Background and Aim: Arterial stiffness is an important marker of vascular health and a recognized predictor of future cardiovascular disease. Carotid-femoral pulse wave velocity is considered the non-invasive reference measure of arterial stiffness and is widely used to characterize vascular aging. While determinants of carotid-femoral pulse wave velocity have been extensively investigated in adult populations, less is known about the factors influencing arterial stiffness during childhood, adolescence, and early adulthood. This study aimed to examine the common cardiovascular risk factors most strongly associated with carotid-femoral pulse wave velocity across childhood to young adulthood.

Methods: Data were analysed from 6,763 participants aged 5 to 40 years included in the Youth Vascular Consortium, all of whom underwent carotid-femoral pulse wave velocity assessment using the SphygmoCor tonometry system. Participants were grouped into five analytical subsets according to the availability of cardiovascular risk factor data. Sex-specific and age-specific (≤19 years and >19 years) multiple linear regression models were developed to identify risk factors associated with carotid-femoral pulse wave velocity. Variable selection was based on model fit, assessed using the Akaike information criterion and adjusted R².

Results: Age and systolic blood pressure were consistently the strongest determinants of carotid-femoral pulse wave velocity across subsets, although the resulting models generally accounted for less than 40% of the observed variability in carotid-femoral pulse wave velocity. Heart rate was also an important contributor (R²=0.25-0.38), whereas lipid measures demonstrated only limited explanatory value and primarily among young adults. Among anthropometric measures, waist circumference was the most informative predictor of carotid-femoral pulse wave velocity in the majority of groups examined (R²=0.21-0.31).

Conclusions: Traditional cardiovascular risk factors, particularly age, systolic blood pressure, and heart rate, were associated with carotid-femoral pulse wave velocity across childhood, adolescence, and young adulthood. Nevertheless, these factors explained only a modest proportion of variability in carotid-femoral pulse wave velocity. The findings emphasize the importance of haemodynamic influences on vascular function during early life while also indicating that substantial unexplained variation remains. Future research should investigate the contribution of genetic predisposition, early-life exposures, lifestyle behaviours, and environmental influences to arterial stiffness in young populations.

Background and Aim: We evaluated the effect of GMRx2 (WIDAPLIKTM), a single pill triple combination (SPC) of telmisartan (T), amlodipine (A) and indapamide (I) on orthostatic and symptomatic hypotension, compared with placebo and dual blood pressure (BP) therapies, in patients with hypertension.

Method: Individual patient data from two RCTs:
1. a placebo-controlled trial (n=295) investigated the efficacy of GMRx2 Dose 1, or Dose 2, versus placebo over 4 weeks;
2. an active-controlled trial (n=1385) comparing GMRx2 Dose 2 over 6 weeks followed by escalation to Dose 3 over weeks 6-12 versus dual therapies at comparable doses.
Orthostatic hypotension was defined as a decrease in clinic SBP of ≥20 mmHg or DBP of ≥10 mmHg from sitting to standing. Symptomatic hypotension was collected as an adverse event.

Results: A total of 1584 participants (mean age: 58 years; 52% female) with ≥2 HBP readings were included. In the PCT, no difference in CV was observed between Widaplik ½ dose and placebo, but Widaplik ¼ dose showed a higher CV (+1.11, CI: 0.01, 2.21) compared with placebo at Week 4. In the ACT, no significant between-group differences were observed between Widaplik, AI, TI and TA.

Conclusion: Overall, in patients with mild-to-moderate BP elevation, no significant between-group differences in systolic BPV were observed between Widaplik ½ and placebo, or between standard-dose Widaplik and dual therapies (AI, TA, TI).

Background and Aim – Low dietary fibre intake is a known hypertension risk factor. Dietary fibre is fermented by the gut microbiome, producing short-chain fatty acids (SCFAs) which have a beneficial effect lowering blood pressure (BP). The immune system plays a critical role in hypertension; however, it is not known how the immune system is activated during hypertension. SCFAs can act directly on immune cells, suggesting a role for gut immune cells in developing hypertension. We aimed to determine the role of gut immune cells in the early stages of hypertension.

Methods – Eight-week-old male (3-5 mice/group) C57BL/6J mice were subcutaneously implanted with minipumps containing saline or Angiotensin II (Ang-II, 0.75 mg/kg/day) for either one or two weeks. These timepoints were chosen to capture the pre-hypertensive stage normally observed with prolonged Ang-II infusion. BP was measured weekly by tail-cuff. Flow cytometry was performed in the mesenteric lymph nodes (mLN) and kidney at endpoint. Data were analysed using unpaired-t test and two-way ANOVA with p<0.05 as significant.

Results- One week of Ang-II treatment led to higher MHC-II expression on dendritic cells (mean ± SEM: 6244±162.7 saline vs. 7795±380.7 Ang-II, p=0.0088) and non-significantly higher CD4+ T cell numbers (21.62±1.99 vs. 27.52±1.29, p=0.0721) in the mLN, despite no difference in systolic BP between saline and Ang-II groups (101 mmHg vs. 106 mmHg, p=0.7636). Higher CD4+ T cells were observed in the kidneys at two weeks (3.564±0.197 vs. 5.227±0.791, p=0.0397), again without a significant difference in systolic BP (102 mmHg vs. 111 mmHg, p=0.3319).

Conclusions- Prior to BP changes, Ang-II-treated mice showed higher dendritic cell activation and CD4+ T cell numbers in the mLN, preceding immune cell changes in the kidney following two weeks of Ang-II infusion. This suggests that the gut may be a site of immune cell activation during early hypertension development. To determine the impact of fibre on this process, we will feed male and female mice a control or low-fibre diet prior to Ang-II treatment, then assess sex differences, gut barrier integrity and immune cell dynamics in gut-associated lymphoid tissues to define the gut-immune axis in early hypertension.

Background: Low dietary fibre intake increases the prevalence of elevated blood pressure (BP), but we do not know how this occurs. this is important because 9/10 Australians do not have an adequate fibre intake.

Aim: To investigate the longitudinal effects of chronic low fibre intake on systemic and tissue-specific immunity and BP in male and female mice.

Methods: Male and female C57BL/6 mice were fed either a low-fibre or control diet after weaning throughout the study (n=8-10). Endpoint data collection characterization were performed at 6, 12, and 15 months of age.
Immune cells in the aorta, kidneys and spleen were examined by flow cytometry (Cytek Aurora). Gut barrier integrity was evaluated by quantifying circulating levels of orally administered FITC-dextran. The level of cecal fibre-derived metabolites known as short-chain fatty acids (SCFAs) was quantified. BP was assessed by tail-cuff plethysmography at 6, 12 months or by radiotelemetry at 15 months. Plasma cytokine concentrations were measured using a multiplex cytometric bead array. Adiposity was measured by EchoMRI.

Results: After 6 months, low-fibre-fed males mice showed early immune activation, compared to control-fed males, with increased splenic natural killer cells (P=0.049, 2.7-fold) and CD4+ T-cell subsets (P=0.045, 1.3-fold), accompanied by accumulation of macrophages (P=0.033, 5.7-fold), neutrophils (P=0.013, 2.1-fold) and monocytes (P=0.015, 3.1-fold) in the aorta. By 12 months, this inflammatory phenotype subsided, but splenic CD8+ T cells displayed an exhausted phenotype (P=0.045, 1.7-fold). In contrast, low-fibre fed females showed minimal immune alterations at 6 months but developed renal inflammation by 12 months, characterized by increased macrophages (P=0.041, 1.5-fold), natural killer cells (P=0.036, 1.4-fold) and CD8+ T cells (P=0.048, 2.1-fold), compared to control-fibre-fed females. At 12 months, SCFAs differed between sexes, with butyrate and propionate lower in low-fibre fed males and females respectively. Despite tissue inflammation, BP remained unchanged irrespective of sex and diet. No differences were detected in circulating cytokines, gut barrier integrity and adiposity.

Conclusion: Chronic low fibre intake drives dynamic, sex-specific immune remodelling across ageing but is insufficient to increase BP. A subpressor dose of a hypertensive trigger may be needed to determine how chronic low-fibre intake increases susceptibility to hypertension.

Background and Aim. An exaggerated blood pressure (BP) response to exercise is associated with undetected/uncontrolled hypertension. It is now understood that exercise BP must be considered relative-to-fitness for optimal clinical interpretation; however, whether consideration of fitness improves the relationship with hypertension detected by ambulatory BP (ABP) remains unknown. This study aimed to investigate the association of exercise systolic BP (SBP) relative-to-fitness with hypertension determined by ABP monitoring.

Methods. This observational study included 109 participants (mean age 50.2±14.8 years, 49.5% males) who completed an incremental maximal cardiopulmonary exercise test (CPET) via cycle ergometry (30-watt increments every two minutes). Fitness was assessed as peak oxygen uptake (VO2peak). BP was measured pre-exercise, during each exercise stage, and at the end of the test. Exercise SBP relative-to-fitness was calculated as SBP/VO2peak at various exercise intensities (%VO2peak). 24-hour ABP monitoring was conducted on three separate occasions, one week apart. Hypertension was defined as mean (of three ABP measures) 24-hour ABP ≥130/80 mmHg or a daytime ABP ≥135/85 mmHg. Generalised linear models examined associations between exercise SBP and SBP/VO2peak with elevated ABP, adjusting for age, sex and pre-exercise SBP. Discriminatory performance of exercise SBP and SBP/VO2peak for detecting hypertension (elevated ABP) were assessed using area under the curve (AUC) analysis.

Results. Exercise SBP/VO2peak was positively associated with ABP across exercise intensities (Beta-coeffcient range: 3.71-4.27; p<0.05) and relationships remained apparent after adjustment for age, sex and pre-exercise SBP (Beta-coeffcient range: 2.39-2.93; p<0.05). In contrast, associations between exercise SBP alone were largely attenuated after adjustment (Beta-coeffcient range: 0.61-2.96; p>0.05). SBP/VO2peak was associated with a higher risk of elevated ABP at 90% and 100%VO2peak (Risk ratio [RR] range:1.33-1.40; p<0.05), whereas exercise SBP alone was not significantly associated with elevated ABP (RR range:0.95-1.48; p>0.05). Moreover, SBP/VO2peak showed moderate discrimination (AUC range:0.752-0.772; p<0.05) across exercise intensities compared with 0.717-0.735 (p<0.05) for exercise SBP alone; however, AUCs did not differ between measures (p>0.05).

Conclusion. Exercise SBP relative-to-fitness, but not exercise SBP alone, was positively and consistently associated with ABP and hypertension. This suggests that incorporating fitness into the interpretation of exercise BP provides additional information for identifying individuals with hypertensive-related CV risk.

Background and aim: Hypertension claims the lives of 46,000 people in Nepal annually, yet fewer than one in ten people with hypertension have their BP controlled reflecting cascading failures across awareness, treatment access, medicine affordability, and health system capacity. The aim of this study is to provide insights on potential health gains from achieving optimal blood pressure (BP) control in Nepal.

Methods: We built on a well-established proportional multistate lifetable methodology to simulate potential gains in health-adjusted life years (HALYs) from achieving systolic BP<140mmHg (scenario 1), <130mmHg (scenario 2), <120mmHg (scenario 3) over different time horizons. Results are presented as HALYs gained with 0% and 3% discounting.

Results: Our simulation showed that under the scenario of achieving SBP <140 mmHg among individuals with diagnosed hypertension, the model projected 1.4 (95% uncertainty interval 0.9 to 2.0) million HALYs gained over 20 years and 27.8 (19.0 to 39.9) million HALYs over the lifetime (undiscounted). Per-capita gains were 51.0 (35.3 to 72.5) HALYs per 1000 population over 20 years and 1005.8 (687.9 to 1437.0) per 1000 over the lifetime. Health gains were higher among males than females (61.1 vs 41.8 HALYs per 1000 over 20 years). Sensitivity analyses indicated larger benefits with more intensive control: achieving SBP <130 mmHg generated 1.9 million and 38.5 million HALYs over 20 years and the lifetime, respectively (undiscounted). Furthermore, achieving SBP <120 mmHg generated 2.4 million HALYs over 20 years and 50.1 million over the lifetime (undiscounted) (see Table 1).

Conclusion: We found that achieving optimal BP control could generate substantial population health gains with more intensive targets delivering greater health benefits, providing a quantitative basis for prioritising the hypertension program within Nepal's non-communicable diseases (NCDs) initiative. As countries scale up the World Health Organization (WHO) HEARTS package and work toward the global BP targets, by implementing intensive BP lowering strategies, including single pill combination, longer prescription period and team-based care, will the full benefits of hypertension management be realized. Country-specific models of this kind are essential to translating global ambitions into locally grounded policy.

Keywords: blood pressure, policy, intervention, Nepal, hypertension, program

Background and Aim: Hypertension is conventionally understood as a disorder of sodium and water retention, but pre-clinical evidence suggests that chronic blood pressure (BP) elevation is part of an adaptive water-conservation response to prevent dehydration. We investigated whether this response is detectable in humans.

Methods: In the Mars500 study, we quantified the effect of 24-h Na⁺ and water balance on morning systolic BP in 6 healthy men living in an enclosed habitat for 205 days on controlled salt intake. We then assessed water-conservation parameters (plasma and urine osmolality, free-water clearance (FWC), urea metabolism) and tissue Na⁺ storage in a cross-sectional comparison of hypertensive (n=47) versus healthy (n=79) participants under daily-life conditions (Sodium Storage in Singaporeans, SSIS; NCT04319068).

Results: In Mars500, BP rose with higher urine osmolality (R²=0.58, p<0.001) and fell with higher water intake (R²=0.22, p<0.05) but was unrelated to Na⁺ intake (R²=0.03, p=0.65). In SSIS, hypertensive patients were older than healthy participants (60.1±6.7 vs 49.2±10.9 years) and showed higher plasma osmolality (300.7±4.8 vs 298.4±4.5 mmol/L) and skin Na⁺ storage (19.1±4.6 vs 16.8±3.9 mmol/L tissue). Both markers correlated with age (r=0.28, p<0.01; r=0.41, p<0.001) and lost significance after age adjustment. 24-h Na⁺ excretion was uncoupled from age or BP. By contrast, a second set of markers was hypertension-specific and age-independent. FWC was markedly reduced (−8.1±14.8 vs −3.1±13.5 mL/kg/d, p<0.01) in hypertension, while urea excretion was increased (325.9±111.0 vs 264.3±92.0 mmol/d, p<0.001) alongside urea-cycle metabolites: citrulline (18.9±20.0 vs 8.7±7.3 mmol/d, p<0.001), ornithine (29.3±26.1 vs 17.1±12.1, p<0.001), argininosuccinate (13.2±5.8 vs 9.9±3.9, p<0.001) and arginine (27.4±21.3 vs 21.1±14.8, p=0.01), indicating increased ureagenesis. Across the cohort, reduced FWC was associated with higher left ventricular mass index, a marker of end-organ damage, independently of systolic BP (β=−0.20 per mL/kg/d, p<0.01; SBP β=0.24 per mmHg, p<0.001).

Conclusion: Hypertension may act as an adaptive, nitrogen-driven mechanism for body water conservation, marked by reduced FWC and increased urea production. Reduced FWC was linked to greater left ventricular mass independently of blood pressure, connecting this state to cardiac remodeling. These findings shift the focus of essential hypertension from traditional sodium-volume retention to a urea-driven, sodium-independent water-conservation mechanism.

Background: Haemodynamic assessment in end-stage heart failure patients with continuous-flow mechanical circulatory support (cfMCS) is challenging because conventional blood pressure and pulse wave measures were developed for pulsatile physiology. In low-pulsatility circulatory states, these measures may not reflect cardiovascular loading conditions in the same way as in normal physiology. We investigated whether integrating pulse-wave analysis (PWA) with Doppler echocardiography could provide a clinically interpretable framework for assessing pressure and flow dynamics in these settings.

Methods: Two patients supported with a HeartMate 3 left ventricular assist device underwent same-day haemodynamic assessment using SphygmoCor XCEL, including brachial and central blood pressure, pulse wave analysis, and carotid-femoral pulse wave velocity (cfPWV). Echocardiographic Doppler waveforms from the carotid and femoral arteries were used to derive flow pulse wave velocity as an alternative measure of arterial stiffness. Pump parameters, including speed, flow, and pulsatility index (PI), were recorded. Pressure-derived and flow-derived velocity measurements were compared.

Results: Case 1 was a 38-year-old male supported at 5000 rpm with a pump flow of 3.6 L/min and PI of 9.0. Brachial blood pressure was 122/86.5 mmHg, while central pressure was 113/92 mmHg (mean 100.5 mmHg). Mean Doppler-derived flow-wave velocity was 0.76 m/s, closely corresponding to cfPWV (0.78 m/s).
Case 2 was a 42-year-old male supported at 5000 rpm with a pump flow of 3.8 L/min and PI of 4.6. Brachial blood pressure was 102/70 mmHg, while central pressure was 98/72 mmHg (mean 83 mmHg). Mean Doppler-derived flow-wave velocity was 0.67 m/s, compared with a cfPWV of 0.8 m/s.
In both cases, temporal alignment of pump parameters, central pressure estimates, and Doppler-derived velocity waveforms were feasible. Image-derived Doppler flow-velocity showed close agreement with cfPWV, although pulse waveform quality control remained a limitation.

Conclusion: In two patients supported by cfMCS, SphygmoCor pulse wave analysis provided measurable estimates of central haemodynamics that could be interpreted alongside echocardiographic Doppler-derived flow velocities and pump parameters. This integrated approach may offer insights into vascular loading and flow dynamics in a low-pulsatility circulation. Further studies with standardised Doppler acquisition, structured echocardiographic assessment, and quality-controlled pulse wave velocity measurements are warranted.

Background: Arterial stiffness predicts cardiovascular risk and mortality, but its role in haemodynamic change after heart transplantation remains unclear. This study assessed whether pre-transplant arterial stiffness in end-stage heart failure patients, measured by carotid-femoral pulse wave velocity (cf-PWV) and pulse waveform analysis (PWA), predicts haemodynamic changes within 6 months after heart transplantation.

Method: Using SphygmoCor XCEL, cf-PWV was measured and radial applanation tonometry was calibrated to brachial cuff pressure to derive PWA parameters, including central systolic pressure, augmentation index and augmentation index normalised to 75 bpm. Assessments were performed before transplant, at discharge and 6 months post-transplant. Wilcoxon signed-rank tests and linear regression were used.

Result: 56 patients underwent baseline PWA assessment (48 with cf-PWV; 56.2±13.3 years, 73% male). Matched post-transplant data were available in 13 patients at discharge (median 8, IQR 6-9, range 4-12; 11 with cf-PWV) and 13 at 6 months (10 with cf-PWV). At discharge, cf-PWV (6.87 to 9.10m/s, p=0.005), CSP (96.5 to 127.5mmHg, p=0.001), AIx (32.3 to 11.0%, p=0.001), AIx@75 (28.8 to 13.2%, p=0.006) and heart rate (67.5 to 83.0bpm, p=0.007) changed significantly. At 6 months, CSP (93.3 to 127.0mmHg, p=0.003), cf-PWV (6.58 to 9.22m/s, p=0.024) and heart rate (66.0 to 93.5bpm, p=0.005) remained elevated, whereas AIx@75 (20.3 to 25.2%, p=0.969) and AIx (28.0 to 18.5%, p=0.078) returned to baseline. A multivariate model combining baseline CSP, cf-PWV and AIx@75 to predict the net CSP change was significant at discharge (R²=0.62, p=0.027). Baseline CSP is the only independent predictor (β=-1.10, p=0.018) while cf-PWV and AIx@75 did not add independent predictive value (p=0.63 and p=0.23). The same multivariate model predicting net CSP change at 6 months was not statistically significant overall (R²=0.36, p=0.234).

Conclusion: Heart transplantation was associated with significant early change in cf-PWV, CSP and AIx@75. At 6 months, cf-PWV, CSP and heart rate remained significantly elevated but AIx@75 returned towards baseline. Baseline CSP independently predicted a smaller net CSP increase at discharge, even after adjusting for cf-PWV and AIx@75, although this reduced by 6 months. Larger samples and longer follow-up in this ongoing study are needed to confirm these findings and determine their clinical significance.

Background and Aim: Central/visceral adiposity is an age-independent risk factor for hypertension, yet chronological age poorly reflects the biological state of adipose tissue, which redistributes from subcutaneous to visceral compartments across the lifespan. We examined whether the MRI-derived visceral-to-subcutaneous adipose tissue ratio (VAT/SAT) captures this redistribution and can generate an individualized adipose biological-age estimate that may flag accelerated hypertension susceptibility before blood pressure itself changes.

Methods: This cross-sectional analysis included 113 adults (33 male, 29.2%) aged 8-63 years (mean 41.8 ± 15.6). Whole-abdominal VAT and SAT volumes were quantified via automated deep-learning MRI segmentation. Age-related trajectories were modelled using linear and quadratic regression with leave-one-out cross-validation, including sex-stratified and sex-specific exponential models. An individualized Risk Equivalent Adipose Age (REAA) was derived by mapping each participant's VAT/SAT ratio onto an age- and sex-specific reference trajectory; deviations were standardized to local age-window variability as an Adipose Age Acceleration (AAA) score (1 SD = 5 years), with REAA defined as chronological age plus AAA.

Results: VAT/SAT ratio showed the strongest association with chronological age among adipose metrics (LOOCV R²=0.459 vs 0.236 for VAT and 0.067 for SAT alone), following a nonlinear, accelerating, sex-divergent trajectory; the fully adjusted VAT/SAT model reached its highest predictive performance at R²=0.530. Weight adjustment substantially improved prediction of absolute adipose volumes but minimally affected the VAT/SAT-age association, indicating redistribution is largely age-driven while expansion is weight-driven. REAA closely approximated chronological age at the population level (42.2 ± 16.2 vs 41.8 ± 15.2 years; R²=0.926), while individual AAA ranged from -7.7 to +13.5 years. Participants with a high VAT/SAT phenotype showed a mean REAA of 58.3 years against a chronological age of 54.8 years (AAA +3.5 years), with 41.4% showing acceleration exceeding 5 years.

Conclusions: The MRI-derived VAT/SAT ratio is a weight-independent, sex-dimorphic correlate of chronological age and supports an individualized adipose biological-age metric (REAA/AAA) that captures substantial inter-individual variability in visceral adiposity, a key hypertension risk factor, beyond what chronological age alone reveals. Longitudinal, blood pressure-linked, and externally validated cohorts are needed to establish its utility for early hypertension risk stratification.

Background and Aim: The benefits of trial participation during the trial period are understood. However, it is not known how trial participation impacts health-seeking behaviours beyond the trial period. Ninety-four percent of QUARTET trial participants consented to data linkage, providing an opportunity to examine behavioural changes using administrative data. We want to examine the impact of trial participation on primary care access and blood-pressure lowering medication possession for QUARTET trial participants and identify the associated with health-seeking behaviour change.

Method: Medicare and Pharmaceutical Benefits Schedule data were extracted for consenting participants. Medication possession ratio (MPR) for the six months before (pre-trial period) and six months after the trial (post-trial period) was compared using t-tests for those on medication before the trial. Pre- and post-trial health service use was compared for all participants using t-tests. Multivariable models assessed the impact of participant socio-demographic characteristics on changing medication adherence and primary care access in the post-trial period.

Results: Data from 409 participants were included in the analyses. In those treated for high blood pressure before the trial (n=207), mean MPR for any blood pressure lowering medication was 0.787 pre-trial and 0.982 post-trial (mean difference 0.195; 95% Confidence Interval [CI] 0.113– 0.276). Among all participants, mean (SD) General Practitioner (GP) visits increased from 3.6 (3.34) visits in the six months before the trial to 4.0 (3.37) in the six months after (mean difference 0.432; 95% CI 0.136 – 0.728). Across both baseline treatment groups, 192 (49.5%) participants had progressed onto combination therapy. There were no statistically significant predictors of health-seeking behaviour change.

Conclusion: Overall, there was evidence of greater blood pressure lowering medication possession and GP visits in the post-trial period, with almost half using combination therapy. Trial participation may foster improved health-seeking behaviours beyond the trial.

Background: Polycystic kidney disease (PKD) is a common genetic condition where fluid filled cysts destroy kidney tissue, ultimately leading to kidney failure. Patients have high blood pressure and are at increased risk of comorbidities including heart attack, stroke and cognitive impairment. Inflammation and vascular changes have been suggested to play a role is all these conditions, yet the exact mechanisms, especially that drive cognitive impairment is not fully understood. We aim to establish the first rat model of PKD-induced cognitive impairment and elucidate potential mechanisms.

Methods: Male and female Lewis wild-type (WT, n=10) and Lewis polycystic kidney (LPK, n=10) rats were studied at 6, 12 and 18 weeks of age. Cognition was assessed using the novel object recognition and Y-maze tests. Aortic thickening and brain changes were assessed using histology. Brain inflammation was measured using qPCR.

Results: LPK rats were hypertensive (p<0.001), had heavier kidneys (p<0.001) and impaired kidney function (p<0.001). LPK rats had intact recognition memory but spatial working memory was impaired at 12 and 18 weeks of age (p<0.05). By 12 weeks the LPK animals had impaired blood brain barrier integrity (p<0.05) and a lower neuron number in the hippocampus of the brains (p<0.05) concurrent with changes in the number of astrocytes and microglia (p<0.05). At 18 weeks, inflammation in the prefrontal cortex was altered. While there was no change in TNFα levels, inflammasome-derived inflammation had decreased (mRNA of NLRP3, IL-18, p<0.05), while IL-1β had increased (p<0.05) in LPK animals. Abdominal aortic thickness increased in LPKs from 6 weeks (0.36±0.01mM) to 18 weeks (0.64±0.06mM, p<0.001).

Conclusion: Our findings support the LPK rat as a model for studying cognitive impairment associated with progression PKD, yet the phenotype is unlikely to result from a single mechanism. Instead, multiple kidney, vascular and neurological processes may contribute to cognitive impairment in this model.

Background and aim: The current prevalence of elevated blood pressure and hypertension in children and adolescents is 1 in 10 children and 1 in 20 children respectively. Hypertension is often asymptomatic, and there is evidence that childhood blood pressure tracks into adulthood, increasing the risk of fatal and non-fatal cardiovascular events in adulthood. International guidelines provide recommendations about screening, diagnosis and management of hypertension in childhood and adolescence. Australia has recently released a paediatric guideline that accounted for population and healthcare differences and promoted best practice locally. This review details the scoping review of international guidelines that informed this guideline.

Methods: A structured search strategy was implemented using PubMed, Medline and Embase to identify clinical practice guidelines published between 2015 and 2025, with a primary focus on screening and diagnosis of hypertension. Selected guidelines were evaluated with the Appraisal of Guidelines for Research and Evaluation (AGREE II) tool with respect to scope and purpose, stakeholder involvement, rigour of development, clarity of presentation, applicability and editorial independence.

Results: International guidelines varied with respect to level of detail and whether they were standalone or incorporated as a section of primarily adult-focused guidelines. There was broad agreement on key recommendations around the need for screening, role of ambulatory monitoring and general approach to investigation and management. Specific differences mainly related to screening frequency/setting, initial investigations, definition of diagnostic thresholds and the age for transition to adult thresholds. Guidelines from the American Academy of Pediatrics (AAP) and European Society of Hypertension (ESH) were subjected to detailed evaluation with AGREE II. The AAP guideline generally scored higher than the ESH guideline. The AAP had the highest domain average score of 100% for “editorial independence”, followed by “scope and purpose” with an average score of 98.6%, and “clarity of presentation” with an average score of 95.7%.

Conclusion: We conclude that there is a broad consensus internationally regarding recommendations for the detection and management of hypertension in children and adolescents, with differences arising from regional differences and specific evidence gaps.

Background and Aim: Blood pressure often deteriorates before hypertension is established, but early susceptibility and individual exercise responses remain poorly characterised in adults with abdominal obesity. We investigated whether visceral adipose tissue (VAT), beyond body mass index (BMI) and conventional metabolic markers, identifies early blood pressure dysregulation, and whether blood pressure trajectories after high-intensity interval training (HIIT) reveal heterogeneous progression toward hypertension.

Methods: We performed a secondary analysis of a single-centre, assessor-blinded RCT of 197 adults with abdominal obesity randomised to control, once-weekly, or three-times-weekly HIIT. BP was categorised as optimal, normal, high-normal, or hypertension-range. Among 166 non-hypertensive participants, early dysregulation (normal/high-normal vs optimal) was modelled via logistic and ordinal regression against age, sex, BMI, VAT volume, fasting glucose, triglycerides, HDL-cholesterol, and VO2max. Longitudinal trajectories were analysed with mixed-effects models, and BP-stage transitions (improvement, persistence, progression) were assessed among 196 participants with paired data.

Results: Early BP dysregulation was present in 78 (47.0%) of 166 participants. VAT was the strongest adiposity correlate: each SD increase was associated with 2.61-fold higher odds of dysregulation after full adjustment (95% CI 1.35-5.02; P=0.004), whereas BMI was not independently associated (OR 0.76, 0.44-1.29; P=0.307). Male sex was also independently associated (OR 4.85, 1.79-14.10; P=0.003), and VAT predicted progressively higher BP stage (OR 1.43 per 100 mL, 1.10-1.89; P=0.009). VAT discriminated dysregulation better than BMI, triglycerides, age, or fitness (AUC 0.738 vs 0.592-0.660); the full model reached AUC 0.806. SBP and DBP fell over time, with no significant time-by-HIIT interaction. Among 196 participants with paired measurements, 64 (32.7%) improved, 107 (54.6%) remained stable, and 25 (12.8%) progressed; progression was unexpectedly more frequent with HIIT (OR 4.20, 1.25-19.62; P=0.035), with a stronger, dose-related signal for three-times-weekly HIIT (OR 5.02, P=0.025) than once-weekly HIIT (OR 3.44, P=0.094).

Conclusions: MRI-derived visceral adiposity was the strongest independent baseline correlate of early BP dysregulation beyond BMI. Despite overall reductions in BP after exercise, individual trajectories were heterogeneous, with a subset progressing to higher stages. These findings support visceral adiposity as a marker of early BP vulnerability and highlight monitoring individual trajectories over mean changes alone.

Background and Aim: Primary aldosteronism (PA) is one of the most common secondary causes of hypertension, affecting 10-30% of hypertensive patients. Despite the increased risk of cardiovascular disease associated with PA compared to essential hypertension, only 1-2% of eligible patients are tested for PA. We evaluated the effectiveness of systematic PA screening among patients with hypertension admitted to a dedicated heart hospital.

Methods: All patients admitted under medical cardiology teams at the Victorian Heart Hospital from March to May 2026 were assessed for PA screening. Patients with documented hypertension or persistent blood pressure >130/80 mmHg were screened using the aldosterone-to-renin ratio (ARR). Overseas visitors and patients receiving dialysis were excluded; patients requiring intensive care were screened after transfer to the ward.
Using the 2025 Endocrine Society criteria, “PA Likely” was defined as ARR >70 pmol/mU, plasma aldosterone ≥277 pmol/L, and direct renin ≤8.2 mU/L. “PA Possible” was defined as ARR >20 pmol/mU while taking interfering antihypertensive medications, or ARR >70 pmol/mU without meeting aldosterone or renin thresholds.

Results: Among 811 admissions, 511 patients (63%) had hypertension and 382 underwent PA screening (median age, 71 years; 34% female). Compared to males, females were older (median age 75.9 vs 68.4 years), had lower diastolic blood pressure, higher ARR and lower potassium levels (p <0.05). Overall, 25 (6.5%) met criteria for PA Likely and 91 (23.8%) for PA Possible. Women had greater odds of an abnormal PA screening result than men (OR, 2.47; 95% CI, 1.47–4.17). Higher systolic and diastolic blood pressure were also associated with abnormal screening results (OR per mmHg, 1.02 [95% CI, 1.01–1.03] and 1.04 [1.02–1.06], respectively). Patients admitted with coronary artery disease had lower odds of an abnormal result (OR, 0.43; 95% CI, 0.23–0.81); other admission diagnoses were not associated with screening outcomes.

Conclusions: Systematic screening in a heart hospital identified likely or possible PA in almost a third of the hypertensive patients. These findings demonstrate the high yield of systematic PA screening among cardiology inpatients and support incorporating PA detection into routine hypertension care.

Background: Blood pressure (BP) regulation is complex, particularly in hypertensive disorders of pregnancy such as preeclampsia. Inducing experimental preeclampsia through uteroplacental ischemia (UPI) leads to BP elevation, proteinuria, and increased circulating
sFlt-1.

Aim: To characterise variation in the experimental preeclampsia model based on changes in soluble fms-like tyrosine kinase-1 (sFlt-1) and BP, and to evaluate BP changes using average BP, BP load, BP variability, and a chaos algorithm.

Methods: Continuous BP was measured via telemetry in nine pregnant Papio hamadryas (baboons) from 2 days before, to 10 days after UPI. Animals were allocated into Group 1 or 2 based on the magnitude of sFlt-1 increase. BP was analysed using four methods: average systolic and diastolic BP (SBP and DBP), BP load, BP variability (SD ratio from Poincaré plots), and chaos analysis.

Results: Both groups showed statistically significant increases in average SBP and DBP after UPI. BP load also increased significantly in both groups. In Group 1, elevated BP load readings increased post-UPI, while critical BP load readings remained unchanged. In Group 2, elevated BP load readings were stable, but critical BP load readings increased. BP variability analysis showed Group 1 SD ratio (SBP and DBP) decreased, indicating and that long-term BP variation is larger relative to short-term BP variation after UPI. In Group 2, the SD ratio (SBP and DBP) increases after UPI, indicating short-term BP variation is larger relative to long-term variation after UPI. Chaos analysis characterised BP dynamics as stochastic before and after UPI.

Conclusion: UPI results in significant increases in BP average, BP load and altered BP variability. Using multiple methods to analyse BP demonstrates that BP dynamics are not captured by average BP alone. Additional methods of BP analysis provide greater understanding into the hemodynamic changes associated with UPI.

Background: Megadose sodium ascorbate is emerging as a potential therapy to improve blood pressure management in septic shock. In a Phase 1a clinical trial, ~1 g/kg intravenous sodium ascorbate administered over 6-h demonstrated reduced requirements for noradrenaline to restore blood pressure in patients with septic shock. However, rapid administration of this dose increased plasma sodium, potentially limiting its safety in patients with pre-existing renal impairments. Preclinical studies subsequently identified 3 g/kg as the minimum therapeutic dose for reversing septic cardiovascular and renal dysfunction.

Aims: To optimise the sodium infusion regimen to minimise hypernatremia while preserving therapeutic efficacy on cardiovascular and renal function.

Methods: Sepsis was induced in adult female sheep (n=5) by intravenous infusion of live Escherichia coli. At 23 h of sepsis, animals received intravenous sodium ascorbate 3 g/kg administered over 18-h. Renal medullary tissue oxygenation was continuously monitored using a surgically implanted fibre-optic probe. Noradrenaline was titrated to restore mean arterial pressure to 75-80 mmHg. Cardiovascular, metabolic and renal physiological responses were assessed throughout the study.

Results: At 23-h, sepsis was characterised by hypotension, tachycardia, fever and hyperlactatemia. Following sodium ascorbate administration, target blood pressure of 75-80 mmHg was achieved, despite all sheep being weaned from noradrenaline at 13-h post-infusion. Sodium ascorbate reduced degree of tachycardia (from 153.0±1.4 to 113.2±11.5 beats/min, P=0.02). Prolonged 18-h infusion prevented the rise in arterial sodium, which remained unchanged from pre-treatment levels (138.2±3.0 vs 138.8±3.7 mmol/L; P=0.41). Sepsis induced renal medullary tissue hypoxia (from 31.6±4.0 to 17.2±6.8 mmHg; P=0.03). Sodium ascorbate restored renal medullary oxygenation to pre-morbid baseline values (to 37.4±11.6 mmHg), reduced body temperature (from 41.2±0.4 to 39.6±0.3 °C, P=0.03) and the severity of hyperlactatemia (1.0±0.2 to 0.66±0.1 mmol/L, P=0.04[YL2.1]).

Conclusion: Extending administration of megadose sodium ascorbate to 18-h prevented treatment-associated hypernatremia while preserving its beneficial effects on cardiovascular function and renal medullary oxygenation in sepsis. This optimized regimen is currently being evaluated in an Australia-wide multicentre Phase 1b clinical trial at 12 hospitals (ANZCTRN12625001401448) to improve blood pressure management in critically ill patients with septic shock.

Background: Pulmonary hypertension (PH) is an independent risk factor for all-cause mortality in patients with chronic kidney disease (CKD). However, data on the burden of PH among non-dialysis-dependent CKD patients remain limited, particularly in low-resource settings.

Methods: We conducted a cross-sectional study among non-dialysis-dependent CKD patients. PH was defined as an echocardiography-estimated pulmonary artery systolic pressure greater than 35 millimetres of mercury. Multivariable logistic regression analyses were performed to identify factors independently associated with PH.

Results: A total of 773 participants were included (mean age 52.4 ± 17.5 years; 57.1 percent male). PH was present in 23.3 percent of patients. In multivariable analyses, older age (odds ratio 1.90 per 10-year increase; 95% confidence interval 1.50–2.40), lower haemoglobin levels (odds ratio 1.40 per standard deviation decrease; 95% confidence interval 1.20–1.60), reduced left ventricular ejection fraction (odds ratio 1.10 per standard deviation decrease; 95% confidence interval 1.00–1.20), and lower estimated glomerular filtration rate (odds ratio 1.10 per standard deviation decrease; 95% confidence interval 1.00–1.10) were independently associated with PH.

Conclusion: PH is common among non-dialysis-dependent CKD patients and is independently associated with older age, anaemia, impaired cardiac systolic function, and reduced kidney function. In settings where right-heart catheterisation is unavailable, echocardiography may help identify CKD patients with elevated pulmonary artery pressures who may benefit from closer cardiopulmonary evaluation.

Background: Raised blood pressure (BP) is the leading modifiable risk factor for preventable deaths worldwide. Accurate BP measurement is essential for the diagnosis and management of hypertension. Novel commercial cuffless BP devices are increasingly available on the market, but their accuracy remains uncertain because they differ in function, calibration method, and have device-specific accuracy challenges. The European Society of Hypertension (ESH) published recommendations in 2023 defining nine device types, each requiring a specific subset of six validation tests. Systematic evaluation is needed to determine whether commercial devices meet the relevant ESH recommendations.

Aim: To systematically identify commercial cuffless BP devices evaluated in published literature, and to compare their reported accuracy outcomes and validation tests with the 2023 ESH recommendations.

Methods: This systematic review followed a prospectively registered protocol (PROSPERO CRD420261302600) and PRISMA guidelines. PubMed, Embase via Ovid, Web of Science, Scopus, CINAHL, and the Cochrane Central Register of Controlled Trials were searched from inception to 13 March 2026 for English-language studies evaluating the accuracy of commercial cuffless BP devices. Two reviewers independently screened and selected studies using Covidence, with data extraction ongoing.

Results: The database search identified 5,889 records, of which 2,935 remained after duplicate removal. Following title and abstract screening, 181 full-text articles were assessed for eligibility, and 52 were included. These reported 65 validation studies evaluating 27 unique cuffless BP devices. Most devices required calibration (n=20): 17 were cuff-calibrated, including nine manual, seven automated, and one automated heart-level device, while three were manual demographic-calibrated devices. The remaining seven devices were calibration-free: six manual and one automated. Of the 65 validation tests, static tests predominated (n=38), while BP-change testing (n=14) comprised 13 awake/asleep tests and one treatment test; device position (n=5), recalibration (n=2), and other tests (n=6) were less common.

Conclusion: Most evaluated cuffless devices require cuff calibration for which the ESH does not require a static test. Yet published studies predominantly reported static testing which misrepresents the device as accurate. Very few reported the ESH required BP-change tests. Although many studies predated the recommendations, substantial gaps remain in device-specific validation evidence required to support clinical use.

Background and Aim: Oral care is important for survivors of stroke but is inconsistently delivered in inpatient settings. Stroke-related impairments can increase dependence on healthcare professionals, while poor oral hygiene may contribute to complications including stroke-associated pneumonia. Evidence on how nurses and allied health professionals experience, prioritise and deliver oral care remains fragmented. Therefore, we aim to map and synthesise evidence on their experiences, challenges and perceptions regarding oral care practices for adult inpatients post-stroke.

Methods: The review is being conducted in accordance with JBI methodology and will be reported using PRISMA-ScR. We searched CINAHL, MEDLINE, PsycINFO and Scopus databases to identify qualitative, quantitative and mixed methods studies published between January 2016 and June 2026. Google Scholar was used to search for grey literature. Eligibility criteria were developed using the Population-Concept-Context framework. Primary research reporting extractable data from nurses or allied health professionals in adult inpatient stroke settings were included. Title and abstract screening and full-text screening were conducted by two reviewers, with conflicts resolved by a third reviewer. Data extraction is in progress.

Preliminary Findings: Full-text screening of database records identified 25 studies meeting eligibility criteria. Preliminary data extraction from three studies identified recurring barriers to oral-care delivery, including limited time and resources, competing clinical priorities, gaps in training and confidence, unclear professional roles and guidance, and patient-related complexity such as dysphagia and cognitive impairment. Potential facilitators included structured education, clearer protocols, accessible resources and multidisciplinary involvement.

Conclusions: Preliminary findings suggest that oral-care delivery after stroke is influenced by a mix of professional, organisational and patient-related factors. Education, clearer guidance, adequate resources and multidisciplinary involvement may support more consistent care.

Introduction: Better management of hypertension starts with measurement. May Measurement Month (MMM) is a global blood pressure (BP) screening initiative conducted in public places, physician offices, workplaces and pharmacies worldwide. Pharmacies are highly accessible primary care hubs. Pharmacists are highly trusted, respected primary care professionals and typically see their patients up to 10 times more frequently than patients see their physician. Indeed, pharmacies might be the ideal venue for BP screening, yet their contribution has not been described on a global level. We sought to describe and quantify the contributions of pharmacy-based BP screening within the MMM initiative.

Methods: We used the MMM dataset from 2018 and 2019 (the years when pharmacy was identified as the screening site). Subjects >18y were recruited to have 3 BP measurements using standardized methods and validated BP devices. Hypertension was defined as a systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg based on the mean of the last 2 measurements or taking BP-lowering medication.

Results: Of the 98 countries participating, 60 provided data from pharmacies for a total of 114,407 subjects (3.8% of total). Average age was 52 (SD 16.8) in pharmacies, vs 45.3 (SD 16.9) in other screening settings, while 57.4% were female in pharmacies, vs 52.0% in other settings. Average BP was 125 (SD 19.2)/77 (SD 11.6) in pharmacies, vs 123 (SD 18.4)/77.7 (SD 11.4) in other screening settings. In pharmacies, 45.7% had hypertension vs 33.1% in other settings (adjusted OR
1.07, 95% CI: 1.04–1.09); 40% screened in pharmacies had awareness of hypertension, vs 23.8% in other settings (adjusted OR 0.98, 95% CI: 0.95–1.00).

Conclusions: Patients screened in pharmacies are typically older, female, and have hypertension vs other venues. Importantly, pharmacists can treat and/or link patients to care, thus improving hypertension care beyond screening.

Background: Women and families often seek information about preeclampsia, a severe form of hypertension in pregnancy. Sources are either highly technical (scholarly information), or heavily anecdotal and skewed towards individual concerns and outcomes. The need for access to trusted information, provided in a readable form has never been greater and could be actioned by an appropriate artificial intelligence strategy. The aim of this prototype was to leverage large language models and knowledge graphs to create an education tool for preeclampsia, using the trusted information in the Society for Obstetric Medicine of Australia and New Zealand (SOAMNZ) 2023 Guideline, with a socratic tone of conversational engagement.

Methods: Using a cross-functional team and co-design methodology, the parameters for the chatbot design evolved over three stages; 1) determining the knowledge corpus anchored to the SOMANZ Guideline; 2) engineering the knowledge graph representation of this corpus validated by subject matter experts; 3) optimising retrieval augmented generation from the knowledge graph using hypothetical document embeddings (HyDE); and 4) develop low-latency conversational speech-to-text and text-to-speech user interface (with potential for multi-lingual capabilities). The usability of the chatbot will be tested and evolved through 3 consumer workshops conducted in South Western Sydney. No personal or clinical data will be collected.

Results: The team has been assembled and the rapid prototyping approach will use prompt “cards” describing proposed intended use, explicit non-use, data positioning, build posture. The team will develop the innovation challenge, the innovation brief, scope decision, critical assumptions and critical unknowns, and subject matter experts.

Conclusion: The PreggoCannon2.0 Bot will be launched by Dec 2026 and evaluated through functional data of the person-bot interactions with a plan for continual refinements and improvement.

Metabolically healthy overweight/obesity are associated with increased risk of cardiovascular disease in adults, even in the absence of metabolic risk factors: A systematic review and meta-analysis of prospective cohort studies
Jacob Opio 1, Emma Croker 2, George S Odongo 3, John Attia 1 4, Katie Wynne 1 2 4, Mark McEvoy 1 4

This review examined the risk of cardiovascular disease in adults with metabolically healthy overweight/obesity. A systematic review and meta-analysis using data from Medline, EMBASE, SCOPUS and Cochrane Library searched from inception up to 31st October 2019. We included prospective cohort studies of adults who are metabolically healthy or unhealthy. Outcomes were fatal and nonfatal cardiovascular events, all-cause mortality. Pooled relative risk was calculated for each outcome in populations with metabolically healthy overweight and metabolically healthy obesity using metabolically healthy normal weight as reference. A random-effects model was used for meta-analysis, and risk of bias assessment tool for nonrandomized studies assessed risk of bias within each study. Twenty-three prospective cohort studies with 4,492,723 participants were included. Cardiovascular disease risk was increased in metabolically healthy groups with overweight (RR = 1.34, CI: 1.23-1.46, n = 20, I2 = 90.3%) and obesity (RR = 1.58, CI: 1.34-1.85, n = 21, I2 = 92.2) compared with a reference group with metabolically healthy normal weight. Cardiovascular disease risk was similar irrespective of the number of risk factors used to define metabolically healthy and the risk remained in the group with no metabolic risk factors.
Cardiovascular disease risk is increased in populations with overweight and obesity classified as metabolically healthy even when there were no metabolic risk factors.

Keywords: cardiovascular disease; metabolic health; obesity; overweight.

Background and Aim: Vulnerable atherosclerotic plaque is the principal pathological substrate underlying most acute coronary syndromes. Conventional cardiovascular risk assessment based on luminal stenosis and traditional risk factors has limited ability to identify plaques at imminent risk of rupture. This systematic review evaluated associations between circulating molecular biomarkers and advanced cardiovascular imaging characteristics of vulnerable atherosclerotic plaque in human studies and assessed their potential role in improving cardiovascular risk stratification.

Methods: A systematic review of PubMed/MEDLINE was conducted in accordance with PRISMA guidelines. Peer-reviewed English-language human studies investigating circulating biomarkers in relation to imaging-defined vulnerable plaque were included. Owing to substantial heterogeneity in study design, biomarker assays, imaging modalities and outcome measures, findings were synthesised narratively.

Results: Forty-three studies comprising 15,892 participants were included. Lipid-related biomarkers, particularly lipoprotein(a), PCSK9, ApoB/ApoA1 ratio and oxidative lipid markers, were associated with adverse plaque morphology. Inflammatory biomarkers, including MMP-9, hsCRP, IL-6, TNF-α, IL-1Ra and resistin, were associated with imaging-defined plaque vulnerability. Metabolic biomarkers, including adiponectin, cardiometabolic index and MASLD/MAFLD, further demonstrated the contribution of systemic metabolic dysfunction. TMAO showed a strong independent association with thin-cap fibroatheroma (OR 7.455, 95% CI 2.753–20.189; P<0.001). MAFLD predicted major adverse cardiovascular events (HR 3.65, 95% CI 1.83–7.26; P<0.001), while MASLD predicted MACE beyond CCTA findings (HR 1.82, 95% CI 1.18–2.83; P=0.007). OCT, IVUS, VH-IVUS, CCTA and FDG-PET provided complementary assessment of plaque morphology, composition and inflammatory activity. No single biomarker or imaging modality reliably identified vulnerable plaque.

Conclusions: Vulnerable plaque is a multifactorial biological process driven by interactions between lipid dysregulation, inflammation, metabolic dysfunction and structural remodelling. Integrating circulating biomarkers with advanced cardiovascular imaging offers a promising strategy for improving identification of high-risk plaque and advancing precision cardiovascular medicine. Further prospective multicentre studies are required to validate this multimodal approach.

Background and aim: Large language models (LLMs) are increasingly applied for many tasks, including clinical research. However, their ability to perform research tasks is largely untested, and retrospective evaluations risk training-data contamination. We prospectively compared predictions from LLMs with those of human experts and with the unpublished observed results of a randomised controlled trial.

Methods: The Shop-to-Stop Hypertension trial is a cluster-randomised opportunistic screening trial conducted in self-operated kiosks, in which text-based nudges prompted participants in the intervention arm to repeat kiosk checks and seek medical follow-up. Before the trial results were published, nine LLMs (Gemini, ChatGPT, Claude Sonnet and Opus, Copilot, Grok, Mistral, Perplexity, Consensus) each received one identical prompt. The prompt provided the published protocol’s identifier and named the primary outcome (between-group difference in repeat blood pressure checks at a health kiosk) and three prespecified secondary outcomes (net change in systolic and diastolic blood pressure, self-reported general practitioner (GP) attendance), requiring a point estimate and predicted significance. Four independent hypertension experts (at least ten years’ experience, no involvement in this trial) provided the same predictions. Predictions were compared descriptively with observed results.

Results: Repeat kiosk checks occurred in 9.8% of control and 12.0% of intervention participants (2.2 percentage points, non-significant). All LLMs overestimated this effect (mean 10.3 percentage points), as did all experts, and all LLMs and experts falsely predicted significance. Observed net systolic change was −0.75 mmHg. All LLMs but one (Claude Opus) overestimated it (LLM mean −3.0 mmHg, expert mean −5.75 mmHg), with five of nine LLMs falsely predicting significance. Observed diastolic change was a non-significant +0.71 mmHg, but all LLMs predicted a reduction. GP attendance was 79% in the control and 88% in the intervention group. LLMs underestimated GP attendance in both arms but on average predicted a difference close to that observed (mean predicted difference 10 percentage points). Expert predictions diverged from observed results more than LLMs on every outcome.

Conclusions: Both LLMs and human experts systematically overestimated intervention effect size and statistical significance when predicting trial outcomes prospectively. These models cannot currently be relied upon to predict clinical trial outcomes.

Background and aim: Hypertension guidelines recommend five-minutes seated rest before blood pressure (BP) measurements to support patient relaxation and accuracy. However, some patients report difficulty in sitting still and relaxing for five minutes. This could influence BP levels but has never been determined and was the aim of this study.

Methods: 344 participants (aged 64.9±15.8 years; 59.3% female) underwent standardised (unattended) automated office BP measurement across general practices, pharmacies and community settings in regional Tasmania, Australia. The BP measurement protocol included 5-minutes seated rest before three measures were recorded 30 seconds apart. Heart rate was also recorded at the same time as BP (all were averaged for analysis). Immediately after measurements, participants were asked to rate perceived relaxation during measurement on a five-point Likert scale from ‘very-relaxed’ (1) to ‘not-relaxed at all’ (5). Associations of perceived relaxation with BP and hypertension status (threshold ≥135/85 mmHg) were examined using multivariable regression adjusted for age, sex, measurement setting, hypertension diagnosis, cholesterol status, diabetes and smoking.

Results: Among all participants, 190 (55.2%) reported being ‘very-relaxed,’ 117 (34.0%) ‘somewhat-relaxed,’ 28 (8.1%) ‘neutral,’ and only 9 (2.6%) reported being ‘not-relaxed’ (either ‘somewhat not-relaxed’ n=5 or ‘not-relaxed at all’ n=4). Lower perceived relaxation was associated with progressively higher systolic BP. Compared with ‘very-relaxed’ participants, systolic BP was 6.25 (95% CI 1.49-11.01) mmHg higher among those ‘somewhat-relaxed’ and 12.50 (95% CI 4.82-20.18; overall p=0.001) mmHg higher among those ‘neutral/not-relaxed.’ Pulse pressure showed a similar pattern (+4.61 and +8.98 mmHg; overall p=0.002). ‘Neutral/not-relaxed’ participants had greater odds of being hypertensive compared with those reporting to be ‘very-relaxed’ or ‘somewhat relaxed’ (OR 2.58, 95% CI 1.05-6.32 p=0.039). Heart rate was not associated with the perceived relaxation levels.

Conclusions: Despite using a standardised measurement protocol, there was a graded association between the patient’s perceived level of relaxation during BP measurement and the measured BP, including greater odds of having hypertension among those less relaxed. While this study cannot determine causal relationships, the findings suggest that patient relaxation is an important consideration for accurate BP measurement.

Background: Blood pressure variability (BPV) is an independent predictor of adverse cardiovascular outcomes beyond mean blood pressure (BP) alone. While some dietary interventions are known to improve mean BP, their specific impact on BPV remains unclear.

Aims: This systematic review aims to synthesise the current evidence evaluating the effects of dietary interventions on BPV in adults.

Methods: Systematic searches of MEDLINE, Embase, CINAHL, Scopus, and CENTRAL were conducted from inception to 1th July 2026 for randomised controlled trials (RCTs) delivering any dietary intervention and reporting a BPV measurement. Risk of bias was assessed using Cochrane Risk of Bias Tool 2.0. Data synthesis was performed using vote counting of direction of effect.

Results: From 19,209 screened records, 23 RCTs met the eligibility criteria. The effects on BPV were highly heterogeneous across dietary categories. Among the included studies, 13 interventions involving antioxidants, vitamins, and beverages showed inconsistent effects. Notably, interventions with olive leaf extract and black tea reduced BPV as measured by standard deviation (SD) and rate of BP variation, respectively. Conversely, alcohol and sugar-sweetened beverages increased BPV indices, specifically coefficient of variation (CV) and spectral powers (Low Frequency, LF; and High Frequency, HF). Salt or sodium manipulation demonstrated a predominantly neutral effect, with six studies indicating no effect. Only two studies suggested a potential benefit, where the DASH diet combined with low sodium and a Japanese cuisine-based DASH diet decreased BPV as measured by average real variability (ARV) and CV, respectively. The overall certainty of evidence was limited, as most studies were judged to have “some concerns” or “high risk” of bias, primarily due to no-pre specified protocol in BPV analysis.

Conclusions: Current evidence suggests that salt or sodium manipulation has no significant effect on BPV. For other dietary categories, conclusions could not be drawn due to inconsistent findings and heterogeneity across studies.

Background: Blood pressure variability (BPV) is an important predictor of cardiovascular events and stroke, independent of mean blood pressure (BP). In TRIDENT trial, a low-dose triple combination reduced mean BP by 9mmHg and reduced stroke compared with placebo in patients with prior intracerebral haemorrhage. However, its effects on BPV remain unclear.

Methods: TRIDENT (n=1670) was a multinational, double-blind, randomised, placebo-controlled trial in patients with prior intracerebral haemorrhage and systolic BP 130–160 mmHg who completed a 2-week single-blind active run-in phase. Participants were randomised to a triple single-pill combination of telmisartan 20 mg, amlodipine 2.5 mg and indapamide 1.25 mg or matching placebo, in addition to usual care, with a mean follow-up of 3 years. BPV was assessed using the standard deviation (SD), coefficient of variation (CV), average real variability (ARV) and variability independent of the mean (VIM). Between-group differences were assessed using a simple two-sample t-test.

Results: A total of 1557 patients (mean age: 58 years; 33% female) with >1 follow-up BP measurement was included. Compared with placebo, the triple single-pill combination significantly reduced systolic BPV, measured by SD (−2.05 mmHg; 95% CI: −2.73 to −1.36; p<0.001), CV (−0.82%; 95% CI −1.29 to −0.34; p<0.001) and ARV (−2.47 mmHg; 95% CI −3.37 to −1.58; p<0.001), but not VIM (+0.07; 95% CI −0.55 to 0.69; p=0.83). Similar reductions were observed for diastolic BPV across SD (−0.84 mmHg; 95% CI −1.24 to −0.43; p<0.001), CV (−0.47%; 95% CI −0.92 to −0.02; p=0.039) and ARV (−0.84 mmHg; 95% CI −1.39 to −0.30; p=0.003), with no difference in VIM (−0.07; 95% CI −0.44 to 0.30; p=0.70).

Conclusion: In patients with prior intracerebral haemorrhage receiving usual care, a low-dose triple single-pill combination reduced SD, CV and ARV of systolic and diastolic BP variability compared with placebo, but not VIM. As VIM adjusts for mean BP, the lack of a significant difference in VIM indicates that reductions in SD, CV and ARV were predominantly attributable to mean BP lowering.

Background and aim: Implementation of automated office blood pressure (AOBP) measurement within routine general practice remains poorly understood. This study evaluated the feasibility, acceptability and implementation of AOBP in general practice and examined contextual factors and implementation determinants influencing its delivery.

Methods: Between May 2025 and June 2026, AOBP was implemented across four general practices in regional Tasmania, Australia, using the recommended AOBP protocol. A mixed-methods evaluation used the Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) framework to evaluate implementation outcomes, intervention impact, and sustainability. The Practical, Robust Implementation and Sustainability Model (PRISM) was used to examine implementation determinants and contextual factors influencing implementation and sustainability. Data included 544 AOBP measurements, 37 patient interviews, 13 staff surveys, 14 fidelity observations and focus groups with 14 staff.

Results: Across the evaluated RE-AIM dimensions, AOBP reached patients in all four practices and was adopted by each practice, although the extent and continuity of adoption varied. Implementation was similarly context-dependent; when AOBP was delivered, protocol fidelity was generally high. PRISM analysis identified workflow fit, workforce capacity, physical space, organisational readiness and digital infrastructure as key contextual determinants and factors relevant to sustainability. Time pressures, competing clinical priorities, staff turnover and documentation burden constrained delivery, whereas dedicated staff, clear scheduling and organisational support facilitated AOBP integration into routine workflows. Patients described AOBP as acceptable and easy to complete, valuing the rest period, repeated measurements and quiet environment. Staff perceived AOBP as more standardised and trustworthy than conventional BP measurement, while general practitioners reported greater confidence in clinical decision-making. Patient interviews further identified inconsistent communication of results and follow-up pathways as important implementation gaps.

Conclusions: AOBP was feasible and acceptable when implemented in general practices, but the extent and consistency of delivery depended on local context. Scale-up requires context-responsive implementation alongside standardised AOBP protocols, including appropriate measurement environments, defined roles and clinical pathways, consistent patient feedback and follow-up, electronic medical record integration, and audit and feedback.

Background: Blood pressure variability (BPV) is an independent predictor of adverse cardiovascular outcomes beyond mean blood pressure (BP). While antihypertensive medications are known to improve mean BP, their impact on BPV remains unclear.

Aims: The primary aim of this systematic review is to evaluate the effect of different antihypertensive medications on BPV.

Methods: Systematic searches of Medline, Embase, Scopus, CENTRAL, Web-of-Science, CINAHL, and Google Scholar were conducted for randomized controlled trials (RCTs) delivering any antihypertensive medication as an intervention and reporting BPV as an outcome, from inception to Aug 2026. Screening, data extraction and risk of bias assessment was completed by two independent reviewers, and a third reviewer was involved in conflict resolution.

Results: From 12,816 records screened, 224 full texts were reviewed and 105 RCTs met eligibility criteria. There were 75 parallel and 30 crossover trials. 88 studies delivered monotherapy (47 calcium-channel-blocker (CCBs) and 41 non-CCB monotherapy), and 31 compared multi-class combination therapy.
Standard deviation (SD) was most widely reported by 78 studies and was used to evaluate the direction of effect. In 88 studies delivered monotherapy, 27 included studies comparing CCBs with non-CCB treatments. Eleven studies (40.7%) reported findings favourable to CCBs, 12 (44.4%) found no significant difference and 4 (14.8%) reported mixed findings. Of the 36 studies of non-CCB monotherapy, 6 (17%) showed a significant reduction in BPV relative to its comparator, 13 (36%) showed no significant difference, 8 (22%) showed a significant increase and 9 (25%) reported no between-group difference. When comparing the combination therapy of Renin-Angiotensin-System-Inhibitors (RASi)+CCB against RASi+Diuretics, four (80%) studies reported RASi+CCB lowered BPV. Certainty of evidence is limited by moderate-to-high risk of bias, often due to lack of pre-specified protocol regarding BPV analysis.

Conclusions: Current evidence suggests that antihypertensive effects on BPV differ by drug class, with CCBs showing a potential advantage. However, conclusions are limited by inconsistent findings and heterogeneity across studies.

Background and aim: Home blood pressure monitoring (HBPM) is recommended by hypertension guidelines and is clinically useful when performed using standardised methods. However, consumers report that existing HBPM educational resources are difficult to understand, contain information that is not readily actionable, and do not adequately address common HBPM questions. We aimed to co-design consumer-centred HBPM resources with people who use HBPM to improve the accessibility, acceptability and implementation of guideline-recommended monitoring practices.

Methods: Participants included adults with lived experience of hypertension and/or HBPM, including a consumer advocate, members of a lived experience advisory group and observers from the Heart Foundation. An iterative co-design process comprised three workshops, each guided by a PowerPoint presentation and involving 7-10 participants/workshop. Participants reviewed three online Australian HBPM resources, including the Heart Foundation resource and provided structured feedback on content, format, usability and readability. Participants were tasked with co-designing a consumer-facing resource that retained essential evidence-based recommendations from the Australian HBPM expert consensus statement while improving understandability, readability (Grade-8-level), practicality and accessibility. Small group discussions and a show-of-hands determined participant preferences and agreement on proposed revisions. Feedback was analysed deductively, and draft resources underwent sequential rounds of review and refinement until consensus was achieved.

Results: Participants identified the Heart Foundation HBPM resource as the preferred base for revision. Key recommendations included simplifying language, improving the visual layout, expanding practical guidance on how to perform HBPM, and developing an accompanying frequently asked questions resource with additional information about hypertension and HBPM. Participants also recommended removing information perceived as difficult for consumers to act upon independently, including instructions for confirming device validation. Following three rounds of revision, the final resource consisted of a concise 1-page double-sided printable format designed to support guideline-concordant HBPM while addressing commonly identified consumer information needs.

Conclusions: Through an iterative co-design process involving consumers and key stakeholders, evidence-based Australian HBPM resources were redesigned to better align with consumer information needs while preserving key guideline recommendations. The revised resources may enable more consumers to correctly apply guideline-concordant HBPM and support broader implementation of HBPM in routine hypertension care. National dissemination is planned for 2027.