bluuebunny/crossref_metadata_2025_split huggingface dataset:
O45 INDIVIDUAL VS. HEALTH SYSTEM FACTORS IN HYPERTENSION CONTROL PERFORMANCE: DISTRICT-LEVEL CARE CASCADE ANALYSIS
Authors: Muharram Farizal Rizky 
Published: September 2024

Background:
High-quality health systems are crucial for achieving optimal health outcomes, particularly in managing chronic conditions like hypertension. Effective hypertension control reduces the risk of cardiovascular diseases (CVD). This study examines the relative importance of individual factors (social determinants of health, SDOH) versus health system factors in influencing the stages of the hypertension care cascade in Indonesia, focusing on the controlled rate as the endpoint. This study aims to analyze which factors impact the hypertension care cascade.

Methods:
The performance of 514 districts in Indonesia was analyzed using multivariate regression. Dependent variables included the percentages of individuals ever tested, diagnosed, treated, and controlled for hypertension. Independent variables encompassed healthcare resource availability, socioeconomic factors, and demographic factors.

Results:
The regression analysis revealed several key findings: The physician ratio positively and significantly impacted all stages of the care cascade, with coefficients increasing from 0.087 in testing to control 0.356 (p<0.01 for all). The midwife ratio positively influenced testing (0.072), diagnosis (0.135), and treatment (0.160) but not control (0.016, p>0.1). Conversely, Average years of schooling positively correlated with testing (0.111, p<0.05). GNI PPP per capita was positively associated with testing (0.235, p<0.01), diagnosis (0.189, p<0.05), and treatment (0.228, p<0.05), but not control (-0.253, p>0.1). Median age showed a strong positive association across all stages, with coefficients of 1.212 for testing, 1.443 for diagnosis, 1.509 for treatment, and 1.274 for control (p<0.01 for all).
Regression shows a pattern that while individual SDOH significantly influenced the early stages of the care cascade (testing and diagnosis), these factors had minimal impact on the control rate. Instead, health system performance was particularly critical for achieving control.

Conclusion:
Individual SDOHs are more influential in the early stages of the care cascade, while health system factors are crucial for controlling hypertension. Efforts to improve hypertension management should focus on enhancing health system resources to achieve better control rates and reduce CVD risks.
O49 DIABETES IS ASSOCIATED TO THE REDUCTION OF CAROTID BODY VOLUME IN RESISTANT HYPERTENSIVE PATIENTS
Authors: Cruz Da Silva Lamoel Mohandas , Vieira de Morais Camilla Giovanna , De Paula Morales Kevin Rafael , Rochitte Carlos Eduardo , Lacchini Silvia 
Published: September 2024

Background and Objective:
Considering that carotid bodies (CB) are involved in the counterregulatory response to hypoglycemia and that their impact on blood pressure control still needs to be better clarified, the objective of this study was to characterize the volumetric reduction of CB in controlled and uncontrolled hypertensive patients.

Methods:
CT angiograms of hypertensive patients treated at the Heart Institute (University of São Paulo Medical School) were studied. The evaluated patients were separated into four groups: hypertensive (receiving 1 to 2 categories of antihypertensives) controlled (H-C, n=42) and uncontrolled (H-U, n=23), and resistant hypertensives (receiving 3 or more categories of antihypertensives) with controlled (HR-C, n=17) and uncontrolled (HR-U, n=23) blood pressure. CT angiograms (Aquilion ONE/PRISM–Canon) of the cervical arteries with iodinated contrast were evaluated. Artery reconstructions used 0.5 mm thick sections, with orthogonal measurements of CB to evaluate bilateral carotid diameters and bifurcations.

Results
The morphology of common, internal and external carotid arteries was very similar between the groups. The mean age between groups was not significantly different (H-C: 67±12; H-U: 63±16; HR-C:65±9; HR-U: 67±13 years). When evaluating the presence of atherosclerotic lesions, a similar proportion, approximately 50%, was found in all groups. On the other hand, the presence of diabetes in HR-U group was 52%, while in other groups it was 30%. Furthermore, CB volume (mm3) in the presence of diabetes, presented an important reduction, especially in resistant hypertensive patients (H-C: -4%; H-U: -27%; HR-C:-55%; HR-U: -64%).

Conclusions:
The reduction of CB volume may be associated with the loss of microvascularization, mediating a possible hyperactivity of CB, which consequently maintain the comorbidities observed in these patients. Experimental studies showed that bilateral resection of the carotid sinus nerve completely prevents insulin resistance and hypertension, reinforcing the strong effect of diabetes upon CB normal function found in the present study. Longitudinal studies will contribute to a better understanding of CB regulation and the impact of diabetic state on blood pressure control.
O75 INHIBITION OF PCSK9/NFAT AMELIORATES CARDIAC DYSMETABOLISM AND FIBROSIS IN EXPERIMENTAL RAT MODEL OF PCOS BY REDUCING ATHEROGENIC LIPID AND IMPROVING INSULIN SENSITIVITY
Authors: Olaniyi Kehinde Samuel , Areloegbe Stephanie , Areloegbe Lawrence 
Published: September 2024

Background:
Polycystic ovarian syndrome (PCOS) remains an independent risk factor of cardiovascular disease (CVD), particularly in women of child-bearing age, and contributes to global increase in the prevalence/incidence of cardiovascular mortality and morbidity in women. Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a promising therapeutic target to reduce residual CVD risk. Similarly, Nuclear factor of activated T cells (NFAT) is a transcription factor that is implicated in cardiac fibrosis. However, the role of PCSK9/NFAT in PCOS-associated cardiometabolic syndrome is not clear. Short chain fatty acids (SCFAs) play a multifaceted regulatory role in metabolic health. The present study therefore investigated the role of PCSK9/NFAT in cardiometabolic syndrome associated with experimental PCOS, and the therapeutic potential of SCFAs, especially butyrate.

Material and Methods:
Eight-week-old female Wistar rats were allotted into four groups (n=5). Polycystic ovarian syndrome was induced by administering letrozole (1 mg/kg p.o.) once daily for 21 days, thereafter the animals were treated with 200 mg/kg (oral gavage) of sodium butyrate for six weeks. Gene expression, biochemical parameters and cardiac/ovarian morphology were evaluated with appropriate methods.

Results:
Rats with PCOS showed androgen excess, multiple ovarian cysts and reduced insulin sensitivity. The rats in addition displayed atherogenic dyslipidemia (triglyceride/HDLc, TC/HDLc and LDLc), hypercorticosteronemia and elevated cardiac triglyceride, inflammatory biomarkers (NF-kappaB and TNF-alpha), caspase-6, 4-hydroxynonenal, inflammasome (NLRP3), fibrosis and depleted antioxidant defense (NrF2 and glutathione) as well as increased expression of PCSK9 and NFAT when compared to the control rats. Nevertheless, these systemic and morphological alterations were ameliorated following treatment with sodium butyrate.

Conclusion:
The present results collectively demonstrate cardiac dysmetabolism, inflammation, fibrosis as well as apoptosis in experimental PCOS rat model, which are driven by elevated expression of PCSK9/NFAT. The results further suggest that SCFAs, butyrate alleviates cardiometabolic syndrome and its attendant cardiomorbidity by suppression of PCSK9/NFAT. The present data provide a preclinical insight to prevention and management of CVD in PCOS individuals.
O79 DAILY URINARY POTASSIUM EXCRETION IS NOT A FIXED PERCENTAGE OF DAILY POTASSIUM INTAKE
Authors: Van Vliet Anne Myrthe , Rauh Manfred , Vogt Liffert , Titze Jens , Olde Engberink Rik 
Published: September 2024

Background and Objective:
High potassium intake is associated with a lower blood pressure and lower incidence of cardiovascular events. For estimation of potassium intake, the World Health Organization advices to multiply the 24-hour renal potassium excretion by 1.3, considering the substantial fecal potassium loss. We examined the variation in the required conversion factor in healthy volunteers and evaluated the effect of factors associated with tissue cation storage on the renal potassium excretion.

Methods:
We performed a post-hoc analysis of the Mars long-term sodium balance studies. Healthy male participants consumed a fixed amount of salt (6, 9 and 12 grams/day for >29 days) and potassium (4 grams/day) for 105 (n=4) and 205 days (n=6). All urine was collected in 24-hour aliquots. We calculated the percentage of potassium intake that was excreted in the corresponding 24-hour urine collection during steady-state. A multivariable mixed-effects model was used to assess associations of this percentage with sodium intake, potassium intake, urinary aldosterone, urinary cortisol and urine volume.

Results:
The median renal potassium excretion was 80% of potassium intake (IQR 65-97%, range 24-304%), corresponding to a conversion factor of 1.25 (IQR 1.03-1.54). Within individual subjects we also observed a marked day-to-day variation in the percentage of renal potassium excretion: the average intraperson width of the IQR was 25%.
Sodium intake (figure A), urinary aldosterone (figure B), urinary cortisol (figure C) and urine volume (figure D) were positively associated with the percentage of renal potassium excretion, whereas potassium intake showed a negative association (figure A). A significant positive interaction between the effects of sodium and potassium intake was present (P<0.001).

Conclusions:
The percentage of dietary potassium that is excreted via urine varies considerably. During steady-state, this percentage is independently affected by sodium intake, potassium intake, urinary aldosterone, urinary cortisol, and urine volume. Our results suggest that the WHO's fixed 1.3 conversion factor may lead to inaccurate estimations of potassium intake.
O88 REDUCTION IN SYSTOLIC BLOOD PRESSURE FOLLOWING DIETARY FIBRE INTERVENTION IS DEPENDENT ON BASELINE GUT MICROBIOTA COMPOSITION
Authors: Snelson Matthew , Jama Hamdi , Rhys-Jones Dakota , Nakai Michael , Anderson Dovile , Creek Darren , Head PGeoffrey , Mackay Charles , Muir Jane , Marques Francine 
Published: September 2024

Background/Objective:
Dietary interventions high in fibre have been shown to lower blood pressure (BP). This effect is via the gut microbiota, via fermentation of fibre and production of metabolites called short-chain fatty acids (SCFAs). Not all patients respond to dietary fibre interventions for unclear reasons. We aimed to determine if we can identify fibre-responders based on their gut microbiota and production of SCFAs.

Methods:
We performed a phase II cross-over placebo-controlled randomised clinical trial in untreated hypertensive patients. Twenty treatment-naive participants with hypertension received 40 g per day of fermentable fibre delivered as acetylated and butyrylated high amylose maize starch (HAMSAB) or the placebo for 3 weeks. Blood pressure was monitored at baseline and endpoint by ambulatory BP monitoring, with those experiencing a reduction of ≥2 mmHg in systolic BP classified as responders. The microbiota was determined by sequencing the V4-V5 region of the 16S rRNA gene in baseline stool samples. The relationship between baseline gut microbiota and response to dietary intervention was assessed with the MaAsLin2 package. Plasma SCFAs levels were quantified by mass spectrometry.

Results:
We observed a placebo-subtracted mean 24-hour systolic BP of –6.1 mmHg (p=0.03, reported in Jama et al., 2023 Nature Cardiovascular Research), with 14 (70%) individuals classified as responders and 6 (30%) as non-responders. Genera significantly enriched in responders included Dialister (β=1.29, q=1.921x10-134), Coprococcus (β=1.26, q=3.282x10-121), Bifidobacterium (β=1.67, q=1.11x10-81), Ruminococcus (β=0.161, q=1.11x10-8), and Roseburia (β=0.82, q=4.275x10-2). Responders also produced higher levels of the SCFAs butyrate (mean±SEM, non-responders 4.95±2.4 vs responders 51.15±14.7, p=0.0096), but no difference in other SCFAs.

Conclusions:
Participants who experienced a decrease in systolic BP following a dietary fibre intervention had increased bacterial genera known to contain species that produce SCFAs (Bifidobacterium, Roseburia, Ruminococcus) at baseline, and were able to produce more butyrate. These data suggest that baseline microbiota composition contributes to the response to dietary fibre intervention trials in people with hypertension, likely via increased capacity to produce butyrate.
O93 BRIGHT LIGHT EXPOSURE ATTENUATES BLOOD PRESSURE REDUCTION POSTEXERCISE
Authors: Oliveira Gustavo , Marin Thais , Azevedo Luan , Thosar Saurabh , Cipolla-Neto José , Forjaz Claudia , Brito Leandro 
Published: September 2024

Background and objective:
A single session of aerobic exercise lowers blood pressure (BP), known as postexercise hypotension (PEH). Bright light (BL) exposure increases BP at rest compared to dim light (DL). However, whether BL exposure can attenuate PEH remains unknown, and this hypothesis was tested in the current study.

Methods:
Twenty healthy men (27±5 years) underwent two experimental sessions: one under BL (5000 lux) and another under dim light (DL ≤8 lux), performed in random order. In each session, subjects executed an aerobic exercise session on a cycle ergometer for 30 min at 50-60-% heart rate (HR) reserve. BP (oscillometric) and HR (HR monitor) were measured, and rate-pressure-product (RPP) was calculated (systolic BP * HR) pre- and postexercise. Additionally, subjects wore an ambulatory BP monitor (ABPM) for 24 hours after postexercise measurements.

Results:
Systolic BP decreased similarly postexercise in both sessions, but its levels were higher in BL than DL throughout the experimental session (Figure 1A). Diastolic and mean BPs decreased postexercise only in DL at 30 min, while they increased in BL at 60 and 90 min (Figure 1B and 1C, respectively). HR and RPP increased in both sessions postexercise, but RPP levels were higher throughout the experimental session in BL than DL (Figure 1D and 1E, respectively) and for the first three hours of ABPM.

Conclusions:
In healthy adult men, BL exposure increased systolic BP and cardiac work and attenuated PEH on diastolic and mean BPs.
O96 NICD LACTYLATION OF NOTCH SIGNALING IMPROVES MICROVASCULATION RAREFACTION IN HYPERTENSION
Authors: Liu Yuxin , Liang Jianwen , Zhang Meixin , Gao Datian , Yang Junqi 
Published: September 2024

Background and Objective:
Microvascular rarefaction is a key pathophysiologic basis of hypertension-related cardiovascular disease. Exercise decreases blood pressure and promotes angiogenesis related to inhibition of NOTCH signaling. The activation of the NOTCH pathway depends on the transcriptional regulation of its intracellular active fragment NICD after nuclear translocation. The post-translational modification status of proteins plays a crucial role in the nuclear translocation effect of transcription factors. Lactylation is influenced by the level of lactate in the body. Exercise can promote glycolysis in endothelial cells, and increase intracellular lactate levels. Therefore, we explored whether the beneficial effects of Exercise were mediated by promoting NICD lactylation, inhibiting the NOTCH signaling, and promoting angiogenesis.

Methods:
To test our hypotheses, WKYs (normotensive rats) and SHRs (spontaneously hypertensive rats) were given exercise for 12 weeks. Blood pressure was determined by the tail-cuff method, and cardiac function was assessed by echocardiography. Using rats’ retina, gastrocnemius, and myocardium detected microvascular density. The expression levels of NOTCH signaling pathway related proteins and angiogenesis related factors were measured by Western Blotting. The level of lactate was measured by using a lactate assay kit. Protein modification omics was used to detect the modification types and levels of NICD in microvascular endothelial cells, followed by liquid chromatography tandem mass spectrometry (LC-MS/MS) to detect the lactylation sites of NICD in microvascular endothelial cells.

Results:
Exercise in SHRs resulted in reduced blood pressure and concentric hypertrophy. Exercise promoted angiogenesis and improved microcirculation rarefaction. Exercise also reduced the production of NOTCH pathway related proteins and increased the expression level of angiogenesis related factors. The lactate level increased after exercise, and the lactylation level of NICD increased.

Conclusions:
In summary, Exercise decreases hypertension and improves cardiac function in SHRs. Our research results indicated that exercise increases lactate production and induces NICD lactylation, thereby inhibiting the NOTCH signaling, upregulating the expression of angiogenic factors, promoting angiogenesis, and lowering blood pressure.
O99 RELATIONSHIP BETWEEN RENIN, ALDOSTERONE, ALDOSTERONE-TO-RENIN RATIO AND LEFT VENTRICULAR MASS INDEX IN YOUNG ADULTS
Authors: Ananda Roshan , Gwini StellaMay , Beilin Lawrence , Schlaich Markus , Stowasser Michael , Fuller Peter , Young Morag , Adler Brendan , Mori Trevor , Yang Jun 
Published: September 2024

Background and Objective:
Primary aldosteronism (PA), characterised by excessive aldosterone production and mineralocorticoid receptor activation, is associated with adverse cardiovascular outcomes including left ventricular hypertrophy and failure. Elevated cardiovascular risk is observed even in milder and subclinical forms of PA, based on studies primarily conducted in middle-aged and elderly populations. It is unclear if the biomarkers of PA, including renin, aldosterone, and aldosterone-to-renin ratio (ARR), are associated with left ventricular mass index (LVMI), which is a strong predictor of cardiovascular diseases, in young adults.

Methods:
The Raine Study is a longitudinal, population-based cohort study in Western Australia that enrolled women during pregnancy. We analysed the data from the offspring of these women at age 27 years. Participants with elevated high-sensitivity C-reactive protein (>10 mg/L) and females who were on oral contraception were excluded. LVMI was measured by cardiac magnetic resonance imaging. We examined the relationship between LVMI and plasma renin, aldosterone, and ARR using multivariate-adjusted linear regression and used mediation analysis to test whether these relationships were dependent on systolic blood pressure (SBP).

Results:
Of 758 participants, 252 (33.2%) were females. Females had lower median plasma renin concentration (12.0 vs 15.4mU/L; p<0.001) and higher median ARR (21.0 vs 15.6; p<0.001) than males. There was no sex-difference in median plasma aldosterone concentration (257 vs 237pmol/L in males; p=0.143). Females had lower LVMI (52.2 vs 70.2 g/m2; p<0.001) than males. A significant association between LVMI and aldosterone was detected in males (β-coefficient 0.009; 95% CI 0.001 to 0.017; p=0.027), and between LVMI and ARR in females (β-coefficient 0.098; 95% CI 0.001 to 0.196; p=0.050) after adjusting for confounders. This relationship was not mediated by brachial SBP.

Conclusions:
An elevated aldosterone concentration or ARR was associated with higher LVMI in young adults, independent of brachial SBP. Long-term follow-up is required to determine if the relationship persists over time and leads to reduced cardiac function.
O100 IL15RA MEDIATES BLOOD PRESSURE ELEVATION, INFLAMMATION AND VASCULAR DAMAGE IN ANGIOTENSIN II-INDUCED HYPERTENSION
Authors: Nosalski Ryszard , Booth Emma , Saju Blessy , Szczepaniak Piotr , Siedlinski Mateusz , Urbanski Karol , Kraler Simon , Camici Giovanni , Bailey Matthew , Maffia Pasquale , Guzik Tomasz J 
Published: September 2024

Cytokines are key mediators regulating blood pressure (BP) and target organ damage in hypertension. IL15 levels increase in cardiovascular diseases, but the role of IL15 and its receptor alpha (IL15R) in hypertension and hypertension-mediated inflammation and vascular damage is still unknown.
Wild-type and IL15Rα-/-mice (n=5-9) were infused with vehicle or angiotensin II (AngII, 490ng/min/kg). Recombinant IL15 was administered to WT mice (1ug, daily, 14 days) during AngII infusion. Telemetry, wire myography, luminometry, PSR staining, qPCR, immunoblotting, flow cytometry, and primary cell lines were used.
Hypertensive patients have increased levels of IL15Rα in arteries, which significantly correlated with systolic (r=0.33, p=0.002), diastolic (r=0.27, p=0.02) pressure and maximal constriction to phenylephrine ex vivo (r=0.27, p=0.03). Similarly, AngII infusion significantly increased serum IL15/IL15Rα (8.8±0.7pg/ml vs 12.1±0.7pg/ml, p<0.01), IL15Rα mRNA (1±0.1 vs 1.8±0.1, p<0.01) and protein (1±0.03 vs 1.8±0.28, p<0.01) levels in the aortas. BP lowering using hydralazine and hydrochlorothiazide treatment prevented these changes in vasculature. IL15Rα was induced by pathophysiological stretch (15%) or interferon-gamma in adventitial fibroblasts, vascular smooth muscles, and endothelial cells in vitro. In contrast, AngII, other inflammatory cytokines or oxidative stress mediators have no such direct effect. Il15Rα-/- blunted AngII-induced hypertension (199±5.6mmHg vs 148±7.3mmHg, p<0.001), protected against endothelial dysfunction (p<0.01) and aortic superoxide production (59.4±7.8 vs 36.4±7.6 RLU/sec/mg) compared to wild-type mice. This was accompanied by reduced perivascular inflammation, lack of immune cell recruitment and effector and memory T cell formation. Similarly, T cell interferon-gamma and interleukin-17 production was attenuated in Il15Rα-/- hypertensive mice. In contrast, simultaneous administration of AngII and rIL15 into WT mice enhanced these outcomes. Perivascular fibrosis was observed in WT, but not Il15Rα-/- hypertensive animals (111036±19117 μm2 vs 48689±5515 μm2, p<0.01) and was in line with significantly lower mRNA of collagen and fibronectin protein levels in Il15Rα-/- aortas.
IL15Rα plays a crucial role in immune activation, vascular damage, and AngII-induced hypertension. Targeting this pathway may offer potential therapeutic benefits for controlling hypertension and preventing associated vascular complications.