School-based programs represent a potential avenue for conducting population-wide paediatric blood pressure (BP) screening. The aim of this review was to systematically scope peer-reviewed literature reporting school-based BP screening, with respect to measurement protocols, diagnostic process coverage, and implementation considerations. Only peer-reviewed articles in English across PubMed, OVID Medline and OVID Embase were included. Two authors independently screened the article titles and abstracts prior to undertaking a full-text review. All disagreements were resolved through discussion and agreement. From each study, four categories of information were extracted: general information, BP measurement methodology, diagnostic process coverage, and implementation strategies. Each article was then assigned to one of three categories regarding the stated or implied study objectives: general school-based research incorporating BP measurement, hypertension prevalence studies, or hypertension screening studies. Of the 112 articles meeting the inclusion criteria, only 17 were categorised as hypertension screening studies. Within these, there was substantial variability in BP measurement techniques and adherence to the diagnostic process recommended by the American Academy of Pediatrics. Additionally, there was minimal reporting on implementation strategies. A pragmatic, standardised protocol for school-based BP screening is needed that includes recommended measurement methods, considers the trade-offs (in terms of feasibility and economics) of covering more or less of the diagnostic process in schools vs health care settings, and covers approaches to optimise implementability.
The renin-angiotensin system (RAS) plays a central role in regulating blood pressure and has recently been implicated in cancer biology. Although angiotensin II (AngII) receptor blockers (ARBs) have shown clinical benefit in bladder cancer, their mechanisms of action remain unclear. Here, we investigated the contribution of AngII type 1 receptor (AGTR1) to bladder cancer progression and assessed the therapeutic potential of the ARB losartan (LOS). In patients with primary non-muscle-invasive bladder cancer, intravesical recurrence following transurethral tumor resection correlated with AGTR1 expression levels. Public database analysis revealed that the expression of AGTR1 and its downstream kinases, extracellular signal-regulated kinase (ERK) 1 and ERK2, was associated with overall survival in bladder urothelial carcinoma. In AGTR1-overexpressing T24 bladder cancer cells, AngII promoted invasion and migration and upregulated neuronal nitric oxide synthase, without affecting proliferation. These effects were accompanied by rapid ERK phosphorylation alongside Akt dephosphorylation. RNA sequencing revealed that AGTR1 expression and AngII stimulation activated NF-κB, mTOR, and epithelial-mesenchymal transition (EMT) pathways. LOS suppressed these AngII-mediated responses, whereas the AngII-independent upregulation of EMT-related proteins and the enhancement of mitochondrial energy metabolism by AngII in AGTR1-overexpressing cells remained unaffected. In vivo, AGTR1 facilitated early tumor engraftment and promoted tumor progression, accompanied by reduced E-cadherin and elevated N-cadherin expression, with most of these changes suppressed by LOS treatment. In conclusion, our findings highlight the crucial role of AGTR1 in bladder cancer and support the repositioning of ARBs, such as LOS, as therapeutics for AGTR1-upregulated bladder cancer, while underscoring the importance of AGTR1 stratification for future clinical evaluation.
It remains unclear whether poor cardiovascular outcomes are associated with the longitudinal changes in inter-arm blood pressure (BP) difference. We aimed to investigate the role of repeated BP measurement in bilateral arms in predicting all-cause mortality. A total of 27,147 hypertensive participants aged ≥18 years (56.6% women; mean age, 67.1 years) were selected from the basic public health system of Samming city and underwent repeated bilateral BP measurement at two health checkups in 2013 and 2018. Multivariable-adjusted Cox regression was used to relate future mortality with change in inter-arm BP difference. The absolute inter-arm difference ≥10 mmHg increased from 12.6 to 13.3% for systolic and 8.18 to 8.27% for diastolic BP over 5 years apart. When assessed using the dichotomous cutoff of 10 mmHg for inter-arm systolic/diastolic BP difference at two examinations, 76.1%/84.4% remained persistently low and 2.00%/0.87% persistently high, and 11.3%/7.40% of the participants changed from low to high and 10.6%/7.31% from high to low. During a median follow-up of 5.43 years, 1703 (6.27%) deaths occurred. Participants who had persistently elevated absolute values of inter-arm BP difference over 5 years were at higher risk for all-cause mortality with adjusted hazard ratios amounting to 1.47 (95% CI: 1.10-1.98; P = 0.010) for systolic BP and 1.68 (95% CI: 1.10-2.56; P = 0.016) for diastolic BP. Repeated bilateral BP measurement indicated that persistently increased absolute levels of inter-arm BP difference over time were associated with future mortality, highlighting that repeated bilateral BP measurements may provide additional risk information for hypertension management.
Whether chronological age affects the ability of vascular aging indicators to predict cardiovascular events risk remains unknown. This study sought to examine whether the predictability of vascular aging indicators is better in middle-aged participants than older participants. This prospective cohort study included 8163 participants from a community-based atherosclerosis cohort in Beijing, China. Vascular age (VA) was defined as the predicted age in a multivariable regression model including cardiovascular risk factors and pulse wave velocity. Residuals by regressing VA on chronological age were defined as ∆-age, reflecting vascular aging. We used Cox proportional hazard regression model to examine the association between ∆-age and the risk of cardiovascular events in different chronological age groups. Of all participants, 5691 (69.7%) were between 40 and 60 years old, and 2472 (30.3%) were over 60 years old. During a median 9.9-year follow-up period, 818 (10%) endpoints were observed. After adjusting for confounders, ∆-age was positively associated with the risk of cardiovascular events in middle-aged participants (HR: 1.13, 95% CI: 1.07-1.21; p < 0.001), whereas no significant association was observed in older participants (HR: 1.03, 95% CI: 0.99-1.06; p = 0.148). Interaction analysis in total participants showed that chronological age significantly modified the relationship between ∆-age and the risk of cardiovascular events (p = 0.017). Our findings indicate that the predictive ability of residuals between VA and chronological age for the risk of cardiovascular events is better in middle-aged people than that in older people. The VA assessment may be more valuable to the middle-aged population. The modifying effect of chronological age showed that vascular aging categories in middle-aged participants have stronger predictive ability for the risk of cardiovascular events than that in older participants. MACE, a composite of non-fatal myocardial infarction, non-fatal stroke, and cardiovascular mortality; normal VA, normal vascular aging; EVA, early vascular aging; SUPERNOVA, supernormal vascular aging.
Background: Non-adherence to antihypertensive regimens undermines both hypertension therapy and the validity of clinical trials. However, existing adherence measures do not effectively reflect bidirectional medication-taking behavior. This secondary SPRINT analysis investigated at how dynamic, bidirectional adherence to medication patterns associated with cardiovascular outcomes.
Methods: We analyzed self-reported medication information for 9343 participants. Adherence was divided into four categorized based on discrepancies between prescribed and taken medication over the first 12 months: full adherence, over-adherence, under-adherence, and fluctuating adherence. The primary outcomes were composite cardiovascular events and all-cause mortality; the secondary outcomes were 12-month systolic blood pressure (SBP) control, SBP variability from visit to visit (coefficient of variance), and serious adverse events (SAEs).
Results: Over a median follow-up of 3.26 years, 53.6% displayed full adherence, while 16.2%, 22.7%, and 7.5% showed over-, under-, and fluctuating adherence. Compared to full adherence, fluctuating adherence was independently associated with significantly elevated risks of composite cardiovascular events (HR: 1.737, 95% CI: 1.250-2.414, P﹤0.001) and all-cause mortality (HR: 1.487, 95% CI: 1.030-2.147, P = 0.029). This pattern was also associated with decreased SBP control (OR: 0.825, 95% CI: 0.700-0.972, P = 0.022), increased SBP variability, and the highest incidence of SAEs in non-adherence groups. There were no significant changes in outcomes between over- or under-adherence and full adherence. Importantly, the detrimental association for fluctuating adherence persisted among a subgroup of patients classified as "fully adherent" by the self-reported Visual Analog Scale.
Conclusions: Fluctuating antihypertensive adherence, characterized by unstable use of medications, was independently linked with poor SBP control increased cardiovascular risk and mortality. Hypertension studies and clinical practice ought to prioritize identifying and managing dynamic adherence patterns to enhance trial validity and optimize the therapeutic benefits. Registration ClinicalTrials.gov (NCT01206062).

