Association between chronic kidney disease stages and changes in ambulatory blood pressure monitoring parameters / Associação entre estágios da doença renal crônica e alterações dos parâmetros da monitorização ambulatorial da pressão arterial

Abstract Introduction: Blood pressure (BP) assessment affects the management of arterial hypertension (AH) in chronic kidney disease (CKD). CKD patients have specific patterns of BP behavior during ambulatory blood pressure monitoring (ABPM). Objectives: The aim of the current study was to evaluate the associations between progressive stages of CKD and changes in ABPM. Methodology: This is a cross-sectional study with 851 patients treated in outpatient clinics of a university hospital who underwent ABPM examination from January 2004 to February 2012 in order to assess the presence and control of AH. The outcomes considered were the ABPM parameters. The variable of interest was CKD staging. Confounding factors included age, sex, body mass index, smoking, cause of CKD, and use of antihypertensive drugs. Results: Systolic BP (SBP) was associated with CKD stages 3b and 5, irrespective of confounding variables. Pulse pressure was only associated with stage 5. The SBP coefficient of variation was progressively associated with stages 3a, 4 and 5, while the diastolic blood pressure (DBP) coefficient of variation showed no association. SBP reduction was associated with stages 2, 4 and 5, and the decline in DBP with stages 4 and 5. Other ABPM parameters showed no association with CKD stages after adjustments. Conclusion: Advanced stages of CKD were associated with lower nocturnal dipping and greater variability in blood pressure.

Resumo Introdução: A avaliação da pressão arterial (PA) tem impacto no manejo da hipertensão arterial (HA) na doença renal crônica (DRC). O portador de DRC apresenta padrão específico de comportamento da PA ao longo da monitorização ambulatorial da pressão arterial (MAPA). Objetivos: O objetivo do corrente estudo é avaliar as associações entre os estágios progressivos da DRC e alterações da MAPA. Metodologia: Trata-se de um estudo transversal com 851 pacientes atendidos nos ambulatórios de um hospital universitário que foram submetidos ao exame de MAPA no período de janeiro de 2004 a fevereiro de 2012 para avaliar a presença e o controle da HA. Os desfechos considerados foram os parâmetros de MAPA. A variável de interesse foi o estadiamento da DRC. Foram considerados como fatores de confusão idade, sexo, índice de massa corporal, tabagismo, causa da DRC e uso de anti-hipertensivos. Resultados: A PA sistólica (PAS) se associou aos estágios 3b e 5 da DRC, independentemente das variáveis de confusão. Pressão de pulso se associou apenas ao estágio 5. O coeficiente de variação da PAS se associou progressivamente aos estágios 3a, 4 e 5, enquanto o coeficiente de variação da pressão arterial diastólica (PAD) não demonstrou associação. O descenso da PAS obteve associação com estágios 2, 4 e 5, e o descenso da PAD, com os 4 e 5. Demais parâmetros da MAPA não obtiveram associação com os estágios da DRC após os ajustes. Conclusão: Estágios mais avançados da DRC associaram-se a menor descenso noturno e a maior variabilidade da pressão arterial.

Study on the occurrence and influencing factors of gastrointestinal symptoms in hemodialysis patients with uremia.

BACKGROUND: Gastrointestinal symptoms are common in patients with uremia undergoing hemodialysis, and these symptoms seriously affect patients' prognosis. AIM: To assess the occurrence and factors influencing gastrointestinal symptoms in patients with uremia undergoing hemodialysis. METHODS: We retrospectively selected 98 patients with uremia who underwent regular hemodialysis treatment in the blood purification center of our hospital from December 2022 to December 2023. The gastrointestinal symptoms and scores of each dimension were evaluated using the Gastrointestinal Symptom Grading Scale (GSRS). Patients were divided into gastrointestinal symptoms and no gastrointestinal symptom groups according to whether they had gastrointestinal symptoms. The factors that may affect gastrointestinal symptoms were identified by single-factor analysis. Multiple logistic regression analysis was performed to identify independent risk factors for gastrointestinal symptoms. RESULTS: Gastrointestinal symptoms included indigestion, constipation, reflux, diarrhea, abdominal pain, and eating disorders, and the total average GSRS score was 1.35 ± 0.47. This study showed that age, number of tablets, dialysis time, glucocorticoid, parathyroid hormone (PTH), combined diabetes mellitus and C-reactive protein (CRP) were independent risk factors for gastrointestinal symptoms in patients with uremia undergoing hemodialysis, whereas body mass index (BMI), hemoglobin (Hb), and urea clearance index were independent protective factors (P < 0.05). CONCLUSION: Gastrointestinal symptoms are mostly mild in patients with uremia undergoing hemodialysis, most commonly including dyspepsia, eating disorders, and gastroesophageal reflux. The independent influencing factors mainly include the BMI, age, number of pills taken, dialysis time, urea clearance index, Hb, use of glucocorticoids, and thyroid hormone level. PTH, CRP, and diabetes are clinically related factors influencing the occurrence of gastrointestinal symptoms, and targeted prevention can be performed.

Effects of single and bilateral limb immersion on systemic and cerebral hemodynamic responses to the cold pressor test.

The cold pressor test (CPT) involves cold water immersion of either the upper or lower limb(s) and elicits autonomic and hemodynamic increases via stimulation of pain and cutaneous thermoreceptors. It is unclear whether the choice of limb(s) in CPT studies differentially affects systemic and cerebral hemodynamic responses. Herein, we assessed systemic and cerebral hemodynamic and ventilatory responses to different CPT protocols of the hand (CPTH), foot (CPTF), or bilateral feet (CPTBF). We hypothesized CPTBF would elicit greatest physiological responses due to increased exposure area to the cold stimulus. Methods. Twenty-eight (14M;14F) healthy young adults [23.4 (SD: 2.4) years] participated in three 3-minute CPT protocols during a single visit. Mean arterial pressure (MAP), heart rate (HR), middle cerebral artery blood velocity (MCAv) and cerebrovascular conductance index, and end-tidal carbon dioxide (PETCO2), and pain perception were recorded throughout CPT protocols. Results. There was a time-CPT protocol interaction on systolic (p=0.02) and diastolic blood pressure (p<0.01), MAP (p<0.01), HR (p<0.001), presented as mean(SD). MCAv and cerebrovascular conductance index did not change with CPTs. Peak delta HR from baseline occurred in CPTBF (Δ13.6(15.5)BPM) compared to CPTH (Δ4.85(12.6)BPM; p=0.01) and CPTF (Δ4.04(13.3)BPM; p=0.02). Delta MAP was greater in CPTH (Δ12.3(7.95)mmHg) and CPTBF (Δ12.9(9.24)mmHg) compared to CPTF (Δ8.42(7.12)mmHg; p<0.01). Perceived pain was higher in CPTBF compared to single limb protocols (p≤0.01). Conclusion. Our findings suggest choice of limb(s) in CPT protocols affects systemic hemodynamic responses and should be considered when designing CPT studies.

Genetic deletion of the kidney sodium/proton exchanger-3 (NHE3) does not alter calcium and phosphate balance due to compensatory responses.

The sodium/proton exchanger-3 (NHE3) plays a major role in acid-base and extracellular volume regulation and is also implicated in calcium homeostasis. As calcium and phosphate balances are closely linked, we hypothesized that there was a functional link between kidney NHE3 activity, calcium, and phosphate balance. Therefore, we examined calcium and phosphate homeostasis in kidney tubule-specific NHE3 knockout mice (NHE3loxloxPax8 mice). Compared to controls, these knockout mice were normocalcemic with no significant difference in urinary calcium excretion or parathyroid hormone levels. Thiazide-induced hypocalciuria was less pronounced in the knockout mice, in line with impaired proximal tubule calcium transport. Knockout mice had greater furosemide-induced calciuresis and distal tubule calcium transport pathways were enhanced. Despite lower levels of the sodium/phosphate cotransporters (NaPi)-2a and -2c, knockout mice had normal plasma phosphate, sodium-dependent 32Phosphate uptake in proximal tubule membrane vesicles and urinary phosphate excretion. Intestinal phosphate uptake was unchanged. Low dietary phosphate reduced parathyroid hormone levels and increased NaPi-2a and -2c abundances in both genotypes, but NaPi-2c levels remained lower in the knockout mice. Gene expression profiling suggested proximal tubule remodeling in the knockout mice. Acutely, indirect NHE3 inhibition using the SGLT2 inhibitor empagliflozin did not affect urinary calcium and phosphate excretion. No differences in femoral bone density or architecture were detectable in the knockout mice. Thus, a role for kidney NHE3 in calcium homeostasis can be unraveled by diuretics, but NHE3 deletion in the kidneys has no major effects on overall calcium and phosphate homeostasis due, at least in part, to compensating mechanisms.

Impact of Land Versus Water Environments on Orthostatic Hypotension in Older Adults: A Randomized Crossover Study.

BACKGROUND/OBJECTIVES: Orthostatic hypotension (OH) is a common condition among older adults that increases the risk of falls. The study objectives are to determine the influence of distinct environments (water vs. land) on OH and the consequent effects of walking in these environments in older adults. Additionally, we aimed to assess the differences in response between two groups: older adults with OH and those without OH. METHODS: A randomized crossover design was utilized including one session involving water walking and the other session involving land walking, with a 1- to 3-day washout period. Orthostatic hemodynamic measurements were obtained before, immediately after, and 2 hr after a 15-min walking session. Two subgroups were formed for analysis: participants with OH (n = 14, 81 ± 7 years) and participants without OH (n = 11, 84 ± 7 years). RESULTS: Compared with the land environment, an 86% reduction in the frequency of OH episodes was noted when the older adults were immersed in water. This reduction was accompanied by greater mean arterial pressure, while participants without OH showed no such changes. The frequency of OH episodes was similar when assessed immediately after emerging from the pool following water-based walking or after land-based walking. All participants exhibited elevated mean arterial pressure immediately after water-based walking, but not after land-based walking. Two hours after walking, all participants demonstrated similar mean arterial pressure and frequency of OH episodes, regardless of the environment. CONCLUSIONS: Water immersion resulted in a substantial reduction in the frequency of OH episodes among older adults. Additionally, the frequency of OH episodes was not affected by prior walking exercise in either environment. Significance/Implication: These findings underscore the safety and potential advantages of water-based exercise for older adults dealing with OH.

Complete autonomic blockade reveals nitric oxide contribution to blood pressure regulation in obese Black women.

PURPOSE: Hypertension is one of the major causes of cardiovascular morbidity and mortality in the USA and disproportionately affects Black women. Endothelial-derived nitric oxide (eNO) substantially regulates blood pressure in humans, and impaired NO-mediated vasodilation has been reported in the Black population. Previous studies using an NO synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA) did not fully determine the NO contribution to blood pressure because of baroreflex buffering. Therefore, in the present study we used trimethaphan, a ganglionic blocker, to inhibit baroreflex buffering and study NO modulation of blood pressure in Black women during L-NMMA infusion. METHODS: L-NMMA at doses of 250 µg/kg per minute was infused in combination with trimethaphan at doses of 4 mg/min to eliminate baroreflex mechanisms. Heart rate (HR) was obtained with continuous electrocardiogram monitoring, and continuous blood pressure was measured with the volume clamp method. The increase in systolic blood pressure (SBP) during both infusions was used to estimate the contribution of NO to blood pressure. RESULTS: Ten Black (age range 30-50 years, body mass index [BMI] 30-45 kg/m2), and nine White women (age range 30-50 years, body mass index 30-45 kg/m2) were enrolled in this study. During autonomic blockade, there was no difference in the decrease in SBP between Black and White women (- 20 ± 16.45 vs. - 24 ± 15.49 mm Hg, respectively; P = 0.659). When autonomic blockade was combined with L-NMMA, Black women had a significant increase in SBP compared to White women (54 ± 13.62 vs. 39 ± 09.64 mm Hg, respectively; P = 0.022, respectively). CONCLUSION: Autonomic blood pressure regulation was similar between Black and White women. However, NO contribution to blood pressure was significantly greater in Black women compared to White women. REGISTRATION: ClinicalTrials.gov: NCT01122407.

Obstructive sleep apnea and hypertension; critical overview.

Obstructive sleep apnea (OSA) and hypertension are two important modifiable risk factors for cardiovascular disease and mortality. Numerous studies have highlighted the interplay between these two conditions. We provide a critical review of the current literature on the role of the OSA as a risk factor for hypertension and its effect on blood pressure (BP). We discuss several key topics: the effect of OSA on nocturnal BP, BP response to continuous positive airway pressure (CPAP) treatment, CPAP effect on BP in refractory hypertension, the role of OSA in BP variability (BPV), and maladaptive cardiac remodeling mediated by OSA's effect on BP. Finally, we discuss the unique aspects of ethnicity and social determinants of health on OSA with a focus on Asian populations and the disparity in BP control and cardiovascular outcomes.

The impact of different recovery positions on the perfusion of the lower forearm and comfort: A cross-over randomized controlled trial.

Background: International guidelines recommend a side-lying recovery position for unresponsive individuals with normal breathing who do not require cardiopulmonary resuscitation. However, high-certainty evidence about an optimal recovery position is lacking. Recent guidelines recommend a position with the arm extended rather than bent, hypothesizing that venous drainage in the dependent lower arm might be compromised. This cross-over randomized controlled trial aims to evaluate the effect of recovery positions with bent or extended arm on perfusion of the lower forearm and comfort. Methods: Eight healthy volunteers were placed in each of the recovery positions for 15 min, in random order, with an interval of 15 min in supine position. Various perfusion indices of the dependent arm were assessed by radial artery tonometry, ulnar artery echo doppler, and venous congestion plethysmography, as well as participant discomfort, pain and skin discoloration. Differences in outcomes were analyzed with linear mixed models. Results: Our study found no statistically significant difference in systolic peripheral arterial pressure in the radial artery, peripheral venous pressure at the back of the hand, oxygen saturation, heart rate, subjective pain and discomfort, when comparing both postures. Participants slightly experienced more skin discoloration in the position with extended arm. Conclusions: We conclude that, since perfusion of the dependent arm was shown to be similar in both positions, both recovery positions can be used. These conclusions fill a gap in evidence and can further support the treatment recommendations regarding the recovery position in first aid settings.

Efficacy of antihypertensive treatment for target organ protection in patients with masked hypertension (ANTI-MASK): a multicentre, double-blind, placebo-controlled trial.

Background: Masked hypertension is associated with target organ damage (TOD) and adverse health outcomes, but whether antihypertensive treatment improves TOD in patients with masked hypertension is unproven. Methods: In this multicentre, randomised, double-blind, placebo-controlled trial at 15 Chinese hospitals, untreated outpatients aged 30-70 years with an office blood pressure (BP) of <140/<90 mm Hg and 24-h, daytime or nighttime ambulatory BP of ≥130/≥80, ≥135/≥85, or ≥120/≥70 mm Hg were enrolled. Patients had ≥1 sign of TOD: electrocardiographic left ventricular hypertrophy (LVH), brachial-ankle pulse wave velocity (baPWV) ≥1400 cm/s, or urinary albumin-to-creatinine ratio (ACR) ≥3.5 mg/mmol in women and ≥2.5 mg/mmol in men. Exclusion criteria included secondary hypertension, diabetic nephropathy, serum creatinine ≥176.8 µmol/L, and cardiovascular disease within 6 months of screening. After stratification for centre, sex and the presence of nighttime hypertension, eligible patients were randomly assigned (1:1) to receive antihypertensive treatment or placebo. Patients and investigators were masked to group assignment. Active treatment consisted of allisartan starting at 80 mg/day, to be increased to 160 mg/day at month 2, and to be combined with amlodipine 2.5 mg/day at month 4, if the ambulatory BP remained uncontrolled. Matching placebos were used likewise in the control group. The primary endpoint was the improvement of TOD, defined as normalisation of baPWV, ACR or LVH or a ≥20% reduction in baPWV or ACR over the 48-week follow-up. The intention-to-treat analysis included all randomised patients, the per-protocol analysis patients who fully adhered to the protocol, and the safety analysis all patients who received at least one dose of the study medication. This study is registered with ClinicalTrials.gov, NCT02893358. Findings: Between February 14, 2017, and October 31, 2020, 320 patients (43.1% women; mean age ± SD 53.7 ± 9.7 years) were enrolled. Baseline office and 24-h BP averaged 130 ± 6.0/81 ± 5.9 mm Hg and 136 ± 8.6/84 ± 6.1 mm Hg, and the prevalence of elevated baPWV, ACR and LVH were 97.5%, 12.5%, and 7.8%, respectively. The 24-h BP decreased on average (±SE) by 10.1 ± 0.9/6.4 ± 0.5 mm Hg in 153 patients on active treatment and by 1.3 ± 0.9/1.0 ± 0.5 mm Hg in 167 patients on placebo. Improvement of TOD occurred in 79 patients randomised to active treatment and in 49 patients on placebo: 51.6% (95% CI 43.7%, 59.5%) versus 29.3% (22.1, 36.5%; p < 0.0001). Per-protocol and subgroup analyses were confirmatory. Adverse events were generally mild and occurred in 38 (25.3%) and 43 (26.4%) patients randomised to active treatment and placebo, respectively (p = 0.83). Interpretation: Our results suggest that antihypertensive treatment improves TOD in patients with masked hypertension, highlighting the need of treatment. However, the long-term benefit in preventing cardiovascular complications still needs to be established. Funding: Salubris China.

Tumor necrosis factor alpha induces NOX2-dependent reactive oxygen species production in hypothalamic paraventricular nucleus neurons following angiotensin II infusion.

There is evidence that tumor necrosis factor alpha (TNFα) influences autonomic processes coordinated within the hypothalamic paraventricular nucleus (PVN), however, the signaling mechanisms subserving TNFα's actions in this brain area are unclear. In non-neuronal cell types, TNFα has been shown to play an important role in canonical NADPH oxidase (NOX2)-mediated production of reactive oxygen species (ROS), molecules also known to be critically involved in hypertension. However, little is known about the role of TNFα in NOX2-dependent ROS production in the PVN within the context of hypertension. Using dual labeling immunoelectron microscopy and dihydroethidium microfluorography, we provide structural and functional evidence for interactions between TNFα and NOX2 in the PVN. The TNFα type 1 receptor (TNFR1), the major mediator of TNFα signaling in the PVN, was commonly co-localized with the catalytic gp91phox subunit of NOX2 in postsynaptic sites of PVN neurons. Additionally, there was an increase in dual labeled dendritic profiles following fourteen-day slow-pressor angiotensin II (AngII) infusion. Using dihydroethidium (DHE) microfluorography, it was also shown that TNFα application resulted in a NOX2-dependent increase in ROS in isolated PVN neurons projecting to the spinal cord. Further, TNFα-mediated ROS production was heightened after AngII infusion. The finding that TNFR1 and gp91phox are positioned for rapid interactions, particularly in PVN-spinal cord projection neurons, provides a molecular substrate by which inflammatory signaling and oxidative stress may jointly contribute to AngII hypertension.

Glycyrrhizin intake higher than the current international guidelines has no detectable hypermineralocorticoid-like effect in dogs.

Glycyrrhizin-enriched extracts from licorice root are associated with numerous health benefits and are widely used in phytotherapy. There is evidence that ingesting glycyrrhizin beyond threshold concentrations can impact the metabolism of cortisol, inhibiting its conversion to an inactive form, cortisone, via 11-hydroxysteroid dehydrogenase. A consequence can be a form of hypermineralocorticoidism, with elevated potassium excretion and associated hypertension, as demonstrated in rats and humans. Here, 3 orally dosed concentrations of glycyrrhizin (0.2, 0.4 and 0.6 mg/kg bodyweight/day) were assessed over 28 days in dogs. As the current guidelines reflect a lack of reliable data in this species, our aim was to provide relevant information for doses above the current guidelines. The specific purpose of this study was to demonstrate that an intake of licorice with a known therapeutic benefit to dogs does not cause hypermineralocorticoidism in this species. No changes in blood pressure, nor electrolyte excretion were observed in the dogs given these three glycyrrhizin concentrations.

Genome-wide association analysis of hypertension and epigenetic aging reveals shared genetic architecture and identifies novel risk loci.

Hypertension is a disease associated with epigenetic aging. However, the pathogenic mechanism underlying this relationship remains unclear. We aimed to characterize the shared genetic architecture of hypertension and epigenetic aging, and identify novel risk loci. Leveraging genome-wide association studies (GWAS) summary statistics of hypertension (129,909 cases and 354,689 controls) and four epigenetic clocks (N = 34,710), we investigated genetic architectures and genetic overlap using bivariate casual mixture model and conditional/conjunctional false discovery rate methods. Functional gene-sets pathway analyses were performed by functional mapping and gene annotation (FUMA) protocol. Hypertension was polygenic with 2.8 K trait-influencing genetic variants. We observed cross-trait genetic enrichment and genetic overlap between hypertension and all four measures of epigenetic aging. Further, we identified 32 distinct genomic loci jointly associated with hypertension and epigenetic aging. Notably, rs1849209 was shared between hypertension and three epigenetic clocks (HannumAge, IEAA, and PhenoAge). The shared loci exhibited a combination of concordant and discordant allelic effects. Functional gene-set analyses revealed significant enrichment in biological pathways related to sensory perception of smell and nervous system processes. We observed genetic overlaps with mixed effect directions between hypertension and all four epigenetic aging measures, and identified 32 shared distinct loci with mixed effect directions, 25 of which were novel for hypertension. Shared genes enriched in biological pathways related to olfaction.

The effect of astaxanthin supplementation on inflammatory markers, oxidative stress indices, lipid profile, uric acid level, blood pressure, endothelial function, quality of life, and disease symptoms in heart failure subjects.

BACKGROUND: Heart failure is a chronic and progressive disease where the heart muscle is unable to pump enough blood and oxygen to meet the body's needs. Oxidative stress and inflammation are key elements in the development and progression of heart failure. Astaxanthin, a carotenoid, has strong anti-inflammatory and antioxidant effects that may protect the cardiovascular system. A study will evaluate the effect of astaxanthin supplementation on inflammatory status, oxidative stress, lipid profile, uric acid levels, endothelial function, quality of life, and disease symptoms in people with heart failure. METHODS: The current study is a double-blind controlled randomized clinical trial for 8 weeks, in which people with heart failure were randomly assigned to two groups: intervention (one capsule containing 20 mg of astaxanthin per day, n = 40) and placebo (one capsule containing 20 mg of maltodextrin per day, n = 40) will be divided. At the beginning and end of the intervention, uric acid, lipid profile, oxidative stress indices, inflammatory markers, blood pressure, nitric oxide, and anthropometric factors will be measured, and questionnaires measuring quality of life, fatigue intensity, shortness of breath, and appetite will be completed. SPSS version 22 software will be used for statistical analysis. DISCUSSION: There is a growing global interest in natural and functional food products. This RCT contributes to the expanding body of research on the potential benefits of astaxanthin in heart failure patients, including its antioxidant, lipid-lowering, and anti-inflammatory effects. TRIAL REGISTRATION: Iranian Registry of Clinical Trials IRCT20200429047235N3. Registered on 26 March 2024.

Validating the accuracy of the Omron HBP-M4500 blood pressure measuring device according to the ISO81060-2:2018+ Amd 1:2020 protocol.

BACKGROUND: Blood pressure (BP) naturally undergoes fluctuations and variations, particularly during anesthesia administration during surgery, hemodialysis, upper and lower gastrointestinal endoscopy, exercise testing, arterial and venous catheterization, and rehabilitation. These changes in BP may lead to life-threatening events. OBJECTIVES: The performance of the Omron HBP-M4500 device in monitoring blood pressure (BP) in the upper arm was validated according to the International Organization for Standardization (ISO) 81060-2:2018+amendment (Amd) 1:2020 protocol. METHODS: The device was used to assess 113 participants in the inflation mode, and 107 participants in the deflation mode. All the patients fulfilled the inclusion criteria, including the arm circumference range and systolic and diastolic BP levels, outlined in the protocol. Data validation and analysis were performed according to the manufacturer's instructions. RESULTS: In criterion 1, the mean ± standard deviation (SD) values of the differences between the test device and reference BP were -0.6 ± 5.80/2.8 ± 6.78 mmHg (systolic/diastolic) and -1.0 ± 5.35/3.2 ± 6.52 mmHg for the inflation and deflation modes, respectively. These data fulfilled the ISO81060-2:2018+Amd1:2020 requirements of ⩽ 5 ±â£â©½ 8 mmHg. In criterion 2, the differences were -0.6 ± 4.44/2.8 ± 6.26 and -1.0 ± 3.84/3.2 ± 6.09 mmHg for the inflation and deflation modes, respectively, fulfilling criterion 2 with SD values of ⩽ 6.91 and ⩽ 6.87 for systolic BP and ⩽ 6.34 and ⩽ 6.14 for diastolic BP in the inflation and deflation modes, respectively. These two criteria were fulfilled in both studies. CONCLUSION: The Omron HBP-M4500 device, either in inflation or deflation mode, fulfilled the criteria outlined in the ISO protocol. Therefore, this device is valuable for BP measurement in clinical and hospital settings.

Epigenetic Clock at Birth and Childhood Blood Pressure Trajectory: A Prospective Birth Cohort Study.

BACKGROUND: The impact of methylation gestational age (GAmAge; a biomarker of fetal maturity) at birth on childhood blood pressure (BP) trajectories is unknown. METHODS: This cohort study included 500 boys and 440 girls with data on cord blood DNA methylation and BP at 3 to 15 years of age. Systolic BP (SBP) and diastolic BP percentiles were calculated based on clinical guidelines. Time-series K-means clustering identified 4 distinct SBP and diastolic BP percentile trajectories: high-steady, high-decrease, normal-increase, and normal-steady. GAmAge was estimated using an existing pediatric epigenetic clock. Extrinsic age acceleration was calculated as residuals of associations between GAmAge and chronological gestational age. Intrinsic age acceleration was calculated using the same method adjusting for cord blood cell compositions. RESULTS: Extrinsic age acceleration and intrinsic age acceleration were inversely associated with repeated measures of BP percentiles. Significant inverse associations were observed between extrinsic age acceleration and SBP percentiles in boys (ß=-2.02; P=0.02) but not in girls (ß=-0.49; P=0.58). Both extrinsic age acceleration and intrinsic age acceleration were inversely associated with SBP percentiles in girls born preterm (<37 weeks; ßEAA=-2.95; ßIAA=-3.00; P<0.05). Compared with the normal-steady SBP trajectory, significant inverse associations were observed between intrinsic age acceleration and high-steady, high-decrease, and normal-increase SBP trajectories in boys (odds ratio, 0.73-0.81; P<0.03), and significant positive associations were observed for high-decrease and normal-increase SBP trajectories in girls (odds ratio, 1.26-1.38; P<0.01). Significant sex differences were observed (Psex-interaction<2×10-16). CONCLUSIONS: GAmAge acceleration at birth was inversely associated with child BP, and such association was more pronounced in boys than in girls. Our findings may shed new light on the developmental origins of high BP and sex differences in cardiovascular risk.

Blood Pressure Control Among Diabetic Patients in the Eastern Mediterranean Region: A Systematic Review and Meta-Analysis.

BACKGROUND: The control of blood pressure (BP) is a challenge in diabetic patients and is associated with adverse outcomes of diabetes. In this systematic review and metaanalysis, we investigated the BP control rate among hypertensive diabetic patients in the Eastern Mediterranean Region (EMR) countries. METHODS: We systematically searched PubMed, Scopus, Embase, Cochrane, and Web of Science databases up to January 2023 for observational studies on BP control among hypertensive diabetic patients in all EMR countries. We included studies reporting the proportion of hypertensive, type 2 diabetic patients with controlled BP, defined as systolic/diastolic BP < 140/90 or <130/80 mmHg. Study quality was assessed using modified STROBE guidelines, and a random- effect meta-analysis was conducted to pool prevalence data and calculate overall rates. Subgroup analysis was performed by gender, study design, country, and BP control cut-offs (140/90 and 130/80). RESULTS: Among the 1949 retrieved studies, 20 studies assessing 27956 individuals were included. The proportion of BP control regardless of cut-off points was 36.8% (95% CI=29.1%- 45.3%) for both genders combined, with a breakdown of 53.2% (95% CI=36.1%-69.6%) for women and 43.5% (95% CI=20.0%-70.3%) for men, respectively. Based on cut-offs of 130/80 and 140/90 mmHg as the target, BP control was estimated by 38.2% (95%CI 24.5, 54.1) and 36.5% (95%CI 27.1, 47.0), respectively. CONCLUSION: Our findings indicate that BP control targets are not successfully achieved in hypertensive diabetic patients in the Eastern Mediterranean region. It is recommended to place greater emphasis on the quality of hypertension care in the management of type 2 diabetes.

Orthostatic hypotension and subjective symptomatic orthostasis in Parkinson's disease: Associations and correlations.

Background: Both measured orthostatic hypotension and symptomatic orthostasis are common in PD but their relationship is unclear. Objective: We aim to determine clinical predictors of both measured orthostatic hypotension and reported symptomatic orthostasis in PD, including the impact of "on"/"off" status and seasons, and to determine the correlation between measured OH and subjective orthostasis. Methods: We analyzed BP readings, demographic and disease state predictors for both 1. Measured blood pressure OH criteria and 2. The subjective report of orthostatic symptoms, using logistic regression analyses from an initial "on" motor state clinical visit in all PD patient visits. We then correlated subjective orthostasis symptoms with BP measurements. We also compared intra-subject BP measures in PD patients seen in both "on" and "off" states, and when seen "on" in both summer and winter. Results: 723 consecutive visits over 2 years identified 250 unique PD individuals. Subjective orthostasis was reported by 44 % and "on" measured OH (>20 drop in SBP or 10 DBP upon standing) was seen in 30 %. Measured OH did not significantly correlate with any assessed clinical feature or specific medicine. Subjective orthostasis correlated most with older age, dementia, and L-dopa use. Subjective orthostasis correlated equally with absolute lower measured standing SBP and the drop in SBP from sitting to standing. Compared to the "off" state, "on" state showed lower sitting and standing SBP, more than DBP, but no significant change in BP drop upon standing. Seasons did not impact measured BP. Conclusions: Both OH and symptomatic orthostasis are common. Dopaminergic medications did not cause traditionally defined OH but lowered all SBP (sitting and standing) and thus reduced pulse pressure, possibly by increasing arteriole compliance simply by reducing motor tone, as this BP-lowering effect may be specific to Parkinsonism.

Age-Related Blood Pressure Gradients Are Associated With Blood Pressure Control and Global Population Outcomes.

BACKGROUND: The strong relationship between blood pressure (BP) and age is well known. Limited evidence suggests that a steeper age-BP slope may be associated with an increased risk of adverse outcomes. The May Measurement Month campaign enables an investigation of geographic, socioeconomic, and sex differences in age-BP gradients and their association with public-health outcomes. METHODS: Cross-sectional, annual global BP May Measurement Month screening data were analyzed. Average systolic BP and age-related BP slopes across different age groups were calculated to assess regional, socioeconomic, and sex-stratified variations. The association of BP slopes derived from adjusted linear regression models with country-level health metrics was investigated. RESULTS: Age-related systolic BP gradients differed distinctly across global geographic regions, income levels, and between sexes. The steepest age gradients of BP were observed in populations from Africa and Europe. Women had lower BP levels than men at younger ages (20s and 30s) but subsequently experienced more pronounced age-related BP gradients. Geographically divergent age-related BP gradients were significantly associated with major national public health indicators. Globally, steeper age-related BP slopes were associated with poor BP control, increased disability-adjusted life years, and death rates. A steeper population age-BP slope of 1 mm Hg per 10 years was associated with a decrease in life expectancy of 3.3 years in this population (95% CI, -5.1 to -1.4; P=0.0007). CONCLUSIONS: Age-related BP gradients vary considerably across global populations and are associated with variability in BP-related risks and adverse outcomes across regions. Effective public health strategies may require region-specific targeting of adverse BP gradients to improve health outcomes.

Elevated blood pressure: a genetically determined risk factor for cerebral artery dissection.

BACKGROUND: We aim to investigate the potential causal link between blood pressure (BP) levels and cerebral artery dissection (CAD) risk employing a two-sample Mendelian randomization (TSMR) framework. METHODS: Utilizing large-scale genome-wide association studies (GWAS)-retrieved data, we employed various MR techniques, including inverse variance weighted (IVW), MR-Egger regression, weighted median, and weighted mode, to ascertain BP's causal impact on CAD. The MR-Egger intercept was calculated to assess pleiotropy presence, determining heterogeneity by Cochran's Q statistic. RESULTS: The findings highlighted a significant association between elevated systolic BP (SBP; IVW: OR=3.09, 95% CI: 1.11-8.61, p=0.031) and increased diastolic BP (DBP; IVW: OR=2.17, 95% CI: 1.14-6.21, p=0.023) with CAD risk. Sensitivity analyses reinforced the robustness and reliability of these results. CONCLUSIONS: The results from this TSMR study suggest a causal link between high SBP and DBP and the increased likelihood of CAD, which provide genetic evidence for a reduced risk of CAD under blood pressure control.

Post-Intervention Acceptability of a Multicomponent Intervention for Hypertension Management in Primary Care Clinics by Health Care Providers and Patients: A Qualitative Study of a Cluster RCT in Singapore.

Background: Hypertension is a major public health challenge, globally. Recently, we reported findings from cluster randomized trial in 8 primary care clinics in Singapore and showed that a multicomponent "SingHypertension" intervention comprising 1) motivational conversation by trained nurses, 2) telephone-based follow-ups, 3) standardized algorithm with single-pill combination (SPC) antihypertensive medications, and 4) subsidy on SPC antihypertensive drugs was effective on improving BP control. This paper presents the acceptability of SingHypertension multicomponent intervention among the key stakeholders. Methods: We conducted post-implementation interviews of 38 stakeholders, including 18 patients and 20 healthcare providers (HCPs) in 4 primary care clinics randomized to the multicomponent "SingHypertension" intervention in Singapore. We used Theoretical Framework for Acceptability (TFA) framework with a focus on affective attitude, burden, ethicality, intervention coherence, opportunity cost, perceived effectiveness and self-efficacy to assess stakeholders' acceptability of the intervention. Results: SingHypertension multicomponent intervention had high perceived effectiveness and a good fit with the value system and ethics of patients and HCPs. Physicians appreciated the guidance from standardized training in hypertension management. Although workload was increased, the nurses felt rewarded for their positive interactions with the patients during motivational conversation sessions and the telephone follow-ups. Most patients reported high self-efficacy levels, improved lifestyles, and adherence to antihypertensive medications. The limited choice of SPC medication, lack of subsidy beyond the trial duration, and shortage of nurses were significant challenges to wide-scale implementation. All HCPs and patients supported scaling up the intervention across primary care clinics. Conclusion: SingHypertension multicomponent intervention is acceptable to the key stakeholders in Singapore. Taken together with the effectiveness of the intervention, our findings make a compelling case for scaling-up SingHypertension in primary care clinics in Singapore and possibly other countries with similar healthcare infrastructure.