Introduction: Psychological stress is a risk factor for cardiovascular disease and is implicated in the development and progression of essential hypertension. Emotionally induced blood pressure (BP) changes are initiated and maintained by the brain. However, the neural mechanisms involved in BP change are highly complex and still not well understood. We assessed brain activity and connectivity during stress-induced BP increase in healthy individuals.
Methods: Magnetoencephalography was recorded at rest and during 10 minutes of timed multi-source numerical and word-based interference tasks in 29 normotensive individuals. T1 weighted magnetic resonance imaging and linearly constrained minimum variance beamforming were applied. Activity was filtered through delta (1-4Hz), theta (4-8Hz), alpha (8-13Hz), beta (13-30Hz) and low gamma (30-80Hz) bands. Whole head and region of interest (ROI) power analyses were performed and changes in brain activity were correlated with brachial BP. Connectivity between regions showing significant change from rest were assessed using Weighted Phase Lag Index (wPLI).
Results: Stress induced significant increases in systolic, diastolic and mean BP (5.2±5.6 ,3.5±5.5 and 4.1±5.1mmHg, P<05) in association with decreased activity in the left and right posterior cingulate, precuneus, hippocampus and right insula and thalamus, in alpha band (P<0.05). Correlation analysis revealed that during stress, decreased brain activity in the right posterior insular cortex, in alpha band, was significantly correlated with higher systolic (r=0.446) and mean (r=0.456) BP, while decreased activity in the left amygdala, in alpha band, was significantly correlated with higher anxiety state (r=0.647), anxiety trait (r=0.442), BDI-II (r=0.446) and systolic BP (r=0.392), P<05. Connectivity analyses revealed that between rest and stress there were reductions between the right posterior parahippocampus and right precuneus and between the right precuneus and left hippocampus in alpha band (P<0.01). Similarly, there were significant reductions in connectivity between the right prefrontal cortex and the right amygdala and brainstem and between the left and right sensorimotor cortex and the right anterior parahippocampus, in theta band, P<0.005.
Conclusion: Our study indicates that short term stress-induced BP elevation in normotensive individuals is associated with reduced power and connectivity of specific temporal and parietal brain regions in alpha (mental aspect) and beta (motor aspect) bands.

Background and Aim:

Elderly patients with aortic stenosis (AS) experience dual afterload imposed by the aortic valvular obstruction and age-related arterial stiffness. Transcatheter aortic valve replacement (TAVR) is an effective treatment for AS. The study aims to investigate the changes in haemodynamic parameters post-TAVR to better understand the interaction between valvular obstruction relief and arterial stiffness.

Methods:

Fifty TAVR patients (aged 82.4±7.5years, 20 female) had their blood pressure and arterial stiffness measured using the gold standard of carotid-femoral pulse wave velocity (PWV) at baseline and day1 post-TAVR using the SphygmoCor® (Sydney,Australia) system, with a same-day transthoracic echocardiogram. The patients were subsequently classified into high flow (HF, stroke volume index [SVi]≥35ml/m²,n=25) and low flow (LF, SVi<35ml/m²,n=25) groups.

Results:

Baseline PWV between the LF and HF groups did not significantly differ (10.7±3.05m/s vs 9.94±2.8m/s) but became significant post-TAVR, with an increase in the LF group to 11.1±2.80m/s, and a decrease in the HF group to 9.59±2.44m/s (P=0.044). This is associated with a significant increase in SVi post-TAVR from 25.97±5.46ml/m² to 33.03±9.82ml/m² in the LF group (P<0.001), which was not observed in the HF group (45.61±10.19ml/m² to 43.03±9.50ml/m², P=0.060). Accordingly, there was a greater reduction in valvulo-arterial impedance (Zva) in the LF patients from 6.73±1.54mmHg/ml/m² to 4.10±1.36mmHg/ml/m² (P<0.05) than in the HF patients (3.92±0.72mmHg/ml/m² to 2.98±0.79mmHg/ml/m², P<0.05). However, Zva remains significantly higher in the LF group at day1 (P<0.001). Both groups experience a significant reduction in central systolic pressure (CSP) post-TAVR, with a decrease from 132.62±13.11mmHg to 115.72±20.12mmHg (P<0.001) in the LF group and 133.58±16.32mmHg to 114.95±16.45mmHg (P<0.001) in the HF group. This correlates with a decrease in augmentation index (AIx) post-TAVR, especially in the HF group (HF, r=0.45,P<0.05; LF, r=0.16,P=0.44). 

Conclusions:

Following TAVR, true arterial stiffness becomes ‘unmasked’ primarily in the LF patients, with the difference between PWV becoming significant between the groups at day1. This may be attributable to the increase in SVi experienced by the LF patients. Reduction in AIx post-TAVR is closely related to the reduction in CSP, making AIx a less reliable measure of true arterial stiffness when compared to PWV in this population with fluctuating blood pressure.

Background and Aim
For uncontrolled blood pressure, Australian and international hypertension treatment guidelines recommend adding a second agent in preference to increasing the dose of monotherapy or switching. They also recommend five or more monthly steps to obtain BP control. It is unclear if current, real-world prescribing practices align with these guidelines, and this research aims to examine this alignment in Australian primary care.
Methods
Patients initiating antihypertensive therapy during 2014-2015 from an Australian primary care electronic health record dataset were analysed longitudinally with 12 months follow up. Post-initiation antihypertensive prescription records were used to determine the presence, type, and timing of therapy changes. Observed patterns of therapy changes were compared with patterns expected if treatment guidelines were being followed.
Results
Of the 37,427 patients initiating therapy, 87% (N=32,492) were initiated on monotherapy and 13% (N=4,935) on combination therapy. Subsequently, 25% (N=9,525) received no post-initiation antihypertensive prescriptions and 41% (N=15,524) were exclusively re-prescribed the initiating regimen. Of the remaining 12,360 patients, 69% (N=8,475) had only one change, 21% (N=2,649) had two changes, and 10% (N=1,236) had three or more changes. Of the 12,360 prescription changes occurring first after initiation, 41% (N=5,046) were dose increases, 21% (N=2,616) were medicine switches, and 20% (N=2,503) additions of a new agent. Therapy changes occurred early, with 43% (N=7,709) of 18,004 individual prescription changes prescribed in the first three months of follow-up. At the end of follow up, 42% (N=15,781) of all patients had an antihypertensive prescription not yet exhausted and also received at least one antihypertensive prescription in the six months immediately post-follow up.
Conclusions
Prescribing practise does not generally align to clinical guidelines, as dose increases are more common than adding a second agent. Most patients have zero or one change to regimen only and proportionally fewer changes are made after three months of treatment initiation, again suggesting guidelines are not followed closely. Different approaches are required to address Australia’s poor hypertension control rates.

Background and Aim: Dietary fibre lowers blood pressure (BP) via short-chain fatty acids, acidic metabolites released from fibre fermentation by bacteria inhabiting the large intestine. This acidic microenvironment may activate pH-sensing receptor GPR68, expressed primarily on immune cells, which play a key role in BP regulation. Here, we investigated whether GPR68 confers the cardioprotective effects of high-fibre in hypertension through the regulation of inflammatory responses.

Methods: Baseline BP was measured via telemetry in 8-10-week-old male C57BL/6J wildtype (WT) and GPR68-deficient (Gpr68-/-) mice (n=4-6/group). In a separate cohort, 6–8-week-old WT and Gpr68-/- mice were fed a control or high-fibre diet following subcutaneous implantation of minipumps containing Angiotensin II (Ang II; 0.75 mg/kg body weight/day, 4 weeks, n=8-12/group). BP was measured weekly by tail-cuff. Cardiac ultrasounds, histological and flow cytometric analyses were performed following the 4-week protocol.

Results: No differences in baseline BP measurements were observed between WT and Gpr68-/- mice (all p>0.05). Compared to control-fed WT mice, high-fibre-fed WT mice exhibited lower systolic BP (control diet vs high-fibre diet: 133.5±6.2mmHg vs 117.5±4.4mmHg, p=0.0508) and cardiac interstitial collagen deposition (0.194±0.06% vs 0.0713±0.02%, p=0.0495), and higher fractional shortening (10.1±0.9% vs 14.1±0.8%, p=0.0146) and aortic elastin content (18.9±1.9% vs 25.2±1.7%, p=0.0503). In comparison, high-fibre did not change these parameters in Gpr68-/- mice relative to the control diet (all p>0.05). Flow cytometric analyses revealed a diet-driven decrease in aortic and renal total immune cell (aorta, p=0.0049; kidney, p=0.0109), macrophage (aorta, p=0.0329; kidney, p=0.0490) and CD8+ T cell (aorta, p=0.0104; kidney, p=0.0211) counts amongst other immune cell types, regardless of genotype.

Conclusions: High-fibre did not protect Gpr68-/- mice from developing hypertension and associated end-organ damage. Independently of the GPR68 genotype, high-fibre-treated mice had lower levels of pro-inflammatory immune cells within the kidney and the aorta. Therefore, this study provides novel insight that GPR68 is involved in the cardioprotective effects of a high-fibre diet. However, this is most likely via in an immune-independent manner, warranting further investigation into its underlying mechanism of action.