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.

Associations between Global Diet Quality Score and Risk of Metabolic Syndrome and Its Components: Tehran Lipid and Glucose Study.

Background: Various food quality indicators have been proposed as tools for predicting metabolic syndrome (MetS). This study investigated the association between global diet quality score (GDQS) and the risks of developing MetS and its components. Methods: In this secondary analysis, we included elective adult participants (n=4,548) from the Tehran Lipid and Glucose Study. Dietary data were collected by a valid and reliable semi-quantitative food frequency questionnaire. MetS was defined according to the Iranian modified National Cholesterol Education Program. Multivariable Cox proportional hazard regression models were used to estimate the incidence of MetS in association with GDQS. Results: This study involved 1,762 men and 2,786 women with a mean±standard deviation age of 38.6±14.3 and 35.9±11.8 years, respectively. A total of 1,279 subjects developed MetS during the mean follow-up of 6.23 years. Incidence of MetS was associated with GDQS (hazard ratio [HR], 1; 0.90 [95% confidence interval, CI, 0.82 to 0.98]; 0.84 [95% CI, 0.76 to 0.91]; 0.80 [95% CI, 0.73 to 0.89]; P for trend <0.001) after adjusting for confounding variables. The healthy food group component of GDQS was related to MetS incidence. GDQS in the range of 12%-17% in the fourth quartile was associated with a decrease in incidence of MetS components. Both healthy and unhealthy food group components of the GDQS decreased the incidence of high triglycerides, high blood pressure, and high fasting blood glucose. Conclusion: Higher GDQS was associated with a lower risk of the incidence of MetS or its components among Tehranian adults. Higher intake of healthy food group components and lower consumption of unhealthy food group components of the GDQS predicted lower MetS incidence and risk factors.

Blood pressure variability and prognostic significance in traumatic brain injury: analysis of the eICU-CRD database.

BACKGROUND: Preliminary evidence demonstrates that visit-to-visit systolic blood pressure (SBP) variability is a prognostic factor of TBI. However, literature regarding the impact of initial blood pressure management on the outcomes of TBI patients is limited. We aimed to further validate the clinical significance of BPV on the prognostic outcomes of patients with TBI. METHODS: We performed the analysis by using individual patient-level data acquired from the eICU-CRD, which collected 200,859 ICU admissions of 139,367 patients in 2014 and 2015 from 208 US hospitals. Adult patients with traumatic intraparenchymal hemorrhage or contusion were included. The primary outcome was in-hospital mortality and the secondary outcome was discharge-home rate. Blood pressure variability (BPV) was calculated according to standard criteria: at least six measurements were taken in the first 24 h (hyperacute group) and 36 over days 2-7 (acute group). We estimated the associations between BPV and outcomes with logistic and proportional odds regression models. The key parameter for BPV was standard deviation (SD) of SBP, categorized into quintiles. We also calculated the average real variability (ARV), as well as maximum, minimum, and mean SBP for comparison in our analysis. RESULTS: We studied 1486 patients in the hyperacute group and 857 in the acute group. SD of SBP had a significant association with the in-hospital mortality for both the hyperacute group (highest quintile adjusted OR 2.28 95% CI 1.18-4.42; ptrend<0.001) and the acute group (highest quintile adjusted OR 2.17, 95% CI 1.08-4.36; ptrend<0.001). The strongest predictors of primary outcome were SD of SBP in the hyperacute phase and minimum SBP in the acute phase. Associations were similar for the discharge-home rate (for the hyperacute group, highest quintile adjusted OR 0.58, 95% CI 0.37-0.89; ptrend<0.001; for the acute group OR 0.55, 95% CI 0.32-0.95; ptrend<0.001). CONCLUSION: Systolic BPV seems to predict a poor outcome in patients with TBI. The benefits of early treatment to maintain appropriate SBP level might be enhanced by smooth and sustained control.

Association between vascular aging and cognitive function in Chinese adults.

BACKGROUND: Vascular health has been associated with cognition but related evidence is limited in Chinese. The objective of this study was to examine the association of vascular aging assessed by arterial stiffness and blood pressure with cognitive function in an unselected Chinese population. METHODS: In the Tianning Cohort (N = 5158), indicators of arterial stiffness and blood pressure including carotid-femoral pulse wave velocity (cfPWV), ankle-brachial index (ABI), pulse pressure (PP), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were measured. Cognitive function was assessed using the Mini Mental State Examination (MMSE) questionnaire. We applied Poisson regression and logistic regression to examine the associations of vascular aging and blood pressure with cognitive function. RESULTS: 76 (1.47%) participants had impaired cognitive function diagnosed by a MMSE score of less than 24 points. Participants with a higher level of PP were more likely to have a decreased score of MMSE (ß=-0.0121, P < 0.001 for log-transformed pulse pressure) and a higher risk of having impaired cognitive function (OR = 5.95, 95%CI: 2.02-17.79, P < 0.001 for log-transformed PP). Per standard deviation increment in SBP was significantly associated with lower MMSE score (ß=-0.0020, P < 0.001) and impaired cognitive function (OR = 1.69, 95%CI: 1.38-2.06, P < 0.001). No significant associations were found regarding other parameters. CONCLUSIONS: Blood pressure and hypertension were associated with cognitive function in Chinese adults. PP may be a potential predictor for impaired cognitive function.

Empagliflozin combined with sacubitril/valsartan in hypertensive patients with heart failure: a retrospective study of efficacy and effect on blood pressure variability and cardiac function.

OBJECTIVE: To evaluate the efficacy of empagliflozin combined with sacubitril/valsartan in treating hypertensive patients with heart failure (HF), focusing on its effects on blood pressure variability (BPV) and cardiac function. METHODS: This retrospective study included 101 patients with hypertension and heart failure with reduced ejection fraction treated at Baoji High-Tech Hospital from October 2021 to October 2023. Patients were divided into two groups: an observation group (n=51), treated with both empagliflozin and sacubitril/valsartan, and a control group (n=50), treated with sacubitril/valsartan alone. We compared the therapeutic effects, BPV (including 24-hour, daytime, and nighttime systolic and diastolic BPV), cardiac function indicators, levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI) before and after treatment, and the incidence of adverse reactions between the groups. Independent risk factors affecting treatment efficacy were also analyzed. RESULTS: The total effective rate of treatment in the observation group was significantly higher than in the control group (P<0.05). Both groups showed reductions in daytime and nighttime systolic and diastolic BPV after treatment, with the observation group displaying more pronounced improvements (all P<0.05). Enhancements in cardiac ultrasound measurements, NT-proBNP levels, and cTnI levels were more significant in the observation group compared to the control group post-treatment (both P<0.05). There was no significant difference in the incidence of adverse reactions during treatment between the two groups (P>0.05). Age and comorbid diabetes were identified as independent risk factors for poor prognosis, while treatment with empagliflozin combined with sacubitril/valsartan was a protective factor. CONCLUSION: Empagliflozin combined with sacubitril/valsartan significantly enhances treatment efficacy in hypertensive patients with heart failure, effectively improves cardiac function and BPV, and demonstrates good safety.

Evidence of a causal relationship between blood pressure and pathological scars: a bidirectional Mendelian randomization study.

Background: Recent advancements in basic medicine and epidemiology suggest a potential influence of blood pressure on scar formation, yet the specifics of this relationship are not fully understood. This study aims to clarify the causal link between blood pressure and the development of pathological scars using Mendelian randomization (MR). Methods: This study employed genetic variants closely linked to blood pressure as instrumental variables to explore the relationship between blood pressure and pathological scars. The inverse variance weighted (IVW) method was used for analysis. Results: Our analysis identified a notable association where higher blood pressure was correlated with a lower risk of pathological scars. Specifically, an increase in diastolic blood pressure (odds ratio [OR] per standard deviation increase: 0.67 [95% Confidence Interval [CI], 0.49-0.99]), systolic blood pressure (OR per standard deviation increase: 0.66 [95% CI, 0.46-0.93]), and hypertension (pooled OR: 0.39 [95% CI, 0.18-0.85]) were significantly associated with a reduced risk of keloids. Similarly, a genetic predisposition to hypertension (pooled OR: 0.31 [95% CI, 0.11-0.89]) was significantly associated with a reduced risk of hypertrophic scars. Neither reverse MR analysis nor Steiger's test indicated a significant reverse causal relationship between hypertension and either keloids or hypertrophic scars. Conclusion: The findings suggest a protective role of higher blood pressure against the development of pathological scars, including keloids and hypertrophic scars. However, the inconsistency observed across different MR methods warrants cautious interpretation and underscores the need for further investigation to confirm these findings.

Educational inequalities in blood pressure across the adult life course: Evidence from a 20-year follow-up study.

AIM: High blood pressure (BP) is a key contributor to the burden of disease. This study aimed to assess: a) educational differences across the entire BP distribution, and b) educational differences in the trajectories of BP across the adult life course. METHOD: Longitudinal data from the Stockholm Diabetes Prevention Program was analysed using quantile regression and linear mixed effects models. Models were adjusted for age, sex, lifestyle, and BP medication. RESULTS: Lower educational level was associated with higher systolic BP (SBP) at all follow-up periods. Age and sex adjusted mean SBP was 2.49 (95% confidence interval (CI) 1.10, 3.87), 3.95 (95% CI 2.45, 5.45) and 2.61 (95% CI 1.09, 4.13) mmHg higher for people with pre-secondary education compared with post-secondary at baseline, 10 years and 20 years follow-up, respectively. Quantile regressions revealed that the inequalities could be observed across the entire BP continuum. Longitudinally analysed, people with pre-secondary education had 3.01 (95% CI 1.91-4.11) mmHg higher SBP than those with post-secondary education, age and sex adjusted. No significant convergence or divergence of the educational gaps in SBP was observed. Educational differences remained even after adjusting for lifestyle and BP medication. CONCLUSIONS: These results imply that public health interventions should aim to bring about distributional shifts in blood pressure, rather than exclusively focusing on hypertensive people, if they are to effectively minimize the educational disparities in blood pressure and its consequences.

Impacts of renal denervation on blood pressure in patients with obstructive sleep apnea.

BACKGROUND: Sympathetic nerve activation followed by obstructive sleep apnea (OSA) accounts for blood pressure elevation. The effectiveness of renal denervation (RDN) in controlling blood pressure in patients with OSA remains controversial. In this systematic review, we tried to pool currently available data to assess the effects of RDN therapy on blood pressure in OSA patients. METHODS: We retrieved Pubmed, EMbase and Cochrane Library through 17 May 2023, using the following key words: "renal denervation" and"obstructive sleep apnea". Full articles reporting the change of blood pressure after RDN procedure were included. RESULTS: A total of five studies were included in the meta-analysis. Pooled analysis showed that RDN markedly reduced both 24-h ambulatory systolic blood pressure (24 h-SBP) (Mean difference (MD): -7.54mmHg; 95%Cl: -10.16 to -4.91mmHg; I2 = 0%) and 24-h ambulatory diastolic blood pressure (24 h-DBP) (MD: -5.28mmHg; 95%Cl: -7.35 to -3.22mmHg; I2=0%). Daytime systolic blood pressure (dSBP) was reduced after RDN (MD: -7.54mmHg; 95%Cl: -10.82 to -4.57mmHg; I2 = 54%). With regards to nocturnal blood pressure, we found that RDN resulted in a significant reduction in nighttime systolic blood pressure (nSBP) (MD: -6.91mmHg; 95%Cl: -10.69 to -2.85mmHg; I2=0%). Subgroup analysis showed that dSBP was reduced by 12.00 mmHg, 12.00 mmHg, and 7.25 mmHg at 1 month, 3 months and 6 months, respectively. Our pooled analysis showed that AHI was not significantly changed by RDN. No major compilations were associated with RDN. CONCLUSIONS: RDN exerts a considerable blood pressure-lowering effect in hypertensive patients with OSA, which was sustained at least 6 months.

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.

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.

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.

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.

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.

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.