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.

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.

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.

#MindinBody - feasibility of vigorous exercise (Bikram yoga versus high intensity interval training) to improve persistent pain in women with a history of trauma: a pilot randomized control trial.

BACKGROUND: The neurobiology of persistent pain shares common underlying psychobiology with that of traumatic stress. Modern treatments for traumatic stress often involve bottom-up sensorimotor retraining/exposure therapies, where breath, movement, balance and mindfulness, are used to target underlying psychobiology. Vigorous exercise, in particular Bikram yoga, combines many of these sensorimotor/exposure therapeutic features. However, there is very little research investigating the feasibility and efficacy of such treatments for targeting the underlying psychobiology of persistent pain. METHODS: This study was a randomized controlled trail (RCT) comparing the efficacy of Bikram yoga versus high intensity interval training (HIIT), for improving persistent pain in women aged 20 to 50 years. The participants were 1:1 randomized to attend their assigned intervention, 3 times per week, for 8 weeks. The primary outcome measure was the Brief Pain Inventory (BPI) and further pain related biopsychosocial secondary outcomes, including SF-36 Medical Outcomes and heart rate variability (HRV), were also explored. Data was collected pre (t0) and post (t1) intervention via an online questionnaire and physiological testing. RESULTS: A total of 34 women were recruited from the community. Analyses using ANCOVA demonstrated no significant difference in BPI (severity plus interference) scores between the Bikram yoga (n = 17) and the HIIT (n = 15). Women in the Bikram yoga group demonstrated significantly improved SF-36 subscale physical functioning: [ANCOVA: F(1, 29) = 6.17, p = .019, partial eta-squared effect size (ηp2) = .175 and mental health: F(1, 29) = 9.09, p = .005, ηp2 = .239; and increased heart rate variability (SDNN): F(1, 29) = 5.12, p = .013, ηp2 = .150, scores compared to the HIIT group. Across both groups, pain was shown to decrease, no injuries were experienced and retention rates were 94% for Bikram yoga and 75% for HIIT . CONCLUSIONS: Bikram yoga does not appear a superior exercise compared to HIIT for persistent pain. However, imporvements in quality of life measures and indicator of better health were seen in the Bikram yoga group. The outcomes of the present study suggest vigorous exercise interventions in persistent pain cohorts are feasible. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ( ACTRN12617001507370 , 26/10/2017).

Does sympathetic dysfunction occur before denervation in pure autonomic failure?

Pure autonomic failure (PAF) is a rare sporadic disorder characterized by autonomic failure in the absence of a movement disorder or dementia and is associated with very low plasma norepinephrine (NE) levels-suggesting widespread sympathetic denervation, however due to its rarity the pathology remains poorly elucidated. We sought to correlate clinical and neurochemical findings with sympathetic nerve protein abundances, accessed by way of a forearm vein biopsy, in patients with PAF and in healthy controls and patients with multiple systems atrophy (MSA) in whom sympathetic nerves are considered intact. The abundance of sympathetic nerve proteins, extracted from forearm vein biopsy specimens, in 11 patients with PAF, 8 patients with MSA and 9 age-matched healthy control participants was performed following a clinical evaluation and detailed evaluation of sympathetic nervous system function, which included head-up tilt (HUT) testing with measurement of plasma catecholamines and muscle sympathetic nerve activity (MSNA) in addition to haemodynamic assessment to confirm the clinical phenotype. PAF participants were found to have normal abundance of the NE transporter (NET) protein, together with very low levels of tyrosine hydroxylase (TH) (P<0.0001) and reduced vesicular monoamine transporter 2 (VMAT2) (P<0.05) protein expression compared with control and MSA participants. These findings were associated with a significantly higher ratio of plasma 3,4-dihydroxyphenylglycol (DHPG):NE in PAF participants when compared with controls (P<0.05). The finding of normal NET abundance in PAF suggests intact sympathetic nerves but with reduced NE synthesis. The finding of elevated plasma ratio of DHPG:NE and reduced VMAT2 in PAF indicates a shift towards intraneuronal NE metabolism over sequestration in sympathetic nerves and suggests that sympathetic dysfunction may occur ahead of denervation.

Sympathetic nervous response to ischemia-reperfusion injury in humans is altered with remote ischemic preconditioning.

Sympathetic neural activation may be detrimentally involved in tissue injury caused by ischemia-reperfusion (IR). We examined the effects of experimental IR in the forearm on sympathetic nerve response, finger reactive hyperemia, and oxidative stress, and the protection afforded by applying remote ischemic preconditioning (RIPC). Ischemia was induced in the forearm for 20 min in healthy volunteers. RIPC was induced by applying two cycles, 5 min each, of ischemia and reperfusion to the upper leg immediately before IR. We examined muscle sympathetic nerve activity (MSNA) in the contralateral leg using microneurography, finger reactive hyperemia [ischemic reactive hyperemia index (RHI)], erythrocyte production of reduced gluthathione (GSH), and plasma nitric oxide (NO) concentration. In controls (no RIPC; n = 15), IR increased MSNA in the early and late phase of ischemia (70% at 5 min; 101% at 15 min). In subjects who underwent RIPC (n = 15), the increase in MSNA was delayed to the late phase of ischemia and increased only by 40%. GSH increased during ischemia in the control group (P = 0.05), but not in those who underwent RIPC. Nitrate and nitrite concentration, taken as an index of NO availability, decreased during the reperfusion period in control individuals (P < 0.05), while no change was observed in those who underwent RIPC. Experimental IR did not affect RHI in the control condition, but a significant vasodilatory response occurred in the RIPC group (P < 0.05). RIPC attenuated ischemia-induced sympathetic activation, prevented the production of an erythrocyte marker of oxidative stress and the reduction of NO availability, and ameliorated RHI.

Should the sympathetic nervous system be a target to improve cardiometabolic risk in obesity?

The sympathetic nervous system (SNS) plays a key role in both cardiovascular and metabolic regulation; hence, disturbances in SNS regulation are likely to impact on both cardiovascular and metabolic health. With excess adiposity, in particular when visceral fat accumulation is present, sympathetic activation commonly occurs. Experimental investigations have shown that adipose tissue releases a large number of adipokines, cytokines, and bioactive mediators capable of stimulating the SNS. Activation of the SNS and its interaction with adipose tissue may lead to the development of hypertension and end-organ damage including vascular, cardiac, and renal impairment and in addition lead to metabolic abnormalities, especially insulin resistance. Lifestyle changes such as weight loss and exercise programs considerably improve the cardiovascular and metabolic profile of subjects with obesity and decrease their cardiovascular risk, but unfortunately weight loss is often difficult to achieve and sustain. Pharmacological and device-based approaches to directly or indirectly target the activation of the SNS may offer some benefit in reducing the cardiometabolic consequences of obesity. Preliminary evidence is encouraging, but more trials are needed to investigate whether sympathetic inhibition could be used in obesity to reverse or prevent cardiometabolic disease development. The purpose of this review article is to highlight the current knowledge of the role that SNS plays in obesity and its associated metabolic disorders and to review the potential benefits of sympathoinhibition on metabolic and cardiovascular functions.

Sympathetic activation and endothelial dysfunction in polycystic ovary syndrome are not explained by either obesity or insulin resistance.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is a common endocrine condition underpinned by insulin resistance and associated with increased risk of obesity, type 2 diabetes and adverse cardiovascular risk profile. Previous data suggest autonomic imbalance [elevated sympathetic nervous system (SNS) activity and decreased heart rate variability (HRV)] as well as endothelial dysfunction in PCOS. However, it is not clear whether these abnormalities are driven by obesity and metabolic disturbance or whether they are independently related to PCOS. PARTICIPANTS AND METHODS: We examined multiunit and single-unit muscle SNS activity (by microneurography), HRV (time and frequency domain analysis) and endothelial function [ischaemic reactive hyperaemia index (RHI) using the EndoPAT device] in 19 overweight/obese women with PCOS (BMI: 31·3 ± 1·5 kg/m(2), age: 31·3 ± 1·6 years) and compared them with 21 control overweight/obese women (BMI: 33·0 ± 1·4 kg/m(2), age: 28·2 ± 1·6 years) presenting a similar metabolic profile (fasting total, HDL and LDL cholesterol, glucose, triglycerides, insulin sensitivity and blood pressure). RESULTS: Women with PCOS had elevated multiunit muscle SNS activity (41 ± 2 vs 33 ± 3 bursts per 100 heartbeats, P < 0·05). Single-unit analysis showed that vasoconstrictor neurons were characterized by elevated firing rate and probability and incidence of multiple spikes (P < 0·01 for all parameters). Women with PCOS also had impaired endothelial function (RHI: 1·77 ± 0·14 vs 2·18 ± 0·14, P < 0·05). HRV did not differ between the groups. CONCLUSION: Women with PCOS have increased sympathetic drive and impaired endothelial function independent of obesity and metabolic disturbances. Sympathetic activation and endothelial dysfunction may confer greater cardiovascular risk in women with PCOS.

Reduction in peripheral vascular resistance predicts improvement in insulin clearance following weight loss.

BACKGROUND: The hyperinsulinemia of obesity is a function of both increased pancreatic insulin secretion and decreased insulin clearance, and contributes to cardiovascular risk. Whilst weight loss is known to enhance insulin clearance, there is a paucity of data concerning the underlying mechanisms. This study was conducted to examine the inter-relationships between changes in sympathetic nervous system (SNS) activity, vascular function and insulin clearance during a weight loss program. METHODS: Seventeen non-smoking, un-medicated individuals aged 55 ± 1 years (mean ± SEM), body mass index (BMI) 33.9 ± 1.7 kg/m(2), underwent a 4-month hypocaloric diet (HCD), using a modified Dietary Approaches to Stop Hypertension diet, whilst seventeen age- and BMI-matched subjects acted as controls. Insulin sensitivity and insulin clearance were assessed via euglycemic hyperinsulinemic clamp (exogenous insulin clearance); hepatic insulin extraction was calculated as fasting C-peptide to insulin ratio (endogenous insulin clearance); SNS activity was quantified by microneurographic nerve recordings of muscle sympathetic nerve activity (MSNA) and whole-body norepinephrine kinetics; and vascular function by calf venous occlusion plethysmography and finger arterial tonometry. RESULTS: Weight loss averaged -8.3 ± 0.6% of body weight in the HCD group and was accompanied by increased clamp-derived glucose utilization (by 20 ± 9%, P = 0.04) and exogenous insulin clearance (by 12 ± 5%, P = 0.02). Hepatic insulin extraction increased from 6.3 ± 0.8 to 7.1 ± 0.9 (P = 0.09). Arterial norepinephrine concentration decreased by -12 ± 5%, whole-body norepinephrine spillover rate by -14 ± 8%, and MSNA by -9 ± 5 bursts per 100 heartbeats in the HCD group (P all >0.05 versus control group). Step-wise regression analysis revealed a bidirectional relationship between enhanced exogenous insulin clearance post weight loss and reduction in calf vascular resistance (r = -0.63, P = 0.01) which explained 40% of the variance. Increase in hepatic insulin extraction was predicted by enhanced finger reactive hyperaemic response (P = 0.006) and improvement in oral glucose tolerance (P = 0.002) which together explained 64% of the variance. CONCLUSIONS: Insulin clearance is independently and reciprocally associated with changes in vascular function during weight loss intervention. Trial registration ClinicalTrials.gov: NCT01771042 and NCT00408850.

Salt sensitivity risk derived from nocturnal dipping and 24-h heart rate predicts long-term blood pressure reduction following renal denervation.

BACKGROUND: Renal denervation (RDN) has been consistently shown in recent sham-controlled clinical trials to reduce blood pressure (BP). Salt sensitivity is a critical factor in hypertension pathogenesis, but cumbersome to assess by gold-standard methodology. Twenty-four-hour average heart rate (HR) and mean arterial pressure (MAP) dipping, taken by ambulatory blood pressure monitoring (ABPM), stratifies patients into high, moderate, and low salt sensitivity index (SSI) risk categories. OBJECTIVES: We aimed to assess whether ABPM-derived SSI risk could predict the systolic blood pressure reduction at long-term follow-up in a real-world RDN patient cohort. METHODS: Sixty participants had repeat ABPM as part of a renal denervation long-term follow-up. Average time since RDN was 8.9 ±â€Š1.2 years. Based on baseline ABPM, participants were stratified into low (HR < 70 bpm and MAP dipping > 10%), moderate (HR ≥70 bpm or MAP dipping ≤ 10%), and high (HR ≥ 70 bpm and MAP dipping ≤ 10%) SSI risk groups, respectively. RESULTS: One-way ANOVA indicated a significant treatment effect ( P  = 0.03) between low ( n  = 15), moderate ( n  = 35), and high ( n  = 10) SSI risk with systolic BP reduction of 9.6 ±â€Š3.7 mmHg, 8.4 ±â€Š3.5 mmHg, and 28.2 ±â€Š9.6 mmHg, respectively. Baseline BP was not significantly different between SSI Risk groups ( P  = 0.18). High SSI risk independently correlated with systolic BP reduction ( P  = 0.02). CONCLUSIONS: Our investigation indicates that SSI risk may be a simple and accessible measure for predicting the BP response to RDN. However, the influence of pharmacological therapy on these participants is an important extraneous variable requiring testing in prospective or drug naive RDN cohorts.

Long-Term Blood Pressure Reductions Following Catheter-Based Renal Denervation: A Systematic Review and Meta-Analysis.

BACKGROUND: Renal denervation is a recognized adjunct therapy for hypertension with clinically significant blood pressure (BP)-lowering effects. Long-term follow-up data are critical to ascertain durability of the effect and safety. Aside from the 36-month follow-up data available from randomized control trials, recent cohort analyses extended follow-up out to 10 years. We sought to analyze study-level data and quantify the ambulatory BP reduction of renal denervation across contemporary randomized sham-controlled trials and available long-term follow-up data up to 10 years from observational studies. METHODS: A systematic review was performed with data from 4 observational studies with follow-up out to 10 years and 2 randomized controlled trials meeting search and inclusion criteria with follow-up data out to 36 months. Study-level data were extracted and compared statistically. RESULTS: In 2 contemporary randomized controlled trials with 36-month follow-up, an average sham-adjusted ambulatory systolic BP reduction of -12.7±4.5 mm Hg from baseline was observed (P=0.05). Likewise, a -14.8±3.4 mm Hg ambulatory systolic BP reduction was found across observational studies with a mean long-term follow-up of 7.7±2.8 years (range, 3.5-9.4 years; P=0.0051). The observed reduction in estimated glomerular filtration rate across the long-term follow-up was in line with the predicted age-related decline. Antihypertensive drug burden was similar at baseline and follow-up. CONCLUSIONS: Renal denervation is associated with a significant and clinically meaningful reduction in ambulatory systolic BP in both contemporary randomized sham-controlled trials up to 36 months and observational cohort studies up to 10 years without adverse consequences on renal function.

A sympathetic view of human obesity.

Excess adiposity is associated with increased incidence of cardiovascular disease (CVD). Importantly, CVD mortality associated with obesity is more prevalent in young individuals. Elevated sympathetic nervous system (SNS) activity is present in obesity, even in individuals who are young and otherwise healthy. Baseline SNS overactivity, as well as blunted sympathetically mediated thermogenic response to a meal may play a critical role in the development and progression of CVD which is likely to develop as a result of multiple factors. Recent data indicate that SNS activity to the skeletal muscle is directly related to the degree of renal, endothelial and cardiac dysfunction in young individuals. Targeting the SNS may be an attractive and important avenue for the pharmacological treatment of obesity-related disturbances.

Renal denervation in moderate to severe CKD.

Sympathetic activation contributes to the progression of CKD and is associated with adverse cardiovascular outcomes. Ablation of renal sympathetic nerves reduces sympathetic nerve activity and BP in patients with resistant hypertension and preserved renal function, but whether this approach is safe and effective in patients with an estimated GFR (eGFR) < 45 ml/min per 1.73 m(2) is unknown. We performed bilateral renal denervation in 15 patients with resistant hypertension and stage 3-4 CKD (mean eGFR, 31 ml/min per 1.73 m(2)). We used CO(2) angiography in six patients to minimize exposure to contrast agents. Estimated GFR remained unchanged after the procedure, irrespective of the use of CO(2) angiography. Mean baseline BP ± SD was 174 ± 22/91 ± 16 mmHg despite the use of 5.6 ± 1.3 antihypertensive drugs. Mean changes in office systolic and diastolic BP at 1, 3, 6, and 12 months were -34/-14, -25/-11, -32/-15, and -33/-19 mmHg, respectively. Night-time ambulatory BP significantly decreased (P<0.05), restoring a more physiologic dipping pattern. In conclusion, this study suggests a favorable short-term safety profile and beneficial BP effects of catheter-based renal nerve ablation in patients with stage 3-4 CKD and resistant hypertension.

Stress and social isolation, and its relationship to cardiovascular risk in young adults with intellectual disability.

PURPOSE: Stress produces many physiological changes, some of which may contribute to the development of cardiovascular disease (CVD). Individuals with intellectual disability (ID) are exposed to multiple and stressful challenges everyday which may put them at increased cardiovascular risk. This current study aimed to establish whether adults with ID experience higher levels of subjective stress and encounter different stressors (including social isolation) than the general population, and whether there is a relationship between stress and cardiometabolic profile in this population. METHODS: Adults with ID (n = 35) aged 18-45 years completed the Subjective Stress Survey, and underwent a physiological assessment to measure blood pressure, metabolic profile and subclinical CVD risk factors, and were compared to a control group (n = 29). Multiple regression was used to investigate whether cardiometabolic parameters were predicative of SSS scores. RESULTS: Findings showed adults with ID have higher perceived stress levels (total score ID: 21.3 ± 11.4 vs control: 13.9 ± 9.0, p = 0.006), which is elicited by unique stressors, when compared to people without ID. Stress was strongly associated with increased social isolation (r = -0.38, p = 0.002) and with obesity in females with mild ID (r = 0.72). Regression showed that arterial stiffness was predictive of total SSS score (p = 0.038). CONCLUSIONS: Adults with ID aged 18-45 years report higher levels of perceived stress when compared to people without ID.Implications for RehabilitationReducing stress in this young population may prevent development of arterial stiffness, and consequently lower the risk of cardiometabolic morbidity and mortality.There are unique targets for stress management in young adults with intellectual disability, including supporting decision-making and improving self-efficacy.Improving community integration and reducing social isolation may decrease perceived stress in young adults with intellectual disability.

Associations of physical activity levels, and attitudes towards physical activity with blood pressure among adults with high blood pressure in Bangladesh.

BACKGROUND: Physical activity is important for the control of high blood pressure (hypertension). We aimed to investigate the associations of current physical activity levels, sedentary time, knowledge of and attitude towards physical activity with blood pressure in people with hypertension in a rural area in Bangladesh. METHODS: A total of 307 adults aged 30 to 75 years with hypertension were recruited from the Banshgram Union of Narial district as part of a cluster-randomized control trial. Current blood pressure was measured as the outcome variable. Associated variables included physical activity at work, travel to and from places, recreational activity, metabolic equivalent task (MET)-min, sedentary time, and awareness of and attitudes towards physical activity. Rasch analysis was used to compute a combined score from the five awareness of and attitudes towards physical activity items and categorized into 0-40 (towards negative attitude), 41-60 score (mixed attitude) and 61-100 (positive attitude). We used a generalised linear model to analyze the data. RESULTS: Participants (n = 68, 22.1%) who engaged in vigorous-intensity physical activity that causes large increases in breathing or heart rate like carrying or lifting heavy loads, digging or construction work for at least 10 minutes continuously had lower systolic blood pressure (SBP) (mean (95% confidence interval (CI)), 143.6 (140.1, 147.2)) compared to those who did not take part in a vigorous-intensity physical activity (mean (95% CI), 150 (147.6, 152.3)). MET-min less than 600 min/week was significantly associated with higher SBP 153.8 (148.1, 159.6) than MET-min 600-2999 min/week 148.0 (143.0, 152.9) and MET-min>3000 min/week 146.9 (144.5, 149.3), p = 0.001 for trend. Sitting time more than four hours a day was associated with higher DBP 91.4 (89.7, 93.0) compared to those who had sitting time less than fours a day 88.6 (87.1, 90.1). People with positive attitudes were associated with a reduced SBP of 10.6 (0.36, 20.8) mmHg and DBP 5.88 (0.47, 11.3) compared to the people who had a negative attitude towards taking part in physical activity. CONCLUSIONS: Participating in high physical activity and positive attitudes towards physical activity were associated with lower blood pressure levels. Physical activity awareness programs should be implemented to increase awareness of health benefits and increase participation in high physical activity.

Catheter-Based Renal Denervation: 9-Year Follow-Up Data on Safety and Blood Pressure Reduction in Patients With Resistant Hypertension.

BACKGROUND: Recent sham-controlled randomized clinical trials have confirmed the safety and efficacy of catheter-based renal denervation (RDN). Long-term safety and efficacy data beyond 3 years are scarce. Here, we report on outcomes after RDN in a cohort of patients with resistant hypertension with an average of ≈9-year follow-up (FU). METHODS: We recruited patients with resistant hypertension who were previously enrolled in various RDN trials applying radiofrequency energy for blood pressure (BP) lowering. All participants had baseline assessments before RDN and repeat assessment at long-term FU including medical history, automated office and ambulatory BP measurement, and routine blood and urine tests. We analyzed changes between baseline and long-term FU. RESULTS: A total of 66 participants (mean±SD, 70.0±10.3 years; 76.3% men) completed long-term FU investigations with a mean of 8.8±1.2 years post-procedure. Compared with baseline, ambulatory systolic BP was reduced by -12.1±21.6 (from 145.2 to 133.1) mm Hg (P<0.0001) and diastolic BP by -8.8±12.8 (from 81.2 to 72.7) mm Hg (P<0.0001). Mean heart rate remained unchanged. At long-term FU, participants were on one less antihypertensive medication compared with baseline (P=0.0052). Renal function assessed by estimated glomerular filtration rate fell within the expected age-associated rate of decline from 71.1 to 61.2 mL/min per 1.73 m2. Time above target was reduced significantly from 75.0±25.9% at baseline to 47.3±30.3% at long-term FU (P<0.0001). CONCLUSIONS: RDN results in a significant and robust reduction in both office and ambulatory systolic and diastolic BP at ≈9-year FU after catheter-based RDN on less medication and without evidence of adverse consequences on renal function.

MicroRNA-132 may be associated with blood pressure and liver steatosis-preliminary observations in obese individuals.

Recent findings in experimental models have shown that the microRNA miR-132 (mir-132) is an important regulator of liver homeostasis and lipid metabolism. We aimed to assess miR-132 expression in liver and fat tissues of obese individuals and examine its association with blood pressure (BP) and hepatic steatosis. We examined obese individuals undergoing bariatric surgery for weight loss (n = 19). Clinical and demographic information was obtained. Quantitative PCR was performed to determine tissue expression of miR-132 in liver and subcutaneous and visceral fat biopsies obtained during bariatric surgery. Liver biopsies were read by a single liver pathologist and graded for steatosis, inflammation and fibrosis. Participants (aged 39 ± 8.1 years) had a body mass index (BMI) of 42 ± 4.5 kg/m2 and presented with 2.2 ± 1.2 metabolic abnormalities. Supine BP was 127 ± 16/74 ± 11 mmHg. Hepatic and visceral fat expression of miR-132 were correlated (r = 0.59, P = 0.033). There was no correlation between subcutaneous and visceral expression of miR-132 (r = -0.31, P = 0.20). Hepatic and visceral fat miR-132 expression were associated with BMI (r = 0.62 and r = 0.68, P = 0.049 respectively) and degree of liver steatosis (r = 0.60 and r = 0.55, P < 0.05, respectively). Subcutaneous fat miRNA-132 expression was correlated to office systolic BP (r = 0.46, P < 0.05), several aspects of 24 h BP (24 h systolic BP: r = 0.52; day systolic BP: r = 0.59, P < 0.05 for all), plasma triglycerides (r = 0.51, P < 0.01) and liver enzymes (ALT: r = -0.52; AST: r = -0.48, P < 0.05 for all). We found an association between miR-132 and markers of cardiovascular and metabolic disease. Reduction of miR-132 may be a target for the regulation of liver lipid homeostasis and control of obesity-related blood pressure.