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Sex is seldom considered as a potential moderator of the impact of bipolar disorder (BD) on cardiovascular disease (CVD) risk. We aimed to characterize the sex-specific association of CVD and BD using data from the UK Biobank.In a cross-sectional analysis, we compared the odds ratio between women and men with BD for seven CVD diagnoses (coronary artery disease, myocardial infarction, angina, atrial fibrillation, heart failure, stroke, and essential hypertension) and four cardiovascular biomarkers (arterial stiffness index, low-density lipoprotein, C-reactive protein, and HbA1c) in 293 participants with BD and 257,380 psychiatrically healthy controls in the UK Biobank.After adjusting for age, we found a two- to three-fold stronger association among women than among men between BD and rates of coronary artery disease, heart failure, and essential hypertension, with a significant sex-by-diagnosis interactions. The association remained significant after controlling for self-reported race, education, income, and smoking status. After controlling for potential confounders, there was no significant association between sex and any cardiovascular biomarkers.These analyses could not disentangle effects of BD from its treatment.Our results underscore the importance of incorporating sex and mental illness in risk estimation tools for CVD, and improving screening for, and timely treatment of, CVD in those with BD. Future research is needed to better understand the contributors and mechanisms of sex differences related to CVD risk in BD.

Context The plasma concentrations of angiotensin-converting enzyme 2 (pACE2) has been independently associated with cardiovascular diseases. Objective Higher pACE2 concentrations may be found in patients with primary aldosteronism (PA) and might lead to increased cardiovascular events. Methods Using an inception observational cohort, we examined pACE2 among 168 incident patients with PA. The expression of ACE2, serine protease 2 (TMPRSS2), and metalloprotease 17 (ADAM17) were assessed in peripheral blood mononuclear cells. Results Incident PA and essential hypertension (EH) patients had similarly elevated pACE2 (47.04 ± 22.06 vs 46.73 ± 21.06 ng/mL; P = .937). Age was negatively (β = −2.15; P = .033) and higher serum potassium level (β = 2.29; P = .024) was positively correlated with higher pACE2 in PA patients. Clinical complete hypertension remission after adrenalectomy (Primary Aldosteronism Surgery Outcome criteria) was achieved in 36 (50%) of 72 surgically treated unilateral PA (uPA) patients. At follow-up, pACE2 decreased in surgically treated patients who had (P < .001) or had no (P = .006) hypertension remission, but the pACE2 attenuation was not statistically significant in uPA (P = .085) and bilateral PA (P = .409) administered with mineralocorticoid receptor antagonist (MRA). Persistently elevated pACE2 (> 23 ng/mL) after targeted treatments was related to all-cause mortality and cardiovascular events among PA patients (hazard ratio = 8.8; P = .04); with a mean follow-up of 3.29 years. TMPRSS2 messenger RNA (mRNA) expression was higher in uPA (P = .018) and EH (P = .038) patients than in normotensive controls; it was also decreased after adrenalectomy (P < .001). Conclusion PA and EH patients had elevated pACE2 and higher expression of TMPRSS2 mRNA compared to those of normotensive population. Persistently elevated pACE2 (> 23 ng/mL) after targeted treatments was associated risk of mortality and incident cardiovascular events.

The aim of this clinical trial was to assess the efficacy and safety of low-dose triple combinations of amlodipine, telmisartan, and chlorthalidone in patients with essential hypertension. After a 2-week placebo run-in period, 176 patients were randomized to seven treatment groups (placebo, quarter-dose combination, third-dose combination, half-dose combination, amlodipine 5 mg, amlodipine 10 mg, and telmisartan 80 mg) and administered the assigned study drug orally for 8 weeks. The primary efficacy endpoint was the change in the mean sitting systolic blood pressure (BP) (MSSBP) at Week 8. The MSSBP and mean sitting diastolic BP in the quarter-dose and half-dose groups were significantly lower compared to the placebo and amlodipine 5 mg groups, with similar BP-lowering effects observed compared to the amlodipine 10 mg and telmisartan 80 mg groups. However, the third-dose group showed significant BP improvement only compared to the placebo group. A similar pattern was observed for the control rate of hypertension and response rates. Additional analysis was conducted after correcting for gender and age effects, and, as a result, the third-dose group showed similar results with regard to the BP-lowering effect as the quarter-dose and half-dose groups. In terms of safety, no special adverse events and clinically significant results were noted, and all dose groups of the triple combination are considered safe for use in essential hypertension patients. The current findings indicated that low-dose triple combination of amlodipine, telmisartan, and chlorthalidone over 8 weeks effectively improved the BP-lowering effect in patients with essential hypertension without any safety concerns.

Background and Purpose: The aim of this study was to investigate the association between daytime napping frequency and the incidence of essential hypertension or stroke as well as to validate causality in this relationship via Mendelian randomization (MR). Methods: We conducted Cox regression analysis on 358 451 participants free of hypertension or stroke from UK Biobank. To validate the results of the observational analysis, we conducted a 2-sample MR for daytime napping frequency (123 single-nucleotide polymorphisms) with essential hypertension in FinnGen Biobank, stroke, and ischemic stroke in MEGASTROKE consortium and performed a corresponding 1-sample MR on the UK Biobank data. Results: Compared with never napping, usually napping was associated with a higher risk of essential hypertension (hazard ratio, 1.12 [95% CI, 1.08–1.17]), stroke (hazard ratio, 1.24 [95% CI, 1.10–1.39], and ischemic stroke (hazard ratio, 1.20 [95% CI, 1.05–1.36]) in our prospective observational analysis. Both the 1-sample and 2-sample MR results indicated that increased daytime napping frequency was likely to be a potential causal risk factor for essential hypertension in FinnGEN (odds ratio, 1.43 [95% CI, 1.06–1.92]) and UK Biobank (odds ratio, 1.40 [95% CI, 1.28–1.58]). The 2-sample MR results supported the potential causal effect of nap frequency on ischemic stroke in MEGASTROKE (odds ratio, 1.29 [95% CI, 1.04–1.62]). Conclusions: Prospective observational and MR analyses provided evidence that increased daytime nap frequency may represent a potential causal risk factor for essential hypertension. The potential causal association of increased nap frequency with ischemic stroke was supported by 2-sample MR and prospective observational results.

Adverse hemodynamic responses to exercise in patients with hypertension, despite antihypertensive medication, indicate a sustained cardiovascular risk. The efficacy of dietary nitrate to improve limb vascular conductance during exercise was inversely dependent on the magnitude of exercising limb vascular conductance at baseline, rather than antihypertensive medication status. The effects of dietary nitrate on hemodynamics during exercise in patients with hypertension are dependent on the values at baseline and independent of antihypertensive medication status.

Background. In recent years, traditional Chinese exercises (TCEs) have been gradually used to reduce the blood pressure levels of patients with essential hypertension. However, there are several types of TCEs, and there is no comparative study on the antihypertensive effects of various TCEs in patients with essential hypertension. Objective. The objective is to compare the therapeutic effects of Taijiquan (TJQ), Baduanjin (BDJ), Wuqinxi (WQX), and Yijinjing (YJJ) on essential hypertension and provide a reference for clinical treatment and scheme optimization. Methods. The China National Knowledge Infrastructure (CNKI), Wanfang, China Scientific Journal Database, China Biology Medicine database (CBM), PubMed, Embase, Cochrane Library, and Web of Science databases were searched to collect all randomized controlled trials (RCTs) of TCEs in the treatment of essential hypertension. The search time was from the establishment of each database to November 2021. After data extraction and quality evaluation, the network meta-analysis was performed with Stata 16.0 and ADDIS 1.16.8. Results. Finally, 45 RCTs involving 3864 patients were included. Network meta-analysis showed that YJJ had the best effect in reducing systolic blood pressure, and the difference was statistically significant [MD = −14.27, 95% CI = (−20.53∼−8.08), P < 0.05 ]. The best probability ranking was YJJ ( P = 0.736 ) > TJQ ( P = 0.203 ) > WQX ( P = 0.059 ) > BDJ ( P = 0.002 ). In terms of reducing diastolic blood pressure, the treatment effect of YJJ was the best, and the difference was statistically significant [MD = −7.77, 95% CI (−12.19∼−3.33), P < 0.05 ]. The best probability ranking was YJJ ( P = 0.702 ) > TJQ ( P = 0.178 ) > WQX ( P = 0.095 ) > BDJ ( P = 0.025 ). Conclusion. The results showed that TCEs significantly reduced systolic and diastolic blood pressure compared with the control group, and YJJ might be the best choice. However, a larger sample, multicenter, double-blinded, high-quality RCTs are needed to make clear conclusions.

The blood pressure (BP) control mechanism for mineralocorticoid receptor blockers is unclear, and analysis of their use as a single agent in the clinical setting is required to resolve this uncertainty. There is a paucity of data on esaxerenone monotherapy assessing its long-term antihypertensive effect and urinary biomarkers.This post hoc exploratory substudy of a long-term phase 3 study evaluated the effect of esaxerenone monotherapy (2.5 or 5 mg/day) in treatment-naïve patients who continued the therapy during the 52-week study period (n = 25). In addition to blood biomarkers, urinary biomarkers were also assessed in 24-h urine collection samples.Esaxerenone monotherapy was associated with consistent reductions in systolic/diastolic BP in the substudy population (- 23.5/- 13.1 mmHg at week 52, p 0.001 vs baseline). Plasma aldosterone concentrations and plasma renin activity significantly increased during esaxerenone monotherapy at all time points. On the basis of the observations that both urine volume and urinary sodium excretion also decreased up to the end of the study, and were significantly lower at 12 weeks, patients were further categorized into higher/lower urinary sodium excretion subgroups according to whether their baseline values were above or below the median. In the group with higher baseline urinary sodium excretion, esaxerenone exhibited a significantly greater decrease in systolic/diastolic BP compared to the lower baseline group.Esaxerenone exhibited sustained and stable antihypertensive activity even when administered as a single agent for 52 weeks in patients with essential hypertension. The additional urinary biomarker analysis suggests that the BP-lowering effects of esaxerenone may be partly exerted via mechanisms related to salt and water retention, and that the effect is particularly pronounced in patients with hypertension and higher baseline urinary sodium excretion, which may reflect a state of excessive salt intake.NCT02722265.

An increase in the renal resistive index (RRI) in patients with essential hypertension (EH) predicts deterioration in renal function. In patients with EH, changes in hemodynamic parameters significantly affect the RRI. This study aimed to define changes in Ambulatory Blood Pressure Monitoring (ABPM) parameters that are significantly associated with a change in RRI in patients with EH. We evaluated ABPM and the RRI in 96 patients with EH without organ extrarenal changes at baseline and after two years of follow-up. The relationships between changes in ABPM parameters and the RRI over the period were evaluated. After two years of follow-up, the increase in RRI was consequential. Simultaneously, 24-h systolic blood pressure increased significantly and 24-h diastolic blood pressure decreased. In the whole group and in the group with calculated cystatin C clearance (eGFRcyst) ≥90 ml/min/1.73 m2, the change in RRI significantly negatively correlated with the change in the ratio of 24-h diastolic to systolic blood pressure (D/S ratio), but also with the change in 24-h pulse blood pressure. However, in patients with eGFRcyst˂90 ml/min/1.73 m2, only the change in the 24-h D/S ratio significantly correlated with the change in RRI. Based on the backward stepwise regression analysis, the change in RRI was significantly dependent only on the change in 24-h D/S ratio and not on the change in 24-h pulse pressure. A change in the ratio of diastolic to systolic pressure better reflects a change in RRI than a change in pulse pressure.

Objective. The present study aims to investigate the relationship between vitamin D deficiency and renin-angiotensin-aldosterone levels in patients with essential hypertension. Methods. The present study observed two groups of patients from Urumqi, Xinjiang, China, from April 2017 to March 2018. There were two subject groups: the hypertension group (80 patients with essential hypertension selected by random cluster sampling) and the control group (76 healthy adults). The 25-hydroxyvitamin D (25(OH)D or vitamin D) levels were measured through electrolytes; fasting blood glucose, blood lipids, and other biochemical indicators were detected using immune chemiluminescence; and plasma renin activity and angiotensin II concentrations were detected with radio-immunity. Results. Comparison between the hypertension group and control group showed statistically significant differences in the systolic pressure and levels of 25(OH)D, renin, and triglycerides ( P < 0.05 ). The correlation analysis showed that 25(OH)D was negatively correlated with renin (r = –0.185; P = 0.021 ) and positively correlated with systolic pressure (r = –0.105; P = 0.035 ). There were no statistically significant differences in diastolic pressure, fasting blood glucose, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides between the two groups. Conclusions. The results of the present study show that vitamin D deficiency is common in Urumqi, Xinjiang, China and vitamin D levels are negatively correlated with renin levels. Vitamin D plays an important role in regulating blood pressure by affecting renin levels through the renin-angiotensin-aldosterone system.

Background: In patients with essential hypertension, fragmented QRS has been associated with many remodeling components that might lead to adverse cardiovascular effects. This study aimed to evaluate the relationship between fragmented QRS and adverse events and its potential long-term prognostic value. Methods: The patients with essential hypertension were divided into two groups according to the presence of fragmented QRS: fragmented QRS (+) and fragmented QRS (−). During long-term follow-up, the relationship of fragmented QRS to coronary artery disease, congestive heart failure, stroke, cardiovascular death, all-cause death, and major adverse cardiovascular and cerebrovascular events was evaluated. Results: The study group included 542 patients with essential hypertension. Fragmented QRS on ECG was observed in 224 (41.3%) patients. Considering the incidence rates at the end of 5.6 ± 1.3 years’ follow-up, the total incidence rate of major adverse cardiovascular and cerebrovascular events (P < .001), coronary artery disease (P < .001), and congestive heart failure (P < .001) were higher in patients with fragmented QRS. No significant difference was observed between the two groups in terms of stroke (P=.734), cardiovascular death (P=1), and all-cause death (P=.574). As a result of multiple cox regression analysis, fragmented QRS (P=.005) was identified as an independent predictor for major adverse cardiovascular and cerebrovascular events development. Conclusion: In patients with hypertension, the presence of fragmented QRS was found as an independent predictor for major adverse cardiovascular and cerebrovascular events development. 35703480

Salt sensitivity is actually a measure of an individual's blood pressure response to salt intake. It has been reported that people who are salt sensitive have high prevalence of hypertension and target organ damage. The link between dietary salt intake and hypertension is well established, and a reduction in salt intake has been shown to lower blood pressure.In Kashmir, this achieves significance because of a high incidence of hypertension along with a high salt intake among ethnic Kashmiris.We analysed clinical variables accompanying salt sensitive hypertension among Kashmiri population in our on-going salt sensitivity study on 770 Kashmiri patients (250 men, 520 women) of age group 18years and above from March 2020 to June 2021. We studied the clinical variables accompanying salt sensitivity and the difference in their blood pressure on. a low salt diet (mean = 2 g/day) vs. their usual salt intake (mean = 11 g/day). To document compliance of salt-restricted diet, we used 24-h urinary NaCl estimation as a surrogate marker for salt intake estimation.We observed, a huge drop in SBP (-28.9 mmHg), DBP (-17.6 mmHg) and mean arterial pressure (-21.3mmHg) in this cohort of 770 ethnic Kashmiris on a strict salt restricted diet. And that women, urban inhabitants, and nonsmokers are more prone to the risk of developing salt sensitive hypertension. Physical activity had no effect on salt sensitivity.As per our study, salt restriction has a major role in treatment of Hypertension in Kashmiri Population. More studies need to be focused on this vital area.

Background: In preclinical models, the pannexin-1 channel has been shown to be involved in blood pressure regulation through an effect on peripheral vascular resistance. Pannexin-1 releases ATP, which can activate constrictive purinergic receptors on the smooth muscle cells. Pannexin-1 opening is proposed to be mediated by α-adrenergic receptors to potentiate sympathetic constriction. This positions pannexin-1 as a putative pharmacological target in blood pressure regulation in humans. The aim was to provide the first translational evidence for a role of pannexin-1 in essential hypertension in humans by use of an advanced invasive mechanistic approach. Methods: Middle-aged stage-1 hypertensive (n=13; 135.7±6.4 over 83.7±3.7 mm Hg) and normotensive men (n=12; 117.3±5.7 over 72.2±3.5 mm Hg) were included. Blood pressure and leg vascular resistance were determined during femoral arterial infusion of tyramine (α-adrenergic receptor stimulation), sodium nitroprusside, and acetylcholine. Measurements were made during control conditions and with pannexin-1 blockade (3000 mg probenecid). Expression of Pannexin-1, purinergic- and α-adrenergic receptors in skeletal muscle biopsies was determined by Western blot. Results: The changes in leg vascular resistance in response to tyramine (+289% versus +222%), sodium nitroprusside (−82% versus −78%) and acetylcholine (−40% versus −44%) infusion were not different between the 2 groups ( P >0.05) and pannexin-1 blockade did not alter these variables ( P >0.05). Expression of pannexin-1 and of purinergic- and α-adrenergic receptors was not different between the 2 groups ( P >0.05). Conclusions: Contrary to our hypothesis, the data demonstrate that pannexin-1 does not contribute to the elevated blood pressure in essential hypertension, a finding, which also opposes that reported in preclinical models.

This study aimed to analyze the effect of felodipine combined with enalapril in the treatment of patients with essential hypertension and coronary artery disease. Also, the effect of these medicines was evaluated on the peripheral blood Salusin-β, Apelin levels, and PON1 gene expression. For this purpose, 110 patients with essential hypertension combined with coronary heart disease, admitted to the hospital from January 2019 to January 2021, were selected and randomly divided into two groups. The control group was given felodipine treatment alone, and the study group was treated with combined application of felodipine and enalapril. The treatment effect, peripheral blood Salusin-β, Apelin, PON1 gene expression, and the safety of medication were compared between the two groups. The results showed that the post-treatment systolic blood pressure in the study group was 119.77 ± 5.23 mm Hg and diastolic blood pressure was 86.84 ± 5.42 mm Hg, both of which were significantly lower than those in the control group (127.81 ± 6.92 mm Hg and 95.13 ± 6.08 mm Hg), with statistically significant differences (p0.05). According to these results, the combination of felodipine and enalapril in patients with essential hypertension combined with coronary artery disease can effectively lower the patients' blood pressure and improve their peripheral blood Salusin-β, Apelin levels, and PON1 gene expression, thus enhancing the patients' therapeutic effect with few adverse effects and high safety.

Previous studies have demonstrated that the levels of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide (NO) synthesis, are strongly associated with hypertension, diabetes, and cardiovascular diseases. Profilin‐1, an actin‐binding protein, has been documented to be involved in endothelial injury and in the proliferation of vascular smooth muscle cells resulting from hypertension. However, the role of profilin‐1 in ADMA‐induced vascular injury in hypertension remains largely unknown. Forty healthy subjects and forty‐two matched patients with essential hypertension were enrolled, and the related indexes of vascular injury in plasma were detected. Rat aortic smooth muscle cells (RASMCs) were treated with different concentrations of ADMA for different periods of time and transfected with profilin‐1 small hairpin RNA to interrupt the expression of profilin‐1. To determine the role of the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway, RASMCs were pretreated with AG490 or rapamycin. The expression of profilin‐1 was tested using real‐time polymerase chain reaction (PCR) and western blot analysis. Cell proliferation was measured by flow cytometry and 3‐(4,5‐dimethylthiazol‐2yl)‐2,5‐diphenyltetrazoliumbromide assays. Compared with healthy subjects, the levels of ADMA and profilin‐1 were markedly elevated in hypertensive individuals, while the levels of NO were significantly decreased (p

Essential hypertension (EH) represents a major risk factor for stroke, myocardial infarction, and heart failure. Dysregulated proliferation and migration of vascular smooth muscle cells (VSMCs) play an important role in pathogenesis of EH. This study aims to investigate the effect of Chromodomain Helicase DNA Binding Protein 1-Like (CHD1L) on Angiotensin II (AngII)-induced VSMCs injury and reveal the underlying mechanism. The expression of CHD1L in EH patients was determined by bioinformatics analysis, and then it was silenced in AngII-induced VSMCs to detect the changes in cellular functions including proliferation, migration, invasion and phenotypic switching via CCK-8, EDU staining, wound healing, transwell and Western blot assays, respectively. Inflammation and oxidative stress were also measured by detecting related markers via commercial kits. After confirming the binding sites between forkhead box O3A (FOXO3a) and CHD1L and their negative association by bioinformatics analysis, FOXO3a was further silenced, and the cellular functions were assessed again to reveal the underlying mechanism. Results showed that CHD1L was highly expressed in EH, and interference of CHD1L suppressed the proliferation, migration, invasion and phenotypic switching in VSMCs. Inflammation and oxidative stress were also restrained by CHD1L knockdown. After validating the negative role of FOXO3a in regulating CHD1L, it was found that FOXO3a abrogated the effect of CHD1L knockdown on the cellular functions of AngII-induced VSMCs. In conclusion, FOXO3a suppresses the proliferation and migration of AngII-induced VSMCs by down-regulating CHD1L.

This phase III study assessed the efficacy and safety of sacubitril/valsartan compared with those of olmesartan in Japanese patients with essential hypertension. Patients (n = 1161, aged ≥20 years) with mild to moderate hypertension (mean sitting systolic blood pressure [msSBP] ≥150 to n = 387), sacubitril/valsartan 400 mg (n = 385), or olmesartan 20 mg (n = 389) once daily for 8 weeks. The primary assessment was a reduction in msSBP from baseline with sacubitril/valsartan 200 mg vs. olmesartan 20 mg at Week 8. Secondary assessments included msSBP reduction with sacubitril/valsartan 400 mg vs. olmesartan at Week 8 and reductions in mean sitting diastolic blood pressure (msDBP), mean sitting pulse pressure (msPP), and overall blood pressure (BP) control rate for all treatment groups at Week 8. Sacubitril/valsartan 200 mg provided a significantly greater reduction in msSBP from baseline than olmesartan at Week 8 (between-treatment difference: −5.01 mmHg [95% confidence interval: −6.95 to −3.06 mmHg, P vs. olmesartan (P

A case-control study was designed to investigate the association between the angiotensin converting enzyme 2 (ACE2) rs879922, glucose-6-phosphate dehydrogenase (G6PD) rs1050828, and tenomodulin (TNMD) rs4828038 single nucleotide polymorphisms (SNPs), and preeclampsia. A total of 356 Han Chinese pregnant women (170 controls and 186 cases) were recruited into the study. ACE2 rs879922, G6PD rs1050828, and TNMD rs4828038 were tested by the targeted next-generation sequencing technology and the data were analyzed using SPSS version 18. Genotyping of results revealed that patients with the CC/CT genotype in SNP rs4828038 or CC/CG genotype in SNP rs879922 had a significantly decreased susceptibility to late-onset preeclampsia (CC/CT versus TT: OR = 0.543, 95% CI = 0.378 to 0.779

Vascular dysfunction and hyperlipidemia are essential risk factors contributing to essential hypertension (EH). The plasmacytoma variant translocation 1 (PVT1) is involved in modulating angiogenesis in tumor tissues and plays an important role in fat differentiation in the progress of obesity. Therefore, we selected two tagSNPs of PVT1 (rs10956390 and rs80177647) to investigate whether they are contributing to the risk of hypertension in Chinese patients. In total, 524 adult patients with EH and 439 matched healthy controls were enrolled for two central of China. Results. PVT1 rs10956390 and rs80177647 polymorphisms were genotyped by using TaqMan assay. PVT1 rs10956390 TT genotype was associated with a decreased risk of EH ( OR = 0.561 , 95% CI = 0.372 -0.846, P = 0.006 ), while rs80177647 TA genotype was associated with an increased risk ( OR = 2.236 , 95% CI = 1.515 -3.301, P < 0.001 ). Rs10956390 T allele was associated with lower triglyceride levels in the plasma both from healthy and EH donors. What is more, there is an association between rs10956390 polymorphism and HDL-C level, as well as LDL-C. Conclusion. PVT1 rs10956390 and rs80177647 polymorphisms may contribute to the risk of EH in Chinese population by regulating blood lipid levels.

Whether arteriosclerosis can influence the hypertension control remains incompletely understood. We hypothesized that higher arteriosclerosis may be associated with uncontrolled hypertension. Arteriosclerosis was assessed by carotid femoral artery pulse wave velocity (CF-PWV) and uncontrolled hypertension (systolic blood pressure [BP] ≥130 mm Hg or diastolic BP ≥80 mm Hg). The multivariable-adjusted logistic regression was used for analysis. A total of 1,428 patients with essential hypertension (mean age 68 years, 49.6% male) were enrolled into the study from 2010 to 2017. The BP was uncontrolled in 50.7% of the participants and the mean level of CF-PWV was 12.3 m/s. All the cardiovascular risk factors were worse and CF-PWV was higher in patients with uncontrolled hypertension (all p < 0.05). Multivariable-adjusted logistic regression analysis showed that CF-PWV as a continuous variable (odd ratio [OR] 1.093, 95% confidence interval [CI] 1.046–1.142) was independently associated with uncontrolled hypertension, after male (OR 1.511) and total cholesterol (OR 1.167), followed by body mass index (OR 1.092), fasting plasma glucose (OR 1.075), and creatinine (OR 1.010) (all p < 0.05). As a binary variable, CF-PWV >12 m/s was also independently associated with uncontrolled hypertension (OR 1.690, 95% CI 1.320–2.164, p < 0.05). Arteriosclerosis is independently associated with uncontrolled BP in patients with hypertension.

Arteriosclerosis leads to various serious diseases that substantially reduce the quality of life. When treating hypertension, it is important to evaluate the degree of arteriosclerosis. In recent years, the cardio-ankle vascular index and augmentation index have been frequently used as indicators of arterial wall sclerosis. However, the superiority of either the cardio-ankle vascular index or the augmentation index as an index of arteriosclerosis remains unclear. Therefore, the present study compared the usefulness of these two indices as an index of arteriosclerosis. Associations between the cardio-ankle vascular index or augmentation index and risk factors for arteriosclerosis and other indices of arteriosclerosis in 535 consecutive patients with essential hypertension were evaluated. The cardio-ankle vascular index was significantly correlated with age, hemoglobin A1c, brain natriuretic peptide, and estimated glomerular filtration rate. In contrast, the augmentation index showed significant correlations only with age, brain natriuretic peptide, and estimated glomerular filtration rate. In addition, these correlations with the augmentation index were generally weaker than those with the cardio-ankle vascular index. The cardio-ankle vascular index, but not the augmentation index, was significantly correlated with flow-mediated dilation, an index of vascular endothelial function, and carotid intima-media thickness, an index of carotid atherosclerosis. Similar results were observed in subgroups stratified by sex and age. These data indicate that the cardio-ankle vascular index is more closely associated with risk factors for arteriosclerosis and other indices of arteriosclerosis than the augmentation index, suggesting that the cardio-ankle vascular index may be superior to the augmentation index as an index of arteriosclerosis.

The aim of the study was to evaluate the efficacy and safety of fixed-dose combination (FDC) of metoprolol, telmisartan, and chlorthalidone in patients with essential hypertension and stable coronary artery disease (CAD) who showed inadequate response to dual therapy.In this phase III, open-label, multicenter study, 254 adults with stable CAD having uncontrolled hypertension despite being treated with FDC of metoprolol (25/50 mg) and telmisartan (40 mg) were included. Patients received either of the following FDC for 24 weeks: metoprolol (25 mg), telmisartan (40 mg), and chlorthalidone (12.5 mg) (FDC1; n = 139) or metoprolol (50 mg), telmisartan (40 mg), and chlorthalidone (12.5 mg) (FDC2; n = 115) tablets once daily. The FDCs were developed using the novel Wrap Matrix™ platform technology. Primary endpoint assessed the mean change in seated diastolic blood pressure (SeDBP) and seated systolic blood pressure (SeSBP) from baseline to 24 weeks. Secondary efficacy endpoints included proportion of patients achieving 90 mmHg SeDBP (SeDBP responder) and 140 mmHg SeSBP (SeSBP responder) at weeks 12, 16, 20, and 24. Safety was assessed throughout the study.A total of 243 (95.70%) patients completed study. The mean change in BP from baseline (FDC1, 155/96 mmHg; FDC2, 165/98 mmHg) to week 24 (FDC1, 128/82 mmHg; FDC2, 131/83 mmHg) was statistically significant (both groups p 0.0001). Within FDC1 and FDC2, the mean change from baseline to week 24 in SeDBP (82.60 mmHg and 83.09 mmHg) and SeSBP (128.07 mmHg and 131.29 mmHg) was statistically significant (both groups p 0.0001). At week 24, in FDC1, 80.15% and 84.73% were SeDBP and SeSBP responders, respectively; in FDC2, 79.46% and 74.11% were SeDBP and SeSBP responders, respectively. No serious adverse events or deaths were reported.Triple FDCs of metoprolol, telmisartan, and chlorthalidone were considered effective and well tolerated in patients with hypertension who respond inadequately to dual therapy.CTRI/2016/11/007491.The increasing prevalence of hypertension in India requires immediate attention. To adequately manage blood pressure and ensure compliance to medications, innovative treatment options involving combination therapy with three or more drugs to treat hypertension need to be explored. Fixed-dose combination (FDC) of three antihypertension drugs, viz., metoprolol, telmisartan, and chlorthalidone, were tested in Indian patients who could not respond adequately to dual treatment. The rationale behind using a combination of three drug types was to take advantage of the complementary actions of each drug class for an enhanced treatment effect. The two variants of FDCs were tested in 254 adults with the most common form of heart disease, i.e., stable coronary artery disease. Changes in seated diastolic and systolic blood pressure (SeDBP and SeSBP) were measured to assess the effectiveness of the FDC. The mean changes in SeDBP and SeSBP were statistically significant by the end of the study, i.e., it determined that results are not explainable by chance alone. A greater proportion of patients (range 74–84%) achieved their target BPs with the FDC used in the study. The FDC variants were well tolerated without any reports of serious adverse events or deaths. Overall, this triple combination therapy option was effective and considered safe to be administered to hypertensive Indian adults with stable coronary artery disease who did not respond adequately to dual antihypertension therapy.

Despite hypertension ranks among the leading causes of chronic kidney disease (CKD), the impact of chronic hypertensive nephropathy, the so-called ‘nephrosclerosis’ (NS), on CKD progression is often unpredictable, particularly in elderly population. We have conducted a prospective, observational study to define renal function patterns and outcomes in elderly CKD individuals with or without NS. Three hundred four individuals with an already established CKD were categorized according to the etiology of CKD. NS was defined as the presence of CKD associated with long-term essential hypertension, hypertensive retinopathy, left ventricular hypertrophy and minimal proteinuria. Time trajectories in estimated glomerular filtration rate (eGFR) (CKD-Epi) were computed over a 4-year follow-up. In addition, we analyzed the occurrence of a composite outcome of doubling of serum creatinine levels, eGFR reduction ≥25% and/or the need of chronic renal replacement therapy. CKD was secondary to nephrosclerosis (CKD-NS) in 220 (72.3%). In the whole cohort, the average estimated annual GFR slope was 1.8 mL/min/1.73 m2. eGFR decline was slower in CKD-NS as compared with others (1.4 vs 3.4 mL/min/1.73 m2; p

Background The relationship between obesity indices and arterial stiffness (AS) has not been fully discovered nor has it been studied in depth in large hypertensive patient populations. The aim of this study was to explore the association between body mass index (BMI) and waist-hip ratio (WHR) levels and AS based on brachial-ankle pulse wave velocity (baPWV) in Chinese rural adults with hypertension. Methods This cross-sectional study analyzed 5049 Chinese rural adults with essential hypertension. BMI was calculated as the body weight in kilograms divided by the square of the height in meters (kg/m2). Central obesity was defined as WHR ≥ 0.9 for males and ≥ 0.85 for females. Measurement of arterial stiffness was carried out via brachial-ankle pulse wave velocity (baPWV). Results The prevalence of overweight, general obesity, central obesity and increased AS were 26.88%, 3.39%, 63.85% and 44.01%, respectively. Multivariate logistic regression analysis indicated that BMI levels were negatively associated with the prevalence of increased AS (adjusted-OR per SD increase: 0.74, 95% CI 0.67–0.81, P SD increase: 1.25, 95% CI 1.14–1.36, P CI 1.28–1.81, P β per SD increase: − 0.57, 95% CI − 0.68 to − 0.46, P β per SD increase: 4.46, 95% CI 3.04–5.88, P Conclusion There was an inverse relationship between BMI levels and increased AS or baPWV levels, whereas WHR levels and central obesity were positively associated with increased AS or baPWV levels in Chinese rural adults with hypertension.

In this study, the evidence mapping was employed to systematically analyze the clinical research literature and learn the distribution of evidence on the prevention and treatment of essential hypertension with Chinese patent medicines in recent six years. CNKI, Wanfang, VIP, SinoMed, PubMed, and Cochrane Library were searched for the relevant literature published from January 2016 to December 2021. The distribution characteristics of evidence were analyzed and presented in charts combined with words. A total of 263 studies were selected, including 238 intervention studies, 17 systematic reviews/Meta-analysis, and 8 observation studies. A total of 72 Chinese patent medicines were involved, among which Songling Xuemaikang Capsules had the highest frequency. In China, the attention to the treatment of essential hypertension with Chinese patent medicines was insufficient, as manifested by the declining number of published literature and the low quality of studies. There were cases of off-label use and medication without syndrome differentiation in clinical practice. Some outcome indicators failed to embody the characteristics of traditional Chinese medicine and there were cases ignoring the end-point outcome indicators. The overall quality of systematic reviews/Meta-analysis was low, and a variety of studies failed to draw valid conclusions. In the future, it is necessary to standardize the clinical medication and improve the quality of randomized controlled trial(RCT), so as to produce high-quality evidence-based medical evidence and provide strong support for the efficacy and safety of Chinese patent medicines in the prevention and treatment of essential hypertension.

Rationale: Hypertension is the most important risk factor for cardiovascular and cerebrovascular diseases. Getting deep insight into the pathogenesis of hypertension is necessary. Objective: To investigate the role of ANK (ankyrin) repeat domain 36 ( ANKRD36 ) in hypertension. Methods and Results: We first recruited an essential hypertension cohort and then performed genome-wide transcriptome analysis with peripheral blood mRNA. ANKRD36 was found to be significantly lower expressed in hypertension. The anchorin repeat domain mediates a variety of protein-protein interactions. The ENaC (epithelial sodium channel) genes expression was found upregulated in human umbilical vein endothelial cells with ANKRD36 knockdown by using Affymetrix expression profile chip. In human embryonic kidney epithelial cells and HEK293T (human embryonic kidney cells), ANKRD36 overexpression significantly downregulated expression of ENaC genes, and ANKRD36 knockdown upregulated their expression. The chromosome immunoprecipitation assay and yin yang 1 ( YY1 ) knockdown showed the expression of ENaC was regulated by ANKRD36 via YY1, a dual-function transcription factor ubiquitously expressed in human tissues. Immunocoprecipitation and fluorescence resonance energy transfer assay confirmed the interaction between ANKRD36 and YY1. The nucleo-cytoplasmic ratio of YY1 decreased when ANKRD36 was overexpressed and also increased when ANKRD36 was knocked down. ANK2 domain of ANKRD36 was critical to its interaction with YY1. Ankrd36 knockout mice showed higher blood pressure levels and Na + reabsorption, especially when fed with high-salt diet. Higher expression of ENaC genes was observed in renal tubular epithelial cells from the knockout mice, and Yy1 knockdown mitigated the alteration. Ankrd36 knockout mice also showed more sensitive response to ENaC inhibitor amiloride treatment. Conclusions: We identified that ANKRD36 was involved in blood pressure regulation by interacting with YY1 and then altering expression of ENaC genes. Lower expressed ANKRD36 in hypertension might be a potential therapeutic target, and the application of ENaC inhibitors on hypertension treatment might be extended when serum K + levels are closely monitored.

Plateau essential hypertension is a common chronic harmful disease of permanent residents in plateau areas. Studies have shown some single nucleotide polymorphisms (SNPs) associations with hypertension, but few have been verified in plateau area-lived people. In this paper, we examined some hypertension-related gene loci to analyze the relationship between risk SNPs and plateau essential hypertension in residents in Qinghai-Tibet plateau area. We screened hypertension-related SNPs from the literature, Clinvar database, GHR database, GTR database, and GWAS database, and then selected 101 susceptible SNPs for detection. Illumina MiSeq NGS platform was used to perform DNA sequencing on the blood samples from 185 Tibetan dwellings of Qinghai, and bioinformatic tools were used to make genotyping. Genetic models adjusted by gender and age were used to calculate the risk effects of genotypes. Four known SNPs as well as a new locus were found associated with PHE, which were rs2493134 (AGT), rs9349379 (PHACTR1), rs1371182 (CYP2C56P-PRPS1P1), rs567481079 (CYP2C56P-PRPS1P1), and chr14:61734822 (HIF1A). Among them, genotypes of rs2493134, rs9349379, and rs567481079 were risk factors, genotypes of rs1371182 and chr14:61734822 were protective factors. The rs2493134 in AGT was found associated with an increased risk of the plateau essential hypertension by 3.24-, 3.24-, and 2.06-fold in co-dominant, dominant, and Log-additive models, respectively. The rs9349379 in PHACTR1 is associated with a 2.61-fold increased risk of plateau essential hypertension according to the dominant model. This study reveals that the alleles of AGT, HIF1A, and PHACTR1 are closely related to plateau essential hypertension risk in the plateau Tibetan population.

Nowadays, there are robust clinical and pathophysiological evidence supporting the beneficial effects of physical activity on cardiovascular (CV) system. Thus, the physical activity is considered a key strategy for CV prevention. In fact, exercise training exerts favourable effects on all risk factors for CV diseases (i.e. essential hypertension, type 2 diabetes mellitus, hypercholesterolemia, obesity, metabolic syndrome, etc…). In addition, all training modalities such as the aerobic (continuous walking, jogging, cycling, etc.) or resistance exercise (weights), as well as the leisure-time physical activity (recreational walking, gardening, etc) prevent the development of the major CV risk factors, or delay the progression of target organ damage improving cardio-metabolic risk. Exercise training is also the core component of all cardiac rehabilitation programs that have demonstrated to improve the quality of life and to reduce morbidity in patients with CV diseases, mostly in patients with coronary artery diseases. Finally, it is still debated whether or not exercise training can influence the occurrence of atrial and ventricular arrhythmias. In this regard, there is some evidence that exercise training is protective predominantly for atrial arrhythmias, reducing the incidence of atrial fibrillation. In conclusion, the salutary effects evoked by physical acitvity are useful in primary and secondary CV prevention.

BACKGROUND AND PURPOSE: Arterial sclerosis resulting from hypertension slows CSF transportation in the perivascular spaces, showing the intrinsic relationship between the CSF and the blood vasculature. However, the exact effect of hypertension on human CSF flow dynamics remains unclear. The present study aimed to evaluate CSF flow dynamics in treatment-naive patients with essential hypertension using phase-contrast cine MR imaging. MATERIALS AND METHODS: The study included 60 never-treated patients with essential hypertension and 60 subjects without symptomatic atherosclerosis. CSF flow parameters, such as forward flow volume, forward peak velocity, reverse flow volume, reverse peak velocity, average flow, and net flow volume, were measured with phase-contrast cine MR imaging. Differences between the 2 groups were assessed to determine the independent determinants of these CSF flow parameters. RESULTS: Forward flow volume, forward peak velocity, reverse flow volume, reverse peak velocity, and average flow in the patients with hypertension significantly decreased (all, P

Recent evidence supports a role for the gut microbiota in hypertension, but whether ambulatory blood pressure is associated with gut microbiota and their metabolites remains unclear. We characterized the function of the gut microbiota, their metabolites and receptors in untreated human hypertensive participants in Australian metropolitan and regional areas. Ambulatory blood pressure, fecal microbiome predicted from 16S rRNA gene sequencing, plasma and fecal metabolites called short-chain fatty acid, and expression of their receptors were analyzed in 70 untreated and otherwise healthy participants from metropolitan and regional communities. Most normotensives were female (66%) compared with hypertensives (35%, P Acidaminococcus spp ., Eubacterium fissicatena, and Muribaculaceae were higher, while Ruminococcus and Eubacterium eligens were lower in hypertensives. Importantly, normotensive and essential hypertensive cohorts could be differentiated based on gut microbiome gene pathways and metabolites. Specifically, hypertensive participants exhibited higher plasma acetate and butyrate, but their immune cells expressed reduced levels of short-chain fatty acid-activated GPR43 (G-protein coupled receptor 43). In conclusion, gut microbial diversity did not change in essential hypertension, but we observed a significant shift in microbial gene pathways. Hypertensive subjects had lower levels of GPR43, putatively blunting their response to blood pressure-lowering metabolites.

Hypertension is a complex disease which is mainly influenced by genetic factors. Recently, genome-wide association study (GWAS) found three novel endothelial dysfunction-related sites: Vascular endothelial growth factor A (VEGFA) rs9472135, Faciogenital dysplasia 5 (FGD5) rs11128722, Zinc Finger C3HC-type Containing 1 (ZC3HC1) rs11556924. Endothelial dysfunction is one of the early events in pathophysiology of essential hypertension. To investigate the association of endothelial dysfunction-related genes with essential hypertension, we conducted a case-control study of 431 patients with hypertension and 345 controls. The polymorphisms were detected using Taqman Probe. The alleles and genotypes of ZC3HC1 rs11556924 and VEGFA rs9472135 were not statistically different between the two groups, while the allele of FGD5 rs11128722 was different [P = 0.045, OR = 1.265, 95% CI = (1.009–1.586)], especially in the male [P = 0.035, OR = 1.496, 95% CI = (1.037–2.158)]. Analyzing the different of genotype distribution of 3 SNPs in the two groups under different genetic models, the genotypes of FGD5 rs11128722 showed difference in male under dominant model [P = 0.049, OR = 1.610, 95% CI = (1.018–2.544)]. The polymorphism of FGD5 rs11128722 had a significant difference in Body Mass Index (BMI) among different genotypes; In the additive genetic model, BMI of GA genotype was higher than that of GG (P = 0.038); GA + AA was higher than GG in the dominant genetic model (P = 0.011). In our study, we found that the polymorphisms of VEGFA rs9472135 and ZC3HC1 rs11556924 may not significantly associated with the risk of essential hypertension, and FGD5 rs11128722 may increase the risk of it, especially in elderly men.

BACKGROUND: Middle meningeal artery embolization (MMAE) has been used as an effective minimally invasive treatment for chronic subdural hematomas (cSDH). The demographics and clinical outcomes after MMAE treatment for cSDH have not yet been studied using the large scale of a national database. METHODS: We queried all MMAE cases up to October 7(th), 2020, from the TriNetX Analytics Network. We identified patients >18 years old who underwent MMAE for the treatment of cSDH. Patient demographics, baseline characteristics, comorbidities, and clinical outcomes were evaluated within 180 days post-MMAE. 180-day mortality and recurrence analyses were performed after propensity score matching to control for baseline characteristics and comorbidities. RESULTS: A total 191 patients were included (mean age: 71.2 ± 13.5, 73.3% male, 69.6% White, 13.6% Black/African American, and 16.8% other). Essential hypertension (71.3%), heart disease (62.8%), type 2 diabetes mellitus (27.2%), nicotine dependence (23.6%), chronic kidney disease (19.4%), and overweight/obesity (19.4%) were among the most prevalent comorbidities. At presentation, 20.4% and 40.3% were on antiplatelet and anticoagulation therapy, respectively. Outcomes within a 180-day follow-up were 6.3% (or 1.0–5.8% when propensity-matched) for mortality (12 patients), 7.3% for craniotomy/craniectomy after MMAE (14 patients), 0.52–5.2% for burr hole procedures (1–10 patients), and no patients with low vision/blindness. CONCLUSION: MMAE is a safe and effective minimally invasive procedure for the treatment of cSDH. This represents the first analysis of patients undergoing MMAE for cSDH using a national database.

Dapeng Ji,&ast; Bo Zhang,&ast; Bo He Department of Cardiac Function, The Sixth Hospital of Wuhan, Affiliated Hospital of Jianghan University, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bo He, Department of Cardiac Function, The Sixth Hospital of Wuhan, Affiliated Hospital of Jianghan University, No. 168 Hong Kong Road, Wuhan, 430050, People’s Republic of China, Tel: +86-13437154321, Email 37569105@qq.comObjective: This study aims to explore the diagnostic value of the deepest S wave (SD) in elderly patients with essential hypertension and left ventricular hypertrophy (LVH).Methods: A retrospective study was conducted in elderly patients with essential hypertension from October 2020 to December 2021. The 12-lead electrocardiogram (ECG) examination was carried out at the time of admission. Echocardiography was performed to estimate left ventricular mass (LVM) and the left ventricular muscle mass index (LVMI) was adjusted by the body surface area (BSA). The Receiver Operating Characteristic (ROC) curve for diagnosing hypertension with LVH was drawn, the cut-off value was determined according to the Youden index, and the area under the curve (AUC) was calculated. The diagnostic values of SD, SD+Sv4, ravl+Sv3, and Sv1+Rv5 were compared.Results: The results of SD, SD+Sv4, RavL+Sv3, and Sv1+Rv5 in the Study group were 2.03 (1.56– 2.57) mV, 3.09 (2.38– 3.98) mV, 2.19 (1.46– 2.78) mV, and 3.38 (2.67– 4.19) mV respectively, which were all higher than those in the Control group [0.93 (0.68– 1.23) mV, 1.37 (1.32– 2.18) mV, 1.03 (0.68– 1.46) mV, and 2.28 (1.67– 2.67) mV], P< 0.001. Compared with the ROC curved by SD+Sv4, RavL+Sv3, and Sv1+Rv5, the AUC of the ROC curved by SD was [0.887, 95% CI (0.837– 0.927)], and the cut-off value was 1.298 with the Sensitivity = 86.03 and Specificity = 86.59 in diagnosing essential hypertension with LVH. In female patients, the AUC of the ROC curved by SD was [0.891, 95% CI (0.841– 0.934)], and the cut-off value was 1.304 with the Sensitivity of 89.32% and Specificity of 88.67%, which were all higher than those in male patients [AUC = 0.887, 95% CI (0.828– 0.943); cut-off value = 1.288; Sensitivity = 82.12%, and Specificity = 84.22%].Conclusion: ECG can effectively diagnose elderly patients with essential hypertension and LVH and the diagnostic value of SD and SD+Sv4 are higher than the current Cornell criteria and Sokolow–Lyon criteria.Keywords: essential hypertension, left ventricular hypertrophy, elderly patients, deepest S wave, electrocardiogram criteria

Among cardiovascular diseases, hypertension is one of the main risk factors predisposing to fatal complications. Oxidative stress and chronic inflammation have been identified as potentially responsible for the development of endothelial damage and vascular stiffness, two of the primum movens of hypertension and cardiovascular diseases. Based on these data, we conducted an open-label randomized study, first, to evaluate the endothelial damage and vascular stiffness in hypertense patients; second, to test the effect of supplementation with a physiological antioxidant (melatonin 1 mg/day for 1 year) in patients with essential hypertension vs. hypertensive controls. Twenty-three patients of either gender were enrolled and randomized 1:1 in two groups (control and supplemented group). The plasmatic total antioxidant capacity (as a marker of oxidative stress), blood pressure, arterial stiffness, and peripheral endothelial function were evaluated at the beginning of the study and after 1 year in both groups. Our results showed that arterial stiffness improved significantly (p = 0.022) in supplemented patients. The endothelial function increased too, even if not significantly (p = 0.688), after 1 year of melatonin administration. Moreover, the supplemented group showed a significative reduction in TAC levels (p = 0.041) correlated with the improvement of arterial stiffness. These data suggest that melatonin may play an important role in reducing the serum levels of TAC and, consequently, in improving arterial stiffness.

This study aimed to investigate the differential expression profiles of microRNAs (miRNAs) in peripheral blood lymphocytes between patients with essential hypertension and healthy individuals in Xinjiang Kazakh and to provide insight into the mechanism involved in the pathogenesis of hypertension in this ethnic group. From April 2016 to May 2019, 30 Kazakh patients with essential hypertension in the inpatient and outpatient departments of Cardiology, First Affiliated Hospital of Shihezi University were used as the hypertension group; 30 healthy Kazakh patients were used as the control group. The miRNA expression profiles in peripheral blood lymphocytes of 6 Kazakh hypertensive patients and 6 matched healthy individuals were compared, and the differentially expressed miRNAs were analyzed by cluster analysis, GSEA enrichment analysis, target gene prediction, target gene annotation and other bioinformatics analyses. In addition, qRT-PCR was used to verify the differentially expressed miRNAs. The results showed that compared with the control group, 73 differentially expressed miRNAs were identified in the hypertension group, of which 39 miRNAs were up-regulated and 34 miRNAs were down-regulated. A total of 11 miRNAs related to hypertension were screened by GSEA enrichment analysis, including hsa-miR-100-5p, hsa-miR-150-5p, hsa-miR-299-5p, hsa-miR-299-3p, hsa-miR-296-5p, hsa-miR-196b-5p, hsa-miR-503-5p, hsa-miR-628-5p, hsa-miR-874-3p, hsa-miR-543 and hsa-miR-940. qRT-PCR test found that the expression of hsa-miR-100-5p, hsa-miR-299-5p, hsa-miR-299-3p, hsa-miR-196b-5p, hsa-miR-503-5p, hsa-miR-628-5p and hsa-miR-543 was up-regulated, while the expression of hsa-miR-150-5p, hsa-miR-296-5p, hsa-miR-874-3p and hsa-miR-940 was down-regulated in the hypertension group compared with the control group. The expression trend in the gene chip was consistent with the results verified by qRT-PCR. Using online database to predict target genes of 11 miRNAs related to hypertension, we found that a total of 1 647 target genes might be regulated by these 11 miRNAs. GO function enrichment showed that (a) in biological processes, the predicted hypertension related target genes are mainly relevant to nervous system development, cellular localization, regulation of cellular metabolic process, generation of neurons and positive regulation of biological process; (b) In terms of cellular components, they are mainly related to membrane-bounded organelle, cytoplasm, intracellular membrane-bounded organelle, synapse part, neuron part, and nucleoplasm; (c) In terms of molecular function, they are mainly related to protein binding, transcription regulatory region DNA binding, RNA polymerase II regulatory region DNA binding, transcription regulator activity, and ion binding. KEGG enrichment analysis showed that the p53 signaling pathway, adrenergic signaling in cardiomyocytes, cAMP signaling pathway, TGF-β signaling pathway, endocrine and other factor-regulated calcium reabsorption, mTOR signaling pathway, and aldosterone-regulated sodium reabsorption may be related to the occurrence and development of hypertension. In conclusion, there are significant differences in the expression of miRNAs in peripheral blood lymphocytes between Kazakh patients with essential hypertension and healthy people. The differentially expressed miRNAs may be related to the occurrence and development of essential hypertension in Kazakh. However, the underlying mechanism needs to be further explored and verified.

Hypertensive kidney damage results in glomerular as well as tubular dysfunction. Albuminuria is a well-known marker of glomerular damage. On the other hand, urinary uromodulin is increasingly considered as a potential biomarker of early tubular dysfunction. The aim of the study was to assess glomerular and tubular function of the kidney by measuring urinary albumin and uromodulin excretion in hypertensive subjects. This cross-sectional study was conducted from July 2018 to June 2019 in Hypertension Clinic of Dhaka Medical College Hospital, Dhaka and Kidney Care and Research Centre, Sonargaon, Narayanganj, Bangladesh. In this study 122 hypertensive subjects with age30 years, duration of hypertension5 years, without accelerated or malignant BP, absence of dipstick proteinuria and eGFR60ml/min were included. There were also 33 normotensive individuals included as healthy controls. Albumin-creatinine ratio (uACR mg/g), urine uromodulin-creatinine ratio (uUMODμg/g), urinary sodium-creatinine ratio (mEq/g) and potassium-creatinine ratio (mEq/g) were measured from single morning spot urine sample. Urinary uromodulin levels were measured by ELISA method. The hypertensive and normotensive subjects were age matched 49.0±12.0 vs. 48.0±11.0, years (p=NS). The mean uACR was 29.0±65.0 versus 5.6±2.7mg/g, (p0.001) respectively. The median uUMOD in hypertensive subjects was 3.38 (1.73-9.06) and in normotensives 3.85(2.28-5.69) μg/g (p=non significant). Multivariate analysis showed significant inverse association between diastolic blood pressure and urinary uromodulin excretion. A uUMOD cut-off of 2.9 (25th percentile) showed eGFR, urinary sodium and potassium excretions were significantly lower at low uromodulin group. The glomerular involvement was found in 21.0% of hypertensive subjects as evidenced by albuminuria. No difference was observed in urinary uromodulin level between hypertensive and normotensive subjects. Low urinary uromodulin level was associated with lower eGFR, Na+ and K+ excretion which indicate simultaneous tubular and glomerular involvement.

The prevalence of essential hypertension increases consistently among middle-aged and older adults in China. Aims of this study are to explore the impact of Tai Chi and square dance, which are popular in China, on antihypertensive effects and cardiovascular disease risk factors in patients with essential hypertension.Patients with essential hypertension were randomly assigned to either a Tai Chi group, a square dance group or a control group. Blood pressure, cardiorespiratory fitness, and cardiovascular disease risk factors were measured at baseline and at the end of the 12-week intervention. The duration and frequency of both intervention exercises were 60 minutes per session, and 5 sessions per week.A total of 144 participants (59.89±6.85 years, 34.72% male) completed the study. The repeated-measures analysis of variance demonstrated a significant effect of time on BMI, systolic and diastolic blood pressure, and cardiorespiratory fitness in patients with essential hypertension (P0.05), whereas no significant effect was observed on waist-to-hip ratio and body fat percentage (P0.05). Post hoc analyses showed that only intervention groups had significant differences in blood pressure and cardiorespiratory fitness compared to the control group, while Tai Chi had greater effect sizes than square dance.Both Tai Chi and square dance can promote cardiorespiratory fitness and reduce BMI and blood pressure among patients with essential hypertension, whereas there was no significant difference between the two exercises. However, both Tai Chi and square dance were ineffective in reducing some of the cardiovascular disease risk factors.

IntroductionEssential hypertension is a major preventable risk factor for early cardiovascular disease, premature death and disability. It has been reported that telemedicine interventions can provide an innovative solution to essential hypertension to overcome the barriers that exist in traditional treatment or control. Nevertheless, this subject has not been thoroughly investigated. The goal of this study is to systematically evaluate and describe the impact of telemedicine interventions on essential hypertension.Methods and analysisTo find relevant research, we will conduct a systematic literature search of three databases (PubMed, Embase and Cochrane Library), with no language limitations, in addition to researching grey literature. Two reviewers will extract the data individually, and any disagreements will be resolved by discussion or by a third reviewer. The randomised controlled trials will be chosen based on predetermined inclusion criteria. Primary outcomes will include systolic blood pressure and diastolic blood pressure after the telemedicine intervention. Secondary outcomes will include medication adherence (eg, the Morisky Medication Adherence Questionnaire), quality of life (eg, the MOS item scale of the Health Survey Short Form 36 questionnaire), blood pressure control rate and adverse events (eg, stroke, chronic renal failure, aortic dissection, myocardial infarction and heart failure). The quality of the included studies will be assessed using the Cochrane risk-of-bias method. The data will be analysed using RevMan V.5.3.5 software and STATA V.16.0 software. If heterogeneity testing reveals little or no statistical heterogeneity, a fixed effect model will be used for data synthesis; otherwise, a random effect model would be employed. We will synthesise the available evidence to perform a high-quality meta-analysis.Ethics and disseminationThis project does not require ethical approval because it will be conducted using publicly available documents. The review’s findings will be published in peer-reviewed journals and publications.PROSPERO registration numberCRD42021293539.

Background We describe sex‐differential disease patterns and outcomes of >20.6 million cardiovascular emergency department encounters in the United States. Methods and Results We analyzed primary cardiovascular encounters from the Nationwide Emergency Department Sample between 2016 and 2018. We grouped cardiovascular diagnoses into 15 disease categories. The sample included 48.7% women; median age was 67 (interquartile range, 54–78) years. Men had greater overall baseline comorbidity burden; however, women had higher rates of obesity, hypertension, and cerebrovascular disease. For women, the most common emergency department encounters were essential hypertension (16.0%), hypertensive heart or kidney disease (14.1%), and atrial fibrillation/flutter (10.2%). For men, the most common encounters were hypertensive heart or kidney disease (14.7%), essential hypertension (10.8%), and acute myocardial infarction (10.7%). Women were more likely to present with essential hypertension, hypertensive crisis, atrial fibrillation/flutter, supraventricular tachycardia, pulmonary embolism, or ischemic stroke. Men were more likely to present with acute myocardial infarction or cardiac arrest. In logistic regression models adjusted for baseline covariates, compared with men, women with intracranial hemorrhage had higher risk of hospitalization and death. Women presenting with pulmonary embolism or deep vein thrombosis were less likely to be hospitalized. Women with aortic aneurysm/dissection had higher odds of hospitalization and death. Men were more likely to die following presentations with hypertensive heart or kidney disease, atrial fibrillation/flutter, acute myocardial infarction, or cardiac arrest. Conclusions In this large nationally representative sample of cardiovascular emergency department presentations, we demonstrate significant sex differences in disease distribution, hospitalization, and death.

Background Blood pressure (BP) exhibits seasonal variations, with peaks reported in winter. However, the association between seasonal variations and blood pressure variability in patients with new-onset essential hypertension is not fully understood. This study evaluated the potential association of seasonal variations with new-onset essential hypertension. Methods This retrospective observational study recruited a total of 440 consecutive patients with new-onset essential hypertension who underwent 24-h ambulatory electrocardiograph (ECG) and BP measurement at our department between January 2019 and December 2019. Demographic and baseline clinical data including BP variability, heart rate variability, and blood tests were retrieved. Multivariate linear regression analysis was performed to identify factors independently associated with mean BP and BP variability. Results Among the 440 patients recruited, 93 cases were admitted in spring, 72 in summer, 151 in autumn, and 124 in winter. Univariate analysis revealed that systolic BP (SBP), diastolic BP (DBP), high-sensitivity C-reactive protein, SBP drop rate, DBP drop rate, 24-h standard deviation of SBP, 24-h standard deviation of DBP, 24-h SBP coefficient of variation, and 24-h DBP coefficient of variation were associated with patients admitted in winter (P B = 1.851, t = 3.719, P B = 1.176, t = 2.917, P = 0.004), 24-h SBP coefficient of variation (B = 0.015, t = 3.670, P B = 0.016, t = 2.849, P = 0.005) in hypertensive patients. Conclusions Seasonal variations are closely associated with BP variability in patients with new-onset essential hypertension. Our study provides insight into the underlying pathogenesis of new-onset essential hypertension.

(1) Background: Carbohydrate combined with dietary fiber (DF) applied as a surrogate marker of overall carbohydrate quality is a more essential determinant of cardiometabolic health. However, to date, no studies have applied this metric to analyze its associations with poor blood pressure control in hypertensive patients. (2) Methods: A cross-sectional design was implemented in one tertiary hospital and one community hospital in China. Using Feihua Nutrition Software to analyze participants’ two-day dietary log, the quantity of carbohydrate and fiber was obtained and the carbohydrate to fiber ratio (CFR) was calculated. The participants were divided into Q1, Q2, Q3, and Q4 groups by quartile method, from low to high according to CFR. The poor systolic and diastolic blood pressure (SBP and DBP) controls were defined as ≥140 mmHg and ≥90 mmHg, respectively. (3) Results: A convenience sample of 459 participants was included and the mean CFR was 29.6. Taking Q1 as reference, after adjusting for covariates, the CFR in Q4 was associated with higher poor SBP-controlled rate (OR, 4.374; 95% CI, 2.236–8.559). Taking Q2 as reference, after adjusting for covariates, the CFRs in Q3 and Q4 were associated with higher poor DBP-controlled rates [(OR = 1.964, 95% CI: 1.016–3.795) and (OR = 4.219, 95% CI: 2.132–8.637), respectively]. The CFR was the stronger protective determinant of SBP and DBP than DF or carbohydrate alone. (4) Conclusions: A higher CFR is a stronger risk factor for blood pressure (BP) control, and low CFR foods or a combination of corresponding food components, should be recommended in the dietary management of hypertensive patients.

Aims Digital therapeutics is a new approach to facilitate the non-pharmacological treatment of hypertension using software programmes such as smartphone applications and/or device algorithms. Based on promising findings from a small pilot trial, the HERB Digital Hypertension 1 (HERB-DH1) pivotal trial investigated the efficacy of digital therapeutics in patients with hypertension not receiving antihypertensive medication. Methods and results This prospective, open-label, randomized controlled study was performed at 12 sites in Japan. Patients with hypertension [office systolic blood pressure (SBP) 140 to, Graphical Abstract

Hypertension is a leading age-related disease in our society and if left untreated, leads to fatal cardiovascular complications. The prevalence of hypertension has increased and becomes a significant global health economic burden, particularly in lower-income societies. Many loci associated with blood pressure and hypertension have been reported by genome-wide association studies that provided potential targets for pharmacotherapy. Pharmacogenetic research had shown interindividual variations in drug efficacy, safety, and tolerability. This could be due to genetic polymorphisms in the pharmacokinetics (genes involved in a transporter, plasma protein binding, and metabolism) or pharmacodynamic pathway (receptors, ion channels, enzymes). Pharmacogenetics promises great hope toward targeted therapy, but challenges remain in implementing pharmacogenetic aided antihypertensive therapy in clinical practice. Using various databases, we analyzed the underlying mechanisms between the candidate gene polymorphisms and antihypertensive drug interactions and the challenges of implementing precision medicine. We review the emergence of pharmacogenetics and its relevance to clinical pharmacological practice.

Background: There has been controversy regarding the association between primary aldosteronism (PA) and dyslipidemia and few studies considered the effects of diabetes and renal function on lipid metabolism. We analyzed lipid profiles of PA patients and compared them to propensity-score (PS)-matched essential hypertension (EH) patients adjusting for glycemic status and renal function.Methods: Patients who were diagnosed with PA using a saline-infusion test at Seoul National University Hospital from 2000 to 2018 were retrospectively analyzed. EH patients who had aldosterone-renin ratio (ARR) results were selected as controls. Covariates, including diabetes, were PS-matched for patients with PA, lateralized PA, non-lateralized PA, and high ARR to EH patients, respectively.Results: Among a total of 80 PA and 80 EH patients, total cholesterol (TC) and triglyceride (TG) levels were significantly lower in the PA patients than in the EH patients (least-squares mean±standard error: 185.5±4.4 mg/dL vs. 196.2±4.4 mg/dL, P=0.047, for TC; and 132.3±11.5 mg/dL vs. 157.4±11.4 mg/dL, P=0.035, for TG) in fully adjusted model (adjusting for multiple covariates, including diabetes status, glycosylated hemoglobin level, and estimated glomerular filtration rate). There were no significant differences in high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol levels between the two groups. According to increments in aldosterone levels, an increasing tendency of HDL-C and decreasing tendencies of TG and non-HDL-C were observed.Conclusion: PA patients had lower TC and TG levels than EH patients, independent of glycemic status and renal function.

Although numerous clinical and experimental studies have clearly identified a sexual dimorphism in blood pressure control, the mechanism(s) underlying gender differences in blood pressure remain unclear. Over the past two decades, numerous laboratories have utilized the spontaneously hypertensive rats (SHR) as an experimental model of essential hypertension to increase our understanding of the mechanisms regulating blood pressure in males and females. Previous work by our group and others have implicated that differential regulation of adrenergic receptors, the renin–angiotensin system, oxidative stress, nitric oxide bioavailability and immune cells contribute to sex differences in blood pressure control in SHR. The purpose of this review is to summarize previous findings to date regarding the mechanisms of blood pressure control in male versus female SHR.

Fibroids are benign tumors caused by the proliferation of myometrial smooth muscle cells in the uterus that can lead to symptoms such as abdominal pain, constipation, urinary retention, and infertility. While traditionally thought of as a disease process intrinsic to the uterus, accumulating evidence suggests that fibroid growth may be linked with the systemic vasculature system, although cell-intrinsic factors are certainly of principal importance in their inception. Fibroids are associated with essential hypertension and preeclampsia, as well as atherosclerosis, for reasons that are becoming increasingly elucidated. Factors such as the renin–angiotensin–aldosterone system, estrogen, and endothelial dysfunction all likely play a role in fibroid pathogenesis. In this review, we lay out a framework for reconceptualizing fibroids as a systemic vascular disorder, and discuss how pharmaceutical agents and other interventions targeting the vasculature may aid in the novel treatment of fibroids.

The disease management of long-term breast cancer survivors (BCS) is hampered by the scarce knowledge of multimorbidity patterns. The aim of our study was to identify multimorbidity clusters among long-term BCS and assess their impact on mortality and health services use. We conducted a retrospective study using electronic health records of 6512 BCS from Spain surviving at least 5 years. Hierarchical cluster analysis was used to identify groups of similar patients based on their chronic diagnoses, which were assessed using the Clinical Classifications Software. As a result, multimorbidity clusters were obtained, clinically defined and named according to the comorbidities with higher observed/expected prevalence ratios. Multivariable Cox and negative binomial regression models were fitted to estimate overall mortality risk and probability of contacting health services according to the clusters identified. 83.7% of BCS presented multimorbidity, essential hypertension (34.5%) and obesity and other metabolic disorders (27.4%) being the most prevalent chronic diseases at the beginning of follow-up. Five multimorbidity clusters were identified: C1-unspecific (29.9%), C2-metabolic and neurodegenerative (28.3%), C3-anxiety and fractures (9.7%), C4-musculoskeletal and cardiovascular (9.6%) and C5-thyroid disorders (5.3%). All clusters except C5-thyroid disorders were associated with higher mortality compared to BCS without comorbidities. The risk of mortality in C4 was increased by 64% (adjusted hazard ratio 1.64, 95% confidence interval 1.52-2.07). Stratified analysis showed an increased risk of death among BCS with 5 to 10 years of survival in all clusters. These results help to identify subgroups of long-term BCS with specific needs and mortality risks and to guide BCS clinical practice regarding multimorbidity.

Essential hypertension is a complex trait where the underlying aetiology is not completely understood. Left untreated it increases the risk of severe health complications including cardiovascular and renal disease. It is almost 15 years since the first genome-wide association study for hypertension, and after a slow start there are now over 1000 blood pressure (BP) loci explaining ∼6% of the single nucleotide polymorphism-based heritability. Success in discovery of hypertension genes has provided new pathological insights and drug discovery opportunities and translated to the development of BP genetic risk scores (GRSs), facilitating population disease risk stratification. Comparing highest and lowest risk groups shows differences of 12.9 mm Hg in systolic-BP with significant differences in risk of hypertension, stroke, cardiovascular disease and myocardial infarction. GRSs are also being trialled in antihypertensive drug responses. Drug targets identified include NPR1, for which an agonist drug is currently in clinical trials. Identification of variants at the PHACTR1 locus provided insights into regulation of EDN1 in the endothelin pathway, which is aiding the development of endothelin receptor EDNRA antagonists. Drug re-purposing opportunities, including SLC5A1 and canagliflozin (a type-2 diabetes drug), are also being identified. In this review, we present key studies from the past, highlight current avenues of research and look to the future focusing on gene discovery, epigenetics, gene-environment interactions, GRSs and drug discovery. We evaluate limitations affecting BP genetics, including ancestry bias and discuss streamlining of drug target discovery and applications for treating and preventing hypertension, which will contribute to tailored precision medicine for patients.

BackgroundPlasma ceramides (Cer) have been used to evaluate risk of cardiovascular (CV) events in patients with coronary heart disease. We investigated the performance of ceramides and ceramide score (CERT) in hypertensive patients at high CV risk.MethodsSeven ceramides were analyzed using ultra-performance liquid chromatography–tandem mass spectrometry in 920 essential hypertension patients at high CV risk, who visited Beijing Anzhen Hospital from September 2016 to September 2018 (median age: 49 years, 562 males). All patients were followed up for major adverse cardiovascular events (MACE), which included incident acute coronary syndrome, heart failure, stroke, and CV death.ResultsDuring mean 2.3-year follow-up, 71 patients experienced MACE. Cer(d18:1/16:0), Cer(d18:1/22:0), and Cer(d18:1/24:0) were highly significant in predicting MACE [multiadjusted hazard ratios (95% confidence interval, CI) per SD were 1.76 (1.34–2.30), 0.55 (0.41–0.73), and 0.66 (0.47–0.92), respectively]. Compared with traditional variables (comprising presence of CV risk factors, hypertension-mediated organ damage, and comorbidities), a novel CERT for hypertensive patients (CERT-HBP), composed of Cer(d18:1/16:0), Cer(d18:1/24:1), and their ratios to Cer(d18:1/24:0) and Cer(d18:1/22:0), respectively, increased the C-statistic from 0.751 (95% CI, 0.697–0.806) to 0.791 (95% CI, 0.737–0.845), P = 0.010. Net reclassification improvement and integrated discrimination improvement were 0.648 (95% CI, 0.421–0.885, P < 0.001) and 0.046 (95% CI, 0.025–0.068, P < 0.001), respectively.ConclusionsA ceramide-based CERT-HBP was established to evaluate risk of MACE in hypertensive patients at high CV risk. This may improve identification of high-risk patients requiring increased attention and aggressive therapy.Clinical trials registrationTrial Number NCT03708601.