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Background Telomere length has been linked to various health outcomes. To comprehensively investigate the causal effects of telomere length throughout the human disease spectrum, we conducted a phenome-wide Mendelian randomization study (MR-PheWAS) and a systematic review of MR studies. Methods We conducted a PheWAS to screen for associations between telomere length and 1 035 phenotypes in the UK Biobank (n = 408 354). The exposure of interest was the genetic risk score (GRS) of telomere length. Observed associations passing multiple testing corrections were assessed for causality by 2-sample MR analysis. A systematic review of MR studies on telomere length was performed to harmonize the published evidence and complement our findings. Results Of the 1 035 phenotypes tested, PheWAS identified 29 and 78 associations of telomere length GRS at a Bonferroni- and false discovery rate-corrected threshold; 24 and 66 distinct health outcomes were causal in the following principal MR analysis. The replication MR using data from the FinnGen study provided evidence of causal effects of genetically instrumented telomere length on 28 out of 66 outcomes, including decreased risks of 5 diseases in respiratory diseases, digestive diseases, and myocardial infarction, and increased risks of 23 diseases, mainly comprised neoplasms, diseases of the genitourinary system, and essential hypertension. A systematic review of 53 MR studies found evidence to support 16 out of the 66 outcomes. Conclusions This large-scale MR-PheWAS identified a wide range of health outcomes that were possibly affected by telomere length, and suggested that susceptibility to telomere length may vary across disease categories. [ABSTRACT FROM AUTHOR]

Chronically elevated blood pressure was a prominent risk factor for cardiovascular diseases. The management of hypertension, especially in community settings, should combine pharmacological and non-pharmacological interventions. This study aimed to evaluate whether music-assisted progressive muscle relaxation (PMR) using Gamelan, Javanese classical music, could reduce blood pressure more effectively in hypertensive elderly individuals in Malang, Indonesia, than PMR alone. This study employed a pre-test and post-test study design with a control group. Fifty-eight respondents were randomly assigned to the intervention group (n=31) and the control group (n=27). Three respondents in the control group did not complete the study; thus, they were excluded from the analysis. The intervention group was trained and guided to perform PMR while listening to Gamelan. Meanwhile, the control group only received PMR. The intervention was conducted twice a week for 20 minutes for eight weeks. Dependent variables in this study were systolic and diastolic blood pressure, which were measured using an aneroid sphygmomanometer. Data were analyzed using descriptive statistics, paired t-tests, independent t-tests, and Mann-Whitney test. We found a significant decrease in systolic and diastolic blood pressure in both groups. A Mann-Whitney test showed that there was a significant difference in the reduction of systolic blood pressure in the intervention group compared to the control group (p=0.000). Meanwhile, the independent t-test showed that the diastolic blood pressure in the intervention group reduced more significantly than that in the control group. The efficacy of Gamelan-assisted PMR in significantly reducing both systolic and diastolic blood pressure showcases the potential of such combined interventions in managing hypertension. We recommend Gamelan-assisted PMR as a complementary therapy for the elderly with primary hypertension. [ABSTRACT FROM AUTHOR]

BACKGROUND: Left ventricular hypertrophy is the adaptive mechanism to increased left ventricular stress is associated with many adverse events. This study was undertaken to study the left ventricular hypertrophy in patients of essential hypertension and to correlate between clinical, electrocardiography (ECG) and echocardiography in the identification of left ventricular hypertrophy. MATERIALS AND METHOD: 100 patients attending the outpatient department and those who were admitted in our teaching institute from January 2022 to june2023 were the study subjects. All cases of essential hypertension, irrespective of duration of hypertension and type of treatment received were included in the study. Patients with secondary hypertension, Ischemic heart disease/Myocardial infarction, Ischemic cardiomyopathy, congenital heart disease and valvular heart disease were excluded. CONCLUSION: Out of different ECG criteria total QRS criteria showed a high sensitivity of 60%. ECG criteria have a high specificity but low sensitivity. Hence, limited use as a screening method. However in a poor resource country like ours where echocardiography facilities are not available in all rural parts, improved ECG criteria like total QRS voltage can be recommended as a routine investigation for LVH because of its cost effectiveness and easy availability with certain limitations. [ABSTRACT FROM AUTHOR]

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Background: Besides being commonly used to treat high blood pressure, beta blockers are a family of drugs that are primarily used to regulate irregular cardiac rhythms. Nebivolol is a third generation of beta blockers, which is highly cardioselective, about three times as selective as bisoprolol. In this study, we aimed to evaluate Nebivolol's effectiveness and safety in comparison to other beta blockers. Methods: We searched the online databases PubMed, ScienceDirect, and Cochrane Library for relevant RCTs evaluating Nebivolol's effect on hypertension management. Relative risk (WRR) and weighted mean difference (WMD), with a 95% confidence interval (CI) were utilized to quantify the impact of nebivolol medication in the treatment of hypertension using a random effects model. Results: Twelve RCTs are included in the study, the patient numbers in every attempt ranged from 42-273 and 1456 patients in all were included in this review. Nebivolol does not significantly reduce SBP, DBP and HR compared to other beta blockers (WMD -0.57 mmHg, 95% CI [-1.55; 0.42 mmHg] p=0.12 ; WMD -0.27 mmHg, 95% CI [-1.36;0.82 mmHg] p=0.63 ; WMD 0.10 BPM, 95% CI [-4.11;1.31 BPM] p=0.96, respectively). Patients treated with Nebivolol has significantly lower LDL-C (WMD - 8.88 mg/dL, 95% CI [-15.28; -2.48 mg/dL] p=0.007) and significantly higher HDL-C (WMD 2.30 mg/dL, 95% CI [0.75; 3.84 mg/dL] p=0.004. Conclusions: According to this study's findings, nebivolol is well tolerated and decreases LDL-C. And higher HDL-C than other beta blocker agents. This review does not recommend nebivolol as first-line treatment in hypertension as Nebivolol does not significantly reduce blood pressure and HR of patients. [ABSTRACT FROM AUTHOR]

Context Confirmatory tests represent a fundamental step in primary aldosteronism (PA) diagnosis, but they are laborious and often require a hospital environment due to the risks involved. Objective To evaluate the efficacy of oral furosemide as a new confirmatory test for PA diagnosis. Methods We prospectively evaluated the diagnostic performance of 80 mg of oral furosemide in 64 patients with PA and 22 with primary hypertension (controls). Direct renin concentration (DRC) was measured before, and 2 hours and 3 hours after the oral furosemide. In addition, the oral furosemide test was compared with 2 other confirmatory tests: the furosemide upright test (FUT) and saline infusion test (SIT) or captopril challenge test (CCT) in all patients with PA. Results The cut-off of 7.6 µU/mL for DRC at 2 hours after oral furosemide had a sensitivity of 92%, specificity of 82%, and accuracy of 90% for PA diagnosis. In 5 out of 6 controls with low-renin hypertension, which might represent a PA spectrum, renin remained suppressed. Excluding these 6 controls with low-renin hypertension, the DRC cut-off of 10 µU/mL at 2 hours after oral furosemide had a sensitivity of 95.3%, specificity of 93.7% and accuracy of 95% for PA diagnosis. DRC after 3 hours of oral furosemide did not improve diagnostic performance. Using the cut-off of 10 µU/mL, the oral furosemide test and the FUT were concordant in 62 out of 64 (97%) patients with PA. Only 4 out of 64 cases with PA (6.4%) ended the oral furosemide test with potassium <3.5 mEq/L. Hypotension was not evidenced in any patient with PA during the test. Conclusion The oral furosemide test was safe, well-tolerated and represents an effective strategy for PA investigation. [ABSTRACT FROM AUTHOR]

Background and objectives: Cumulative lipid profile burden is designed to dynamically measure lipid accumulation, and its effect on hypertension has been poorly studied. Our main purpose was to investigate the effect of cumulative lipid profile burden on the incidence of essential hypertension (EH) and to investigate whether cumulative lipid burden mediates the pathogenesis of the effects of diet and obesity on EH. Subjects and methods: A total of 1295 participants were included in the study, which started in 2017. The average follow-up time was 2.98 years. A total of 240 EH patients occurred during the follow-up period. Results: The HR (95% CI) of the highest quartile in cumulative Total cholesterol (TC), triglyceride (TG) and high density lipoprotein (HDL) burden were 1.747 (1.145 - 2.664), 1.502 (1.038 - 2.173), 0.615 (0.413 - 0.917) for incidence of EH respectively, compared to the respective reference groups. Participants with EH consumed more red meat and refined grains, and red meat was positively associated with cumulative TC burden. BMI and Waist-To-Height Ratio (WHtR) increased the incidence of EH, and obesity was positively correlated with cumulative TG burden. Mediating analysis showed that cumulative TG had a partial mediating effect in the causal relationship between obesity and EH, and Mendelian randomization (MR) also proved this result. Diet was not found to influence EHn through cumulative lipid profile burden. Conclusions: The cumulative TG burden partially mediates the effect of obesity on EH. [ABSTRACT FROM AUTHOR]

Purpose: To explore the topology of the white matter network in individuals with essential hypertension by graph theory.Patients and Methods: T1-weighted image and diffusion tensor imaging (DTI) data from 43 patients diagnosed with essential hypertension (EHT) and 33 individuals with normotension (healthy controls, HCs) were incorporated in this cross-sectional study. Furthermore, structural networks were constructed by graph theory to calculate whole brain network characteristics and intracerebral node characteristics.Results: Both EHT and HC groups displayed small-worldness in their structural networks. The area under the curve (AUC) of the small-worldness coefficient (σ) was higher in the EHT group compared to the HC group, whereas the AUC of assortativity was lower in the EHT group in contrast to the HC group. The nodal clustering coefficient (CP) and local efficiency (Eloc) of the EHT group decreased in the right dorsolateral superior frontal gyrus and the left medial superior frontal gyrus. These values increased in the left anterior cingulate and paracingulate gyrus. Furthermore, weight and body mass index (BMI) were positively correlated with σ.Conclusion: The EHT group showed brain network separation and integration dysfunction. Weight and BMI were positively correlated with σ. The data acquired in this investigation implied that altered structural connectivity in the prefrontal region may be a potential neuroimaging marker in EHT patients. [ABSTRACT FROM AUTHOR]

BackgroundWhile aldosterone plays an important role in blood pressure regulation, its role in essential hypertension (EHT) remains unclear. Here, we systematically investigated the secretion of biologically-active free aldosterone in saliva in response to awakening (AldAR) and during the day (AldDay) in EHT compared to normotensive controls (NT).MethodsIn 30 men with EHT and 30 age-matched NT, AldAR saliva samples were collected immediately after awakening and 15, 30, 45, and 60 min thereafter and AldDay samples were collected from 08:30–22:00 h on two consecutive days.ResultsOver the course of the day, men with EHT had higher repeated AldDay levels compared to NT (p = .002) with higher concentrations in the morning hours (p's ≤ .047), a steeper decline over the course of the day (p's ≤ .018), and similar concentrations in the evening (p's ≥ .21). Regarding AldAR, we observed higher concentrations in EHT at awakening (p = .017) and borderline higher concentrations at 15 min (p = .086). No differences were found 30–60 min after awakening (p's ≥ .34). Analyses with repeated and aggregated AldAR levels resulted in borderline significantly higher free aldosterone in EHT (p's ≤ .077). Complementary analyses confirmed linear associations between higher blood pressure and higher AldAR and AldDay levels.ConclusionsOur data point to elevated salivary free aldosterone secretion in EHT over the course of the day, particularly in the morning hours. As the free aldosterone fraction is considered biologically active, our data may point to a biological mechanism underlying EHT.

BackgroundPrevious studies have indicated a strong link between blood metabolites and hypertension, however the causality of metabolites and hypertension is unknown.MethodsTwo-sample Mendelian randomization (MR) analysis was performed to assess the causal relationship between 486 blood metabolites and essential hypertension (EHT). Blood metabolite GWAS data was utilized as the exposure, with EHT GWAS data as the outcome. To further verify the results, another different source of EHT GWAS data was repeatedly analyzed. The major MR analytic approach used to determine causality was inverse variance weighted (IVW), with MR-Egger, Weighted Median, and MR-PRESSO models serving as supplements. We used the Cochran Q test to examine heterogeneity. Horizontal pleiotropy was examined using MR-Egger intercept and MR-PRESSO global test. The MR Steiger test confirmed the causal relationship between blood metabolites and EHT.ResultsIn this study, nine blood metabolites associated with EHT were preliminarily identified by MR analysis, including four known metabolites (N-acetylornithine, X-12510–2-aminooctanoic acid, creatine, hexadecanedioate) and five unknown metabolites. Then another source of EHT GWAS data was repeatedly analyzed for further verification, and two overlapped metabolites (N-acetylornithine, X-12510-2-aminooctanoic acid) were found. There was a negative correlation between N-acetylornithine and EHT (OR = 0.987, 95% CI = 0.980–0.993, P = 1.01 × 10−4), Cochran's Q test suggested there was no heterogeneity (Q = 31.7586, P = 0.1331), MR-Egger intercept and MR-PRESSO global test suggested there was no horizontal pleiotropy (P > 0.05), Leave-one-out analysis indicated that no single single-nucleotide polymorphism (SNP) had a significant effect on the results, and MR Steiger test confirmed that the direction of causality was correct (P

Background: Hypertension is a medical condition with global public health importance that is associated with significant morbidity and mortality in both developed and developing countries. It is important to identify readily available parameters that may indicate the level of inflammation that is associated with hypertension. Objective: To assess the relationship between highly-sensitive C-Reactive Protein (hs-CRP) and neutrophil-to-lymphocyte ratio (NLR) in hypertensive adults. Methods: Three hundred and sixty adults comprising 240 hypertensive and 120 healthy normotensive subjects (control) were studied. The full blood count (FBC) and highly-sensitive C-Reactive Protein (hs-CRP) levels were determined using standard methods. Results: The mean values of Total White Blood Cells count (WBC) (p = 0.03), absolute neutrophil count (p = 0.03), absolute lymphocyte count (p = 0.01), NLR (p = 0.001) and hs-CRP (p

Abstract Background Uric acid (UA) is an independent prognostic factor for cardiovascular events, but there are no data demonstrating a different risk profile between women and men. Thus, we tested whether UA is associated with a possible sex-related difference in fatal and non-fatal cardiovascular events. Methods In this prospective population-based study we enrolled 1,650 never-treated Caucasian hypertensive outpatients referred to Catanzaro University Hospital (Italy). Inclusion criteria were newly diagnosed hypertensive patients, aged 20 years or more. Exclusion criteria were secondary form of hypertension, previous cardiovascular events, rheumatic and non-rheumatic valvular heart disease, prosthetic valves, cardiomyopathies, type-2 diabetes, chronic kidney disease, malignant diseases, gout arthritis and secondary forms of hyperuricemia, liver diseases, peripheral vascular diseases, and heart failure. Anthropometric, clinical, and biochemical parameters were measured. UA prognostic role was investigated by Cox regression analyses. Receiver-operating characteristic curve analyses and area under the curve were used to determine the predictive validity and the optimal cut-off point of UA. We investigated following endpoints: coronary events (fatal and nonfatal myocardial infarction, unstable angina, coronary revascularization procedures, coronary death); fatal and nonfatal stroke; all-cause mortality and major adverse cardiovascular events (MACE). Results We enrolled 830 males and 820 females aged 52.2 ± 11.3 years. During 9.5 ± 3.1 years follow-up, there were 424 new clinical events (2.71%): 250 coronary (1.59%), 118 (0.75%) cerebrovascular, and 56 (0.40%) deaths. Comparison between groups demonstrated a higher and significant difference in incidence rate in females for MACE (3.08 vs 2.33%, P = 0.001), coronary (1.82 vs 1.36%, P = 0.014) and cerebrovascular events (0.93 vs 0.57%, P = 0.006). UA at multiple Cox regression analysis resulted a strong and significant predictor of coronary events (HR = 1.493;95% CI 1.375–1.621), cerebrovascular events (HR = 1.256;95% CI 1.109–1.423), MACE (HR = 1.415;95% CI 1.328- 53 1.508), and all-cause mortality (HR = 1.469;95% CI 1.237–1.745) in the whole population and in both groups with a HR higher in females. The best estimated cut-off values of uric acid for males and females predicted these endpoints equally well, but it was always lower in females than males. Conclusions We demonstrate, that UA operates with a sex-related impact and best cut-off value in predicting cardiovascular outcomes and all-cause mortality, reflecting a possible sex difference in disease pathophysiology.

Background: Fetuin-B, a cytokine that regulates lipid metabolism, has recently been linked to cardiovascular diseases such as coronary heart disease. In this study, we discussed the relationship between fetuin-B and essential hypertension. Method: A bioinformatics analysis of fetuin-B was performed. A total of 206 with essential hypertension and 180 age- and-sex-matched healthy sub jects were enrolled. Plasma fetuin-B, endothelin 1 (ET-1), nitric oxide (NO), and adiponectin (ADI) levels were measured using ELISA kits. Results: Bioinformatics analysis has revealed that fetuin-B plays an important role in pathways such as lipid metabolism. Compared with healthy subjects, serum fetuin-B levels in patients with essential hypertension were significantly increased. Correlation analysis showed that the serum fetuin-B level was positively correlated with systolic blood pressure (SBP), diastolic blood pressure, body mass index, fat percentage in vivo, waist–hip ratio, intima–media thickness, low-density lipoprotein cholesterol (LDL-C), glutamyl transpeptidase, alanine transaminase, albumin, fasting blood glucose (FBG), glycated hemoglobin, and ET-1 in the overall study subjects (all P < 0.05) and negatively correlated with HDL-C, ADI, and NO (all P < 0.05). Multivariate linear regression analysis showed that SBP, FBG, LDL-C, ADI, and ET-1 were independent factors affecting serum fetuin-B. A binary logistic regression analysis showed that fetuin-B was an independent risk factor for primary hypertension (odds ratio: 1.060, 95% CI: 1.034–1.086, P < 0.001). Receiver operating characteristic curve analysis was used to evaluate the predictive value of fetuin-B for primary hypertension, and the optimal cutoff point was 83.14 μg/mL (sensitivity 77.4%, specificity 63.3%) (area under the curve) = 0.7738, 95% CI 0.7276–0.8200, P < 0.001). Conclusion: Elevated fetuin-B levels are associated with an increased risk of essential hypertension.

Abstract Background Angiotensin converting enzyme 2 (ACE2) plays a crucial role in the infection cycle of SARS-CoV-2 responsible for formation of COVID-19 pandemic. In the cardiovascular system, the virus enters the cells by binding to the transmembrane form of ACE2 causing detrimental effects especially in individuals with developed hypertension or heart disease. Zofenopril, a H2S-releasing angiotensin-converting enzyme inhibitor (ACEI), has been shown to be effective in the treatment of patients with essential hypertension; however, in conditions of ACE2 inhibition its potential beneficial effect has not been investigated yet. Therefore, the aim of the study was to determine the effect of zofenopril on the cardiovascular system of spontaneously hypertensive rats, an animal model of human essential hypertension and heart failure, under conditions of ACE2 inhibition induced by the administration of the specific inhibitor MLN-4760 (MLN). Results Zofenopril reduced MLN-increased visceral fat to body weight ratio although no changes in systolic blood pressure were recorded. Zofenopril administration resulted in a favorable increase in left ventricle ejection fraction and improvement of diastolic function regardless of ACE2 inhibition, which was associated with increased H2S levels in plasma and heart tissue. Similarly, the acute hypotensive responses induced by acetylcholine, L-NAME (NOsynthase inhibitor) and captopril (ACEI) were comparable after zofenopril administration independently from ACE2 inhibition. Although simultaneous treatment with zofenopril and MLN led to increased thoracic aorta vasorelaxation, zofenopril increased the NO component equally regardless of MLN treatment, which was associated with increased NO-synthase activity in aorta and left ventricle. Moreover, unlike in control rats, the endogenous H2S participated in maintaining of aortic endothelial function in MLN-treated rats and the treatment with zofenopril had no impact on this effect. Conclusions Zofenopril treatment reduced MLN-induced adiposity and improved cardiac function regardless of ACE2 inhibition. Although the concomitant MLN and zofenopril treatment increased thoracic aorta vasorelaxation capacity, zofenopril increased the participation of H2S and NO in the maintenance of endothelial function independently from ACE2 inhibition. Our results confirmed that the beneficial effects of zofenopril were not affected by ACE2 inhibition, moreover, we assume that ACE2 inhibition itself can lead to the activation of cardiovascular compensatory mechanisms associated with Mas receptor, nitrous and sulfide signaling.

Abstract Objective To study the development of microalbuminuria (MAU) in essential hypertension (EHT), we investigated the association of MAU with central blood pressure (CBP), direct renin concentration (DRC), plasma aldosterone (PA), and uric acid (UA). Method We determined 24 h-urinary albumin excretion (24 h-UAE) in patients with EHT who were hospitalized at TEDA International Cardiovascular Hospital from June 2020 to May 2022. We defined MAU as 24 h-UAE in the range of 30 mg/24 h to 300 mg/24 h. Univariate and multivariate analyses were conducted to determine the associations of MAU with CBP, DRC, PA, and UA in EHT, considering demographic and clinical information. We also plotted receiver operating characteristic curves (ROCs) for predicting MAU using these results. Results More than a quarter of patients (26.5%, 107/404, 95% CI: 22.2–31.1%) were diagnosed with MAU in EHT. A higher body mass index (BMI), longer duration of hypertension, and higher severity were associated with MAU. Also, nearly 10% more creatinine levels were recorded in the MAU group than in the control group (69.5 ± 18.7 µmol/L vs. 64.8 ± 12.5 µmol/L, P = 0.004). The increase was also observed for PA (15.5, 9.7–20.6 ng/dL vs. 12.3, 9.0–17.3 ng/dL, P = 0.024) and UA (419.8 ± 105.6 µmol/L vs. 375.1 ± 89.5 µmol/L, P

Background: Hypertensive patients have several common and other comorbidities that can affect cardiovascular risk and treatment strategies. Present study was aimed to study clinical profile of patients with essential hypertension at a tertiary hospital. Material and Methods: Present study was prospective, comparative study, conducted in cases (patients of age between 18 and 75 years, diagnosed with hypertension) & controls (same age and sex, normotensive subjects). Results: In our study, 40 cases & 40 subjects were studied. Age & gender of cases & controls were comparable, no significant difference was noted (p > 0.05). In present study, hypertension was more common in BMI = 25 kg/m², patients with Diabetes, family history of hypertension, smoking habit, alcohol use, habits of adding extra salt while eating food, eating foods with high salt content, eating junk food, had nil to moderate Physical activity, had high & very high perceived stress levels and there was significant statistical difference noted (p value < 0.001). There was also a statistically significant difference noted in serum cholesterol (193 ± 14.768 vs 183.15 ± 13.275, p value 0.0024) & average serum sodium (140.43 ± 4.031 vs 138.28 ± 2.837, p value 0.007) among cases & controls. Conclusion: Healthy lifestyle choices can prevent or delay the onset of high BP and can reduce cardiovascular risk. Long term reduction in salt intake would significantly reduce the prevalence of hypertension and thereby decrease associated morbidity and mortality due to cardiovascular disease and stroke. [ABSTRACT FROM AUTHOR]

Hyperuricemia (elevated serum uric acid) has emerged as one of the strongest risk factors for the development of prehypertension, primary hypertension and resistant hypertension. Hyperuricemia also confers increased risk for cardiovascular mortality, especially in women. Hospital based prospective observational study was done on 60 cases for Period of 3 years in the department of General Medicine. Microalbuminuria was present in 81.6% (41/60). 18.3% showed no urine albumin excretion. 83.3% cases showed ECG changes of left ventricular hypertrophy (>5). 70% (42/60) showed Grade II retinal changes. 16.6% (10/60) showed Grade III retinal changes. [ABSTRACT FROM AUTHOR]

Objective. To investigate the association between β1 adrenergic receptor autoantibodies (β1-AA) and angiotensin II type-1 receptor autoantibodies (AT1-AA) and cardiac function in patients with hypertension complicated with left ventricular diastolic function limitation. Methods. A total of 120 patients with essential hypertension who were not taking drug treatment and were hospitalised in the Department of Cardiology at the authors' hospital from April 2018 to December 2018 were enrolled in this study and divided into a diastolic dysfunction group (65 cases) and a normal diastolic group (55 cases) according to their left ventricular diastolic function. The levels of cardiac parameters, β1-AA, AT1-AA, and other indicators were compared. Logistic regression analysis was used to analyse the related factors affecting left ventricular diastolic dysfunction (LVDD). The diagnostic efficacy of related factors in the diagnosis of diastolic dysfunction was evaluated. Results. Univariate analysis demonstrated that the left ventricular posterior wall diameter (10.29 ± 1.23 vs. 9.12 ± 1.53), left ventricular systolic dysfunction (10.56 ± 1.37 vs. 9.43 ± 1.44), systolic blood pressure (152.37 ± 10.24 vs. 140.33 ± 5.99), diastolic blood pressure (95.66 ± 6.34 vs. 87.33 ± 7.28), β1-AA (33 vs. 9 cases), and AT1-AA (35 cases vs. 12 cases) were higher in the dysfunction group than in the control group (all P < 0.05). Multivariate regression analysis showed that β1-AA (odds ratio OR = 1.96 , 95% confidence interval CI : 1.369 – 4.345) and AT1-AA (OR = 2.02 , 95% CI: 1.332–6.720) were independent risk factors for cardiac diastolic dysfunction (P < 0.05). Both autoimmune antibodies had a certain predictive value, and the combined prediction value of the two was the highest, with an area under the curve of 0.942 (95% CI: 0.881~0.985). Conclusion. The positive rate of β1-AA and AT1-AA in essential hypertension patients with LVDD was higher than that in the normal group. Both β1-AA and AT1-AA could be used as early markers of LVDD in essential hypertension patients. [ABSTRACT FROM AUTHOR]

Background: Multimorbidity is better prevented in younger ages than in older ages. This study aims to identify the differences in comorbidity patterns in middle-aged inpatients from China and the United Kingdom (UK). Methods: We utilized 184,133 and 180,497 baseline hospitalization records in middle-aged populations (40–59 years) from Shaanxi, China, and UK Biobank. Logistic regression was used to calculate odds ratios and P values for 43,110 unique comorbidity patterns in Chinese inpatients and 21,026 unique comorbidity patterns in UK inpatients. We included the statistically significant (P values adjusted by Bonferroni correction) and common comorbidity patterns (the pattern with prevalence > 1/10,000 in each dataset) and employed network analysis to construct multimorbidity networks and compare feature differences in multimorbidity networks for Chinese and UK inpatients, respectively. We defined hub diseases as diseases having the top 10 highest number of unique comorbidity patterns in the multimorbidity network. Results: We reported that 57.12% of Chinese inpatients had multimorbidity, substantially higher than 30.39% of UK inpatients. The complete multimorbidity network for Chinese inpatients consisted of 1367 comorbidities of 341 diseases and was 2.93 × more complex than that of 467 comorbidities of 215 diseases in the UK. In males, the complexity of the multimorbidity network in China was 2.69 × more than their UK counterparts, while the ratio was 2.63 × in females. Comorbidities associated with hub diseases represented 68.26% of comorbidity frequencies in the complete multimorbidity network in Chinese inpatients and 55.61% in UK inpatients. Essential hypertension, dyslipidemia, type 2 diabetes mellitus, and gastritis and duodenitis were the hub diseases in both populations. The Chinese inpatients consistently demonstrated a higher frequency of comorbidities related to circulatory and endocrine/nutritional/metabolic diseases. In the UK, aside from these comorbidities, comorbidities related to digestive and genitourinary diseases were also prevalent, particularly the latter among female inpatients. Conclusions: Chinese inpatients exhibit higher multimorbidity prevalence and more complex networks compared to their UK counterparts. Multimorbidity with circulatory and endocrine/nutritional/metabolic diseases among both Chinese and UK inpatients necessitates tailored surveillance, prevention, and intervention approaches. Targeted interventions for digestive and genitourinary diseases are warranted for the UK. [ABSTRACT FROM AUTHOR]

In order to investigate the relationship between perceived stress, anxiety, depression and hypertension in patients with essential hypertension, a case-control study was conducted among community residents. A total of 312 residents participated in the study by completing a self-reported questionnaire, 156 of whom were hypertensive patients and 156 were healthy. The questionnaire included demographic information, Perceived Stress Scale, Beck Anxiety Inventory and Beck Depression Inventory-II. The data were analyzed using t-test, correlation analysis, Logistic regression analysis, and structural equation modeling procedure to validate the mediation model. The results of Logistic regression analysis showed that anxiety (OR = 1.082, 95% CI 1.011–1.133, P < 0.01), depression (OR = 1.041, 95% CI 1.006–1.078, P < 0.05) and age (OR = 1.033, 95% CI 1.008–1.058, P < 0.01) were risk factors for hypotension, however, perceived stress (OR = 0.955, 95% CI 0.921–0.990, P < 0.05) was a protective factor against hypertension. Furthermore, structural equation model results reported that anxiety and depression play a mediating role between perceived stress and essential hypertension. These results suggest that anxiety and depression can raise the risk of developing essential hypertension. ​While the relationship between perceived stress and hypertension is still debated, it is well established that perceived stress can positively predict hypertension through the mediating role of anxiety and depression. Therefore, healthcare workers should take care of the mental health of patients and provide more psychological support to help them move away from negative emotions and better control their blood pressure. [ABSTRACT FROM AUTHOR]

Background: Thrombospondins (TSPs) play important roles in several cardiovascular diseases. However, the association between circulating (plasma) thrombospondin 2 (TSP2) and essential hypertension remains unclear. The present study was aimed to investigate the association of circulating TSP2 with blood pressure and nocturnal urine Na+ excretion and evaluate the predictive value of circulating TSP2 in subjects with hypertension. Methods and Results: 603 newly diagnosed essential hypertensive subjects and 508 healthy subjects were preliminarily screened, 47 healthy subjects and 40 newly diagnosed essential hypertensive subjects without any chronic diseases were recruited. The results showed that the levels of circulating TSP2 were elevated in essential hypertensive subjects. The levels of TSP2 positively associated with systolic blood pressure (SBP), diastolic blood pressure (DBP), and other clinical parameters, including homeostasis model assessment of insulin resistance (HOMA-IR), brachial-ankle pulse wave velocity, and serum triglycerides, but negatively associated with nocturnal urine Na+ concentration and excretion and high-density lipoprotein cholesterol. Results of multiple linear regressions showed that HOMA-IR and nocturnal Na+ excretion were independent factors related to circulating TSP2. Mantel-Haenszel chi-square test displayed linear relationships between TSP2 and SBP (χ2 = 35.737) and DBP (χ2 = 26.652). The area under receiver operating characteristic curve (AUROC) of hypertension prediction was 0.901. Conclusion: Our study suggests for the first time that the circulating levels of TSP2 may be a novel potential biomarker for essential hypertension. The association between TSP2 and blood pressure may be, at least in part, related to the regulation of renal Na+ excretion, insulin resistance, and/or endothelial function. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to explore whether circadian rhythm of blood pressure is associated with brachial-ankle pulse wave velocity (baPWV) and brachial artery flow-mediated dilation (FMD) in patients with essential hypertension. Method: This cross-sectional study included 4,217 patients with essential hypertension who completed 24-hour ambulatory blood pressure monitoring, baPWV, and FMD. BaPWV and FMD were measured to evaluate arterial stiffness and endothelial dysfunction. Participants were divided into dipper, non-dipper, and reverse dipping groups according to the nocturnal systolic blood pressure dipping percentage. Results: In this study, baPWV was highest in the reverse dipping groups, followed by non-dipper and dipper groups (1667.11 ± 327.90 vs. 1613.88 ± 325.11 vs. 1577.45 ± 306.15 cm/s, P < .001) and FMD gradually increased (4.41 ± 2.87 vs. 4.70 ± 2.84 vs. 4.92 ± 2.79%, P = .001). baPWV and FMD were significantly associated with declining nocturnal systolic blood pressure (SBP). Interestingly, FMD (ß = 0.042, P = .014) was only positively associated with a drop in nocturnal SBP decline in patients <65 years of age. Whereas baPWV was consistently negatively associated with nocturnal SBP decline regardless of age (ß = -0.065, P < .001, age <65 years; ß = -0.149, P = .002, age = 65). Receiver operating characteristics (ROC) curves analysis showed areas under the curve (AUC) of baPWV/FMD for predicting circadian rhythm of blood pressure are 0.562/0.554 with a sensitivity of 51.7%/53.9% and specificity of 56.4%/53.4. Conclusion: Impairment of baPWV and FMD were correlated with abnormal circadian rhythm of blood pressure in essential hypertension, suggesting a decrease in nighttime SBP may associate with endothelial function and arterial stiffness. [ABSTRACT FROM AUTHOR]

Objective: Endothelial function may improve with enhanced external counterpulsation (EECP) or acupuncture. This study aimed to evaluate the feasibility of acupoint stimulation combined with EECP (acupoint-EECP) for endothelial cell function in patients with essential hypertension. Methods: Thirty essential hypertensive patients were, randomly divided into two groups, with 15 patients in the acupoint-EECP group, and 15 patients in the control group, of which 3 cases were lost by week 6. Both groups were treated with continued medicine. The participants in the acupoint-EECP group received acupoint stimulation combined with EECP therapy, 45 min for each time, 5 times weekly for 6 weeks for a total of 22.5 hours. The selected acupoints are Zusanli (ST36), Fenglong (ST40) and Sanyinjiao (SP6). The curative effects of the two groups were compared. Results: The acupoint-EECP group (n=15) showed significant improvement in endothelial function [nitric oxide (NO), endothelin-1 (ET-1) and carotid-femoral pulse wave velocity (cf-PWV), respectively] values compared to the control group (n=12). Multiple imputation (n = 20 imputations) was performed to account for potential bias due to missing data. In stratified analyses, SBP and DBP values decreased when the baseline SBP was =120 mmHg and DBP was =80 mmHg. Conclusions: These findings suggest the feasibility of acupoint-EECP in improving endothelial function and treating hypertension. [ABSTRACT FROM AUTHOR]

Backgroud and aim: T lymphocytes are involved in the occurrence and development of essential hypertension, and potassium channels are thought to be critical for lymphocyte activation. This study is to examine the roles of the voltage-gated potassium channels (Kv1.3) and calcium-activated potassium channels (KCa3.1) in peripheral blood T lymphocytes in Kazakh hypertensive patients of Xinjiang, China, mainly focusing on the effects of these channels on nuclear factor of activated T cells (NFAT) and inflammatory cytokines of T lymphocytes. Method: Kv1.3 and KCa3.1 gene silencing were performed in cultured T lymphocytes from Kazakh patients with severe hypertension. T cell proliferation after gene silencing was measured using CCK-8. The mRNA and protein expression levels were measured using RT-qPCR and Western blot analysis, respectively. Nuclear translocation of NFAT was observed using laser confocal fluorescence microscopy. Inflammatory cytokine levels were detected with ELISA. Results: Compared with control group, gene silencing of Kv1.3 and KCa3.1 respectively inhibited the proliferation of T cells. Moreover, compared with the control group, the mRNA expression levels of NFAT, IL-6 and IFN-γ were significantly decreased after gene silencing. Furthermore, the NFAT protein expression level was significantly down-regulated. In addition, the levels of IFN-γ and IL-6 in the cell culture supernatant were significantly decreased. Conclusion: Both Kv1.3 and KCa3.1 potassium channels activated T lymphocytes and enhanced the cytokine secretion possibly through CaN/NFAT signaling pathway, which may in turn induce microinflammatory responses and trigger the occurrence and progression of hypertension. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether GRK4 regulates the phosphorylation and function of renal CCKBR. Methods: GRK4 A142V transgenic mice were used as an animal model of enhanced GRK4 activity, and siRNA was used to silence the GRK4 gene to investigate the regulatory effect of GRK4 on CCKBR phosphorylation and function. Finally, the co-localization and co-connection of GRK4 and CCKBR in RPT cells were observed by laser confocal microscopy and immunoprecipitation to explore the mechanism of GRK4 regulating CCKBR. Results: Gastrin infusion significantly increased urinary flow and sodium excretion rates in GRK4 WT mice (P < .05). GRK4 siRNA did not affect CCKBR protein expression in WKY RPT cells and SHR RPT cells, but remarkably reduced CCKBR phosphorylation in WKY and SHR RPT cells (P < .05). The inhibitory effect of gastrin on Na+-K+ -ATPase activity in WKY RPT cells was further enhanced by the reduction of GRK4 expression (P < .05), while GRK4 siRNA restored the inhibitory effect of gastrin on Na+-K+ -ATPase activity in SHR RPT cells. Laser confocal and Co-immunoprecipitation results showed that GRK4 and CCKBR colocalized in cultured RPT cells' cytoplasm. Conclusion: GRK4 participates in the development of hypertension by regulating the phosphorylation of renal CCKBR leading to impaired CCKBR function and water and sodium retention. Knockdown of GRK4 restored the function of CCKBR. The enhanced co-connection between GRK4 and CCKBR may be an important reason for the hyperphosphorylation of GRK4 and CCKBR involved in the pathogenesis of hypertension. [ABSTRACT FROM AUTHOR]

Background: As one of the essential hypertension (EH)-mediated target organ damage, carotid plaque is a crucial subclinical precursor for cardiovascular events. Therefore, it is vital to identify the risk factors and pathogenesis for EH with carotid plaque. Methods: Based on our previous microarray analysis, we selected four circRNAs as the candidate circRNAs and detected their expression levels in blood of 192 subjects (64 healthy controls, 64 EH patients, and 64 EH patients with carotid plaque) by qRT-PCR analysis. The regulatory mechanism of circRNAs involved in carotid plaque was predicted by bioinformatics analysis. Results: The level of hsa_circ_0124782 increased significantly and the levels of hsa_circ_0131618 and hsa_circ_0127342 decreased significantly in the EH group and EH with carotid plaque group compared with the control group (P < .05). Functional enrichment analysis showed that three circRNAs might be implicated in pathogenesis for carotid plaque. Conclusion: Our study revealed the relationship between three circRNAs and carotid plaque, suggesting that they may serve as potential biomarkers for EH with carotid plaque. [ABSTRACT FROM AUTHOR]

Background: Randomized controlled trials have demonstrated that Songling Xuemaikang capsule (SXC) is effective in blood pressure (BP) lowering for essential hypertension. However, the effectiveness of SXC in real-world clinical practice remains unknown. We aimed to investigate whether the BP-lowering effectiveness of SXC in the real-world practice setting is comparable to the efficacy of the intervention in a randomized controlled trial. Methods: We included 1325 patients treated with SXC monotherapy from a real-world registry and 300 from the SXC-BP trial. A propensity score matching (PSM) approach was used to select participants from the two cohorts. The primary outcome was a change in the office of BP from baseline to 8 weeks. Results: After PSM, there were 552 patients for the comparative analysis. Clinically meaningful BP reductions were observed both in the real world and in the RCT cohorts after 8-week SXC treatment. The 8-week systolic/diastolic BP was 129.50/81.33 mm Hg vs. 134.97/84.14 mm Hg in the real-world population and the RCT population, respectively. The changes in systolic BP (15.82 ± 10.71 vs. 10.48 ± 10.24; P < .001), and diastolic BP (10.01 ± 7.73 vs. 7.75 ± 8.14; P = .001) from baseline to 8 weeks were significantly greater in the real-world population. Conclusion: The current comparison demonstrated that SXC monotherapy is at least as effective in realworld settings as within the randomized controlled trial for BP lowering in patients with grade 1 hypertension. [ABSTRACT FROM AUTHOR]

The current study was designed to assess the association of serum transforming growth factor β1 (TGF-β1) with left ventricular hypertrophy (LVH) in children with primary hypertension. The present single-center prospective trial examined 182 patients diagnosed with primary hypertension in Children's Hospital, Capital Institute of Pediatrics, between January 2021 and September 2022. Clinical data were analyzed, and ambulatory blood pressure was assessed for 24 h. LVH, the commonest subclinical cardiac feature of hypertension, was assessed by echocardiography. According to left ventricular geometry, cases were assigned to the LVH (n = 44) and normal geometry (n = 138) groups. Serum TGF-β1 amounts were quantitated by enzyme-linked immunosorbent assay (ELISA). Receiver operating characteristic (ROC) curves were established to analyze various variables for their predictive values in LVH. Among 182 children with primary hypertension, the concentrations of serum TGF-β1 were higher in stage 2 hypertension than in stage 1 (47.3 (38.8, 52.5) vs. 46.0 (38.6, 48.2) ng/L, Z = − 2.376; P = 0.018). Additionally, serum TGF-β1 content showed a positive correlation with BP levels (P < 0.05). TGF-β1 amounts were significantly elevated in the LVH group compared with the normal geometry group (51.7 (46.1, 54.9) vs. 46.1 (38.7, 48.1) ng/L, Z = − 4.324; P = 0.0000). Serum TGF-β1 content was positively associated with LVH (r = 0.321, P = 0.0000). Multivariable logistic regression analysis showed BMI (OR = 1.188, 95% CI 1.082–1.305; P = 0.0000) and elevated serum TGF-β1 content (OR = 1.063, 95% CI 1.016–1.113; P = 0.009) independently predicted LVH. A multivariable logistic regression model considering BMI and TGF-β1 content in LVH prediction was 0.771, with sensitivity and specificity of 72.7% and 70.3%, respectively. Conclusion: These data revealed an association of serum TGF-β1 with BP in children with primary hypertension. Serum TGF-β1 concentration was positively correlated with hypertensive cardiac damage. Serum TGF-β1 might constitute a valuable molecular marker for the prediction of LVH in children with primary hypertension. The combination of BMI and TGF-β1 has a certain diagnostic and predictive value for LVH in children with primary hypertension, which may provide a new reference index for early clinical identification of hypertensive cardiac damage. What is Known: • Experimental and clinical data indicated TGF-β1 is involved in BP elevation. • TGF-β1 is positively correlated with LVMI and hypertrophy in adults. What is New: • Our current study reveals an association of serum TGF-β1 with BP in children with primary hypertension. • Elevated serum TGF-β1 level is positively associated with LVH in children with primary hypertension. • The combination of BMI and TGF-β1 has a certain diagnostic and predictive value for LVH in children with primary hypertension. [ABSTRACT FROM AUTHOR]

Changes in the activity of the renin–angiotensin–aldosterone system are responsible for a stable shift in the regulation of the cardiovascular system in essential hypertension (EH). They can be characterized as hemodynamic allostasis. The purpose of our study was to determine the role of hemodynamic parameters in allostatic load in patients with EH without metabolic syndrome. Twenty-four hours of ambulatory blood pressure monitoring was performed, followed by linear and non-linear rhythm analysis. Based on the daily index, patients with EH were divided into two groups: group 1—patients with no significant nighttime decrease in blood pressure (BP); group 2—patients who had a nocturnal decrease in BP. The control group included healthy persons aged 25 to 69 years. A linear analysis was used to determine the mean values of systolic and diastolic BP, heart rate (HR), time load of BP, circadian index, and structural point of BP. Non-linear analysis was applied to determine the mesor, amplitude, range of oscillations and % rhythm of BP and HR. The allostatic load index (ALI) was also calculated on the basis of the corresponding biomarkers. It was found that ALI was significantly higher in groups 1 and 2 in comparison with the control group. The hemodynamic mechanisms of this increase were different. [ABSTRACT FROM AUTHOR]

Introduction: Hypertension is a major and modifiable risk factor for cardiovascular diseases. Essential, primary, or idiopathic hypertension accounts for 90–95% of all cases. Identifying novel biomarkers specific to essential hypertension may help in understanding pathophysiological pathways and developing personalized treatments. We tested whether the integration of circulating microRNAs (miRNAs) and clinical risk factors via machine learning modeling may provide useful information and novel tools for essential hypertension diagnosis and management. Materials and methods: In total, 174 participants were enrolled in the present observational case–control study, among which, there were 89 patients with essential hypertension and 85 controls. A discovery phase was conducted using small RNA sequencing in whole blood samples obtained from age- and sex-matched hypertension patients (n = 30) and controls (n = 30). A validation phase using RT-qPCR involved the remaining 114 participants. For machine learning, 170 participants with complete data were used to generate and evaluate the classification model. Results: Small RNA sequencing identified seven miRNAs downregulated in hypertensive patients as compared with controls in the discovery group, of which six were confirmed with RT-qPCR. In the validation group, miR-210-3p/361-3p/362-5p/378a-5p/501-5p were also downregulated in hypertensive patients. A machine learning support vector machine (SVM) model including clinical risk factors (sex, BMI, alcohol use, current smoker, and hypertension family history), miR-361-3p, and miR-501-5p was able to classify hypertension patients in a test dataset with an AUC of 0.90, a balanced accuracy of 0.87, a sensitivity of 0.83, and a specificity of 0.91. While five miRNAs exhibited substantial downregulation in hypertension patients, only miR-361-3p and miR-501-5p, alongside clinical risk factors, were consistently chosen in at least eight out of ten sub-training sets within the SVM model. Conclusions: This study highlights the potential significance of miRNA-based biomarkers in deepening our understanding of hypertension's pathophysiology and in personalizing treatment strategies. The strong performance of the SVM model highlights its potential as a valuable asset for diagnosing and managing essential hypertension. The model remains to be extensively validated in independent patient cohorts before evaluating its added value in a clinical setting. [ABSTRACT FROM AUTHOR]

Background: Systemic hypertension is an important condition in childhood, with an estimated global population prevalence of 1-2%. The public health significance of hypertension is based on observations that confirm a strong tracking of blood pressure levels from childhood to adolescence. Commonly used medications as first line in children include Angiotensin Converting Enzyme Inhibitors (ACEI), Calcium Channel Blockers (CCB), and β Blockers. Adult clinical practice guidelines such as Joint National Committe-8 (JNC-8) have clear recommendations based on clinical trial evidence for the first line drug. However, in children there is lack of evidence for clear recommendations for the first line drug Design: Double blinded Randomized control trial Setting: The study was conducted in Indira Gandhi institute of child health, Bangalore from January 2016 to January 2017. Participants :The study comprised of Children aged 3-18 years with hypertension. Objectives : (1) Whether the hypertension was controlled with the drug used (2) Dose required for the control of hypertension (3) Duration needed for the control of hypertension(4) The need to use additional antihypertensive drugs to control hypertension. (5) Adverse drug reactions (ADR) Results: The mean age at presentation was 9.23±0.35 years with males being 57.5 % and females being 42.5%. Renal cause of hypertension was the most common cause with nephrotic syndrome accounting for 46.25% and Acute Glomerulonephritis 42.5 %. Primary hypertension was seen 6.25%. Amlodipine controlled blood pressure in 97.5 % children and Enalapril in 92.5%.. The reduction in blood pressure were comparable at 24, 48 and 72 hours. Mean dose required for control of blood pressure in Amlodipine group was 0.26±0.01mg/kg/day and Enalapril group was 0.25±0.01mg/kg/day. No adverse reactions was noted to either drug. Conclusion: 1) Amlodipine and Enalapril are both efficacious in the control of Paediatric Hypertension and there is no statistically significant difference between the two groups in terms of Blood Pressure control.2) Administration of Enalapril and Amlodipine was not associated with any adverse effects. [ABSTRACT FROM AUTHOR]