evidence suggesting systemic inflammation, which could be attributable to dysfunction of the gut microbiome and adipose tissue, as well as deleterious epigenetic changes, may promote EDS while also increasing cardiovascular risk; however, these pathways may be reciprocal and/or circumstantial. Additionally, gaps within the literature are noted followed by directions for future research.