Background and Aim: Ambulatory blood pressure monitoring (ABPM) provides superior cardiovascular risk stratification, yet most human studies assessing the relationship between the gut microbiota and blood pressure (BP) rely on office BP and low‑resolution profiling of microbial species. We aimed to identify gut microbial, metabolic, and host proteomic signatures associated with ABPM measurements adults with untreated BP using an integrated multi‑omics approach.

Methods: Faecal metagenomic shotgun sequencing was performed on 118 untreated participants across three Australian cohorts with 24‑hour ABPM. A subset (n=61) underwent faecal metaproteomics, untargeted plasma metabolomics, plasma and faecal short‑chain fatty acid (SCFA) quantification, and dietary assessment using 3-day food records. Associations between microbial diversity, species abundances, host plasma proteomics, SCFAs, diet, and ABPM metrics were assessed using multivariate regression, PERMANOVA, and multiblock sparse PLS.

Results: Gut bacterial diversity was inversely associated with diastolic BP (DBP), including 24‑hour (P = 0.01), daytime (P = 0.02), and night‑time DBP (P = 0.008). Gut bacterial diversity analyses showed significant compositional differences with DBP (weighted UniFrac PERMANOVA: P = 3×10⁻⁴, R² = 0.05).
Fifteen microbial species were associated with elevated systolic or diastolic BP (all q < 0.05). A key BP‑associated species identified is Akkermansia biwaensis, a pro-inflammatory mucin‑degrading bacteria.
Multi‑omics integration revealed two host molecular clusters correlated with BP‑associated taxa. Features negatively correlated with these taxa played roles in vascular function (e.g., sodium/potassium-transporting ATPase subunit alpha-2) and oxidative stress‑handling (e.g., L-tryptophan), while positively associated features were implicated in lipid‑related processes (including many fatty acids), vascular dysfunction (e.g., TMAO), immune activation (including many immunoglobulins) and epithelial‑barrier function (e.g., mucins 5AC and 12). Total faecal SCFAs were positively associated with D. fastidiosa (P=7.8x10-5). Diets low in fibre and high in refined grains and fat were associated with enrichment of BP‑associated taxa (all q < 0.1), with refined‑grain intake correlating with BP (P = 0.02).

Conclusions: Gut microbial composition and host metabolic signatures track with 24‑hour BP in untreated adults. Clinically relevant taxa and mechanisms include a pro-inflammatory mucin‑degrading Akkermansia lineage, altered SCFA metabolism, and oxidative stress biology, highlighting a gut–vascular axis with potential relevance for future risk stratification and therapeutic development.

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 July 24th 2026. Screening, data extraction and risk of bias assessment was completed by two independent reviewers, with a third reviewer for 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), 25 angiotensin-II-receptor-blocker (ARBs), 15 angiotensin-converting-enzyme-inhibitor (ACEi), and 8 diuretics), and 31 compared multi-class combination therapy.
Standard deviation (SD) was the most widely used measure of BPV, reported in 78 studies and was used to evaluate the direction of effect. In 88 studies evaluating 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.
Regarding the 6 diuretic studies, 1 (16.6%) showed favourable findings, 2 (33.3%) showed no significant result, and 3 (50%) showed mixed results. Most ARB studies (n=21) showed no significant effect (42.9%), with the remainder distributed across favourable, increased, and mixed findings. Findings for ACEi (n=9) were split roughly evenly across outcome categories.
When comparing the combination therapy of Renin-Angiotensin-System-Inhibitors (RASi)+CCB against RASi+Diuretics, four (80%) studies reported RASi+CCB lowered BPV most effectively. 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: Sepsis is characterised by a dysregulated host response to infection, resulting in circulatory dysfunction, multi-organ failure and death. Preclinical and early-phase clinical studies suggest that mega-dose sodium ascorbate may improve haemodynamic stability and organ function during sepsis. However, whether these effects are mediated, in part, through enhanced innate immune function and resolution of underlying infection remains unknown.

Aim: To determine whether intravenous mega-dose sodium ascorbate enhances bacterial clearance and neutrophil function in male and female rats with live Gram-negative sepsis.

Methods: Sprague-Dawley male and female rats were infected intravenous with live Escherichia. coli (E. coli) bolus (4 x 10⁹ colony forming units [CFU]/mL) and then randomised to be treated with intravenous sodium ascorbate (N = 7) or fluid and sodium-matched placebo (N = 7) for 3-h. Blood samples were collected prior to sepsis-induction, at 1-h of untreated sepsis, and then at 1.5 and 3-h following after treatment. Blood bacterial counts were determined by CFU assay. Blood was stimulated in vitro with Staphylococcus aureus (S. aureus)-coated beads, and neutrophil phagocytosis and reactive oxygen species production quantified using a 14-colour spectral flow cytometry panel. Neutrophil phenotypes were analysed using unbiased dimensionality reduction and clustering plugins in FlowJo.

Results: Sodium ascorbate treatment significantly reduced live blood bacterial counts compared to vehicle (3.56 ± 0.14 vs 4.43 ± 0.09 log₁₀[CFU/mL]; PGroup = 0.035). Sodium ascorbate treated rats exhibited a 5-fold increase in phagocytic neutrophils (RP-1+, SSC-high) producing reactive oxygen species following in vitro stimulation compared to vehicle (26.5 ± 6.63 vs 5.55 ± 2.38%, p = 0.026). These reactive oxygen species producing neutrophils had a proinflammatory phenotype (CD163neg) during bacterial clearance. Following bacterial clearance, ascorbate-treated septic rats were positively correlated (R² = 0.69; p = 0.02) with an anti-inflammatory neutrophil phenotype (CD163+).

Conclusion: Intravenous mega-dose sodium ascorbate enhanced bacterial clearance during rodent Gram-negative sepsis and was associated with increased neutrophil function. These findings suggest that mega-dose sodium ascorbate may enhance innate immune-mediated infection resolution, providing a mechanistic rationale for further evaluation in clinical trials.

Background: Home blood pressure monitoring (HBPM) and regular physical activity are central to hypertension self-management. The My Intelligent Cardiac Assistant (MICArdiac) trial delivered an artificial intelligence (AI)-optimized mobile health intervention that integrated blood pressure, physical activity, and heart-rate data and supplemented these data with personalized health messages. How participants engage with such interventions is not well characterised.

Aims: To describe longitudinal trends in engagement with HBPM and step-count goals over 26-weeks, to identify distinct engagement trajectory classes among participants in the MICArdiac intervention arm, and to examine baseline predictors of trajectory-class membership, with evaluation of participant experiences to contextualise these findings.
Methods: This process evaluation analysed intervention-arm data (N=222) from the completed MICArdiac trial in adults with uncontrolled hypertension. Overall temporal trends for HBPM and step-goal achievement were modelled with mixed-effects regressions. Distinct trajectories were identified with latent class mixed models (LCMM). Baseline predictors of class membership were examined, and qualitative interviews of participant experiences thematically analysed.

Results: Over 26-weeks, HBPM engagement declined over time (IRR 0.943 per week, 95% CI 0.939–0.947, p<.001). A 3-class LCMM identified sustained high engagement, moderate–declining engagement, and early non-engagement groups. South Asian ethnicity predicted non-engagement class membership relative to sustained engagement (RRR 7.00, 95% CI 1.57–31.1, p=.011). Step-goal achievement declined over time (OR 0.951 per week, 95% CI 0.940–0.962, p<.001); a 2-class step goal model (N=196) separated a consistently high-achieving group from a lower, steadily-declining group. Greater baseline physical activity independently predicted higher-achieving step trajectory class membership (RRR 1.003 per min/week, 95% CI 1.001–1.005, p<.001). We did not interpret a specific, shared driver of declining engagement across participant experiences.

Discussion and Conclusions: This is the first study to identify distinct HBPM and physical-activity engagement groups within the same digital intervention cohort. Findings show that engagement with MICArdiac was heterogeneous and not adequately captured by average adherence trends alone. Early disengagement highlights the need for more personalised and timely support, behaviour-specific tailoring, and smoother technological integration.