Obesity does not alter vascular function and handgrip exercise hemodynamics in middle-aged patients with hypertension.

Lifestyle modification including exercise training is often the first line of defense in the treatment of obesity and hypertension (HTN), however, little is known regarding how these potentially compounding disease states impact vasodilatory and hemodynamic responses at baseline and exercise. Therefore, this study sought to compare the impact of obesity on vascular function and hemodynamics at baseline and during handgrip (HG) exercise among individuals with HTN. Non-obese (13M/7F, 56 ± 16 yr, 25 ± 4 kg/m2) and obese (17M/4F, 50 ± 7 yr, 35 ± 4 kg/m2) middle-aged individuals with HTN forwent antihypertensive medication use for ≥2 wk before assessment of vascular function by brachial artery flow-mediated dilation (FMD) and exercise hemodynamics during progressive HG exercise at 15-30-45% maximal voluntary contraction (MVC). FMD was not different between Non-Obese (4.1 ± 1.7%) and Obese (5.2 ± 1.9%, P = 0.11). Systolic blood pressure (SBP) was elevated by ∼15% during the supine baseline and during HG exercise in the obese group. The blood flow response to HG exercise at 30% and 45% MVC was ∼20% greater (P < 0.05) in the obese group but not different after normalizing for the higher, albeit, nonsignificant differences in workloads (MVC: obese: 24 ± 5 kg, non-obese: 21 ± 5 kg, P = 0.11). Vascular conductance and the brachial artery shear-induced vasodilatory response during HG were not different between groups (P > 0.05). Taken together, despite elevated SBP during HG exercise, obesity does not lead to additional impairments in vascular function and peripheral exercising hemodynamics in patients with HTN. Obesity may not be a contraindication when prescribing exercise for the treatment of HTN among middle-aged adults, however, the elevated SBP should be appropriately monitored.NEW & NOTEWORTHY This study examined vascular function and handgrip exercise hemodynamics in obese and nonobese individuals with hypertension. Obesity, when combined with hypertension, was neither associated with additional vascular function impairments at baseline nor peripheral hemodynamics and vasodilation during exercise compared with nonobese hypertension. Interestingly, systolic blood pressure and pulse pressure were greater in the obese group during supine baseline and exercise. These findings should not be ignored and may be particularly important for rehabilitation strategies.

Association of APP gene polymorphisms and promoter methylation with essential hypertension in Guizhou: a case-control study.

BACKGROUND: Single-nucleotide polymorphisms (SNPs) and DNA methylation are crucial regulators of essential hypertension (EH). Amyloid precursor protein (APP) mutations are implicated in hypertension development. Nonetheless, studies on the association of APP gene polymorphism and promoter methylation with hypertension are limited. Therefore, this case-control aims to evaluate the genetic association of APP gene polymorphism and promoter methylation with EH in Guizhou populations. OBJECTIVE AND METHODS: We conducted a case-control study on 343 EH patients and 335 healthy controls (including Miao, Buyi, and Han populations) in the Guizhou province of China to analyze 11 single-nucleotide polymorphisms (rs2040273, rs63750921, rs2211772, rs2830077, rs467021, rs368196, rs466433, rs364048, rs364051, rs438031, rs463946) in the APP gene via MassARRAY SNP. The MassARRAY EpiTYPER was employed to detect the methylation levels of the promoters. RESULTS: In the Han population, the rs2211772 genotype distribution was significantly different between disease and control groups (χ2 = 6.343, P = 0.039). The CC genotype reduced the risk of hypertension compared to the TT or TC genotype (OR 0.105, 95%CI 0.012-0.914, P = 0.041). For rs2040273 in the Miao population, AG or GG genotype reduced the hypertension risk compared with the AA genotype (OR 0.533, 95%CI 0.294-0.965, P = 0.038). Haplotype TCC (rs364051-rs438031-rs463946) increased the risk of EH in Guizhou (OR 1.427, 95%CI 1.020-1.996, P = 0.037). Each 1% increase in CpG_19 (- 613 bp) methylation level was associated with a 4.1% increase in hypertension risk (OR 1.041, 95%CI 1.002-1.081, P = 0.039). Each 1% increase in CpG_1 (- 296 bp) methylation level was associated with an 8% decrease in hypertension risk in women (OR 0.920, 95%CI 0.860-0.984, P = 0.015). CpG_19 significantly correlated with systolic blood pressure (r = 0.2, P = 0.03). The methylation levels of CpG_19 in hypertensive patients with rs466433, rs364048, and rs364051 minor alleles were lower than that with wild-type alleles (P < 0.05). Moreover, rs467021 and rs364051 showed strong synergistic interaction with EH (χ2 = 7.633, P = 0.006). CpG_11, CpG_19, and rs364051 showed weak synergistic interaction with EH (χ2 = 19.874, P < 0.001). CONCLUSION: In summary, rs2211772 polymorphism and promoter methylation level of APP gene may be linked to EH in Guizhou populations. Our findings will provide novel insights for genetic research of hypertension and Alzheimer's disease.

Heart rate deceleration and acceleration capacities associated with circadian rhythm of blood pressure in essential hypertension.

BACKGROUND: This study aimed to investigate the potential association between the circadian rhythm of blood pressure and deceleration capacity (DC)/acceleration capacity (AC) in patients with essential hypertension. METHODS: This study included 318 patients with essential hypertension, whether or not they were being treated with anti-hypertensive drugs, who underwent 24-hour ambulatory blood pressure monitoring (ABPM). Patients were categorized into three groups based on the percentage of nocturnal systolic blood pressure (SBP) dipping: the dipper, non-dipper and reverse dipper groups. Baseline demographic characteristics, ambulatory blood pressure monitoring parameters, Holter recordings (including DC and AC), and echocardiographic parameters were collected. RESULTS: In this study, the lowest DC values were observed in the reverse dipper group, followed by the non-dipper and dipper groups (6.46 ± 2.06 vs. 6.65 ± 1.95 vs. 8.07 ± 1.79 ms, P < .001). Additionally, the AC gradually decreased (-6.32 ± 2.02 vs. -6.55 ± 1.95 vs. -7.80 ± 1.73 ms, P < .001). There was a significant association between DC (r = .307, P < .001), AC (r=-.303, P < .001) and nocturnal SBP decline. Furthermore, DC (ß = 0.785, P = .001) was positively associated with nocturnal SBP decline, whereas AC was negatively associated with nocturnal SBP (ß = -0.753, P = .002). By multivariate logistic regression analysis, deceleration capacity [OR (95% CI): 0.705 (0.594-0.836), p < .001], and acceleration capacity [OR (95% CI): 1.357 (1.141-1.614), p = .001] were identified as independent risk factors for blood pressure nondipper status. The analysis of ROC curves revealed that the area under the curve for DC/AC in predicting the circadian rhythm of blood pressure was 0.711/0.697, with a sensitivity of 73.4%/65.1% and specificity of 66.7%/71.2%. CONCLUSIONS: Abnormal DC and AC density were correlated with a blunted decline in nighttime SBP, suggesting a potential association between the circadian rhythm of blood pressure in essential hypertension patients and autonomic nervous dysfunction.

Yield of diagnostic testing in evaluating etiology and end organ effects of pediatric hypertension.

BACKGROUND: Current recommendations regarding the utility of diagnostic investigations for pediatric hypertension are based on limited evidence, leading to wide practice variation. The objective of this study was to characterize the cohort of children that may benefit from secondary hypertension workup, and determine the diagnostic yield of investigations. METHODS: This was a single-center, retrospective cohort study of 169 children aged 1-18 years referred between 2000 and 2015, to a tertiary pediatric nephrology center in Canada, for evaluation of hypertension. The number of investigations completed, abnormal findings, and diagnostic findings that helped establish hypertension etiology was determined. RESULTS: 56 children were diagnosed with primary and 72 children with secondary hypertension in the outpatient setting. Secondary hypertension was predominant at all ages except for obese adolescents ≥ 12 years. Half of children with traditional risk factors for primary hypertension, including obesity, were diagnosed with secondary hypertension. Kidney ultrasound had the highest yield of diagnostic results (19.8%), with no difference in yield between age groups (P = 0.19). Lipid profile had a high yield of abnormal results (25.4%) as part of cardiovascular risk assessment but was only abnormal in overweight/obese children. Echocardiogram had a high yield for identification of target-organ effects in hypertensive children (33.3%). CONCLUSION: A simplified secondary hypertension workup should be considered for all hypertensive children and adolescents. High yield investigations include a kidney ultrasound, lipid profile for overweight/obese children, and echocardiograms for assessment of target-organ damage. Further testing could be considered based on results of initial investigations for the most cost-effective management. A higher resolution version of the Graphical abstract is available as Supplementary information.

Adrenoceptors and Hypertension.

Hypertension is a very prevalent condition associated with high mortality and morbidity, secondary to changes resulting in blood vessels and resultant end-organ damage. Haemodynamic changes, including an initial rise in cardiac output followed by an increase in total peripheral resistance, denote the early changes associated with borderline or stage 1 hypertension, especially in young men. Increased sodium reabsorption leading to kidney damage is another mechanism proposed as one of the initial triggers for essential hypertension. The underlying pathophysiological mechanisms include catecholamine-induced α1- and ß1-adrenoceptor stimulation, and renin-angiotensin-aldosterone system activation leading to endothelial dysfunction which is believed to lead to persistent blood pressure elevation.α1 blockers, α2 agonists, and ß blockers were among the first oral anti-hypertensives. They are no longer first-line therapy after outcome trials did not demonstrate any benefits over and above other agents, despite similar blood pressure reductions. Angiotensin-converting enzyme inhibitors (or angiotensin receptor blockers), calcium channel blockers, and thiazide-like diuretics are now considered the first line of therapy, although adrenoceptor agents still have a role as second- or third-line therapy. The chapter also highlights hypertension in specific medical conditions such as pregnancy, phaeochromocytoma, hyperthyroidism, portal hypertension, pulmonary arterial hypertension, and ocular hypertension, to provide an overview for clinicians and researchers interested in the role of adrenoceptors in the pathophysiology and management of hypertension.

Gastroesophageal reflux disease increases the risk of essential hypertension: results from the Nationwide Readmission Database and Mendelian randomization analysis.

BACKGROUND: The link between gastroesophageal reflux disease (GERD) and essential hypertension (EH) and its causal nature remains controversial. Our study examined the connection between GERD and the risk of hypertension and assessed further whether this correlation has a causal relationship. METHODS: First, we utilized the National Readmission Database including 14 422 183 participants to conduct an observational study. Dividing the population into GERD and non-GERD groups, we investigated the correlation between GERD and EH using multivariate logistic regression. Next, bidirectional two-sample Mendelian randomization was adopted. The summary statistics for GERD were obtained from a published genome-wide association study including 78 707 cases and 288 734 controls. We collected summary statistics for hypertension containing 70 651 cases and 223 663 controls from the FinnGen consortium. We assessed causality primarily by the inverse-variance weighted method with validation by four other Mendelian randomization approaches as well as an array of sensitivity analyses. RESULTS: In the unadjusted model, GERD patients had a higher risk of EH than the non-GERD group, regardless of gender (odds ratio, 1.43; 95% confidence interval: 1.42-1.43; P < .001). Further adjusting for critical confounders did not change this association. For Mendelian randomization, we found that genetically predicted GERD was causally linked to an enhanced risk of EH in inverse-variance weighted technique (odds ratio, 1.52; 95% confidence interval: 1.39-1.67; P = 3.51 × 10-18); conversely, EH did not raise the risk of GERD causally. CONCLUSIONS: GERD is a causal risk factor for EH. Further research is required to probe the mechanism underlying this causal connection.

Peripheral Blood miRNA Expression in Patients with Essential Hypertension in the Han Chinese Population in Hefei, China.

Primary hypertension is a significant risk factor for cardiovascular diseases. However, the pathogenesis of primary hypertension involves multiple biological processes, including the nervous system, circulatory system, endocrine system, and more. Despite extensive research, there is no clear understanding of the regulatory mechanism underlying its pathogenesis. In recent years, miRNAs have gained attention as a regulatory factor capable of modulating the expression of related molecules through gene silencing. Therefore, exploring differentially expressed miRNAs in patients with essential hypertension (EH) may offer a novel approach for future diagnosis and treatment of EH. This study included a total of twenty Han Chinese population samples from Hefei, China. The samples consisted of 10 healthy individuals and 10 patients with EH. Statistical analysis was conducted to analyze the general information of the two-sample groups. High-throughput sequencing and base identification were performed to obtain the original sequencing sequences. These sequences were then annotated using various databases including Rfam, cDNA sequences, species repetitive sequences library, and miRBase database. The number of miRNA species contained in the samples was measured. Next, TPM values were calculated to determine the expression level of each miRNA. The bioinformatics of the differentiated miRNAs were analyzed using the OECloud tool, and RPM values were calculated. Furthermore, the reliability of the expression was analyzed by calculating the area under the Roc curve using the OECloud tools. Statistical analysis revealed no significant differences between the two samples in terms of age distribution, gender composition, smoking history, and alcohol consumption history (P > 0.05). However, there was a notable presence of family genetic history and high BMI in the EH population (P < 0.05). The sequencing results identified a total of 245 miRNAs, out of which 16 miRNAs exhibited differential expression. Among the highly expressed miRNAs were let-7d-5p, miR-101-3p, miR-122-5p, miR-122b-3p, miR-192-5p, and miR-6722-3p. On the other hand, the lowly expressed miRNAs included miR-103a-3p, miR-16-5p, miR-181a-2-3p, miR-200a-3p, miR-200b-3p, miR-200c-3p, miR-221-3p, miR-30d-5p, miR-342-5p, and miR-543. This study initially identified 16 miRNAs that are aberrantly expressed and function in various processes associated with the onset and progression of essential hypertension. These miRNAs have the potential to be targeted for future diagnosis and treatment of EH. However, further samples are required to provide additional support for this study.

Left ventricle hypertrophy and re-modeling in children with essential hypertension: does the race matter?

BACKGROUND: This is the first study to report on the impact of race on differences in the prevalence of echocardiographic left ventricular hypertrophy and left ventricular adaptation at the time of diagnosis of essential hypertension in children. METHODS: This cross-sectional, single-centre study included patients aged 3-18 years who had newly diagnosed essential hypertension. Echocardiography was used to assess left ventricular mass index and left ventricular relative wall thickness. An left ventricular mass index > the 95th percentile for age and gender, and an left ventricular relative wall thickness > 0.42, were used to diagnose left ventricular hypertrophy and concentric adaptation. Various echocardiographic parameters were compared between African Americans and Caucasians. RESULTS: The study included 422 patients (289 African Americans and 133 Caucasians) diagnosed with essential hypertension at a median age of 14.6 (interquartile range; 12.1-16.3) years. Eighty-eight patients (20.9%) had left ventricular hypertrophy. There was no statistically significant difference in the prevalence of left ventricular hypertrophy between African Americans and Caucasians (22.5% versus 17.3%, p=0.22). The median left ventricular relative wall thickness was 0.35 (0.29-0.43), and 114 patients (27.0%) had an left ventricular relative wall thickness > 0.42. The presence of an left ventricular relative wall thickness > 0.42 was significantly higher among African Americans compared to Caucasians (30.1% versus 20.3%, p = 0.04). The African American race was a strong predictor for an left ventricular relative wall thickness > 0.42 (odds ratio 1.7, p = 0.04), but not for left ventricular mass index > the 95th percentile (p = 0.22). Overweight/obesity was a strong predictor for an left ventricular mass index > the 95th percentile. CONCLUSIONS: There was no difference in the prevalence of left ventricular hypertrophy in children with essential hypertension of different races. Obesity, rather than being African American, is associated with left ventricular hypertrophy.

Evaluation of the Canonical Wnt Signaling Pathway in the Hearts of Hypertensive Rats of Various Etiologies.

Wnt/ß-catenin signaling dysregulation is associated with the pathogenesis of many human diseases, including hypertension and heart disease. The aim of this study was to immunohistochemically evaluate and compare the expression of the Fzd8, WNT1, GSK-3ß, and ß-catenin genes in the hearts of rats with spontaneous hypertension (SHRs) and deoxycorticosterone acetate (DOCA)-salt-induced hypertension. The myocardial expression of Fzd8, WNT1, GSK-3ß, and ß-catenin was detected by immunohistochemistry, and the gene expression was assessed with a real-time PCR method. In SHRs, the immunoreactivity of Fzd8, WNT1, GSK-3ß, and ß-catenin was attenuated in comparison to that in normotensive animals. In DOCA-salt-induced hypertension, the immunoreactivity of Fzd8, WNT1, GSK-3ß, and ß-catenin was enhanced. In SHRs, decreases in the expression of the genes encoding Fzd8, WNT1, GSK-3ß, and ß-catenin were observed compared to the control group. Increased expression of the genes encoding Fzd8, WNT1, GSK-3ß, and ß-catenin was demonstrated in the hearts of rats with DOCA-salt-induced hypertension. Wnt signaling may play an essential role in the pathogenesis of arterial hypertension and the accompanying heart damage. The obtained results may constitute the basis for further research aimed at better understanding the role of the Wnt/ß-catenin pathway in the functioning of the heart.

The efficacy of Tai Chi for essential hypertension: A systematic review and meta-analysis.

AIM: We aimed to assess the impact of Tai Chi interventions on individuals with essential hypertension and to compare the effects of Tai Chi versus control in this population. BACKGROUND: Tai Chi has been extensively utilized in the prevention of essential hypertension. Nevertheless, there is a lack of consensus regarding its benefits for treating essential hypertension. DESIGN: A systematic review and meta-analysis was conducted. DATA SOURCES: We conducted a systematic literature search of the Medline, Scholar, Elsevier, Wiley Online Library, Chinese Academic Journal (CNKI) and Wanfang databases from January 2003 to August 2023. REVIEW METHODS: Using the methods of the Cochrane Collaboration Handbook, a meta-analysis was conducted to assess the collective impact of Tai Chi exercise in controlling hypertension. The primary outcomes measured included blood pressure and nitric oxide levels. RESULTS: The participants consisted of adults with an average age of 57.1 years who had hypertension (mean ± standard deviation systolic blood pressure at 148.2 ± 12.1 mmHg and diastolic blood pressure at 89.2 ± 8.3 mmHg). Individuals who practiced Tai Chi experienced reductions in systolic blood pressure of 10.6 mmHg, diastolic blood pressure of 4.7 mmHg and an increase in nitric oxide levels. CONCLUSIONS: Tai Chi can be a viable lifestyle intervention for managing hypertension. Greater promotion of Tai Chi by medical professionals could extend these benefits to a larger patient population.

Clinical and genetic analysis of essential hypertension with mitochondrial tRNAMet 4435A>G and YARS2 mutation. / 携带线粒体tRNAMet 4435A>Gå’Œæ ¸åŸºå› YARS2çªå˜çš„åŽŸå‘æ€§é«˜è¡€åŽ‹å®¶ç³»é—ä¼ å­¦åˆ†æž.

OBJECTIVES: To investigate the role of m.4435A>G and YARS2 c.572G>T (p.G191V) mutations in the development of essential hypertension. METHODS: A hypertensive patient with m.4435A>G and YARS2 p.G191V mutations was identified from previously collected mitochondrial genome and exon sequencing data. Clinical data were collected, and a molecular genetic study was conducted in the proband and his family members. Peripheral venous blood was collected, and immortalized lymphocyte lines constructed. The mitochondrial transfer RNA (tRNA), mitochondrial protein, adenosine triphosphate (ATP), mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) in the constructed lymphocyte cell lines were measured. RESULTS: Mitochondrial genome sequencing showed that all maternal members carried a highly conserved m.4435A>G mutation. The m.4435A>G mutation might affect the secondary structure and folding free energy of mitochondrial tRNA and change its stability, which may influence the anticodon ring structure. Compared with the control group, the cell lines carrying m.4435A>G and YARS2 p.G191V mutations had decreased mitochondrial tRNA homeostasis, mitochondrial protein expression, ATP production and MMP levels, as well as increased ROS levels (all P<0.05). CONCLUSIONS: The YARS2 p.G191V mutation aggravates the changes in mitochondrial translation and mitochondrial function caused by m.4435A>G through affecting the steady-state level of mitochondrial tRNA and further leads to cell dysfunction, indicating that YARS2 p.G191V and m.4435A>G mutations have a synergistic effect in this family and jointly participate in the occurrence and development of essential hypertension.

Changes in the indicators of stiffness and remodeling of magistral arteries in young patients at the early stage of essential hypertension under conditions of syntropy with obesity.

OBJECTIVE: Aim: The study and analysis of indicators of remodeling and rigidity of magistral vessels in young essential hypertension patients with abdominal obesity and determination of the detected changes as a possible criterion for their remodeling.. PATIENTS AND METHODS: Materials and Methods: 98 young people with essential hypertension and obesity were included in the study. The structure of the carotid artery and its stiffness were assessed using the ultrasound method, and the level of abdominal fat was determined using dual-energy X-ray absorptiometry. RESULTS: Results: Carotid Intima-Media Thickness in patients with essential hypertension reliably exceeded the corresponding indicator of the control group. We observed a significant increase in arterial stiffness indicators, which is explained by the increased stiffness of blood vessels in patients with obesity. During the correlation analysis, it was established that the relationship between the level of abdominal fat and the elasticity of the vascular wall was positive and strong, which indicated the dominant role of the abdominal type of obesity in the remodeling of the vascular wall in young patients with essential hypertension in combination with obesity. CONCLUSION: Conclusions: In young patients at the early stage of the formation of essential hypertension, there are signs of a decrease in resilient-elastic properties and remodeling of magistral vessels, whose severity is significantly stronger in combination with abdominal obesity.

Sex-related differences for uric acid in the prediction of cardiovascular events in essential hypertension. A population prospective study.

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.

The impact of different diuretics on regression of myocardial reperfusion injury in spontaneously hypertensive rats.

The study's objective was to ascertain the results of sub-chronic therapy of various diuretics on the ischemia/reperfusion dysfunction of the heart in hypertensive rats by a global ischemia in an isolated rat heart model. The research included 40 spontaneously hypertensive male rats (Wistar Kyoto strain, body mass 250 ± 30 g, 8 weeks old) grouped into four groups. The animals were treated for 4 weeks with 10 mg/kg of hydrochlorothiazide, indapamide, or spironolactone per os. After a period of sub-chronic treatment, we analyzed hemodynamic measurements, echocardiography, and myocardial function according to the Langendorff retrograde perfusion method. The hearts were subjected to 20 min of global ischemia and then reperfused for 30 min (I20:R30). Cardiovascular parameters that depict the left ventricle functions were continuously monitored, while flowmetry was used to determine coronary flow values. Markers of oxidative stress were estimated from coronary venous effluent using spectrophotometry. All three examined diuretics (hydrochlorothiazide, spironolactone, indapamide) lowered the production of the majority of the detected prooxidants, reducing myocardial oxidative damage. The cardiological examination of heart function in vivo demonstrated that treatment with indapamide and spironolactone mitigates left ventricular hypertrophy but without significant lowering of blood pressure or increment in ejection fraction. Additionally, monitoring of cardiac function ex vivo indicated the cardiodepressant effect of spironolactone in spontaneously hypertensive rats.

Low-dose aspirin for the prevention of superimposed preeclampsia in women with chronic hypertension: a systematic review and meta-analysis.

OBJECTIVE: This systematic review and meta-analysis investigated whether the use of low-dose aspirin during pregnancy by women with chronic hypertension reduces the odds of superimposed preeclampsia and poor perinatal outcomes. DATA SOURCES: In September 2021, the following sources were searched: Embase, MEDLINE, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, and EU Clinical Trials Register. Only human studies were included, with no time or language restrictions. STUDY ELIGIBILITY CRITERIA: Cohort, case-control, and randomized controlled studies reporting women with chronic hypertension pregnant with a singleton were included. Eligible studies compared low-dose aspirin use during pregnancy with a control arm. METHODS: Risk of bias was assessed using the RoB 2 and ROBINS-I tools. A meta-analysis was performed using a random-effects model, estimating odds ratios and 95% confidence and prediction intervals, and the quality of data was assessed with the GRADE approach. Heterogeneity was investigated in regard to study methodology, timing of commencement of aspirin, and the outcome of preterm preeclampsia. RESULTS: Nine studies (3 retrospective cohort studies and 6 randomized trials) including 2150 women with chronic hypertension were included. Low-dose aspirin prophylaxis did not significantly reduce the odds of superimposed preeclampsia in the randomized controlled trials (odds ratio, 0.83; 95% confidence interval, 0.55-1.25; prediction interval, 0.27-2.56; low-quality evidence) or observational studies (odds ratio, 1.21; 95% confidence interval, 0.78-1.87; prediction interval, 0.07-20.80; very low-quality evidence). Low-dose aspirin also did not reduce the odds of preterm preeclampsia (odds ratio, 1.17; 95% confidence interval, 0.74-1.86), and early aspirin initiation had no significant impact. There was no significant effect on small-for-gestational-age neonates or perinatal mortality; however, there was a significant reduction in preterm birth (odds ratio, 0.63; 95% confidence interval, 0.45-0.89; moderate-quality evidence). The quality of the evidence is limited by heterogeneity and risk of bias. CONCLUSION: This meta-analysis was unable to demonstrate a significant change in the odds of superimposed preeclampsia, small-for-gestational-age infants, or perinatal mortality with the use of low-dose aspirin in women with chronic hypertension. However, significant reduction in preterm birth justifies the continued use of aspirin prophylaxis. This work was prospectively registered on the International Prospective Register of Systematic Reviews (registration number CRD42021285921).

ANKRD36 Is Involved in Hypertension by Altering Expression of ENaC Genes.

[Figure: see text].

Colchicine enhances ß adrenoceptor-mediated vasodilation in men with essential hypertension.

AIMS: The aim of this study is to examine whether colchicine improves ß adrenoceptor-mediated vasodilation in humans by conducting a double-blinded, placebo-controlled intervention study. Colchicine treatment has known beneficial effects on cardiovascular health and reduces the incidence of cardiovascular disease. Studies in isolated rodent arteries have shown that colchicine can enhance ß adrenoceptor-mediated vasodilation, but this has not been determined in humans. METHODS: Middle-aged men with essential hypertension were randomly assigned firstly to acute treatment with either 0.5 mg colchicine (n = 19) or placebo (n = 12). They were subsequently re-randomized for 3 weeks of treatment with either colchicine 0.5 mg twice daily (n = 16) or placebo (n = 15) followed by a washout period of 48-72 h. The vasodilator responses to isoprenaline, acetylcholine and sodium nitroprusside were determined as well as arterial pressure, arterial compliance and plasma inflammatory markers. RESULTS: Acute colchicine treatment increased isoprenaline (by 38% for the highest dose) as well as sodium nitroprusside (by 29% main effect) -induced vasodilation but had no effect on the response to acetylcholine. The 3-week colchicine treatment followed by a washout period did not induce an accumulated or sustained effect on the ß adrenoceptor response, and there was no effect on arterial pressure, arterial compliance or the level of measured inflammatory markers. CONCLUSION: Colchicine acutely enhances ß adrenoceptor- and nitric oxide-mediated changes in vascular conductance in humans, supporting that the mechanism previously demonstrated in rodents, translates to humans. The results provide novel translational evidence for a transient enhancing effect of colchicine on ß adrenoceptor-mediated vasodilation in humans with essential hypertension. CONDENSED ABSTRACT: Preclinical studies in isolated rodent arteries have shown that colchicine can enhance ß adrenoceptor-mediated vasodilation. Here we show that this effect of colchicine can be translated to humans. Acute colchicine treatment was found to increase both isoprenaline- and sodium nitroprusside-induced vasodilation. The study provides the first translational evidence for a transient ß adrenoceptor-mediated vasodilatory effect of colchicine in humans. The finding of an acute effect suggests that it may be clinically important to maintain an adequate bioavailability of colchicine.

Genetic polymorphisms of purinergic P2Y2 receptor were associated with the susceptibility to essential hypertension in Chinese postmenopausal women.

Hypertension has become a prominent public health concern. Essential hypertension (EH) is a polygenic disorder caused by multiple susceptibility genes. It has been previously shown that the purinergic P2Y2 receptor (P2Y2R) regulates blood pressure; however, whether P2Y2R genetic polymorphisms correlate with EH has not been investigated in Chinese. Our study included 500 EH cases and 504 controls who are Chinese postmenopausal women. We used allele-specific polymerase chain reaction (ASPCR) to genotype five single-nucleotide polymorphism (SNPs) in the P2Y2R gene, i.e., rs4944831, rs12366239, rs1783596, rs4382936, and rs10898909. We assessed the association of P2Y2R genetic polymorphisms with EH susceptibility. The results demonstrated that P2Y2R rs4382936A was correlated with a high risk of EH; particularly, the participants with the rs4382936A allele and CA/AA/(CA+AA) genotypes were at higher risks to EH compared to the subjects with the rs4382936C allele and CC genotype. Moreover, haplotype CAG combined by rs1783596-rs4382936-rs10898909 was a susceptible haplotype for EH, whereas haplotype CCG was a protective haplotype for EH. These results may provide new evidence for applying P2Y2R genetic polymorphisms as useful markers in clinic screening or monitoring potential EH cases in a population of Chinese postmenopausal women.

A nomogram based on endothelial function and conventional risk factors predicts coronary artery disease in hypertensives.

BACKGROUND: There is currently a lack of a precise, concise, and practical clinical prediction model for predicting coronary artery disease (CAD) in patients with essential hypertension (EH). This study aimed to construct a nomogram to predict CAD in patients with EH based on flow-mediated dilation (FMD) of brachial artery and traditional risk factors. METHODS: Clinical data of 1752 patients with EH were retrospectively collected. High-resolution vascular ultrasound was used to detect FMD in all patients at the Fujian Hypertension Research Institute, China. Patients were divided into two groups, i.e. training group (n = 1204, from August 2000 to December 2013) and validation group (n = 548, from January 2014 to May 2016) according to the time of enrollment. Independent predictors of CAD were analyzed by multivariable logistic regression in the training group, and a nomogram was constructed accordingly. Finally, we evaluated the discrimination, calibration, and clinical applicability of the model using the area under curve (AUC) of receiver operating characteristic analysis, calibration curve combined with Hosmer-Lemeshow test, and decision curve, respectively. RESULTS: There were 263 (21.8%) cases of EH combined with CAD in the training group. Multivariate logistic regression showed that FMD, age, duration of EH, waist circumference, and diabetes mellitus were independent influencing factors for CAD in EH patients. Smoking which was close to statistical significance (P = 0.062) was also included in the regression model to increase the accuracy. Ultimately, the nomogram for predicting CAD in EH patients was constructed according to above predictors after proper transformation. The AUC values of the training group and the validation group were 0.799 (95%CI 0.770-0.829) and 0.836 (95%CI 0.787-0.886), respectively. Calibration curve and Hosmer-Lemeshow test showed that the model had good calibration (training group: χ2 = 0.55, P = 0.759; validation group: χ2 = 1.62, P = 0.446). The decision curve also verified the clinical applicability of the nomogram. CONCLUSION: The nomogram based on FMD and traditional risk factors (age, duration of EH disease, smoking, waist circumference and diabetes mellitus) can predict CAD high-risk group among patients with EH.

Central diastolic blood pressure, plasma aldosterone and uric acid are associated with microalbuminuria in essential hypertension: a case-control study.

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 < 0.001) in the MAU group compared to that in the control group. Several variables were associated with MAU, including central diastolic blood pressure (CDBP) (OR = 1.017, 95% CI: 1.002-1.032, P = 0.027), PA (OR = 1.043, 95% CI: 1.009-1.078, P = 0.012) and UA (OR = 1.005, 95% CI: 1.002-1.008, P < 0.001). For MAU prediction, the area under the curve (AUC) was 0.709 (95% CI: 0.662-0.753; P < 0.001) when CDBP, PA, and UA were used in combination, and the optimal probability of the cut-off value was 0.337. CONCLUSION: We found that CDBP, PA, and UA, used for MAU prediction, might be associated with its development during EHT.