Central stress pathways in the development of cardiovascular disease.

PURPOSE: Mental stress is of essential consideration when assessing cardiovascular pathophysiology in all patient populations. Substantial evidence indicates associations among stress, cardiovascular disease and aberrant brain-body communication. However, our understanding of the flow of stress information in humans, is limited, despite the crucial insights this area may offer into future therapeutic targets for clinical intervention. METHODS: Key terms including mental stress, cardiovascular disease and central control, were searched in PubMed, ScienceDirect and Scopus databases. Articles indicative of heart rate and blood pressure regulation, or central control of cardiovascular disease through direct neural innervation of the cardiac, splanchnic and vascular regions were included. Focus on human neuroimaging research and the flow of stress information is described, before brain-body connectivity, via pre-motor brainstem intermediates is discussed. Lastly, we review current understandings of pathophysiological stress and cardiovascular disease aetiology. RESULTS: Structural and functional changes to corticolimbic circuitry encode stress information, integrated by the hypothalamus and amygdala. Pre-autonomic brain-body relays to brainstem and spinal cord nuclei establish dysautonomia and lead to alterations in baroreflex functioning, firing of the sympathetic fibres, cellular reuptake of norepinephrine and withdrawal of the parasympathetic reflex. The combined result is profoundly adrenergic and increases the likelihood of cardiac myopathy, arrhythmogenesis, coronary ischaemia, hypertension and the overall risk of future sudden stress-induced heart failure. CONCLUSIONS: There is undeniable support that mental stress contributes to the development of cardiovascular disease. The emerging accumulation of large-scale multimodal neuroimaging data analytics to assess this relationship promises exciting novel therapeutic targets for future cardiovascular disease detection and prevention.

Central mechanisms in sympathetic nervous dysregulation in obesity.

Cardiovascular and metabolic complications associated with excess adiposity are linked to chronic activation of the sympathetic nervous system, resulting in a high risk of mortality among obese individuals. Obesity-related positive energy balance underlies the progression of hypertension, end-organ damage, and insulin resistance, driven by increased sympathetic tone throughout the body. It is, therefore, important to understand the central network that drives and maintains sustained activation of the sympathetic nervous system in the obese state. Experimental and clinical studies have identified structural changes and altered dynamics in both grey and white matter regions in obesity. Aberrant activation in certain brain regions has been associated with altered reward circuitry and metabolic pathways including leptin and insulin signaling along with adiposity-driven systemic and central inflammation. The impact of these pathways on the brain via overactivity of the sympathetic nervous system has gained interest in the past decade. Primarily, the brainstem, hypothalamus, amygdala, hippocampus, and cortical structures including the insular, orbitofrontal, temporal, cingulate, and prefrontal cortices have been identified in this context. Although the central network involving these structures is much more intricate, this review highlights recent evidence identifying these regions in sympathetic overactivity in obesity.

Mental health and quality of life during weight loss in females with clinically severe obesity: a randomized clinical trial.

The purpose of this investigation was to explore the effects of dietary weight loss intervention, with and without the addition of exercise on health-related quality of life, depressive symptoms, and anxiety. As part of the EMPOWER study for women, sixty premenopausal women (BMI of 40.4 ± 6.7) were randomized to energy restriction only (ER) or to exercise plus energy restriction (EXER) for 12 months. Health-related quality of life was assessed using the SF-36, depressive symptoms were assessed using the Beck Depression Inventory II (BDI), and anxiety symptoms using the Spielberger state and trait anxiety questionnaire. All measures were completed at baseline, 3, 6 and 12 months. At 12 months, there were significant (p < 0.05) group-by-time interactions favouring the EXER group for five of the eight domains and the mental component summary score. At 12 months, a significant group-by-time interaction favouring the EXER group is reported for both state and trait anxiety (p = .005 and p = .001, respectively). At 12 months, there was a significant group-by-time interaction for depressive symptoms favouring EXER (p < 0.05). Within-group changes for BDI scores were improved at all follow-up time points in the EXER group. Exercise training confers an additional benefit to energy restriction in the absence of additional weight loss at 12 months for health-related quality of life, depressive symptoms, and state and trait anxiety scores when compared to energy restriction only. Exercise and an energy-restricted diet improve health-related quality of life and mental health. Exercise may protect mental health without further weight loss for women with severe obesity.

Autonomic nervous system function in women with anorexia nervosa.

PURPOSE: Abnormalities in autonomic function have been observed in people with anorexia nervosa. However, the majority of investigations have utilised heart rate variability as the sole assessment of autonomic activity. The current study utilised a variety of methodologies to assess autonomic nervous system function in women with a current diagnosis of anorexia, a past diagnosis of anorexia who were weight-restored, and healthy controls. METHODS: The sample included 37 participants: 10 participants with anorexia, 17 weight-restored participants (minimum body mass index > 18.5 for minimum of 12 months) and 10 controls. Assessments of autonomic function included muscle sympathetic nerve activity (MSNA) using microneurography, heart rate variability, baroreflex sensitivity, blood pressure variability, head-up tilt table test, sudomotor function and assessment of plasma catecholamines. RESULTS: MSNA (bursts/min) was significantly decreased in both anorexia (10.22 ± 6.24) and weight-restored (17.58 ± 1.68) groups, as compared to controls (23.62 ± 1.01, p < 0.001 and p = 0.033, respectively). Participants with anorexia had a significantly lower standard deviation in heart rate, lower blood pressure variability and decreased sudomotor function as compared to controls. Weight-restored participants demonstrated decreased baroreflex sensitivity in response to head-up tilt as compared to controls. CONCLUSION: Women with a current or previous diagnosis of anorexia have significantly decreased sympathetic activity, which may reflect a physiological response to decreased energy intake. During the state of starvation, women with anorexia also displayed decreased sudomotor function. The consequences of a sustained decrease in MSNA are unknown, and future studies should investigate autonomic function in long-term weight-restored participants to determine whether activity returns to normal.

Poorer Self-Reported Physical Health and Higher Anxiety Trait in Young Adults With Previous Coarctation Repair.

BACKGROUND: Little is known about the impact of a coarctation repair on the functional outcomes of young adults. This study aimed to determine (1) the functional and mental health status in young adults with previous coarctation repair, and (2) the impact of late hypertension on their quality of life. METHODS: A cross-sectional study using validated self-reported questionnaires (Short Form 36 version 2 [SF-36v2], Beck Depression Inventory [BDI], and State-Trait Anxiety Inventory [STAI]) was performed in 54 patients aged 15-47 years with previous paediatric coarctation repair. Questionnaire scores were compared to healthy age- and gender-matched controls. Patients' previously published 24-hour blood pressure monitoring results were included. RESULTS: Late hypertension was present in 64% (34/54) at a mean of 29±8 years after coarctation repair. SF-36v2 mean physical component summary score was significantly lower in coarctation patients compared with controls (53.1±6.8 vs 56.0±4.7, p=0.02), but there was no significant difference in mean mental component summary score (p=0.2). SF-36v2 mean role emotional score tended to be associated with 10 mmHg increases in mean 24-hour systolic blood pressure (regression coefficient 4.3 p=0.06). STAI mean trait anxiety score tended to be higher in coarctation patients compared with controls (36.6±9.0 vs 33.5±7.8, p=0.06). There was no significant difference in BDI scores between patients and controls. CONCLUSIONS: Young adults with previous coarctation repair report poorer physical health and tended towards higher anxiety trait compared to healthy controls. Strategies to improve self-reported physical health and anxiety should be explored. Long-term assessment of quality of life outcomes in coarctation patients is warranted.

Characteristics and physiological basis of falls in ventricular outputs after immediate cord clamping at delivery in preterm fetal lambs.

KEY POINTS: Controversy exists about the physiological mechanism(s) underlying decreases in cardiac output after immediate clamping of the umbilical cord at birth. To define these mechanisms, the four major determinants of ventricular output (afterload, preload, heart rate and contractility) were measured concurrently in fetal lambs at 15 s intervals over a 2 min period after cord clamping and before ventilation following delivery. After cord clamping, right (but not left) ventricular output fell by 20% in the initial 30 s, due to increased afterload associated with higher arterial blood pressures, but both outputs then halved over 45 s, due to a falling heart rate and deteriorating ventricular contractility accompanying rapid declines in arterial oxygenation to asphyxial levels. Ventricular outputs subsequently plateaued from 75 to 120 s, associated with rebound rises in ventricular contractility accompanying asphyxia-induced surges in circulating catecholamines. These findings provide a physiological basis for the clinical recommendation that effective ventilation should occur within 60 s after immediate cord clamping. ABSTRACT: Controversy exists about the physiological mechanism(s) underlying large decreases in cardiac output after immediate clamping of the umbilical cord at birth. To define these mechanisms, anaesthetized preterm fetal lambs (127(1)d, n = 12) were instrumented with flow probes and catheters in major central arteries, and a left ventricular (LV) micromanometer-conductance catheter. Following immediate cord clamping at delivery, haemodynamics, LV and right ventricular (RV) outputs, and LV contractility were measured at 15 s intervals during a 2 min non-ventilatory period, with aortic blood gases and circulating catecholamine (noradrenaline and adrenaline) concentrations measured at 30 s intervals. After cord clamping, (1) RV (but not LV) output fell by 20% in the initial 30 s, due to a reduced stroke volume associated with increased arterial blood pressures, (2) both outputs then halved over the next 45 s, associated with falls in heart rate, arterial blood pressures and ventricular contractility accompanying a rapid decline in arterial oxygenation to asphyxial levels, (3) reduced outputs subsequently plateaued from 75 to 120 s, associated with rebound rises in blood pressures and ventricular contractility accompanying exponential surges in circulating catecholamines. These findings are consistent with a time-dependent decline of ventricular outputs after immediate cord clamping, which comprised (1) an initial, minor fall in RV output related to altered loading conditions, (2) ensuing large decreases in both LV and RV outputs related to the combination of bradycardia and ventricular dysfunction during emergence of an asphyxial state, and (3) subsequent stabilization of reduced LV and RV outputs during ongoing asphyxia, supported by cardiovascular stimulatory effects of marked sympathoadrenal activation.

Deficiency of Prebiotic Fiber and Insufficient Signaling Through Gut Metabolite-Sensing Receptors Leads to Cardiovascular Disease.

BACKGROUND: High blood pressure (BP) continues to be a major, poorly controlled but modifiable risk factor for cardiovascular death. Among key Western lifestyle factors, a diet poor in fiber is associated with prevalence of high BP. The impact of lack of prebiotic fiber and the associated mechanisms that lead to higher BP are unknown. Here we show that lack of prebiotic dietary fiber leads to the development of a hypertensinogenic gut microbiota, hypertension and its complications, and demonstrate a role for G-protein coupled-receptors (GPCRs) that sense gut metabolites. METHODS: One hundred seventy-nine mice including C57BL/6J, gnotobiotic C57BL/6J, and knockout strains for GPR41, GPR43, GPR109A, and GPR43/109A were included. C57BL/6J mice were implanted with minipumps containing saline or a slow-pressor dose of angiotensin II (0.25 mg·kg-1·d-1). Mice were fed diets lacking prebiotic fiber with or without addition of gut metabolites called short-chain fatty acids ([SCFA)] produced during fermentation of prebiotic fiber in the large intestine), or high prebiotic fiber diets. Cardiac histology and function, BP, sodium and potassium excretion, gut microbiome, flow cytometry, catecholamines and methylation-wide changes were determined. RESULTS: Lack of prebiotic fiber predisposed mice to hypertension in the presence of a mild hypertensive stimulus, with resultant pathological cardiac remodeling. Transfer of a hypertensinogenic microbiota to gnotobiotic mice recapitulated the prebiotic-deprived hypertensive phenotype, including cardiac manifestations. Reintroduction of SCFAs to fiber-depleted mice had protective effects on the development of hypertension, cardiac hypertrophy, and fibrosis. The cardioprotective effect of SCFAs were mediated via the cognate SCFA receptors GPR43/GPR109A, and modulated L-3,4-dihydroxyphenylalanine levels and the abundance of T regulatory cells regulated by DNA methylation. CONCLUSIONS: The detrimental effects of low fiber Westernized diets may underlie hypertension, through deficient SCFA production and GPR43/109A signaling. Maintaining a healthy, SCFA-producing microbiota is important for cardiovascular health.

Does autonomic nervous system dysfunction influence cardiovascular disease risk in young adults with intellectual disability?

People with intellectual disability (ID) experience cardiometabolic-related morbidity and mortality. However, it has been suggested that this population presents and lives with underestimated cardiovascular risk factors at a younger age, hence affecting their overall health and quality of life and contributing to early mortality. We assessed autonomic nervous system function in subjects with ID (n = 39), aged 18-45 yr, through measures of sudomotor function, heart rate and systolic blood pressure variability, and cardiac baroreflex function. Traditional clinical cardiovascular measurements and a biochemical analysis were also undertaken. We found that young adults with ID presented with sudomotor dysfunction, impaired cardiac baroreflex sensitivity, and systolic blood pressure variability, when compared with age-matched control subjects (n = 38). Reduced hand and feet electrochemical skin conductance and asymmetry were significantly associated with having a moderate-profound ID. Autonomic dysfunction in individuals with ID persisted after controlling for age, sex, and other metabolic parameters. Subjects in the ID group also showed significantly increased blood pressure, body mass index, and waist/hip circumference ratio, as well as increased plasma hemoglobin A1c and high-sensitivity C-reactive protein levels. We conclude that autonomic dysfunction is present in young adults with ID and is more marked in those with more severe disability. These finding have important implications in developing preventative strategies to reduce the risk of cardiovascular disease in people with ID.NEW & NOTEWORTHY Adults with intellectual disability experience higher risk of premature death than the general population. Our investigation highlights increased cardiovascular risk markers and autonomic dysfunction in young adults with intellectual disability compared with control adults. Autonomic dysfunction was more marked in those with a more severe disability but independent of cardiovascular parameters. Assessment of autonomic nervous system (ANS) function may provide insight into the mechanisms of cardiometabolic disease development and progression in young adults with intellectual disability.

Factors associated with antihypertensive medication use and blood pressure control in a rural area in Bangladesh: baseline data from a cluster randomised control trial.

BACKGROUND: The use of antihypertensive medications is critical for controlling high blood pressure. We aimed to investigate associations between socio-demographic factors and antihypertensive medications use, and antihypertensive medications use with different types of drugs use with levels of systolic blood pressure (SBP) and diastolic blood pressure (DBP). METHODS: For the present report we derived data from the baseline measurements of a cluster randomised control trial on 307 participants with previously diagnosed hypertension from the rural district of Narial in Bangladesh. We measured the participant's current blood pressure levels and recorded antihypertensive medications uses. Associated factors included socio-economic status, diabetes, antihypertensive medications use, and types of drugs and doses used for controlling blood pressure. We applied analysis of variance and logistic regression techniques to identify factors associated with blood pressure. RESULTS: Of the total participants, 144 (46.9%) were on antihypertensive medications. After multivariate adjustment, binary logistic regression revealed that employees (odds ratio, (95% confidence interval (CI)) (OR 3.58, 95%CI 1.38-9.28) compared to farmers, and people with diabetes (OR 2.43, 95%CI 1.13-5.26) compared to people without diabetes were associated with a higher proportion of antihypertensive medications use. Of 144 participants on antihypertensive medications, 7 (5%) had taken two doses, 114 (79%) had taken one dose per day and the rest were irregular in medication use. The mean (standard deviation) [min, max] SBP and DBP were 149 (19) mmHg [114, 217] and 90 (10) mmHg [75, 126], respectively. Overall, there was no significant difference in SBP (p = 0.10) or DBP (p = 0.67) between participants with or without antihypertensive medications or using any type of medications (p = 0.54 for SBP and 0.76 for DBP). There was no significant association between antihypertensive medications use and elevated BP levels SBP/DBP≥140/90 mmHg (p = 0.42) CONCLUSION: Less than half of the people with hypertension were on medication. Irrespective of the antihypertensive medications use, most of the participant's blood pressure was high. Further study is needed with a large sample to understand the factors and aetiology of unmanaged hypertension in rural areas of Bangladesh where the prevalence of hypertension is very high.

Understanding the sociodemographic factors associated with intention to receive SMS messages for health information in a rural area of Bangladesh.

BACKGROUND: The use of digital interventions for managing chronic diseases is significantly increasing. The aim of this study was to estimate the proportion of ownership of a mobile phone, and factors associated with the ability to read and access SMS delivered health information, and willingness to pay for it among people with hypertension in a rural area in Bangladesh. METHODS: Data were collected from 307 participants aged 30 to 75 years with hypertension from a rural area in Bangladesh from December 2020 to January 2021. Outcome measures included ownership of a mobile phone, ability to read SMS, willingness to receive and pay for health information by SMS. Associated factors included age, gender, level of education, occupation, and socioeconomic status. We used regression analysis to identify variables associated with the outcome variables. RESULTS: Overall, 189 (61.6%) people owned a mobile phone which was higher in men (73.3% vs. 50%, p < 0.001), younger people (82.6% aged 30-39 years vs. 53.5% aged 60-75 years, p < 0.001). Of the total participants, 207 (67.4%) were willing to receive SMS, and 155 (50.5%) were willing to pay for receiving SMS for health information. The prevalence was significantly higher among professionals (odds ratio (OR), 95% confidence interval (CI): 4.58, 1.73-12.1) and businesspersons (OR 3.68, 95% CI 1.49-9.10) compared to farmers, respectively. The median (interquartile range [IQR]) of willingness to pay for health information SMS was 10 (28) Bangladesh Taka (BDT) (1 BDT ~ 0.013 US$), and there were no specific factors that were associated with the willingness of any higher amounts of payment. In terms of reading SMS of people who own a mobile, less than half could read SMS. The proportion of people who could read SMS was significantly higher among men, younger people, educated people, middle class or rich people, professionals or businesspersons. Of people who could read SMS, the majority read SMS occasionally. CONCLUSION: A significant proportion of people are unable to read SMS. However, people are willing to receive and pay to receive SMS for health information. Education and awareness programs should be conducted among targeted groups, including people with low education and women.

Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD)-A Condition Associated with Heightened Sympathetic Activation.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is the most common liver disease affecting a quarter of the global population and is often associated with adverse health outcomes. The increasing prevalence of MAFLD occurs in parallel to that of metabolic syndrome (MetS), which in fact plays a major role in driving the perturbations of cardiometabolic homeostasis. However, the mechanisms underpinning the pathogenesis of MAFLD are incompletely understood. Compelling evidence from animal and human studies suggest that heightened activation of the sympathetic nervous system is a key contributor to the development of MAFLD. Indeed, common treatment strategies for metabolic diseases such as diet and exercise to induce weight loss have been shown to exert their beneficial effects at least in part through the associated sympathetic inhibition. Furthermore, pharmacological and device-based approaches to reduce sympathetic activation have been demonstrated to improve the metabolic alterations frequently present in patients with obesity, MetSand diabetes. Currently available evidence, while still limited, suggests that sympathetic activation is of specific relevance in the pathogenesis of MAFLD and consequentially may offer an attractive therapeutic target to attenuate the adverse outcomes associated with MAFLD.

Empagliflozin modulates renal sympathetic and heart rate baroreflexes in a rabbit model of diabetes.

AIMS/HYPOTHESIS: We determined whether empagliflozin altered renal sympathetic nerve activity (RSNA) and baroreflexes in a diabetes model in conscious rabbits. METHODS: Diabetes was induced by alloxan, and RSNA, mean arterial pressure (MAP) and heart rate were measured before and after 1 week of treatment with empagliflozin, insulin, the diuretic acetazolamide or the ACE inhibitor perindopril, or no treatment, in conscious rabbits. RESULTS: Four weeks after alloxan administration, blood glucose was threefold and MAP 9% higher than non-diabetic controls (p < 0.05). One week of treatment with empagliflozin produced a stable fall in blood glucose (-43%) and increased water intake (+49%) but did not change RSNA, MAP or heart rate compared with untreated diabetic rabbits. The maximum RSNA to hypotension was augmented by 75% (p < 0.01) in diabetic rabbits but the heart rate baroreflex was unaltered. Empagliflozin and acetazolamide reduced the augmentation of the RSNA baroreflex (p < 0.05) to be similar to the non-diabetic group. Noradrenaline (norepinephrine) spillover was similar in untreated diabetic and non-diabetic rabbits but twofold greater in empagliflozin- and acetazolamide-treated rabbits (p < 0.05). CONCLUSIONS/INTERPRETATION: As empagliflozin can restore diabetes-induced augmented sympathetic reflexes, this may be beneficial in diabetic patients. A similar action of the diuretic acetazolamide suggests that the mechanism may involve increased sodium and water excretion. Graphical abstract.

Differential sympathetic response to lesion-induced chronic kidney disease in rabbits.

Chronic kidney disease (CKD) is associated with greater sympathetic nerve activity but it is unclear if this is a kidney-specific response or due to generalized stimulation of sympathetic nervous system activity. To determine this, we used a rabbit model of CKD in which quantitative comparisons with control rabbits could be made of kidney sympathetic nerve activity and whole-body norepinephrine spillover. Rabbits either had surgery to lesion 5/6th of the cortex of one kidney by electro-lesioning and two weeks later removal of the contralateral kidney, or sham lesioning and sham nephrectomy. After three weeks, the blood pressure was statistically significantly 20% higher in conscious rabbits with CKD compared to rabbits with a sham operation, but their heart rate was similar. Strikingly, kidney nerve activity was 37% greater than in controls, with greater burst height and frequency. Total norepinephrine spillover was statistically significantly lower by 34%, and kidney baroreflex curves were shifted to the right in rabbits with CKD. Plasma creatinine and urine output were elevated by 38% and 131%, respectively, and the glomerular filtration rate was 37% lower than in sham-operated animals (all statistically significant). Kidney gene expression of fibronectin, transforming growth factor-ß, monocyte chemotactic protein1, Nox4 and Nox5 was two- to eight-fold greater in rabbits with CKD than in control rabbits. Overall, the glomerular layer lesioning model in conscious rabbits produced a moderate, stable degree of CKD characterized by elevated blood pressure and increased kidney sympathetic nerve activity. Thus, our findings, together with that of a reduction in total norepinephrine spillover, suggest that kidney denervation, rather than generalized sympatholytic treatments, may represent a preferable management for CKD associated hypertension.

Sedentary Behavior and Public Health: Integrating the Evidence and Identifying Potential Solutions.

In developed and developing countries, social, economic, and environmental transitions have led to physical inactivity and large amounts of time spent sitting. Research is now unraveling the adverse public health consequences of too much sitting. We describe improvements in device-based measurement that are providing new insights into sedentary behavior and health. We consider the implications of research linking evidence from epidemiology and behavioral science with mechanistic insights into the underlying biology of sitting time. Such evidence has led to new sedentary behavior guidelines and initiatives. We highlight ways that this emerging knowledge base can inform public health strategy: First, we consider epidemiologic and experimental evidence on the health consequences of sedentary behavior; second, we describe solutions-focused research from initiatives in workplaces and schools. To inform a broad public health strategy, researchers need to pursue evidence-informed collaborations with occupational health, education, and other sectors.

Does moxonidine reduce Achilles tendon or musculoskeletal pain in women with polycystic ovarian syndrome? A secondary analysis of a randomised controlled trial.

BACKGROUND: Sympathetic activity and insulin resistance have recently been linked with chronic tendon and musculoskeletal pain. Polycystic ovarian syndrome is linked with insulin resistance and increased sympathetic drive and was therefore an appropriate condition to study the effects of modulating sympathetic activity on Achilles tendon and musculoskeletal symptoms. METHODS: A secondary analysis of a double-blinded, randomised controlled trial on women with polycystic ovarian syndrome was conducted. Participants received 12 weeks of moxonidine (n = 14) or placebo (n = 18). Musculoskeletal symptom and Victorian Institute of Sport Assessment - Achilles (VISA-A) questionnaires were distributed, and ultrasound tissue characterisation quantified tendon structure at 0 and 12 weeks. 2-way ANOVA was used for multiple comparisons. RESULTS: There was no difference in mean change in musculoskeletal symptoms (- 0.6 ± 1.7 vs - 0.4 ± 1.8, p = 0.69) or VISA-A (moxonidine - 0.2 ± 8.8 vs placebo + 4.2 ± 14.6, p = 0.24) attributable to the intervention. There was no difference in any measures of Achilles structure. Moxonidine did not reduce sympathetic drive when compared to placebo. CONCLUSIONS: This was the first study to investigate the effects of blocking sympathetic drive on musculoskeletal and Achilles tendon symptoms in a metabolically diverse population. While the study was limited by small sample size and lack of sympathetic modulation, moxonidine did not change tendon pain/structure or musculoskeletal symptoms. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01504321 . Registered 5 January 2012.

May Measurement Month 2018: an analysis of blood pressure screening results from Australia.

May Measurement Month (MMM), originally initiated as a temporary solution to address the lack of blood pressure (BP) screening programs worldwide, emerged as an effective annual campaign to increase the awareness of hypertension. MMM18, a cross-sectional survey of volunteers aged ≥18 years was carried out during May 2018 predominantly in capital cities across Australia following the standard MMM protocol. Blood pressure screening along with additional information including anthropometric data and responses to questionnaires on demographic, lifestyle, and environmental factors were collected from 3 352 individuals across Australia. After multiple imputation, 1 026 (30.6%) adult Australians had hypertension. Of the 2 936 individuals not on antihypertensive treatment, 610 (20.8%) were hypertensive, and 237 (57.1%) of the 416 individuals receiving antihypertensive treatment had uncontrolled BP. In line with MMM17 results and other previous surveys, MMM18 revealed that close to one-third of the screened population (30.6%) had hypertension, 57.1% of individuals treated with BP-lowering medication remained uncontrolled indicating suboptimal management of the condition in the majority of patients. Most importantly, only 49.0% of those with hypertension were aware of their elevated BP, highlighting lack of awareness of elevated BP in nearly half of the affected population. Elevated BP was directly associated with alcohol consumption, overweight, and obesity. Our findings demonstrate the need for (i) continued efforts to increase BP awareness in the population, (ii) optimization of BP management strategies, and (iii) tackling some of the major contributors to BP elevation, including alcohol consumption and obesity.

Distinct effects of acute exercise and breaks in sitting on working memory and executive function in older adults: a three-arm, randomised cross-over trial to evaluate the effects of exercise with and without breaks in sitting on cognition.

BACKGROUND: Sedentary behaviour is associated with impaired cognition, whereas exercise can acutely improve cognition. OBJECTIVE: We compared the effects of a morning bout of moderate-intensity exercise, with and without subsequent light-intensity walking breaks from sitting, on cognition in older adults. METHODS: Sedentary overweight/obese older adults with normal cognitive function (n=67, 67±7 years, 31.2±4.1 kg/m2) completed three conditions (6-day washout): SIT (sitting): uninterrupted sitting (8 hours, control); EX+SIT (exercise + sitting): sitting (1 hour), moderate-intensity walking (30 min), uninterrupted sitting (6.5 hours); and EX+BR (exercise + breaks): sitting (1 hour), moderate-intensity walking (30 min), sitting interrupted every 30 min with 3 min of light-intensity walking (6.5 hours). Cognitive testing (Cogstate) was completed at four time points assessing psychomotor function, attention, executive function, visual learning and working memory. Serum brain-derived neurotrophic growth factor (BDNF) was assessed at six time points. The 8-hour net area under the curve (AUC) was calculated for each outcome. RESULTS: Working memory net AUC z-score·hour (95% CI) was improved in EX+BR with a z-score of +28 (-26 to +81), relative to SIT, -25 (-79 to +29, p=0.04 vs EX+BR). Executive function net AUC was improved in EX+SIT, -8 (- 71 to +55), relative to SIT, -80 (-142 to -17, p=0.03 vs EX+SIT). Serum BDNF net AUC ng/mL·hour (95% CI) was increased in both EX+SIT, +171 (-449 to +791, p=0.03 vs SIT), and EX+BR, +139 (-481 to +759, p=0.045 vs SIT), relative to SIT, -227 (-851 to +396). CONCLUSION: A morning bout of moderate-intensity exercise improves serum BDNF and working memory or executive function in older adults, depending on whether or not subsequent sitting is also interrupted with intermittent light-intensity walking. TRIAL REGISTRATION NUMBER: ACTRN12614000737639.

Neurohumoral interactions contributing to renal vasoconstriction and decreased renal blood flow in heart failure.

In heart failure (HF), increases in renal sympathetic nerve activity (RSNA), renal norepinephrine spillover, and renin release cause renal vasoconstriction, which may contribute to the cardiorenal syndrome. To increase our understanding of the mechanisms causing renal vasoconstriction in HF, we investigated the interactions between the increased activity of the renal nerves and the renal release of norepinephrine and renin in an ovine pacing-induced model of HF compared with healthy sheep. In addition, we determined the level of renal angiotensin type-1 receptors and the renal vascular responsiveness to stimulation of the renal nerves and α1-adrenoceptors. In conscious sheep with mild HF (ejection fraction 35%-40%), renal blood flow (276 ± 13 to 185 ± 18 mL/min) and renal vascular conductance (3.8 ± 0.2 to 3.1 ± 0.2 mL·min-1·mmHg-1) were decreased compared with healthy sheep. There were increases in the burst frequency of RSNA (27%), renal norepinephrine spillover (377%), and plasma renin activity (141%), whereas the density of renal medullary angiotensin type-1 receptors decreased. In anesthetized sheep with HF, the renal vasoconstrictor responses to electrical stimulation of the renal nerves or to phenylephrine were attenuated. Irbesartan improved the responses to nerve stimulation, but not to phenylephrine, in HF and reduced the responses in normal sheep. In summary, in HF, the increases in renal norepinephrine spillover and plasma renin activity are augmented compared with the increase in RSNA. The vasoconstrictor effect of the increased renal norepinephrine and angiotensin II is offset by reduced levels of renal angiotensin type-1 receptors and reduced renal vasoconstrictor responsiveness to α1-adrenoceptor stimulation.

Brown adipose tissue thermogenesis in polycystic ovary syndrome.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is associated with increased obesity with a greater propensity to weight gain and a lack of sustainable lifestyle interventions. Altered brown adipose tissue (BAT) thermogenesis is a potential contributor to obesity in PCOS. BAT activity and modulation have not been studied in PCOS. This observational study explored BAT thermogenesis and its associations in women with and without PCOS. PARTICIPANTS AND METHODS: Cutaneous temperature was recorded from supraclavicular (indicator of BAT activity) and upper arm regions using dataloggers (SubCue, Calgary, Canada) in a cross-sectional substudy, nested within a randomized control trial, of community-recruited premenopausal women with (n = 47, Rotterdam diagnostic criteria) and without (n = 11) PCOS. RESULTS: Complete temperature data were available in 44 PCOS (mean age: 30.0 ± 6.2, mean BMI: 29.3 ± 5.5) and 11 non-PCOS (mean age: 33.0 ± 7.0, mean BMI: 25 ± 3) women. Women with PCOS had lower supraclavicular skin temperature compared to controls overall (33.9 ± 0.7 vs 34.5 ± 1, P < 0.05) and during sleep (34.5 ± 0.6 vs 35.2 ± 0.9, P < 0.001). In the PCOS group, supraclavicular skin temperature overall and over sleep and waking hours correlated inversely with testosterone (r = -0.41 P < 0.05, r = -0.485 P < 0.01 and r = -0.450 P < 0.01 respectively). Testosterone levels explained approximately 15%, 30% and 20% of the variability in supraclavicular skin temperature overall and over sleep and waking hours in women with PCOS, respectively. CONCLUSION: Women with PCOS have lower BAT activity compared to controls. BAT thermogenesis is negatively associated with androgen levels in PCOS.

Chronic sympathetic driven hypertension promotes atherosclerosis by enhancing hematopoiesis.

Hypertension is a major, independent risk factor for atherosclerotic cardiovascular disease. However, this pathology can arise through multiple pathways, which could influence vascular disease through distinct mechanisms. An overactive sympathetic nervous system is a dominant pathway that can precipitate in elevated blood pressure. We aimed to determine how the sympathetic nervous system directly promotes atherosclerosis in the setting of hypertension. We used a mouse model of sympathetic nervous system-driven hypertension on the atherosclerotic-prone apolipoprotein E-deficient background. When mice were placed on a western type diet for 16 weeks, we showed the evolution of unstable atherosclerotic lesions. Fortuitously, the changes in lesion composition were independent of endothelial dysfunction, allowing for the discovery of alternative mechanisms. With the use of flow cytometry and bone marrow imaging, we found that sympathetic activation caused deterioration of the hematopoietic stem and progenitor cell niche in the bone marrow, promoting the liberation of these cells into the circulation and extramedullary hematopoiesis in the spleen. Specifically, sympathetic activation reduced the abundance of key hematopoietic stem and progenitor cell niche cells, sinusoidal endothelial cells and osteoblasts. Additionally, sympathetic bone marrow activity prompted neutrophils to secrete proteases to cleave the hematopoietic stem and progenitor cell surface receptor CXCR4. All these effects could be reversed using the ß-blocker propranolol during the feeding period. These findings suggest that elevated blood pressure driven by the sympathetic nervous system can influence mechanisms that modulate the hematopoietic system to promote atherosclerosis and contribute to cardiovascular events.