Long-Term Effect of Home Blood Pressure Self-Monitoring Plus Medication Self-Titration for Patients With Hypertension: A Secondary Analysis of the ADAMPA Randomized Clinical Trial.

Importance: Patient empowerment through pharmacologic self-management is a common strategy for some chronic diseases such as diabetes, but it is rarely used for controlling blood pressure (BP). Several trials have shown its potential for reducing BP in the short term, but evidence in the longer term is scarce. Objective: To evaluate the longer-term effectiveness of BP self-monitoring plus self-titration of antihypertensive medication vs usual care for patients with poorly controlled hypertension, with passive follow-up and primary-care nursing involvement. Design, Setting, and Participants: The ADAMPA (Impact of Self-Monitoring of Blood Pressure and Self-Titration of Medication in the Control of Hypertension) study was a randomized, unblinded clinical trial with 2 parallel arms conducted in Valencia, Spain. Included participants were patients 40 years or older, with systolic BP (SBP) over 145 mm Hg and/or diastolic BP (DBP) over 90 mm Hg, recruited from July 21, 2017, to June 30, 2018 (study completion, August 25, 2020). Statistical analysis was conducted on an intention-to-treat basis from August 2022 to February 2024. Interventions: Participants were randomized 1:1 to usual care vs an individualized, prearranged plan based on BP self-monitoring plus medication self-titration. Main Outcomes and Measures: The main outome was the adjusted mean difference (AMD) in SBP between groups at 24 months of follow-up. Secondary outcomes were the AMD in DBP between groups at 24 months of follow-up, proportion of patients reaching the BP target (SBP <140 mm Hg and DBP <90 mm Hg), change in behaviors, quality of life, health service use, and adverse events. Results: Among 312 patients included in main trial, data on BP measurements at 24 months were available for 219 patients (111 in the intervention group and 108 in the control group). The mean (SD) age was 64.3 (10.1) years, and 120 patients (54.8%) were female; the mean (SD) SBP was 155.6 (13.1) mm Hg, and the mean (SD) diastolic BP was 90.8 (7.7) mm Hg. The median follow-up was 23.8 months (IQR, 19.8-24.5 months). The AMD in SBP at the end of follow-up was -3.4 mm Hg (95% CI, -4.7 to -2.1 mm Hg; P < .001), and the AMD in DBP was -2.5 mm Hg (95% CI, -3.5 to -1.6 mm Hg; P < .001). Subgroup analysis for the main outcome showed consistent results. Sensitivity analyses confirmed the robustness of the main findings. No differences were observed between groups in behaviors, quality of life, use of health services, or adverse events. Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, BP self-monitoring plus self-titration of antihypertensive medication based on an individualized prearranged plan used in primary care reduced BP in the longer term with passive follow-up compared with usual care, without increasing health care use or adverse events. These results suggest that simple, inexpensive, and easy-to-implement self-management interventions have the potential to improve the long-term control of hypertension in routine clinical practice. Trial Registration: ClinicalTrials.gov Identifier: NCT03242785.

The association between the urinary chromium and blood pressure: a population-based study.

BACKGROUND AND AIM: The impact of trace elements and heavy metals on human health has attracted widespread attention. However, the correlation between urinary chromium concentrations and blood pressure remains unclear and inadequately reported, and the aim of this study was to investigate the relationship between urinary chromium concentrations and blood pressure in adults in the United States (US). METHODS: We utilized data from the National Health and Nutrition Examination Survey (NHANES) 2017-2018 for this study. Multivariate logistic regression and multivariate linear regression were used to explore the association of urinary chromium concentrations with hypertension and blood pressure. Additionally, we also performed subgroup analysis and restricted cubic splines (RCS). RESULTS: A total of 2958 participants were enrolled in this study. The overall mean systolic blood pressure and diastolic blood pressure were 123.98 ± 0.60, 72.66 ± 0.57 mmHg, respectively. The prevalence of hypertension was found in 41.31% of the whole participants. In the fully adjusted model, we did not observe a correlation between urinary chromium concentrations and the risk of hypertension and systolic blood pressure. However, we found a negative association between urinary chromium concentrations and diastolic blood pressure. In subgroup analysis, we observed a positive association between urinary chromium and the risk of hypertension among participants older than 60 years of age and those who were Non-Hispanic Black. The interaction term highlighted the influence of age and race on this positive association. We also found a negative association of urinary chromium with diastolic blood pressure in male, participants who were current smokers, overweight, and other races, as well as those without alcohol use and anti-hypertensive drug use. However, the interaction term only revealed the influence of alcohol consumption on the negative association. CONCLUSION: Our study suggested that urinary chromium concentrations may show a negative association with diastolic blood pressure and this association was significantly dependent on alcohol consumption. Besides, a positive association between urinary chromium and the risk of hypertension was also found among participants older than 60 years of age and those who were Non-Hispanic Black.

Association of RASGRP1 polymorphism with vascular complications in Chinese diabetic patients with glycemic control and antihypertensive treatment.

BACKGROUND: Studies have shown that RASGRP1 was potently associated with the onset of type 2 diabetes mellitus (T2DM), and RASGRP1 rs7403531 was significantly correlated with islet function in T2DM patients. However, the effect of RASGRP1 polymorphism on blood glucose and blood pressure in T2DM patients after continuous treatment has yet to be fully elucidated. OBJECTIVE: This study aimed to explore the association between RASGRP1 genetic polymorphism and cardiovascular complications in T2DM patients, so as to provide more evidence for the individualized treatment of T2DM patients. METHODS: We retrospectively analyzed a large-scale multicenter drug clinical study cohort that based on a 2 × 2 factorial (glucose control axis and blood pressure lowering axis) randomized controlled design, with follow-up for 5 years. The major vascular endpoint events included cardiovascular death, non-fatal stroke, coronary heart disease, new-onset or worsening renal disease, and diabetic retinopathy. RASGRP1 rs12593201, rs56254815 and rs7403531 were finally selected as candidate single nucleotide polymorphisms. Mixed linear model and Cox hazard ratio (HR) model were used for data analysis with IBM SPSS (version 20.0 for windows; Chicago, IL). RESULTS: Our study enrolled 1357 patients with high-risk diabetes, with a mean follow-up duration of 4.8 years. RASGRP1 rs7403531 was associated with vascular events in hypoglycemic and antihypertensive therapy. Specifically, compared with CC carriers, patients with CT/TT genotype had fewer major microvascular events (HR = 0.41, 95% confidence interval (CI) 0.21-0.80, P = 0.009), and reduced the risk of major eye disease events (HR = 0.44, 95% CI 0.20-0.94, P = 0.03). For glucose lowering axis, CT/TT carriers had a lower risk of secondary nephropathy (HR = 0.48, 95% CI 0.25-0.92, P = 0.03) in patients with standard glycemic control. For blood pressure lowering axis, all cerebrovascular events (HR = 2.24, 95% CI 1.11-4.51, P = 0.025) and stroke events (HR = 2.07, 95% CI 1.03-4.15, P = 0.04) were increased in patients with CC genotype compared to those with CT/TT genotype in the placebo group, respectively. Furthermore, patients with CC genotype showed a reduced risk of major cerebrovascular events in antihypertensive group (HR = 0.36, 95% CI 0.15-0.86, P = 0.021). For RASGRP1 rs56254815, compared with the AA genotype carriers, the systolic blood pressure of AG/GG carriers in the antihypertensive group decreased by 1.5mmhg on average (P = 0.04). In the placebo group, the blood pressure of AG/GG carriers was 1.7mmHg higher than that of AA carriers (P = 0.02). CONCLUSION: We found that patients with G allele of RASGRP1 (rs56254815) showed a better antihypertensive therapy efficacy in T2DM patients. The rs7403531 T allele could reduce the risk of major microvascular events and major eye diseases in T2DM patients receiving either hypoglycemic or antihypertensive therapy. Our findings suggest that RASGRP1 genetic polymorphism might predict the cardiovascular complications in T2DM patients.

Association between untreated and treated blood pressure levels and cognitive decline in community-dwelling middle-aged and older adults in China: a longitudinal study.

BACKGROUND: Optimal blood pressure (BP) levels to reduce the long-term risk of cognitive decline remains controversial. We aimed to investigate the association between BP and anti-hypertensive treatment status with cognitive decline in older adults. METHODS: This study used data from the China Health and Retirement Longitudinal Study. Cognitive function was assessed at year 2011, 2013, 2015, and 2018. Global cognitive Z-score was calculated as the average score of episodic memory and mental intactness. BP were measured at the first and second wave. Pulse pressure (PP) was calculated as systolic BP (SBP) minus diastolic BP. Cumulative BP was calculated as the area under the curve using BP measurements from 2011 to 2013. Linear mixed models were used to assess the longitudinal association between BP-related measurements and cognitive decline. RESULTS: We included 11,671 participants (47.3% men and mean age 58.6 years). Individual with BP > 140/90 mm Hg or taking anti-hypertensive medication were independently associated with accelerated cognitive decline (ß=-0.014, 95% CI: -0.020 to -0.007). Individuals with anti-hypertensive medication use, but with controlled SBP to less than 120 mm Hg did not have a significantly increased risk of cognitive decline compared with normotension (ß=-0.003, 95% CI: -0.021 to 0.014). Individuals on anti-hypertensive treatment with PP of more than 70 mm Hg had a significantly higher risk of cognitive decline (ß=-0.033, 95% CI: -0.045 to -0.020). Regardless of anti-hypertensive treatment status, both elevated baseline and cumulative SBP and PP were found to be independently associated with accelerated cognitive decline. CONCLUSIONS: Cumulatively elevated SBP, PP and uncontrolled BP were associated with subsequent cognitive decline. Effectively controlling BP with anti-hypertensive treatment may be able to preserve cognitive decline in older adults.

Hydroxytyrosol, a Promising Supplement in the Management of Human Stroke: An Exploratory Study.

Hydroxytyrosol (HT) is a bioactive olive oil phenol with beneficial effects in a number of pathological situations. We have previously demonstrated that an HT-enriched diet could serve as a beneficial therapeutic approach to attenuate ischemic-stroke-associated damage in mice. Our exploratory pilot study examined this effect in humans. Particularly, a nutritional supplement containing 15 mg of HT/day was administered to patients 24 h after the onset of stroke, for 45 days. Biochemical and oxidative-stress-related parameters, blood pressure levels, serum proteome, and neurological and functional outcomes were evaluated at 45 and 90 days and compared to a control group. The main findings were that the daily administration of HT after stroke could: (i) favor the decrease in the percentage of glycated hemoglobin and diastolic blood pressure, (ii) control the increase in nitric oxide and exert a plausible protective effect in oxidative stress, (iii) modulate the evolution of the serum proteome and, particularly, the expression of apolipoproteins, and (iv) be beneficial for certain neurological and functional outcomes. Although a larger trial is necessary, this study suggests that HT could be a beneficial nutritional complement in the management of human stroke.

[Changing Concepts About Optimal Target Blood Pressure and the Therapeutic Advantages of Azilsartan for Achieving it].

The article discusses current issues of the treatment of arterial hypertension. According to presented data, so-called therapeutic nihilism is becoming one of the main barriers to achieving target blood pressure (BP). This nihilism is that despite evidence of the effectiveness of achieving lower BP values, practitioners do not intensify antihypertensive therapy sufficiently to achieve such values. The article specially addresses new criteria for the effectiveness of antihypertensive therapy, which reflect the therapy sustainability. The most commonly used indicator is the duration of the period, during which systolic BP remains in the therapeutic range. The prognostic significance of such indicators is discussed. In these conditions, it is very important to use the most effective antihypertensive drugs for initial antihypertensive therapy, including as a part of combination therapy. This tactic provides more frequent achievement of BP goals without the need for dose adjustment. In this regard, a systematic review was performed, which included sufficiently large randomized studies of the antihypertensive effectiveness of azilsartan medoxomil. This systematic review will provide comprehensive information on a possible role of using the angiotensin II receptor blocker azilsartan as a basic drug for the treatment of a wide range of patients with high BP. Most of the studies included in the systematic review assessed the effectiveness of combination therapy including azilsartan.

siRNA takes a jab at hypertension.

Hypertension is a modifiable risk factor for cardiovascular disease, the leading cause of death worldwide, yet most US adults with hypertension do not meet goal blood pressure. KARDIA-1 demonstrates the efficacy of zilebesiran, a subcutaneously administered small interfering RNA, for lowering blood pressure, presenting a novel treatment option for this deadly disease.1.

Effect of lidocaine on intraoperative blood pressure variability in patients undergoing major vascular surgery.

BACKGROUND: Dynamic fluctuations of arterial blood pressure known as blood pressure variability (BPV) may have short and long-term undesirable consequences. During surgical procedures blood pressure is usually measured in equal intervals allowing to assess its intraoperative variability, which significance for peri and post-operative period is still under debate. Lidocaine has positive cardiovascular effects, which may go beyond its antiarrhythmic activity. The aim of the study was to verify whether the use of intravenous lidocaine may affect intraoperative BPV in patients undergoing major vascular procedures. METHODS: We performed a post-hoc analysis of the data collected during the previous randomized clinical trial by Gajniak et al. In the original study patients undergoing elective abdominal aorta and/or iliac arteries open surgery were randomized into two groups to receive intravenous infusion of 1% lidocaine or placebo at the same infusion rate based on ideal body weight, in concomitance with general anesthesia. We analyzed systolic (SBP), diastolic (DBP) and mean arterial blood (MAP) pressure recorded in 5-minute intervals (from the first measurement before induction of general anaesthesia until the last after emergence from anaesthesia). Blood pressure variability was then calculated for SBP and MAP, and expressed as: standard deviation (SD), coefficient of variation (CV), average real variability (ARV) and coefficient of hemodynamic stability (C10%), and compared between both groups. RESULTS: All calculated indexes were comparable between groups. In the lidocaine and placebo groups systolic blood pressure SD, CV, AVR and C10% were 20.17 vs. 19.28, 16.40 vs. 15.64, 14.74 vs. 14.08 and 0.45 vs. 0.45 respectively. No differences were observed regarding type of surgery, operating and anaesthetic time, administration of vasoactive agents and intravenous fluids, including blood products. CONCLUSION: In high-risk vascular surgery performed under general anesthesia, lidocaine infusion had no effect on arterial blood pressure variability. TRIAL REGISTRATION: ClinicalTrials.gov; NCT04691726 post-hoc analysis; date of registration 31/12/2020.

Endobronchial Phenylephrine in Airway Bleeding During Bronchoscopy Does not Cause Hypertension: A Retrospective Observational Study.

BACKGROUND: Bleeding is a known complication during bronchoscopy, with increased incidence in patients undergoing a more invasive procedure. Phenylephrine is a potent vasoconstrictor that can control airway bleeding when applied topically and has been used as an alternative to epinephrine. The clinical effects of endobronchial phenylephrine on systemic vasoconstriction have not been clearly evaluated. Here, we compared the effects of endobronchial phenylephrine versus cold saline on systemic blood pressure. METHODS: In all, 160 patients who underwent bronchoscopy and received either endobronchial phenylephrine or cold saline from July 1, 2017 to June 30, 2022 were included in this retrospective observational study. Intra-procedural blood pressure absolute and percent changes were measured and compared between the 2 groups. RESULTS: There were no observed statistical differences in blood pressure changes between groups. The median absolute change between the median and the maximum intra-procedural systolic blood pressure in the cold saline group was 29 mm Hg (IQR 19 to 41) compared with 31.8 mm Hg (IQR 18 to 45.5) in the phenylephrine group. The corresponding median percent changes in SBP were 33.6 % (IQR 18.8 to 39.4) and 28% (IQR 16.8 to 43.5) for the cold saline and phenylephrine groups, respectively. Similarly, there were no statistically significant differences in diastolic and mean arterial blood pressure changes between both groups. CONCLUSIONS: We found no significant differences in median intra-procedural systemic blood pressure changes comparing patients who received endobronchial cold saline to those receiving phenylephrine. Overall, this argues for the vascular and systemic safety of phenylephrine for airway bleeding as a reasonable alternative to epinephrine.

Integrated metabolomics analysis reveals mechanistic insights into variability in blood pressure response to thiazide diuretics and beta blockers.

Hypertensive patients with a higher proportion of genetic West African ancestry (%GWAA) have better blood pressure (BP) response to thiazide diuretics (TDs) and worse response to ß-blockers (BBs) than those with lower %GWAA, associated with their lower plasma renin activity (PRA). TDs and BBs are suggested to reduce BP in the long term through vasodilation via incompletely understood mechanisms. This study aimed at identifying pathways underlying ancestral differences in PRA, which might reflect pathways underlying BP-lowering mechanisms of TDs and BBs. Among hypertensive participants enrolled in the Pharmacogenomics Evaluation of Antihypertensive Responses (PEAR) and PEAR-2 trials, we previously identified 8 metabolites associated with baseline PRA and 4 metabolic clusters (including 39 metabolites) that are different between those with GWAA <45% versus ≥45%. In the current study, using Ingenuity Pathway Analysis (IPA), we integrated these signals. Three overlapping metabolic signals within three significantly enriched pathways were identified as associated with both PRA and %GWAA: ceramide signaling, sphingosine 1- phosphate signaling, and endothelial nitric oxide synthase signaling. Literature indicates that the identified pathways are involved in the regulation of the Rho kinase cascade, production of the vasoactive agents nitric oxide, prostacyclin, thromboxane A2, and endothelin 1; the pathways proposed to underlie TD- and BB-induced vasodilatation. These findings may improve our understanding of the BP-lowering mechanisms of TDs and BBs. This might provide a possible step forward in personalizing antihypertensive therapy by identifying patients expected to have robust BP-lowering effects from these drugs.

Effects of Vitamin D Supplementation on Central Hemodynamic Parameters and Autonomic Nervous System in Obese or Overweight Individuals. / Efeitos da Suplementação de Vitamina D sobre Parâmetros Hemodinâmicos Centrais e Sistema Nervoso Autônomo em Indivíduos com Obesidade ou Sobrepeso.

BACKGROUND: Previous studies have been inconsistent in demonstrating beneficial cardiovascular effects of vitamin D supplementation. OBJECTIVE: To evaluate the effects of vitamin D3 supplementation on central hemodynamic parameters and autonomic activity in obese/overweight individuals with low vitamin D levels (<30ng/dl). METHODS: Adults 40-65 years old with body mass index ≥25<40 kg/m2 were enrolled in this prospective, randomized, double-blind clinical trial (NCT05689632). Central hemodynamics was assessed using the oscillometric method (Mobil-O-Graph®), and heart rate variability using a Polar heart rate monitor (Kubios® software). Patients (n=53) received a placebo in the control group (CO, n=25) or vitamin D3 (VD, n=28) 7000 IU/day, and were evaluated before (W0) and after 8 weeks (W8) with a significance level of 0.05. RESULTS: The groups were homogeneous regarding age (51±6 vs 52±6 years, p=0.509) and vitamin D levels (22.8±4.9 vs 21.7±4.5ng/ml, p=0.590). At W8, the VD group had significantly higher levels of vitamin D (22.5 vs 35.6ng/ml, p<0.001). Only the VD group showed a significant reduction in systolic blood pressure (SBP; 123±15 vs 119±14mmHg, p=0.019) and alkaline phosphatase (213±55 vs 202±55mg/dl, p=0.012). The CO group showed an increase in augmentation pressure (AP: 9 vs 12 mmHg, p=0.028) and augmentation index (AIx: 26 vs 35%, p=0.020), which was not observed in the VD group (AP: 8 vs 8 mmHg, AIx: 26 vs 25%, p>0.05). VD group showed an increase in the parasympathetic nervous system index (PNSi) (-0.64±0.94 vs -0.16±1.10, p=0.028) and the R-R interval (866±138 vs 924±161 ms, p= 0.026). CONCLUSION: In this sample, eight weeks of daily vitamin D supplementation resulted in an improvement in blood pressure levels and autonomic balance.

FUNDAMENTO: Estudos prévios têm sido inconsistentes em demonstrar efeitos cardiovasculares benéficos da suplementação de vitamina D. OBJETIVO: Avaliar efeitos da suplementação de vitamina D3 sobre parâmetros hemodinâmicos centrais e atividade autonômica em indivíduos obesos/sobrepeso e baixos níveis de vitamina D (<30ng/dl). MÉTODOS: Ensaio clínico prospectivo, randomizado, duplo-cego (NCT05689632), adultos 40-65 anos com índice de massa corporal ≥25<40 kg/m2. Hemodinâmica central avaliada por método oscilométrico (Mobil-O-Graph®), variabilidade da frequência cardíaca utilizando frequencímetro Polar (software Kubios®). Os pacientes (n=53) receberam placebo no grupo controle (CO, n=25) ou vitamina D3 (VD, n=28) 7000 UI/dia, avaliados antes (S0) e após 8 semanas (S8) com nível de significância de 0,05. RESULTADOS: Os grupos foram homogêneos na idade (51±6 vs. 52±6 anos, p=0,509) e níveis de vitamina D (22,8±4,9 vs. 21,7±4,5ng/ml, p=0,590). Na S8, o grupo VD apresentou níveis significativamente maiores de vitamina D (22,5 vs. 35,6ng/ml, p<0,001). Apenas o grupo VD mostrou redução significativa da pressão arterial sistólica (PAS; 123±15 vs. 119±14mmHg, p=0,019) e fosfatase alcalina (213±55 vs. 202±55mg/dl, p=0,012). O grupo CO mostrou elevação da pressão de aumento (AP: 9 vs. 12mmHg, p=0,028) e do índice de incremento (Aix: 26 vs. 35%, p=0,020), o que não foi observado no grupo VD (AP: 8 vs. 8mmHg, Aix: 26 vs. 25%, p>0,05). Grupo VD apresentou aumento no índice do sistema nervoso (iSN) parassimpático (-0,64±0,94 vs. -0,16±1,10, p=0,028) e no intervalo R-R (866±138 vs. 924±161ms, p=0,026). CONCLUSÃO: Nesta amostra, a suplementação diária de vitamina D durante oito semanas resultou em melhora dos níveis pressóricos, parâmetros hemodinâmicos centrais e do equilíbrio autonômico.

The pan-PPAR agonist lanifibranor improves cardiometabolic health in patients with metabolic dysfunction-associated steatohepatitis.

Lanifibranor, a pan-PPAR agonist, improves liver histology in patients with metabolic dysfunction-associated steatohepatitis (MASH), who have poor cardiometabolic health (CMH) and cardiovascular events as major mortality cause. NATIVE trial secondary and exploratory outcomes (ClinicalTrials.gov NCT03008070) were analyzed for the effect of lanifibranor on IR, lipid and glucose metabolism, systemic inflammation, blood pressure (BP), hepatic steatosis (imaging and histological grading) for all patients of the original analysis. With lanifibranor, triglycerides, HDL-C, apolipoproteins, insulin, HOMA-IR, HbA1c, fasting glucose (FG), hs-CRP, ferritin, diastolic BP and steatosis improved significantly, independent of diabetes status: most patients with prediabetes returned to normal FG levels. Significant adiponectin increases correlated with hepatic and CMH marker improvement; patients had an average weight gain of 2.5 kg, with 49% gaining ≥2.5% weight. Therapeutic benefits were similar regardless of weight change. Here, we show that effects of lanifibranor on liver histology in MASH are accompanied with CMH improvement, indicative of potential cardiovascular clinical benefits.

Anti-Hypertensive Drugs Moderate the Relationship of Blood Pressure with Alzheimer's Pathologies and Neurodegenerative Markers in Non-Demented Hypertensive Older Adults.

BACKGROUND: We aimed to explore whether the relationships of blood pressures (BPs) with Alzheimer's disease (AD) endophenotypes varied by usage of antihypertensive drugs (AHDs). METHODS: A total of 765 non-demented older adults (mean age: 74.4 years; female: 43.1%) with a self-reported history of hypertension were followed for 6 years. Multiple linear regression and linear-mixed effect models were used to investigate the interaction effects of five categories of AHDs (angiotensin-converting enzyme inhibitors [ACEI], angiotensin II receptor blockers [ARBs], ß-blocker, calcium channel blockers [CCB], diuretic) with BPs (systolic blood pressure [SBP], diastolic blood pressure [DBP], and pulse pressure [PP]) on AD core pathology and neurodegenerative markers. RESULTS: After Bonferroni correction, significant interaction effects of BPs with AHDs were observed. Elevated SBP or PP in late-life was associated with higher levels of cerebral Aß burden (diuretic alone/ß-blocker × SBP), higher levels of CSF tau proteins (diuretic × SBP/PP, ARBs/CCB × SBP), and lower volume of entorhinal region (ß-blocker × SBP, diuretic × PP) only among hypertensive patients who received no anti-hypertensive treatments, while these associations became compromised or null for users of specific AHDs except for ACEI. Compared to taking other classes of AHDs, elevated SBP in late-life was associated with lower cerebral Aß burden in diuretic users (padjusted = 0.08) and was associated with higher CSF tau proteins in ACEI alone users (padjusted = 0.03). Longitudinal data validated the above-mentioned interaction effects on changes of cerebral Aß burden (padjusted < 0.05), CSF tau proteins (padjusted < 0.10), and brain atrophy (padjusted < 0.05). CONCLUSIONS: The relationships of late-life BP with AD pathology and neurodegeneration could be modified by anti-hypertensive treatments and varied by AHD classification. These findings provide preliminary evidence for tailored BP management strategy for preventing AD among late-life hypertensive adults.

Effects of intrarenal pelvic infusion of tumour necrosis factor-α and interleukin 1-ß on reno-renal reflexes in anaesthetised rats.

OBJECTIVE: Reno-renal reflexes are disturbed in cardiovascular and hypertensive conditions when elevated levels of pro-inflammatory mediators/cytokines are present within the kidney. We hypothesised that exogenously administered inflammatory cytokines tumour necrosis factor alpha (TNF-α) and interleukin (IL)-1ß modulate the renal sympatho-excitatory response to chemical stimulation of renal pelvic sensory nerves. METHODS: In anaesthetised rats, intrarenal pelvic infusions of vehicle [0.9% sodium chloride (NaCl)], TNF-α (500 and 1000 ng/kg) and IL-1ß (1000 ng/kg) were maintained for 30 min before chemical activation of renal pelvic sensory receptors was performed using randomized intrarenal pelvic infusions of hypertonic NaCl, potassium chloride (KCl), bradykinin, adenosine and capsaicin. RESULTS: The increase in renal sympathetic nerve activity (RSNA) in response to intrarenal pelvic hypertonic NaCl was enhanced during intrapelvic TNF-α (1000 ng/kg) and IL-1ß infusions by almost 800% above vehicle with minimal changes in mean arterial pressure (MAP) and heart rate (HR). Similarly, the RSNA response to intrarenal pelvic adenosine in the presence of TNF-α (500 ng/kg), but not IL-1ß, was almost 200% above vehicle but neither MAP nor HR were changed. There was a blunted sympatho-excitatory response to intrapelvic bradykinin in the presence of TNF-α (1000 ng/kg), but not IL-1ß, by almost 80% below vehicle, again without effect on either MAP or HR. CONCLUSION: The renal sympatho-excitatory response to renal pelvic chemoreceptor stimulation is modulated by exogenous TNF-α and IL-1ß. This suggests that inflammatory mediators within the kidney can play a significant role in modulating the renal afferent nerve-mediated sympatho-excitatory response.

Benefits of Puerarin on Metabolic Syndrome and Its Associated Cardiovascular Diseases in Rats Fed a High-Fat/High-Sucrose Diet.

Metabolic syndrome (MetS) is a cluster of risk factors for cardiovascular diseases (CVDs) that has become a global public health problem. Puerarin (PUE), the principal active compound of Pueraria lobata, has the effects of regulating glucose and lipid metabolism and protecting against cardiovascular damage. This study aimed to investigate whether dietary supplementation with PUE could ameliorate MetS and its associated cardiovascular damage. Rats were randomly divided into three groups: the normal diet group (NC), the high-fat/high-sucrose diet group (HFHS), and the HFHS plus PUE diet group (HFHS-PUE). The results showed that PUE-supplemented rats exhibited enhanced glucose tolerance, improved lipid parameters, and reduced blood pressure compared to those on the HFHS diet alone. Additionally, PUE reversed the HFHS-induced elevations in the atherogenic index (AI) and the activities of serum lactate dehydrogenase (LDH) and creatine kinase (CK). Ultrasonic evaluations indicated that PUE significantly ameliorated cardiac dysfunction and arterial stiffness. Histopathological assessments further confirmed that PUE significantly mitigated cardiac remodeling, arterial remodeling, and neuronal damage in the brain. Moreover, PUE lowered systemic inflammatory indices including C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and systemic immune-inflammation index (SII). In conclusion, dietary supplementation with PUE effectively moderated metabolic disorders, attenuated systemic inflammation, and minimized cardiovascular damage in rats with MetS induced by an HFHS diet. These results provide novel insights into the potential benefits of dietary PUE supplementation for the prevention and management of MetS and its related CVDs.

Two-Month Consumption of Orange Juice Enriched with Vitamin D3 and Probiotics Decreases Body Weight, Insulin Resistance, Blood Lipids, and Arterial Blood Pressure in High-Cardiometabolic-Risk Patients on a Westernized Type Diet: Results from a Randomized Clinical Trial.

This study examined the effects of orange juice (OJ) supplemented with vitamin D3 (2000 IU) and probiotics (Lacticaseibacillus casei Shirota and Lacticaseibacillus rhamnosus GG, 108 cfu/mL) on cardiometabolic risk factors in overweight and obese adults following a Westernized-type diet. Fifty-three high-risk individuals were randomly assigned to one of two groups. Over 8 weeks, one group consumed a vitamin D3 and probiotic-enriched OJ and the other regular OJ (control). Diets remained unchanged and were documented through food diaries. Measures of metabolic and inflammatory markers and blood pressure were measured at the start and end of the study. Post-intervention, the enriched OJ group showed the following significant metabolic improvements (without changes in triglycerides, inflammation, or central blood pressure): reduced fasting insulin, peripheral blood pressure, body weight (-1.4 kg 95% CI: -2.4, -0.4), energy (-270 kcal 95% CI: -553.2, -13.7), macronutrient (dietary fat -238 kcal 95% CI: -11.9, -1.0; carbohydrates -155 kcal 95% CI: -282.4, -27.3; sugars -16.1 g 95% CI: -11.9, -1.0) intake, and better lipid profiles (total cholesterol -10.3 mg/dL 95% CI: -21.4, 0.9; LDL-C -7 mg/dL 95% CI: -13.5, -0.5). The enriched OJ led to weight loss, less energy/macronutrient consumption, improved lipid profiles, and increased insulin sensitivity after 8 weeks in those following a Westernized diet, thus indicating potential benefits for cardiometabolic risk. This study was a part of FunJuice-T2EDK-01922, which was funded by the EU Regional Development Fund and Greek National Resources.

A Retrospective Study to Evaluate Real-world Evidence of Azelnidipine in Indian Patients (REDEFINE Study).

INTRODUCTION: Azelnidipine, a selective calcium channel blocker, effectively lowers blood pressure (BP) and heart rate (HR) in hypertensive patients, as demonstrated in a retrospective real-world evidence (RWE) study in Indian patients. MATERIALS AND METHODS: This was a retrospective cohort study that included 882 patients aged 18 years or older who had been on azelnidipine treatment for the last 3 months for mild to moderate hypertension (HTN). A structured proforma was utilized to gather data from prescribing physicians to assess the efficacy of azelnidipine (8 and 16 mg) as monotherapy or in combination with other antihypertensive drugs. The primary endpoints of the study were to capture changes in systolic blood pressure (SBP) and diastolic BP (DBP) from baseline to the subsequent visits (4 and 12 weeks), while the secondary endpoints were to measure similar changes in the diabetic group and to estimate the proportion of patients achieving target BP of <130/80 mm Hg and <140/90 mm Hg, respectively. RESULTS: The overall mean reduction of systolic/diastolic BP from baseline to 12 weeks was 13.92/7.91 mm Hg (p-value < 0.0001). The mean reduction of systolic/diastolic BP from baseline to 12 weeks was 11.77/7.43 mm Hg (p-value < 0.0001) in newly diagnosed HTN patients, while in known cases of HTN, it was 16.50/8.48 mm Hg (p-value < 0.0001). In the diabetic group, the mean reduction was 15.35/8.69 mm Hg (p-value < 0.0001). Overall the study showed that in 44 (4.99%) and 408 (46.26%) patients, target BP of <130/80 mm Hg and <140/90 mm Hg, respectively was achieved. The mean change in HR from baseline was a reduction of 5.22 beats/minute. CONCLUSION: Azelnidipine can be an effective antihypertensive drug to treat mild to moderate HTN in Indian patients.