Effect of mandibular advancement splint therapy on cardiac autonomic function in obstructive sleep apnoea.

PURPOSE: This study aimed to evaluate the effect of mandibular advancement splint (MAS) therapy on cardiac autonomic function in patients with obstructive sleep apnoea (OSA) using heart rate variability (HRV) analysis. METHODS: Electrocardiograms (ECG) derived from polysomnograms (PSG) of three prospective studies were used to study HRV of patients with OSA before and after MAS treatment. HRV parameters were averaged across the entire ECG signal during N2 sleep using 2-min epochs shifted by 30 s. Paired t-tests were used to compare PSG and HRV measures before and after treatment, and the percent change in HRV measures was regressed on the percent change in apnoea-hypopnea index (AHI). RESULTS: In 101 patients with OSA, 72% were Caucasian, 54% men, the mean age was 56 ± 11 years, BMI 29.8 ± 5.3 kg/m2, and treatment duration was 4.0 ± 3.2 months. After MAS therapy, there was a significant reduction in OSA severity (AHI, - 18 ± 16 events per hour, p < 0.001) and trends towards increased low-frequency to high-frequency ratio, low-frequency power, and reduced high-frequency power (LF:HF, - 0.4 ± 1.5, p = 0.01; LF, - 3 ± 16 nu, p = 0.02, HF, 3.5 ± 13.7 nu, p = 0.01). Change in NN intervals correlated with the change in AHI (ß(SE) = - 2.21 (0.01), t = - 2.85, p = 0.005). No significant changes were observed in the time-domain HRV markers with MAS treatment. CONCLUSION: The study findings suggest that successful MAS treatment correlates with changes in HRV, specifically the lengthening of NN intervals, a marker for improved cardiac autonomic adaptability.

Cardiac autonomic function in REM-related obstructive sleep apnoea: insights from nocturnal heart rate variability profiles.

PURPOSE: In light of the reported association between REM-related obstructive sleep apnoea (OSA) and heightened cardiovascular risk, this study aims to compare cardiac autonomic function in patients with REM-OSA and OSA independent of sleep stage. We hypothesized that REM-OSA patients would exhibit higher sympathetic cardiac modulation based on heart rate variability (HRV) profiles. METHODS: HRV was compared between the OSA group (AHI ≥ 5 events/h, n = 252) and the REM-OSA group (AHI ≥ 5 events/h, AHIREM:AHINREM ≥ 2, n = 137). Time- and frequency-domain measures of HRV were analysed during N2 and REM sleep. RESULTS: Clinical characteristics between the two test groups differed significantly, 45% of REM-OSA patients were female, with mild OSA (median, interquartile range (IQR)) AHI of 10 (7) events/h. Only 26% of the OSA cohort were female with moderate OSA (AHI = 17 (20) events/h, p < 0.001). Compared with the OSA group, the low frequency to high frequency ratio (LF:HF) and LF power were lower and HF power was higher in the REM-OSA group during N2 (LF:HF, p = 0.012; LF; p = 0.013; HF, p = 0.007) and in REM sleep (LF:HF, p = 0.002; LF, p = 0.004; HF, p < 0.001). Patient sex and OSA severity had a significant combined effect on average N to N interval, LF power, and LF:HF ratio during N2 and REM sleep (all p < 0.001). CONCLUSION: Contrary to our hypothesis, REM-OSA patients demonstrated consistently higher cardiac vagal modulation, reflecting better cardiac autonomic adaptation. These results were attributed to differences in OSA severity and sex in these two groups, both independently affecting HRV. This study emphasises the need for future research into the underlying pathophysiology of REM-OSA and the potential implications of sex and OSA severity on cardiovascular risk.

Heart rate variability and obstructive sleep apnea: Current perspectives and novel technologies.

Obstructive sleep apnea (OSA) is a highly prevalent condition, resulting in recurrent hypoxic events, sleep arousal, and daytime sleepiness. Patients with OSA are at an increased risk of cardiovascular morbidity and mortality. The mechanisms underlying the development of cardiovascular disease in OSA are multifactorial and cause a cascade of events. The primary contributing factor is sympathetic overactivity. Heart rate variability (HRV) can be used to evaluate shifts in the autonomic nervous system, during sleep and in response to treatment in patients with OSA. Newer technologies are aimed at improving HRV analysis to accelerate processing time, improve the diagnosis of OSA, and detection of cardiovascular risk. The present review will present contemporary understandings and uses for HRV, specifically in the realms of physiology, technology, and clinical management.

Influence of Obstructive Sleep Apnoea Severity on Coronary Collateral Recruitment During Coronary Occlusion.

PURPOSE: Obstructive sleep apnoea (OSA) which results in hypoxia may affect the ability to recruit coronary collaterals. The aim of this study was to determine whether the severity of OSA affects collateral recruitment in patients with total coronary occlusions. METHODS: Patients with total coronary artery occlusion were reviewed. Records from the sleep investigation laboratory were reviewed to identify those patients who had undergone diagnostic polysomnography. Robust coronary collaterals were those with Rentrop grade 2 or 3 collaterals. RESULTS: Sixty-four patients with a total coronary occlusion had polysomnography performed, of whom 60 patients had OSA. Thirty-two patients (53.3%) had poor collaterals, whilst 28 (46.7%) had robust collaterals. Twenty-four (40%) patients had mild OSA, 10 (16.7%) had moderate OSA and 26 (43.3%) had severe OSA. Patients with robust collaterals were more likely to be males (96.4% vs 74.3%, p < 0.05) and have a history of hypercholesterolaemia (88.9% vs 51.6%, p < 0.01). Patients with robust collaterals had a lower apnoea-hypopnoea index (13.6 vs 45.5, p < 0.05), a higher MinSaO2 (85.4% vs 79.8%, p < 0.05), less time SaO2 < 90% (0 min vs 30.4 min, p < 0.05) and lower oxygen desaturation index (6.9 vs 26.8, p < 0.05). Those with moderate OSA had a higher mean Rentrop grade (1.6 ± 0.3) than those with mild OSA (1.5 ± 1.1) and severe OSA (0.6 ± 0.2). CONCLUSION: The presence of more severe OSA is associated with poorer coronary collateral recruitment in patients with total coronary artery occlusion. The effect of treatment of OSA on subsequent ability to recruit collaterals and other cardioprotective mechanisms requires further research.

Influence of Obstructive Sleep Apnoea on Outcomes in Patients With ST Elevation Myocardial Infarction (STEMI): the Role of the Coronary Collateral Circulation.

BACKGROUND: Obstructive sleep apnoea (OSA) occurs frequently in patients with coronary artery disease, with associated intermittent hypoxia a possible stimulus for coronary collateral recruitment through ischaemic preconditioning. We sought to determine whether OSA affects recruitment of coronary collaterals and prognosis of patients presenting with ST elevation myocardial infarction (STEMI). METHODS: Patients with a STEMI undergoing percutaneous coronary intervention (PCI) from July 2010 to December 2019 were reviewed. Electronic medical records were accessed to determine documented patient history of OSA. Patients with robust collaterals were defined as Rentrop Grade 2 or 3. RESULTS: 1,863 patients were included, of which 143 (7.7%) patients had documented evidence of OSA in their health record. Patients with OSA had a higher body mass index (BMI) (30.2 kg/m2 vs 27 kg/m2, p<0.0001), greater rate of hypertension (61.1% vs 45.1%, p<0.0001), hypercholesterolaemia (47.4% vs 38.4%, p<0.05) and diabetes mellitus (22.6% vs 15.9%, p<0.05). Patients with OSA were more likely to have robust coronary collaterals (OR: 2.2 [95% CI: 1.5-3.2]) and a lower rate of left ventricular (LV) impairment (50.7% vs 63.1%, p<0.01), a higher LV ejection fraction (50.3% vs 46.7%, p<0.0001) and a lower peak troponin-I level (26,452 ng/L vs 39,469 ng/L, p<0.01). There were no differences in rates of in-hospital or longer term mortality, in patients with OSA compared to those without. CONCLUSIONS: Patients with documented OSA presenting with STEMI appear to have more robust coronary collaterals observed on angiography which likely mediates lower myocardial necrosis. Broader implications of this finding on treatment require further investigation.

Influence of maternal and placental factors on newborn body composition.

AIM: The objective of this study was to assess whether maternal characteristics, placental size or histological chorioamnionitis was associated with newborn body composition. Furthermore, we sought to determine whether placental weight may mediate the association between maternal pre-pregnancy weight and age with newborn body composition. METHODS: A cross-sectional study was conducted at Royal Prince Alfred Hospital, Sydney, Australia. This study included 136 healthy, singleton, term-born newborns. Recruitment was stratified by newborn body fat percentiles (gender and gestational adjusted). Body fat was assessed by air displacement plethysmography. Placental examination was conducted by an anatomical pathologist. Maternal (chorioamnionitis) and fetal (chorionic and umbilical vasculitis, funisitis) inflammatory responses were classified according to Redline criteria. RESULTS: Maternal pre-pregnancy weight, parity, labour, placental weight and surface area were associated with newborn fat mass and fat-free mass. Gestational diabetes and maternal age were associated with newborn fat mass but not fat-free mass. There was no association between histological chorioamnionitis and newborn body composition; however, spontaneous onset of labour was strongly associated with the presence of histological chorioamnionitis. Only 25-31% of the association of maternal weight and age with newborn fat mass was mediated via the placenta. CONCLUSIONS: Maternal factors associated with newborn fat mass and fat-free mass differed, indicating that different mechanisms control fat mass and fat-free mass. Our mediation analysis suggests that placental weight partly mediates the association of maternal factors with newborn body composition. Histological chorioamnionitis was not associated with newborn body composition.

Heart rate variability analysis in obstructive sleep apnea patients with daytime sleepiness.

STUDY OBJECTIVES: Recent studies suggest that sleepy patients with obstructive sleep apnea (OSA) are at higher risk for incident cardiovascular disease. This study assessed cardiac autonomic function in sleepy versus non-sleepy patients with OSA using heart rate variability (HRV) analysis. We hypothesized that HRV profiles of sleepy patients would indicate higher cardiovascular risk. METHODS: Electrocardiograms (ECG) derived from polysomnograms (PSG) collected by the Sydney Sleep Biobank were used to study HRV in groups of sleepy (ESS ≥ 10) and non-sleepy OSA patients (ESS < 10). HRV parameters were averaged across available ECG signals during N2 sleep. RESULTS: A total of 421 patients were evaluated, with a mean age of 54 (14) years, body mass index of 33 (9) kg/m2, apnea-hypopnea index of 21 (28) events/h, and 66% male. The sleepy group consisted of 119 patients and the non-sleepy group 302 patients. Sleepy patients exhibited lower HRV values for: root mean square successive difference (RMSSD, p = 0.028), total power (TP, p = 0.031), absolute low frequency (LF, p = 0.045), and high-frequency (HF, p = 0.010) power compared to non-sleepy patients. Sleepy patients with moderate-to-severe OSA exhibited lower HRV values for: (RMSSD, p = 0.045; TP, p = 0.052), absolute LF (p = 0.051), and HF power (p = 0.025). There were no differences in other time and frequency domain HRV markers. CONCLUSIONS: This study shows a trend toward parasympathetic withdrawal in sleepy OSA patients, particularly in moderate-to-severe cases, lending mechanistic support to the link between the sleepy phenotype and CVD risk in OSA.

Does obstructive sleep apnoea modulate cardiac autonomic function in paroxysmal atrial fibrillation?

PURPOSE: The autonomic nervous system may mediate acute apnoea-induced atrial fibrillation (AF). We compared cardiac autonomic function in paroxysmal atrial fibrillation (PAF) patients with and without obstructive sleep apnoea (OSA). METHODS: Case control study of 101 patients with PAF recruited at two tertiary centres. All patients underwent in-laboratory polysomnography. ECG signal demonstrating "steady state" sinus rhythm (i.e. with arrhythmic beats and respiratory events excluded) was included in the analysis. Cardiac autonomic function was assessed via measures of heart rate variability (HRV) and reported by sleep stage (REM vs Non-REM) for patients with and without OSA. RESULTS: Sixty-five (66.3%) of patients were male, mean age 61.5 ± 11.6 years, mean BMI 27.1 ± 4.3 kg/m2. Global measures of HRV (triangular index, total power) did not differ between PAF patients with and without OSA in either REM or non-REM sleep. Frequency-domain analysis during non-REM sleep in PAF patients with OSA showed increased cardiac parasympathetic modulation (HF-nu: 39.1 ± 15.7 vs 48.0 ± 14.6, p = 0.008) and reduced cardiac sympathetic modulation (LF-nu 54.1 ± 19.7 vs 43.7 ± 18.0, p = 0.012, LF/HF ratio: 2.1 ± 2.0 vs 1.2 ± 1.0, p = 0.007). Results remained significant after adjusting for age, sex, and BMI (adjusted p values 0.024, 0.045 and 0.018 respectively). There were no differences in HRV parameters during REM sleep. CONCLUSIONS: This is the first study of HRV in PAF patients with and without OSA. Our results indicate limited differences in HRV between groups. However, this work suggests a chronic increase in parasympathetic nervous modulation and relative reduction in sympathetic modulation in PAF patients with OSA during steady-state non-REM sleep.

The effect of obstructive sleep apnea therapy on cardiovascular autonomic function: a systematic review and meta-analysis.

STUDY OBJECTIVES: Autonomic function is impaired in obstructive sleep apnea (OSA) and may mediate the association between OSA and cardiovascular risk. We investigated the effect of OSA therapy on autonomic function through a systematic review and meta-analysis of intervention studies. METHODS: A systematic search using three databases (Medline, Embase, and Scopus) was performed up to December 9, 2020. Studies of OSA patients ≥ 18 years with autonomic function assessed before and after treatment with positive airway pressure, oral appliance, positional therapy, weight loss, or surgical intervention were included for review. Random effects meta-analysis was carried out for five groups of autonomic function indices. Risk of bias was assessed using the Cochrane Collaboration tool. RESULTS: Forty-three eligible studies were reviewed with 39 included in the meta-analysis. OSA treatment led to large decreases in muscle sympathetic nerve activity (Hedges' g = -1.08; 95% CI -1.50, -0.65, n = 8) and moderate decreases in catecholamines (-0.60; -0.94, -0.27, n = 3) and radio nucleotide imaging (-0.61; -0.99, -0.24, n = 2). OSA therapy had no significant effect on baroreflex function (Hedges' g = 0.15; 95% CI -0.09, 0.39, n = 6) or heart rate variability (0.02; -0.32, 0.36, n = 14). There was a significant risk of bias due to studies being primarily non-randomized trials. CONCLUSIONS: OSA therapy selectively improves autonomic function measures. The strongest evidence for the effect of OSA therapy on autonomic function was seen in reduced sympathetic activity as assessed by microneurography, but without increased improvement in parasympathetic function. OSA therapy may reduce the risk of cardiovascular disease in OSA through reduced sympathetic activity.

Comparative associations of oximetry patterns in Obstructive Sleep Apnea with incident cardiovascular disease.

STUDY OBJECTIVES: Intermittent hypoxia is a key mechanism linking Obstructive Sleep Apnea (OSA) to cardiovascular disease (CVD). Oximetry analysis could enhance understanding of which OSA phenotypes are associated with CVD risk. The aim of this study was to compare associations of different oximetry patterns with incident CVD in men and women with OSA. METHODS: Sleep Heart Health Study data were used for analysis. n = 2878 Participants (51.8% female; mean age 63.5 ±â€…10.5 years) with OSA (Apnea Hypopnea Index [AHI] ≥ 5 events/h) and no pre-existing CVD at baseline or within the first 2 years of follow-up were included. Four oximetry analysis approaches were applied: desaturation characteristics, time series analysis, power spectral density, and non-linear analysis. Thirty-one resulting oximetry patterns were compared to incident CVD using proportional hazards regression models adjusted for age, race, smoking, BMI, and sex. RESULTS: There were no associations between OSA oximetry patterns and incident CVD in the total sample or in men. In women, there were some associations between incident CVD and time series analysis (e.g. SpO2 distribution standard deviation, HR 0.81, 95% CI 0.68-0.96, p = 0.014) and power spectral density oximetry patterns (e.g. Full frequency band mean HR 0.75; 95% CI 0.59-0.95; p = 0.015). CONCLUSIONS: Comprehensive comparison of baseline oximetry patterns in OSA found none were related to development of CVD. There were no standout individual oximetry patterns that appear to be candidates for CVD risk phenotyping in OSA, but some showed marginal relationships with CVD risk in women. Further work is required to understand whether OSA phenotypes can be used to predict susceptibility to cardiovascular disease.

Cardiac and vascular health in late preterm infants.

Adults who were born preterm are at increased risk of hypertension and cardiovascular disease in later life. Infants born late preterm are the majority of preterm births; however, the effect of late preterm on risk of cardiovascular disease is unclear. The objective of this study was to assess whether vascular health and cardiac autonomic control differ in a group of late preterm newborn infants compared to a group of term-born infants.A total of 35 healthy late preterm newborn infants, with normal growth (34-36 completed weeks' gestation) and 139 term-born infants (37-42 weeks' gestation) were compared in this study. Aortic wall thickening, assessed as aortic intima-media thickness (IMT) by high-resolution ultrasound, and cardiac autonomic control, assessed by heart rate variability, were measured during the first week of life. Postnatal age of full-term and late preterm infants at the time of the study was 5 days (standard deviation [SD] 5) and 4 days (SD 3), respectively.Infants born late preterm show reduced aortic IMT (574 µm [SD 51] vs. 612 µm [SD 73]) and reduced heart rate variability [log total power 622.3 (606.5) ms2 vs. 1180. 6 (1114.3) ms2], compared to term infants. These associations remained even after adjustment for sex and birth weight.Infants born late preterm show selective differences in markers of cardiovascular risk, with potentially beneficial differences in aortic wall thickness in contrast to potentially detrimental differences in autonomic control, when compared with term-born control infants. These findings provide pathophysiologic evidence to support an increased risk of hypertension and sudden cardiac death in individuals born late preterm.

Maternal dietary fatty acid composition and newborn epigenetic aging-a geometric framework approach.

BACKGROUND: Maternal nutrition is associated with epigenetic and cardiometabolic risk factors in offspring. Research in humans has primarily focused on assessing the impact of individual nutrients. OBJECTIVES: We sought to assess the collective impact of maternal dietary MUFAs, PUFAs, and SFAs on epigenetic aging and cardiometabolic risk markers in healthy newborn infants using a geometric framework approach. METHODS: Body fatness (n = 162), aortic intima-media thickness (aIMT; n = 131), heart rate variability (n = 118), and epigenetic age acceleration (n = 124) were assessed in newborn infants. Maternal dietary intake was cross-sectionally assessed in the immediate postpartum period via a validated 80-item self-administered FFQ. Generalized additive models were used to explore interactive associations of nutrient intake, with results visualized as response surfaces. RESULTS: After adjustment for total energy intake, maternal age, gestational age, and sex there was a 3-way interactive association of MUFAs, PUFAs, and SFAs (P = 0.001) with newborn epigenetic aging. This suggests that the nature of each fat class association depends upon one another. Response surfaces revealed MUFAs were positively associated with newborn epigenetic age acceleration only at proportionately lower intakes of SFAs or PUFAs. We also demonstrate a potential beneficial association of omega-3 (n-3) PUFAs with newborn epigenetic age acceleration (P = 0.008). There was no significant association of fat class with newborn aIMT, heart rate variability, or body fatness. CONCLUSIONS: In this study, we demonstrated an association between maternal dietary fat class composition and epigenetic aging in newborns. Future research should consider other characteristics such as the source of maternal dietary fatty acids.

Circadian blood pressure profile and blood pressure changes following oral appliance therapy for obstructive sleep apnoea.

OBJECTIVES: Oral appliance therapy for obstructive sleep apnoea (OSA) reduces blood pressure (BP) but there is little information on relationship to circadian BP pattern (nocturnal BP dipping or non-dipping). The aims of this study were to determine whether nocturnal dipping pattern influences BP changes following oral appliance therapy, and to determine the effect of oral appliance therapy on circadian BP pattern. METHODS: Participants in two randomized trials of oral appliance therapy (1-2 months) with 24-h ambulatory BP monitoring (ABPM) data were included (N = 152). Nocturnal BP Dippers (nocturnal/diurnal SBP ratio <0.9) and non-dippers were compared for BP changes following oral appliance therapy and the effect of oral appliance therapy on nocturnal BP dipping was assessed. RESULTS: Of 152 participants, 64.5% were dippers. Dippers were on average younger and less likely to be hypertensive (42 vs. 82.7%, P < 0.001). Nondippers showed greater reduction in nocturnal BP measures, related to higher BP measures at baseline. There was no difference in the relationship between treatment effectiveness and BP changes between groups. Oral appliance therapy converted only 23% of baseline non-dippers to a nocturnal dipping profile. CONCLUSION: Baseline circadian BP profile influenced the BP response to oral appliance therapy, largely because of higher baseline BP in the non-dipper subgroup. Oral appliance therapy did not convert OSA patients to a more favourable circadian BP profile. Further work is required to understand the effect of oral appliance therapy on circadian BP profile and of the individuals who will receive cardiovascular benefit from oral appliance therapy.

Modeling the Effect of Environmentally Sustainable Food Swaps on Nutrient Intake in Pregnant Women.

Food production greatly contributes to greenhouse gas emissions (GHG), but there remain concerns that consuming environmentally sustainable foods can increase the likelihood of nutritional deficiencies during pregnancy. We identified commonly consumed foods of pregnant women and determined the effect of their replacement with environmentally sustainable alternatives on nutrient intake and measures of environmental sustainability. Dietary intake data from 171 pregnant women was assessed and foods that contributed the most to energy and protein intake were identified. Of these, foods producing the highest GHG emissions were matched with proposed environmentally sustainable alternatives, and their impact on nutrient provision determined. Meats, grains, and dairy products were identified as important sources of energy and protein. With the highest GHG emissions, beef was selected as the reference food. Proposed alternatives included chicken, eggs, fish, tofu, legumes, and nuts. The most pronounced reductions in CO2 emissions were from replacing beef with tofu, legumes, and nuts. Replacing one serve per week of beef with an isocaloric serve of firm tofu during pregnancy could reduce GHG emissions by 372 kg CO2 eq and increase folate (+28.1 µg/serve) and fiber (+3.3 g/serve) intake without compromising iron (+1.1 mg/serve) intake. Small dietary substitutions with environmentally sustainable alternatives can substantially reduce environmental impact without compromising nutrient adequacy.

Association between autonomic function and obstructive sleep apnea: A systematic review.

Obstructive sleep apnea (OSA) is an independent risk factor for hypertension and cardiovascular disease. Effects of OSA on the autonomic nervous system may mediate this association. We performed a systematic literature review to determine the profile of autonomic function associated with OSA. Three electronic databases were searched for studies of OSA patients aged ≥18 years in which autonomic function was assessed. Studies comparing patients with and without OSA, or examining the association of OSA severity with changes in autonomic function were included. Seventy-one studies met the inclusion criteria and autonomic function has been assessed using a range of techniques. The profile of autonomic function found in OSA include increased sympathetic activity, reduced parasympathetic activity and less consistently found low heart rate variability. Altered autonomic function in OSA may explain the pathophysiology of increased cardiovascular risk. Evidence from intervention studies is required to determine if treatment improves autonomic function associated with OSA.

Maternal Dietary Carbohydrate Intake and Newborn Aortic Wall Thickness.

Evidence from animal models indicates that maternal diet during pregnancy affects offspring cardiometabolic health. Improving carbohydrate quality during high-risk pregnancies reduces aortic intima-medial thickness; a marker for early atherosclerosis; in the infant offspring. We sought to determine whether maternal carbohydrate quantity and quality are associated with newborn aortic intima-medial thickness in healthy pregnancies. Maternal diet throughout pregnancy was evaluated in 139 mother-child dyads using a validated food frequency questionnaire. Carbohydrate intake was expressed as quantity (% total energy), quality (fibre, glycaemic index), and glycaemic burden (glycaemic load). Aortic intima-medial thickness was measured by high-frequency ultrasound of the neonatal abdominal aorta. Neither quantity nor quality of maternal carbohydrate intake during pregnancy was associated with meaningful differences in offspring maximum aortic intima-medial thickness with the exception of fibre intake in women with overweight or obesity which was inversely associated (-8 µm [95% CI -14, -1] per g fibre, p = 0.04). In healthy pregnancy, the quantity and quality of maternal carbohydrate intake is likely not a meaningful modifiable lifestyle factor for influencing offspring vascular health. The effect of carbohydrate quality may only be evident in high-risk pregnancies, consistent with previous findings. These findings may be confirmed in prospective dietary trials in pregnancy.

Comparative effects of CPAP and mandibular advancement splint therapy on blood pressure variability in moderate to severe obstructive sleep apnoea.

BACKGROUND: Obstructive sleep apnoea (OSA) is associated with increased blood pressure variability (BPV) and are risk factors for cardiovascular disease. We aimed to assess the comparative effects of two OSA therapies, continuous positive airway pressure (CPAP) and mandibular advancement splint (MAS), on BPV. METHODS: This is a secondary analysis of data collected as part of a previously published randomised crossover trial of one month each of CPAP and MAS therapy. BPV was determined from 24-h-ambulatory blood pressure recordings in 92 patients with moderate to severe OSA at baseline and after one month of optimised treatment with each modality. BPV was assessed by three measures: Standard deviation of the mean (SD), Coefficient of variation (CoV), and the Average Real Variability (ARV) index. RESULTS: Neither CPAP nor MAS therapy improved BPV, with no difference between treatments. BPV did not change in hypertensive OSA patients, however, there was a reduction in ARV of diastolic blood pressure in the effectively treated compared to ineffectively treated CPAP patients, Δ ARV 24-h-DBP (mmHg), -0.72 ± 2.14, 0.34 ± 1.52, P = 0.02, respectively. There was no difference between effective versus ineffective MAS treatment, Δ ARV 24-h-DBP (mmHg), -0.04 ± 2.4, 0.02 ± 1.9, P = 1.00, respectively. CONCLUSIONS: One month of optimised CPAP or MAS therapy did not improve short term BPV in patients with moderate to severe OSA. The subgroup of patients on effective CPAP showed some improvement in BPV with CPAP but not MAS. Further work on the effect of OSA therapy on BPV following long-term therapy is needed.

Relation of Obstructive Sleep Apnea in Patients With a Coronary Chronic Total Occlusion to Coronary Collaterals and Mortality.

A chronic total occlusion (CTO) is frequently identified in patients undergoing coronary angiography. The prognostic implications of intermittent hypoxia from obstructive sleep apnea (OSA) on patients with a CTO, and effects on collateral recruitment are unknown. The aim of this study was to determine the prevalence, vascular effects, and prognostic implications of the presence of OSA in patients with a CTO. Patients with a CTO between July 2010 and December 2019 were reviewed. Electronic medical records were accessed to determine documented patient history of OSA, demographics, and clinical course. Patients with robust collateral recruitment were defined as Rentrop grade 2 or 3. A total of 948 patients were included in the study, of which 127 (13.4%) had a documented history of OSA. These patients were younger (67.0 years vs 70.6 years, p < 0.01), had a higher body mass index (29.6 kg/m2 vs 26.7 kg/m2, p < 0.0001), higher rates of hypertension (91.3% vs 83.2%, p < 0.05), higher rates of smokers (63.3% vs 49.0%, p < 0.01) and more use of ß-blockers (79% vs 68.5%, p < 0.05) and statins (92.7% vs 82.1%, p < 0.01). A documented history of OSA was independently associated with robust collaterals (OR 3.0 95%CI 1.5 to 5.8, p < 0.01) and lower mortality (HR 0.3 95% CI 0.1 to 0.7, p < 0.01) with a mean survival of 10.8 years, as compared to 8.1 years (log rank p < 0.0001). In conclusion, in patients with a CTO, documented OSA is independently associated with more robust coronary collaterals and lower mortality. The possible cardioprotective implications of intermittent hypoxia in OSA, as well as treatment effect requires further investigation.

Obstructive sleep apnea therapy for cardiovascular risk reduction-Time for a rethink?

Obstructive sleep apnea (OSA) is a highly prevalent and underdiagnosed medical condition, which is associated with various cardiovascular and metabolic diseases. The current mainstay of therapy is continuous positive airway pressure (CPAP); however, CPAP is known to be poorly accepted and tolerated by patients. In randomized controlled trials evaluating CPAP in cardiovascular outcomes, the average usage was less than 3.5 hours, which is below the 4 hours per night recommended to achieve a clinical benefit. This low adherence may have resulted in poor effectiveness and failure to show cardiovascular risk reduction. The mandibular advancement device (MAD) is an intraoral device designed to advance the mandible during sleep. It functions primarily through alteration of the jaw and/or tongue position, which results in improved upper airway patency and reduced upper airway collapsibility. The MAD is an approved alternative therapy that has been consistently shown to be the preferred option by patients who are affected by OSA. Although the MAD is less efficacious than CPAP in abolishing apnea and hypopnea events in some patients, its greater usage results in comparable improvements in quality-of-life and cardiovascular measures, including blood pressure reduction. This review summarizes the impact of OSA on cardiovascular health, the limitations of CPAP, and the potential of OSA treatment using MADs in cardiovascular risk reduction.

Epigenetic aging in newborns: role of maternal diet.

BACKGROUND: Epigenetic aging is associated with higher risk of cardiovascular disease, cancer, and all-cause mortality and may be a mechanistic link between early-life exposures, such as maternal dietary characteristics during pregnancy, and risk of adult disease. OBJECTIVES: We sought to determine the early-life risk factors for newborn epigenetic aging, specifically maternal dietary macronutrient intake, and whether epigenetic aging is associated with cardiovascular health markers in the newborn. METHODS: Epigenetic age acceleration of 169 newborns was measured from saliva using the Horvath age calculator. Maternal diet during pregnancy was assessed using food-frequency questionnaires. RESULTS: Newborns with positive age acceleration were more likely to be female and have greater body fatness. Maternal intakes of saturated fat [6.2 wk epigenetic age acceleration (95% CI: 1.0, 11.3) per 5% of energy; P = 0.02] and monounsaturated fat [12.4 wk (95% CI: 4.2, 20.5) per 5% of energy; P = 0.003] were associated with higher epigenetic age acceleration in the newborn. The strongest association of individual fatty acids were for palmitoleic acid (25.3 wk; 95% CI: 11.4, 39.2; P = 0.0004), oleic acid (2.2 wk; 95% CI: 0.8, 3.6; P = 0.002), and palmitic acid (2.9 wk; 95% CI: 1.0, 4.9; P = 0.004) per 1% of energy intake. Vitamin D supplementation was associated with lower epigenetic age acceleration (-8.1 wk; 95% CI: -14.5, -1.7; P = 0.01). Epigenetic age acceleration was associated with aortic intima-media thickness in preterm infants [1.0 µm (95% CI: 0.2, 1.8) per week of epigenetic age acceleration; P = 0.01], but not among those born at term (P = 0.78). Epigenetic age acceleration was not associated with heart rate variability in either preterm or term born infants (both P > 0.2). CONCLUSIONS: This study provides evidence of maternal dietary characteristics that are associated with epigenetic aging in the offspring. Prospective intervention studies are required to determine whether such associations are causal.