Cardiovascular disease hospitalizations among women who undergo fertility treatment.

RESEARCH QUESTION: Are women who receive fertility treatment at increased risk of cardiovascular disease (CVD) hospitalization compared with women who do not? DESIGN: A retrospective cohort study of all women registered for fertility treatment at Monash IVF between 1998 and 2014. This cohort was linked to the Victorian Admitted Episodes Dataset, which contains records of all hospital admissions in the Australian state of Victoria. Age- and Index of Relative Socioeconomic Disadvantage (IRSD)-adjusted relative risks of CVD hospitalization for women who did or did not undergo fertility treatment were determined using Poisson regression. Risks were calculated overall by CVD subtype and stratified by area-based social disadvantage using IRSD fifths, number of stimulated cycles and mean oocytes per cycle. RESULTS: Of 27,262 women registered for fertility treatment, 24,131 underwent treatment and 3131 did not. No significant difference was found in risk of CVD hospitalization between treated and untreated women overall (adjusted RR 0.93, 95% 0.82 to 1.05) or by CVD subtype. The admission risk for CVD was significantly lower in treated women who had a mean of fewer than five oocytes per cycle (adjusted RR 0.80, 95% CI 0.70 to 0.92) compared with untreated women. Treated women residing in areas within the second IRSD fifth were less likely to be hospitalized for CVD compared with untreated women (age-adjusted RR 0.66, 95% CI 0.49 to 0.89). CONCLUSIONS: Fertility treatment is not associated with increased risk of CVD hospitalization. Lower risk among some subgroups of treated women may be explained by social disadvantage.

Cross-sectional associations between neighborhood characteristics, cognition and dementia risk factor burden in middle-aged and older Australians.

Dementia disproportionately affects individuals from disadvantaged backgrounds, including those living in areas of lower neighborhood-level socioeconomic status. It is important to understand whether there are specific neighborhood characteristics associated with dementia risk factors and cognition which may inform dementia risk reduction interventions. We sought to examine whether greenspace, walkability, and crime associated with the cumulative burden of modifiable dementia risk factors and cognition. This was a cross-sectional analysis of 2016-2020 data from the Healthy Brain Project, a population-based cohort of community-dwelling individuals across Australia. Participants were aged 40-70 and free of dementia. Measures included greenspace (greenspace % in the local area, and distance to greenspace, n = 2,181); and intersection density (n = 1,159), and crime (rate of recorded offences; n = 1,159). Outcomes included a modified Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) dementia risk score to index the burden of modifiable vascular dementia risk factors; and composite scores of both memory and attention, derived from the Cogstate Brief Battery. Linear regressions adjusted for age, sex, education, and personal socio-economic status, demonstrated distance to greenspace (b ± SE per 2-fold increase = 0.09 ± 0.03, p =.005) and crime rate (b ± SE per 2-fold increase = 0.07 ± 0.03, p =.018) were associated with higher modified CAIDE. Higher crime was associated with lower memory performance (b ± SE = -0.03 ± 0.01, p =.018). The association between distance to greenspace and modified CAIDE was only present in low-moderate socioeconomic status neighborhoods (p interaction = 0.004). Dementia prevention programs that address modifiable risk factors in midlife should consider the possible role of neighborhood characteristics.

Association of the Sleep Regularity Index With Incident Dementia and Brain Volume.

BACKGROUND AND OBJECTIVES: Irregular sleep may increase the risk of cardiometabolic conditions, but its association with incident dementia is unclear. The aim of this study was to assess the association between sleep regularity, that is, the day-to-day consistency in sleep-wake patterns and the risk of incident dementia and related brain MRI endophenotypes. METHODS: We used Cox proportional hazard models to investigate the relationships between sleep regularity and incident dementia in 88,094 UK Biobank participants. The sleep regularity index (SRI) was calculated as the probability of being in the same state (asleep/awake) at any 2 time points 24 hours apart, averaged over 7 days of accelerometry. RESULTS: The mean age of the sample was 62 years (SD = 8), 56% were women, and the median SRI was 60 (SD = 10). There were 480 cases of incident dementia over a median 7.2 years of follow-up. Following adjustments for demographic, clinical, and genetic confounders (APOE ε4), there was a nonlinear association between the SRI and dementia hazard (p [global test of spline term] < 0.001) with hazard ratios (HRs) following a U-shape pattern. HRs, relative to the median SRI, were 1.53 (95% CI 1.24-1.89) for participants with SRI at the 5th percentile (SRI = 41) and 1.16 (95% CI 0.89-1.50) for those with SRI at the 95th percentile (SRI = 71). In a subset with brain MRI (n = 15,263), gray matter and hippocampal volume tended to be lowest at the extremes of the SRI. DISCUSSION: Sleep regularity displayed a U-shaped association with risk of incident dementia. Irregular sleep may represent a novel dementia risk factor.

Association of Sleep Duration and Change Over Time With Imaging Biomarkers of Cerebrovascular, Amyloid, Tau, and Neurodegenerative Pathology.

BACKGROUND AND OBJECTIVES: Both short and long sleep duration were previously associated with incident dementia, but underlying mechanisms remain unclear. We evaluated how self-reported sleep duration and its change over time associate with (A)myloid, (T)au, (N)eurodegeneration, and (V)ascular neuroimaging markers of Alzheimer disease. METHODS: Two Framingham Heart Study overlapping samples were studied: participants who underwent 11C-Pittsburg Compound B amyloid and 18F-flortaucipir tau PET imaging and participants who underwent an MRI. MRI metrics estimated neurodegeneration (total brain volume) and cerebrovascular injuries (white matter hyperintensities [WMHs] volume, covert brain infarcts, free-water [FW] fraction). Self-reported sleep duration was assessed and split into categories both at the time of neuroimaging testing and approximately 13 years before: short ≤6 hours. average 7-8 hours, and long ≥9 hours. Logistic and linear regression models were used to examine sleep duration and neuroimaging metrics. RESULTS: The tested cohort was composed of 271 participants (age 53.6 ± 8.0 years; 51% male) in the PET imaging sample and 2,165 participants (age 61.3 ± 11.1 years; 45% male) in the MRI sample. No fully adjusted association was observed between cross-sectional sleep duration and neuroimaging metrics. In fully adjusted models compared with consistently sleeping 7-8 hours, groups transitioning to a longer sleep duration category over time had higher FW fraction (short to average ß [SE] 0.0062 [0.0024], p = 0.009; short to long ß [SE] 0.0164 [0.0076], p = 0.031; average to long ß [SE] 0.0083 [0.0022], p = 0.002), and those specifically going from average to long sleep duration also had higher WMH burden (ß [SE] 0.29 [0.11], p = 0.007). The opposite associations (lower WMH and FW) were observed in participants consistently sleeping ≥9 hours as compared with people consistently sleeping 7-8 hours in fully adjusted models (ß [SE] -0.43 [0.20], p = 0.028; ß [SE] -0.019 [0.004], p = 0.020). Each hour of increasing sleep (continuous, ß [SE] 0.12 [0.04], p = 0.003; ß [SE] 0.002 [0.001], p = 0.021) and extensive increase in sleep duration (≥2 hours vs 0 ± 1 hour change; ß [SE] 0.24 [0.10], p = 0.019; ß [SE] 0.0081 [0.0025], p = 0.001) over time was associated with higher WMH burden and FW fraction in fully adjusted models. Sleep duration change was not associated with PET amyloid or tau outcomes. DISCUSSION: Longer self-reported sleep duration over time was associated with neuroimaging biomarkers of cerebrovascular pathology as evidenced by higher WMH burden and FW fraction. A longer sleep duration extending over time may be an early change in the neurodegenerative trajectory.

Poor sleep and shift work associate with increased blood pressure and inflammation in UK Biobank participants.

Disrupted circadian rhythms have been linked to an increased risk of hypertension and cardiovascular disease. However, many studies show inconsistent findings and are not sufficiently powered for targeted subgroup analyses. Using the UK Biobank cohort, we evaluate the association between circadian rhythm-disrupting behaviours, blood pressure (SBP, DBP) and inflammatory markers in >350,000 adults with European white British ancestry. The independent U-shaped relationship between sleep length and SBP/DBP is most prominent with a low inflammatory status. Poor sleep quality and permanent night shift work are also positively associated with SBP/DBP. Although fully adjusting for BMI in the linear regression model attenuated effect sizes, these associations remain significant. Two-sample Mendelian Randomisation (MR) analyses support a potential causal effect of long sleep, short sleep, chronotype, daytime napping and sleep duration on SBP/DBP. Thus, in the current study, we present a positive association between circadian rhythm-disrupting behaviours and SBP/DBP regulation in males and females that is largely independent of age.

Sleep regularity and mortality: a prospective analysis in the UK Biobank.

Background: Irregular sleep-wake timing may cause circadian disruption leading to several chronic age-related diseases. We examined the relationship between sleep regularity and risk of all-cause, cardiovascular disease (CVD), and cancer mortality in 88,975 participants from the prospective UK Biobank cohort. Methods: The sleep regularity index (SRI) was calculated as the probability of an individual being in the same state (asleep or awake) at any two time points 24 hr apart, averaged over 7 days of accelerometry (range 0-100, with 100 being perfectly regular). The SRI was related to the risk of mortality in time-to-event models. Results: The mean sample age was 62 years (standard deviation [SD], 8), 56% were women, and the median SRI was 60 (SD, 10). There were 3010 deaths during a mean follow-up of 7.1 years. Following adjustments for demographic and clinical variables, we identified a non-linear relationship between the SRI and all-cause mortality hazard (p [global test of spline term]<0.001). Hazard ratios, relative to the median SRI, were 1.53 (95% confidence interval [CI]: 1.41, 1.66) for participants with SRI at the 5th percentile (SRI = 41) and 0.90 (95% CI: 0.81, 1.00) for those with SRI at the 95th percentile (SRI = 75), respectively. Findings for CVD mortality and cancer mortality followed a similar pattern. Conclusions: Irregular sleep-wake patterns are associated with higher mortality risk. Funding: National Health and Medical Research Council of Australia (GTN2009264; GTN1158384), National Institute on Aging (AG062531), Alzheimer's Association (2018-AARG-591358), and the Banting Fellowship Program (#454104).

Association Between Slow-Wave Sleep Loss and Incident Dementia.

Importance: Slow-wave sleep (SWS) supports the aging brain in many ways, including facilitating the glymphatic clearance of proteins that aggregate in Alzheimer disease. However, the role of SWS in the development of dementia remains equivocal. Objective: To determine whether SWS loss with aging is associated with the risk of incident dementia and examine whether Alzheimer disease genetic risk or hippocampal volumes suggestive of early neurodegeneration were associated with SWS loss. Design, Setting, and Participants: This prospective cohort study included participants in the Framingham Heart Study who completed 2 overnight polysomnography (PSG) studies in the time periods 1995 to 1998 and 2001 to 2003. Additional criteria for individuals in this study sample were an age of 60 years or older and no dementia at the time of the second overnight PSG. Data analysis was performed from January 2020 to August 2023. Exposure: Changes in SWS percentage measured across repeated overnight sleep studies over a mean of 5.2 years apart (range, 4.8-7.1 years). Main Outcome: Risk of incident all-cause dementia adjudicated over 17 years of follow-up from the second PSG. Results: From the 868 Framingham Heart Study participants who returned for a second PSG, this cohort included 346 participants with a mean age of 69 years (range, 60-87 years); 179 (52%) were female. Aging was associated with SWS loss across repeated overnight sleep studies (mean [SD] change, -0.6 [1.5%] per year; P < .001). Over the next 17 years of follow-up, there were 52 cases of incident dementia. In Cox regression models adjusted for age, sex, cohort, positivity for at least 1 APOE ε4 allele, smoking status, sleeping medication use, antidepressant use, and anxiolytic use, each percentage decrease in SWS per year was associated with a 27% increase in the risk of dementia (hazard ratio, 1.27; 95% CI, 1.06-1.54; P = .01). SWS loss with aging was accelerated in the presence of Alzheimer disease genetic risk (ie, APOE ε4 allele) but not hippocampal volumes measured proximal to the first PSG. Conclusions and Relevance: This cohort study found that slow-wave sleep percentage declined with aging and Alzheimer disease genetic risk, with greater reductions associated with the risk of incident dementia. These findings suggest that SWS loss may be a modifiable dementia risk factor.

The association between sleep duration and muscle sympathetic nerve activity.

PURPOSE: Sleep duration is associated with risk of hypertension and cardiovascular diseases. It is thought that shorter sleep increases sympathetic activity. However, most studies are based on acute experimental sleep deprivation that have produced conflicting results. Furthermore, there are limited data available on habitual sleep duration and gold-standard measures of sympathetic activation. Hence, this study aimed to assess the association between habitual sleep duration and muscle sympathetic nerve activity. METHODS: Twenty-four participants aged ≥ 18 years were included in the study. Sleep was assessed using at-home 7-day/night actigraphy (ActiGraph™ GT3X-BT) and sleep questionnaires (Pittsburgh Sleep Quality Index and Epworth Sleepiness Scale). Microelectrode recordings of muscle sympathetic nerve activity were obtained from the common peroneal nerve. Participants were categorised into shorter or longer sleep duration groups using a median split of self-report and actigraphy sleep measures. RESULTS: Compared to longer sleepers, shorter sleepers averaged 99 ± 40 min and 82 ± 40 min less sleep per night as assessed by self-report and objective measures, respectively. There were no differences in age (38 ± 18 vs 39 ± 21 years), sex (5 male, 7 female vs 6 male, 6 female), or body mass index (23 ± 3 vs 22 ± 3 kg/m2) between shorter and longer sleepers. Expressed as burst frequency, muscle sympathetic nerve activity was higher in shorter versus longer sleepers for both self-report (39.4 ± 12.9 vs 28.4 ± 8.5 bursts/min, p = 0.019) and objective (37.9 ± 12.4 vs 28.1 ± 8.8 bursts/min, p = 0.036) sleep duration. CONCLUSIONS: Shorter sleep duration assessed in a home setting was associated with higher muscle sympathetic nerve activity. Sympathetic overactivity may underlie the association between short sleep and hypertension.

The Association Between 24-Hour Blood Pressure Profiles and Dementia.

Midlife hypertension increases risk for dementia. Around one third of adults have diagnosed hypertension; however, many adults are undiagnosed, or remain hypertensive despite diagnosis or treatment. Since blood pressure (BP) follows a circadian rhythm, ambulatory BP monitoring allows for the assessment of BP over a 24-hour period and provides an important tool for improving the diagnosis and management of hypertension. The measurement of 24-hour BP profiles, especially nocturnal BP, demonstrate better predictive ability for cardiovascular disease and mortality than office measurement. However, few studies have examined 24-hour BP profiles with respect to dementia risk. This is an important topic since improvements in BP management could facilitate the primary prevention of vascular cognitive impairment and dementia. Therefore, this review discusses the evidence linking BP to dementia, with a focus on whether the implementation of 24-hour BP measurements can improve risk prediction and prevention strategies. Pathways linking nocturnal BP to dementia are also discussed as are risk reduction strategies. Overall, limited research suggests an association between 24-hour BP elevation and poorer cognition, cerebral small vessel disease, and dementia. However, most studies were cross-sectional. Further evidence is needed to substantiate 24-hour BP profiles, over and above office BP, as predictors of vascular cognitive impairment and incident dementia.

Sleep Architecture, Obstructive Sleep Apnea, and Cognitive Function in Adults.

Importance: Good sleep is essential for health, yet associations between sleep and dementia risk remain incompletely understood. The Sleep and Dementia Consortium was established to study associations between polysomnography (PSG)-derived sleep and the risk of dementia and related cognitive and brain magnetic resonance imaging endophenotypes. Objective: To investigate association of sleep architecture and obstructive sleep apnea (OSA) with cognitive function in the Sleep and Dementia Consortium. Design, Setting, and Participants: The Sleep and Dementia Consortium curated data from 5 population-based cohorts across the US with methodologically consistent, overnight, home-based type II PSG and neuropsychological assessments over 5 years of follow-up: the Atherosclerosis Risk in Communities study, Cardiovascular Health Study, Framingham Heart Study (FHS), Osteoporotic Fractures in Men Study, and Study of Osteoporotic Fractures. Sleep metrics were harmonized centrally and then distributed to participating cohorts for cohort-specific analysis using linear regression; study-level estimates were pooled in random effects meta-analyses. Results were adjusted for demographic variables, the time between PSG and neuropsychological assessment (0-5 years), body mass index, antidepressant use, and sedative use. There were 5946 participants included in the pooled analyses without stroke or dementia. Data were analyzed from March 2020 to June 2023. Exposures: Measures of sleep architecture and OSA derived from in-home PSG. Main Outcomes and Measures: The main outcomes were global cognitive composite z scores derived from principal component analysis, with cognitive domains investigated as secondary outcomes. Higher scores indicated better performance. Results: Across cohorts, 5946 adults (1875 females [31.5%]; mean age range, 58-89 years) were included. The median (IQR) wake after sleep onset time ranged from 44 (27-73) to 101 (66-147) minutes, and the prevalence of moderate to severe OSA ranged from 16.9% to 28.9%. Across cohorts, higher sleep maintenance efficiency (pooled ß per 1% increase, 0.08; 95% CI, 0.03 to 0.14; P < .01) and lower wake after sleep onset (pooled ß per 1-min increase, -0.07; 95% CI, -0.13 to -0.01 per 1-min increase; P = .02) were associated with better global cognition. Mild to severe OSA (apnea-hypopnea index [AHI] ≥5) was associated with poorer global cognition (pooled ß, -0.06; 95% CI, -0.11 to -0.01; P = .01) vs AHI less than 5; comparable results were found for moderate to severe OSA (pooled ß, -0.06; 95% CI, -0.11 to -0.01; P = .02) vs AHI less than 5. Differences in sleep stages were not associated with cognition. Conclusions and Relevance: This study found that better sleep consolidation and the absence of OSA were associated with better global cognition over 5 years of follow-up. These findings suggest that the role of interventions to improve sleep for maintaining cognitive function requires investigation.

Sleep Regularity and Mortality: A Prospective Analysis in the UK Biobank.

Background: Irregular sleep-wake timing may cause circadian disruption leading to several chronic age-related diseases. We examined the relationship between sleep regularity and risk of all-cause, cardiovascular disease (CVD), and cancer mortality in 88,975 participants from the prospective UK Biobank cohort. Methods: The sleep regularity index (SRI) was calculated as the probability of an individual being in the same state (asleep or awake) at any two time points 24 hours apart, averaged over 7-days of accelerometry (range 0-100, with 100 being perfectly regular). The SRI was related to the risk of mortality in time-to-event models. Findings: The mean sample age was 62 years (SD, 8), 56% were women, and the median SRI was 60 (SD, 10). There were 3010 deaths during a mean follow-up of 7.1 years. Following adjustments for demographic and clinical variables, we identified a non-linear relationship between the SRI and all-cause mortality hazard (p [global test of spline term] < 0·001). Hazard Ratios, relative to the median SRI, were 1·53 (95% confidence interval [CI]: 1·41, 1·66) for participants with SRI at the 5th percentile (SRI = 41) and 0·90 (95% CI: 0·81, 1·00) for those with SRI at the 95th percentile (SRI = 75), respectively. Findings for CVD mortality and cancer mortality followed a similar pattern. Conclusions: Irregular sleep-wake patterns are associated with higher mortality risk. Funding: National Health and Medical Research Council of Australia (GTN2009264; GTN1158384), National Institute on Aging (AG062531), Alzheimer's Association (2018-AARG-591358), and the Banting Fellowship Program (#454104).

Insomnia Symptoms and Biomarkers of Alzheimer's Disease in the Community.

BACKGROUND: Insomnia is one of the most common sleep disorders yet its relationship to the biology of Alzheimer's disease remains equivocal. OBJECTIVE: We investigated the cross-sectional relationship between insomnia symptom severity and cerebrospinal fluid (CSF) concentrations of Alzheimer's disease biomarkers in a cognitively unimpaired middle-aged community sample. METHODS: A total of 63 participants from the Healthy Brain Project (age = 59±7 years; 67% women) completed a lumbar puncture and two weeks of actigraphy to measure two of insomnia's core features: difficulty initiating sleep (prolonged sleep onset latency) and difficulty maintaining sleep (wake after sleep onset [WASO] and number of awakenings). Additionally, the Insomnia Severity Index (ISI) was completed by 58 participants. Linear and Tobit regression were used to estimate the associations between each insomnia variable and CSF Aß42, phosphorylated tau 181 (p-tau181), total-tau, and neurofilament light chain protein (NfL), adjusting for age, sex, and APOEɛ4 genotype. RESULTS: Higher ISI score was associated with greater average levels of CSF Aß42 (per point: 30.7 pg/mL, 95% CI: 4.17-57.3, p = 0.023), as was higher WASO (per 10 min: 136 pg/mL, 95% CI: 48-223, p = 0.002) and more awakenings (per 5:123 pg/mL, 95% CI = 55-192, p < 0.001). Difficulty initiating sleep was not associated with CSF Aß42, nor were insomnia features associated with p-tau181, total-tau, or NfL levels. CONCLUSION: Insomnia symptoms were associated with higher CSF Aß42 levels in this relatively young, cognitively unimpaired sample. These findings may reflect increased amyloid production due to acute sleep disruption.

The treatment of sleep dysfunction to improve cognitive function: A meta-analysis of randomized controlled trials.

OBJECTIVE: This meta-analysis of randomized controlled trials (RCTs) evaluates if treating sleep disturbances improves cognitive function over at least 12 weeks. METHODS: Multiple data sources were searched until November 1, 2021. RCTs were included if they examined the effect of an intervention (behavioral or medical) on sleep and cognition in an adult sample with sleep disturbances and had an intervention duration and follow-up of at least 12 weeks. Two independent reviewers located 3784 studies; 16 satisfied the inclusion criteria. Primary outcomes included the broad cognitive domains of visual processing, short-term memory, long-term storage and retrieval, processing speed, and reaction time. RESULTS: Most trials were conducted in participants with obstructive sleep apnea (OSA; N = 13); the most studied intervention was continuous positive airway pressure (CPAP; N = 10). All RCTs were 12 months in duration or less. The estimates of mean pooled effects were not indicative of significant treatment effect for any primary outcome. Although the interventions reduced daytime sleepiness (Hedge's g, 0.51; 95% confidence interval, 0.29-0.74; p < 0.01), this did not lead to cognitive enhancement. CONCLUSIONS: Overall, there was insufficient evidence to suggest that treating sleep dysfunction can improve cognition. Further studies with longer follow-up duration and supporting biomarkers are needed.

Long term all-cause and cardiovascular disease mortality among women who undergo fertility treatment.

OBJECTIVES: To compare age-adjusted all-cause and CVD mortality, relative to the general female population, for women registered for fertility treatment who received it and those who did not. DESIGN: Prospective cohort study; analysis of Monash IVF clinical registries data, 1975-2018, linked with National Death Index mortality data. PARTICIPANTS: All women who registered for fertility treatment at Monash IVF (Melbourne, Victoria), 1 January 1975 - 1 January 2014, followed until 31 December 2018. MAIN OUTCOME MEASURES: Standardised mortality ratios (SMRs) for all-cause and CVD mortality, for women who did or did not undergo fertility treatment; SMRs stratified by area-level socio-economic disadvantage (SEIFA Index of Relative Socioeconomic Disadvantage [IRSD]) and (for women who underwent treatment), by stimulated cycle number and mean oocytes/cycle categories. RESULTS: Of 44 149 women registered for fertility treatment, 33 520 underwent treatment (66.4%), 10 629 did not. After adjustment for age, both all-cause (SMR, 0.58; 95% CI, 0.54-0.62) and CVD mortality (SMR, 0.41; 95% CI, 0.32-0.53) were lower than for the general female population. All-cause mortality was similar for women registered with Monash IVF who did (SMR, 0.55; 95% CI, 0.50-0.60) or did not undergo fertility treatment (SMR, 0.63; 95% CI, 0.56-0.70). The SMR was lowest for both treated and untreated women in the fifth IRSD quintile (least disadvantage), but the difference was statistically significant only for untreated women. CVD mortality was lower for registered women who underwent fertility treatment (SMR, 0.29; 95% CI, 0.19-0.43) than for those who did not (SMR, 0.58; 95% CI, 0.42-0.81). CONCLUSION: Fertility treatment does not increase long term all-cause or CVD mortality risk. Lower mortality among women registered for fertility treatment probably reflected their lower socio-economic disadvantage.

Association Between the Gut Microbiome and Their Metabolites With Human Blood Pressure Variability.

BACKGROUND: Blood pressure (BP) variability is an independent risk factor for cardiovascular events. Recent evidence supports a role for the gut microbiota in BP regulation. However, whether the gut microbiome is associated with BP variability is yet to be determined. Here, we aimed to investigate the interplay between the gut microbiome and their metabolites in relation to BP variability. METHODS: Ambulatory BP monitoring was performed in 69 participants from Australia (55.1% women; mean±SD, 59.8±7.26 years; body mass index, 25.2±2.83 kg/m2). These data were used to determine nighttime dipping, morning BP surge (MBPS) and BP variability as SD. The gut microbiome was determined by 16S ribosomal RNA (rRNA) sequencing and metabolite levels by gas chromatography. RESULTS: We identified specific taxa associated with systolic BP variability, nighttime dipping, and MBPS. Notably, Alistipesfinegoldii and Lactobacillus spp. were only present in participants within the normal ranges of BP variability, MBPS and dipping, while Prevotella spp. and Clostridium spp., were found to be present in extreme dippers and the highest quartiles of BP SD and MBPS. There was a negative association between MBPS and microbial α-diversity (r=-0.244, P=0.046). MBPS was also negatively associated with plasma levels of microbial metabolites called short-chain fatty acids (r=-0.305, P=0.020), particularly acetate (r=-0.311, P=0.017). CONCLUSIONS: Gut microbiome diversity, levels of microbial metabolites, and the bacteria Alistipesfinegoldii and Lactobacillus were associated with lower BP variability and Clostridium and Prevotella with higher BP variability. Thus, our findings suggest the gut microbiome and metabolites may be involved in the regulation of BP variability.

Sleep health and its implications in First Nation Australians: A systematic review.

Understanding the state of sleep health in First Nations Australians offers timely insight into intervention and management opportunities to improve overall health and well-being. This review explored the determinants and burden of poor sleep in First Nations Australians. A systematic search was conducted to identify studies published until August 2020 in First Nations Australian adults. Nine studies (n = 2640) were included, three in community settings, six in clinical populations. Across studies compared with non-Indigenous people, 15-34% of First Nations Australians experience less than recommended hours (<7 h/night), 22% reported fragmented, irregular, and unrefreshing sleep with a high prevalence of OSA in clinical populations (39-46%). Findings show First Nations Australians are significantly more likely to report worse sleep health than Non-Indigenous Australians in all measured domains of sleep. Co-designed sleep programs and service delivery solutions are necessary to ensure timely prevention and management of sleep issues in First Nations communities which to date have been underserved. FUNDING: No external funding was provided for this work.

Imaging-guided evaluation of subclinical atherosclerosis to enhance cardiovascular risk prediction in asymptomatic low-to-intermediate risk individuals: A systematic review.

Carotid intima-media thickness (cIMT), plaque quantification and coronary artery calcium (CAC) scoring have been suggested to improve risk prediction of cardiovascular disease (CVD), particularly for asymptomatic individuals classified as low-to-intermediate risk. We aimed to compare the predictive value of cIMT, carotid plaque identification, and CAC scoring for identifying sub-clinical atherosclerosis and assessing future risk of CVD in asymptomatic, low-to-intermediate risk individuals. We conducted a comprehensive search of Ovid (Embase and Medline), Cochrane Central Register of Controlled Trials (CENTRAL) and Medline complete (EBSCO health). A total of 30 papers were selected and data were extracted. Comparisons were made according to the cIMT measurement (mean, maximum), carotid plaque evaluation (presence or area), and CAC scoring. CVD event rates, hazard ratios (HR), net reclassification index (NRI), and c-statistic of the markers were compared. There were 27 studies that reported cIMT, 24 reported carotid plaque, and 6 reported CAC scoring. Inclusion of CAC scores yielded the highest HR ranging from 1.45 (95% CI, 1.11-1.88, p = 0.006) to 3.95 (95% CI, 2.97-5.27, p < 0.001), followed by maximum cIMT (HR 1.08; 95% CI, 1.06-1.11, p < 0.001 to 2.58; 95% CI, 1.83-3.62, p < 0.001) and carotid plaque presence (HR 1.21; 95% CI, 0.5-1.2, p = 0.39 to 2.43; 95% CI, 1.7-3.47, p < 0.001). The c-statistic enhanced predictive value by a minimum increase of 0.7. Finally, the NRI ranked higher with CAC (≥11.2%), followed by carotid plaque (≥2%) and cIMT (3%). CAC scoring was superior compared to carotid plaque and cIMT measurements in asymptomatic individuals classified as being at low-to-intermediate risk.

The Gut Microbiota and Their Metabolites in Human Arterial Stiffness.

AIM: Gut microbiota-derived metabolites, such as short-chain fatty acids (SCFAs) have vasodilator properties in animal and human ex vivo arteries. However, the role of the gut microbiota and SCFAs in arterial stiffness in humans is still unclear. Here we aimed to determine associations between the gut microbiome, SCFA and their G-protein coupled sensing receptors (GPCRs) in relation to human arterial stiffness. METHODS: Ambulatory arterial stiffness index (AASI) was determined from ambulatory blood pressure (BP) monitoring in 69 participants from regional and metropolitan regions in Australia (55.1% women; mean, 59.8± SD, 7.26 years of age). The gut microbiome was determined by 16S rRNA sequencing, SCFA levels by gas chromatography, and GPCR expression in circulating immune cells by real-time PCR. RESULTS: There was no association between metrics of bacterial α and ß diversity and AASI or AASI quartiles in men and women. We identified two main bacteria taxa that were associated with AASI quartiles: Lactobacillus spp. was only present in the lowest quartile, while Clostridium spp. was present in all quartiles but the lowest. AASI was positively associated with higher levels of plasma, but not faecal, butyrate. Finally, we identified that the expression of GPR43 (FFAR2) and GPR41 (FFAR3) in circulating immune cells were negatively associated with AASI. CONCLUSIONS: Our results suggest that arterial stiffness is associated with lower levels of the metabolite-sensing receptors GPR41/GPR43 in humans, blunting its response to BP-lowering metabolites such as butyrate. The role of Lactobacillus spp. and Clostridium spp., as well as butyrate-sensing receptors GPR41/GPR43, in human arterial stiffness needs to be determined.

Essential Hypertension Is Associated With Changes in Gut Microbial Metabolic Pathways: A Multisite Analysis of Ambulatory Blood Pressure.

[Figure: see text].