Hypertensive Target Organ Damage Research Articles

Exaggerated blood pressure response to submaximal exercise must be considered relative to fitness: strong associations with hypertensive target organ damage

Abstract Exaggerated systolic blood pressure (SBP) during submaximal exercise is associated with increased cardiovascular (CV) risk. However, findings are mixed and new evidence indicates that cardiorespiratory fitness should be considered for proper clinical interpretation of exercise SBP responses. This study aimed to determine the relationship between SBP response to submaximal effort corrected for fitness and abnormalities of cardiac structure and function. Methods Each of 231 participants (age 54±12 years; 53% females) with controlled clinic BP, no evidence for ischemic heart disease, valvular heart disease or heart failure underwent cardiopulmonary exercise testing (Bruce protocol), resting and exercise echocardiography and 24h ABPM. Submaximal exercise SBP (measured at the 2nd stage of Bruce protocol) was corrected for two fitness variables: 1) peak VO2 and 2) maximal workload in METs (SBP/peakVO2 and SBP/METs). Results There were no, or weak, associations with exercise SBP and target organ damage. However, there was a progressive deterioration of cardiac function and structure parameters across the exercise SBP tertiles corrected for fitness (Table 1). Both SBP/peakVO2 and SBP/METs significantly correlated with left ventricular (LV) mass, LV diastolic and systolic, and left atrial parameters (Table 2). ROC analysis revealed good performance of corrected SBP response to submaximal exercise in detection of LV hypertrophy and diastolic dysfunction (AUC 0.792 and 0.808, and 0.771 and 0.802 for SBP/peakVO2 and SBP/METs, respectively; Figure). Conclusions Fitness-corrected SBP responses to submaximal exercise can identify more profound target organ damage with respect to cardiac function and structure even among patients with controlled clinic BP. Exaggerated BP response to exercise must be considered relative to fitness for proper clinical interpretation of BP responses to exercise testing.Figure

Role of aldosterone in various target organ damage in patients with hypertensive emergency: a cross-sectional study

BackgroundHypertensive emergency is a critical disease that causes multiple organ injuries. Although the renin-angiotensin-aldosterone system (RAS) is enormously activated in this disorder, whether the RAS contributes to the development of the organ damage has not been fully elucidated. This cross-sectional study was conducted to characterize the association between RAS and the organ damage in patients with hypertensive emergencies.MethodsWe enrolled 63 patients who visited our medical center with acute severe hypertension and multiple organ damage between 2012 and 2020. Hypertensive target organ damage was evaluated on admission, including severe kidney impairment (eGFR less than 30 mL/min/1.73 m2, SKI), severe retinopathy, concentric left ventricular hypertrophy (c-LVH), thrombotic microangiopathy (TMA), heart failure with reduced ejection fraction (HFrEF) and cerebrovascular disease. Then, whether each organ injury was associated with blood pressure or a plasma aldosterone concentration was analyzed.ResultsAmong 63 patients, 31, 37, 43 and 8 cases manifested SKI, severe retinopathy, c-LVH and ischemic stroke, respectively. All populations with the organ injuries except cerebral infarction had higher plasma aldosterone concentrations than the remaining subset but exhibited a variable difference in systolic or diastolic blood pressure. Twenty-two patients had a triad of SKI, severe retinopathy and c-LVH, among whom 5 patients manifested TMA. Furthermore, the number of the damaged organs was correlated with plasma aldosterone levels (Spearman’s coefficient = 0.50), with a strong association observed between plasma aldosterone (≥ 250 pg/mL) and 3 or more complications (odds ratio = 9.16 [95%CI: 2.76–30.35]).ConclusionIn patients with hypertensive emergencies, a higher aldosterone level not only contributed to the development of the organ damage but also was associated with the number of damaged organs in each patient.

Metformin modulates microbiota and improves blood pressure and cardiac remodeling in a rat model of hypertension.

Metformin has been attributed to cardiovascular protection even in the absence of diabetes. Recent observations suggest that metformin influences the gut microbiome. We aimed to investigate the influence of metformin on the gut microbiota and hypertensive target organ damage in hypertensive rats. Male double transgenic rats overexpressing the human renin and angiotensinogen genes (dTGR), a model of angiotensin II-dependent hypertension, were treated with metformin (300 mg/kg/day) or vehicle from 4 to 7 weeks of age. We assessed gut microbiome composition and function using shotgun metagenomic sequencing and measured blood pressure via radiotelemetry. Cardiac and renal organ damage and inflammation were evaluated by echocardiography, histology, and flow cytometry. Metformin treatment increased the production of short-chain fatty acids (SCFA) acetate and propionate in feces without altering microbial composition and diversity. It significantly reduced systolic and diastolic blood pressure and improved cardiac function, as measured by end-diastolic volume, E/A, and stroke volume despite increased cardiac hypertrophy. Metformin reduced cardiac inflammation by lowering macrophage infiltration and shifting macrophage subpopulations towards a less inflammatory phenotype. The observed improvements in blood pressure, cardiac function, and inflammation correlated with fecal SCFA levels in dTGR. Invitro, acetate and propionate altered M1-like gene expression in macrophages, reinforcing anti-inflammatory effects. Metformin did not affect hypertensive renal damage or microvascular structure. Metformin modulated the gut microbiome, increased SCFA production, and ameliorated blood pressure and cardiac remodeling in dTGR. Our findings confirm the protective effects of metformin in the absence of diabetes, highlighting SCFA as a potential mediators.

O100 IL15RA MEDIATES BLOOD PRESSURE ELEVATION, INFLAMMATION AND VASCULAR DAMAGE IN ANGIOTENSIN II-INDUCED HYPERTENSION

Cytokines are key mediators regulating blood pressure (BP) and target organ damage in hypertension. IL15 levels increase in cardiovascular diseases, but the role of IL15 and its receptor alpha (IL15R) in hypertension and hypertension-mediated inflammation and vascular damage is still unknown. Wild-type and IL15Rα-/-mice (n=5-9) were infused with vehicle or angiotensin II (AngII, 490ng/min/kg). Recombinant IL15 was administered to WT mice (1ug, daily, 14 days) during AngII infusion. Telemetry, wire myography, luminometry, PSR staining, qPCR, immunoblotting, flow cytometry, and primary cell lines were used. Hypertensive patients have increased levels of IL15Rα in arteries, which significantly correlated with systolic (r=0.33, p=0.002), diastolic (r=0.27, p=0.02) pressure and maximal constriction to phenylephrine ex vivo (r=0.27, p=0.03). Similarly, AngII infusion significantly increased serum IL15/IL15Rα (8.8±0.7pg/ml vs 12.1±0.7pg/ml, p<0.01), IL15Rα mRNA (1±0.1 vs 1.8±0.1, p<0.01) and protein (1±0.03 vs 1.8±0.28, p<0.01) levels in the aortas. BP lowering using hydralazine and hydrochlorothiazide treatment prevented these changes in vasculature. IL15Rα was induced by pathophysiological stretch (15%) or interferon-gamma in adventitial fibroblasts, vascular smooth muscles, and endothelial cells in vitro. In contrast, AngII, other inflammatory cytokines or oxidative stress mediators have no such direct effect. Il15Rα-/- blunted AngII-induced hypertension (199±5.6mmHg vs 148±7.3mmHg, p<0.001), protected against endothelial dysfunction (p<0.01) and aortic superoxide production (59.4±7.8 vs 36.4±7.6 RLU/sec/mg) compared to wild-type mice. This was accompanied by reduced perivascular inflammation, lack of immune cell recruitment and effector and memory T cell formation. Similarly, T cell interferon-gamma and interleukin-17 production was attenuated in Il15Rα-/- hypertensive mice. In contrast, simultaneous administration of AngII and rIL15 into WT mice enhanced these outcomes. Perivascular fibrosis was observed in WT, but not Il15Rα-/- hypertensive animals (111036±19117 μm2 vs 48689±5515 μm2, p<0.01) and was in line with significantly lower mRNA of collagen and fibronectin protein levels in Il15Rα-/- aortas. IL15Rα plays a crucial role in immune activation, vascular damage, and AngII-induced hypertension. Targeting this pathway may offer potential therapeutic benefits for controlling hypertension and preventing associated vascular complications.

Abstract P347: Association between Blood Pressure, Left Ventricular Structure and Cognitive Function: Evidence from a Cohort Study in Preschool-aged Children

Objective: Serving as a common hypertensive target organ damage, left ventricular (LV) structure alteration has been found to be associated with cognition decline in the elderly. However, its mediating role in the association between decreased cognitive function and elevated blood pressure (BP) remains controversial, owing to several inherent confounder in adults that could distort observed associations. The study was first known conducted to examine the association between LV structure, BP and cognitive function in preschool-aged children, a population without disturbance of various cardiovascular risk factors. Methods: This study included 1279 children from Shanghai Birth Cohort (SBC) during 2018 to 2021. Using the Wechsler Preschool and Primary Scales of Intelligence-Fourth Edition (WPPSI-IV), children’s intelligence quotient (IQ) was evaluated at 4-year-old. Detailed anthropometrics and BP measurements and echocardiography were conducted during follow-up. Multivariable linear regression models and restricted cubic spline were applied to estimate the association between individual BP, LV structure parameters and IQ scores. Results: There was no significant association found between cognitive function and LV structure in preschool-aged children, while higher BP levels was found to be correlated with lower scores in cognitive function. Children in the elevated BP and non-LVH group tended to have lower full-scale IQ (FSIQ). In detail, children with elevated BP tended to have lower scores in FSIQ (β: -2.95, 95%CI: -4.65, -1.25), processing speed index (β: -1.77, 95%CI: -3.41, -0.14), working memory index (β: -2.79, 95%CI: -4.70, -0.88) and visual spatial index (β: -2.64, 95%CI: -4.74, -0.55), and these associations were independent of LV structure. Conclusion: Higher BP levels was related to poor cognitive development during childhood as early as four, while LV structure alteration was not. The associations between BP and children’s decreased cognitive function was independent of LV structure.

Effect of early endothelial function improvement on subclinical target organ damage in hypertensives

Endothelial dysfunction is acknowledged as a marker for subclinical target organ damage (STOD) in hypertension, though its therapeutic potential has not yet been clarified. This study assessed whether early endothelial function improvement (EEFI) reduced STOD in patients with essential hypertension (EH). We conducted a retrospective cohort analysis of 456 EH patients initially free from STOD. Endothelial function was assessed using brachial artery flow-mediated dilation (FMD), with values ≤ 7.1% indicating dysfunction. Patients were initially categorized by endothelial status (dysfunction: n = 180, normal: n = 276), and further divided into improved or unimproved groups based on changes within three months post-enrollment. During a median follow-up of 25 months, 177 patients developed STOD. The incidence of STOD was significantly higher in patients with initial dysfunction compared to those with normal function. Kaplan–Meier analysis indicated that the improved group had a lower cumulative incidence of STOD compared to the unimproved group (p < 0.05). Multivariable Cox regression confirmed EEFI as an independent protective factor against STOD in EH patients (p < 0.05), regardless of their baseline endothelial status, especially in those under 65 years old, non-smokers, and with low-density lipoprotein cholesterol levels ≤ 3.4 mmol/L. In conclusion, EEFI significantly reduces STOD incidence in EH patients, particularly in specific subgroups, emphasizing the need for early intervention in endothelial function to prevent STOD.

Risk prediction of pulse wave for hypertensive target organ damage based on frequency-domain feature map

The application of deep learning to the classification of pulse waves in Traditional Chinese Medicine (TCM) related to hypertensive target organ damage (TOD) is hindered by challenges such as low classification accuracy and inadequate generalization performance. To address these challenges, we introduce a lightweight transfer learning model named MobileNetV2SCP. This model transforms time-domain pulse waves into 36-dimensional frequency-domain waveform feature maps and establishes a dedicated pre-training network based on these maps to enhance the learning capability for small samples. To improve global feature correlation, we incorporate a novel fusion attention mechanism (SAS) into the inverted residual structure, along with the utilization of 3 × 3 convolutional layers and BatchNorm layers to mitigate model overfitting. The proposed model is evaluated using cross-validation results from 805 cases of pulse waves associated with hypertensive TOD. The assessment metrics, including Accuracy (92.74 %), F1-score (91.47 %), and Area Under Curve (AUC) (97.12 %), demonstrate superior classification accuracy and generalization performance compared to various state-of-the-art models. Furthermore, this study investigates the correlations between time-domain and frequency-domain features in pulse waves and their classification in hypertensive TOD. It analyzes key factors influencing pulse wave classification, providing valuable insights for the clinical diagnosis of TOD.

Dietary Fructose and Sodium Consumed during Early Mid-Life Are Associated with Hypertensive End-Organ Damage by Late Mid-Life in the CARDIA Cohort.

We aimed to investigate how dietary fructose and sodium impact blood pressure and risk of hypertensive target organ damage 10 years later. Data from n = 3116 individuals were obtained from the Coronary Artery Risk Development in Young Adults (CARDIA) study. Four groups were identified based on the four possible combinations of the lower and upper 50th percentile for sodium (in mg) and fructose (expressed as percent of total daily calories). Differences among groups were ascertained and logistic regression analyses were used to assess the risk of hypertensive target organ damage (diastolic dysfunction, coronary calcification and albuminuria). Individuals in the low-fructose + low-sodium group were found to have lower SBP compared to those in the low-fructose + high-sodium and high-fructose + high-sodium groups (p < 0.05). The highest risk for hypertensive target organ damage was found for albuminuria only in the high-fructose + high-sodium group (OR = 3.328, p = 0.006) while female sex was protective across all groups against coronary calcification. Our findings highlight that sodium alone may not be the culprit for hypertension and hypertensive target organ damage, but rather when combined with an increased intake of dietary fructose, especially in middle-aged individuals.

Alpha-adducin 1 (rs4961) gene and its expression associated with sodium sensitivity in hypertensive patients: a cohort study in the western Ukrainian population.

Objective. The aim of this study was to evaluate the association of the α-adducin-1 gene (ADD1) (Gly460Trp [rs4961]) polymorphism and its expression in association with renal dysfunction and sodium sensitivity in hypertensive patients in western Ukrainian population. Methods. One-hundred patients with essential arterial hypertension (EAH) and hypertensive-mediated target organ damage (stage 2), moderate, high, and very high cardiovascular risk were enrolled in case-control study. Sixty healthy individuals were assigned as controls. Sodium sensitivity and sodium resistance were determined by salt load reaction. The ADD1 (rs4961) genotyping was performed in RT-PCR. Results. The expression of the quantitative trait loci (eQTL) of ADD1 gene (rs4961) (chr4:2906707 [hg19]) was confirmed in 37 tissues and organs with 23 phenotypic traits. Two hundred eQTL associations revealed - all cis-variants (cis-QTL); 73 methylation QTL (mQTL), 34 splicing QTL (sQTL), 14 histone modification QTL (hQTL), 2 protein QTL (pQTL), 23 transcript utilization QTL (tuQTL), and 4 loci of incorporated long noncoding areas of RNA (lncRNA). GG-genotype unreliably enhances EAH risk (OR=1.92; 95%CI: 0.90-4.10; p=0.066). Sodium sensitivity was observed in 54.0% of patients and in 20.0% of controls (c2=17.89; p<0.001). Sodium sensitivity in T-allele carriers of the ADD1 gene (1378G>T; rs4961) dominated 12-fold in general (OR 95%CI: 2.24-64.29; p=0.001), in women - 4.71 times (OR 95%CI: 1.92-11.56; p<0.001), and in men - 4.09 times (OR 95%CI: 1.03-16.28; p=0.041). Sodium sensitivity elevated the likelihood of severe EAH twice (OR=2.19; OR 95%CI: 1.00-5.05; p=0.049). Conclusion. T-allele associates with sodium sensitivity in essential arterial hypertension patients and increases the risk of hypertension regardless the gender. Sodium sensitivity enhances the probability of severe essential arterial hypertension in observed population.

The Depiction of Hypertension in Heart Imaging Examinations: An Up-to-Date Review of the Evidence.

Hypertension is one of the main preventable cardiovascular (CV) risk factors all over the years, closely related to CV morbidity and mortality. One of the most common hypertensive target organ damages is hypertensive heart disease (HHD), including left ventricular hypertrophy, which progresses gradually and leads to systolic or diastolic dysfunction of the left ventricular, and finally to end-stage heart failure. Regarding its prevalence and the need for early diagnosis, assessment of heart imaging examination is of major importance. Echocardiography has been used as the standard imaging technique to evaluate HHD for years, providing an accurate evaluation of the left ventricular geometry, along with the systolic and diastolic function. However, nowadays there is a growing interest in cardiovascular magnetic resonance (CMR). Despite the importance of the use of echocardiography in everyday clinical practice, numerous studies have shown the superiority of CMR as an imaging technique for clinical and research purposes, mainly due to its strength to provide an unlimited area of view, as well as the identification and quantification of the type and extent of myocardial fibrosis. Hence, this review aims to analyze the importance of heart imaging in the hypertensive population, with a special interest in CMR imaging.

Arterial hypertension and stiffness in women of different age groups and reproductive status

Objective: study of the relationship between arterial hypertension and arterial stiffness in women to identify potential markers of target organ damage and therapeutic targets of antihypertensive therapy.Materials and methods: the study involved 161 women who were divided into three groups depending on age and reproductive function. Group 1 consisted of 52 women aged 18 to 30; group 2 – 54 women aged 31 years before menopause; 3rd group – 55 women in the postmenopausal period. All women were questioned, clinical examination, determination of anthropometric data, measurement of carotid-femoral pulse wave velocity, determination of arterial stiffness by volumetric sphygmography, 24-hour blood pressure monitoring with assessment of aortic stiffness and characteristics of the central pulse wave.Results: 24-hour blood pressure monitoring revealed arterial hypertension in 38 (34,8%) women: 15 (27,8%) women in the 2nd group and 23 (41,8%) women in the 3rd group. Correlation analysis revealed the most significant correlations between the presence of arterial hypertension (R=0,45-0,71; p&lt;&lt;0,01) with central aortic pressure, double product index and average daily aortic pulse wave velocity in the aorta (PWVao), regardless of the state reproductive function. For women of reproductive age with arterial hypertension, the ambulatory vascular stiffness index (AASI: R=0,36; p=0,01) is more significant, while in the menopausal period, the arterial stiffness index (ASI: R=0,33; p=0,01). Correlation analysis did not reveal significant relationships between carotid-femoral pulse wave velocity and cardio-ankle vascular index (CAVI) with arterial hypertension in women of the 2nd and 3rd groups. The relationship between carotid-femoral pulse wave velocity and arterial hypertension in women was confirmed by analysis of variance (p=0,007).Conclusion: Central aortic pressure, carotid-femoral pulse wave velocity, AASI, ASI, PWVao – direct and indirect indicators of arterial stiffness – are interconnected with the presence of arterial hypertension in women of reproductive and menopausal age. In this regard, these indicators are potential markers of target organ damage in arterial hypertension.

Left ventricular hypertrophy and mortality in ethnic minority groups in the UK: e-ECHOES study.

Hypertension is the key modifiable cardiovascular risk factor but is underdiagnosed, and its scale in South Asian and African-Caribbean communities is unknown. Left ventricular hypertrophy (LVH) is a measure of target organ damage in uncontrolled hypertension. The study assesses LVH prevalence in South Asian and African-Caribbean communities and its impact on mortality. This study is based on the large prospective UK community Ethnic-Echocardiographic Heart of England Screening Study (E-ECHOES, age ≥45 years). Left ventricular mass index (LVMI) was calculated using echocardiography to establish LVH. The predictive value of LVH all-cause and cardiovascular mortality was assessed using Cox regression. The study included 3200 South Asians (age 59 ± 10 years, 52% women, 45% had a history of hypertension, 5.8 ± 1.0-year follow-up). LVH was found in 1568 (49%), of whom 45% did not have hypertension diagnosis. On Cox regression, LVH was independently associated with all-cause mortality [hazard ratio 1.38, 95% confidence interval (95% CI) 1.01-1.88], cardiovascular mortality (hazard ratio 2.64, 95% CI 1.21-3.73). The projected overall hypertension prevalence was 82%, undiagnosed hypertension prevalence 37%. The study included 1858 African-Caribbeans (age 62 ± 12, 45% women, 45% had history of hypertension, 5.1 ± 0.9-year follow-up). LVH was found in 1186 (64%), of whom 32% did not have hypertension diagnosis. LVH was borderline associated with all-cause mortality (hazard ratio 1.57, 95% CI 1.01-2.44), but not cardiovascular mortality (hazard ratio 1.82, 95% CI 0.80-4.16). The projected overall hypertension prevalence was 78.5%, and undiagnosed hypertension prevalence was 20.8%. UK South Asians and African-Caribbeans have a high prevalence of hypertension, which is often underdiagnosed and poorly controlled.

Targeting the NLRP3 inflammasome for the treatment of hypertensive target organ damage: Role of natural products and formulations.

Hypertension is a major global health problem that causes target organ damage (TOD) in the heart, brain, kidney, and blood vessels. The mechanisms of hypertensive TOD are not fully understood, and its treatment is challenging. This review provides an overview of the current knowledge on the role of Nod-like receptor pyrin domain containing 3 (NLRP3) inflammasome in hypertensive TOD and the natural products and formulations that inhibit it. We searched PubMed, Web of Science, Google Scholar, and CNKI for relevant articles using the keywords "hypertension," "target organ damage," "NLRP3 inflammasome," "natural products," and "formulations." We reviewed the effects of the NLRP3 inflammasome on hypertensive TOD in different organs and discussed the natural products and formulations that modulate it. In hypertensive TOD, the NLRP3 inflammasome is activated by various stimuli such as oxidative stress and inflammation. Activation of NLRP3 inflammasome leads to the production of pro-inflammatory cytokines that exacerbate tissue damage and dysfunction. Natural products and formulations, including curcumin, resveratrol, triptolide, and allicin, have shown protective effects against hypertensive TOD by inhibiting the NLRP3 inflammasome. The NLRP3 inflammasome is a promising therapeutic target in hypertensive TOD. Natural products and formulations that inhibit the NLRP3 inflammasome may provide novel drug candidates or therapies for hypertensive TOD. Further studies are needed to elucidate the molecular mechanisms and optimize the dosages of these natural products and formulations and evaluate their clinical efficacy and safety.

Antihypertensive activity of different components of Veratrum alkaloids through metabonomic data analysis

BackgroundHypertension is a serious global public health issue. Blood pressure (BP) is still not effectively controlled in about 20 – 30% of hypertensive patients. Therefore, it is imperative to develop new treatments for hypertension. Veratrum alkaloids were once used for the clinical treatment of hypertension, the mechanism of which is still unclear. It was gradually phased out due to adverse reactions. PurposeThis study aimed to investigate the short-term and long-term hypotensive profiles of different components of Veratrum alkaloids in spontaneously hypertensive rats (SHRs) to unveil their mechanisms of action. ResultsTotal Veratrum alkaloid (V), component A (A), and veratramine (M) quickly decreased BP within 30 min of treatment, reduced renal and cardiovascular damage, and improved relevant biochemical indicators (nitric oxide [NO], endothelin-1 [ET-1], angiotensin II [Ang II)], noradrenaline [NE], etc) in SHRs to delay stroke occurrence. Thereinto, A exhibited excellent protective effects in cardiovascular disease. The metabolomic profiles of SHRs treated with V, A, and M were significantly different from those of SHRs treated with vehicle. Thirteen metabolites were identified as potential pharmacodynamic biomarkers. Through Kyoto Encyclopedia of Genes and Genomes analysis, V, A, and M-induced hypotension was mainly related to alterations in nicotinate and nicotinamide metabolism, GABAergic synapses, linoleic acid metabolism, ketone body synthesis and degradation, arginine and proline metabolism, and urea cycle, of which nicotinate and nicotinamide metabolism was the key metabolic pathway to relieve hypertension. ConclusionThis work shows that A is an effective and promising antihypertensive agent for hypertension treatment to reduce BP and hypertensive target organ damage, which is mainly mediated through modulating nicotinate and nicotinamide metabolism, RAS, and NO–ET homeostasis.

Antihypertensive, antioxidant, and renal protective impact of integrated GJD with captopril in spontaneously hypertensive rats

Hypertension is the most prevalent chronic disease World-wide, and the leading preventable risk factor for cardiovascular disease (CVD). Few patients accomplish the objective of decreasing blood pressure and avoiding hypertensive target organ damage after treatments with antihypertensive agents which opens the door for other treatments, such as herbal-and antihypertensive combination therapy. Captopril (CAP), as a-pril which inhibits angiotensin converting enzyme has long been used in the management of hypertension and CVD. Gedan Jiangya Decoction (GJD) is known for antihypertensive effects in prior studies. The research is aimed to determine whether GJD in combination with captopril has antihypertensive, kidney protective, antioxidant, and vasoactive effects in spontaneously hypertensive rats (SHR). Regular measurements of systolic and diastolic blood pressure (SBP and DBP), and body weight were monitored weekly. H&E staining was utilized to examine histopathology. The combined effects were studied using ELISA, immunohistochemistry, and qRT-PCR. Significant reductions in SBP, DBP, aortic wall thickness, and improvement in renal tissue were observed following GJD + CAP treatment, with increased serum levels of NO, SOD, GSH-Px, and CAT and decreases in Ang II, ET-1, and MDA. Similarly, GJD + CAP treatment of SHR's significantly decreased ET-1 and AGTR1 mRNA and protein expression while increasing eNOS mRNA and protein expression in thoracic aorta and kidney tissue. In conclusion, the present investigation found that GJD + CAP treatment decreases SHR blood pressure, improves aorta remodeling and renal protection, and that this effect could be attributable, in part, due to antioxidant and vascular tone improvement.

Natural compounds targeting mitochondrial dysfunction: emerging therapeutics for target organ damage in hypertension.

Hypertension generally causes target organ damage (TOD) in the heart, brain, kidney, and blood vessels. This can result in atherosclerosis, plaque formation, cardiovascular and cerebrovascular events, and renal failure. Recent studies have indicated that mitochondrial dysfunction is crucial in hypertensive target organ damage. Consequently, mitochondria-targeted therapies attract increasing attention. Natural compounds are valuable resources for drug discovery and development. Many studies have demonstrated that natural compounds can ameliorate mitochondrial dysfunction in hypertensive target organ damage. This review examines the contribution of mitochondrial dysfunction to the development of target organ damage in hypertension. Moreover, it summarizes therapeutic strategies based on natural compounds that target mitochondrial dysfunction, which may be beneficial for preventing and treating hypertensive target organ damage.

MULTIPLE RENAL ARTERIES AS A RISK FACTOR FOR SEVERE HYPERTENSION IN YOUNG ADULTS?

Objective: The significance of multiple renal arteries (MRAs) in arterial hypertension (AH) is not fully understood. Lower perfusion pressure due to longer length and narrower caliber of MRAs could cause segmental hyperreninemia sufficient to result in renin-dependent systemic hypertension. Sympathetic renal nerve activity might be affected by hyperreninema as well. The aim of the study was to examine the characteristics of young adult hypertensives in relation to the existence of MRAs that were diagnosed during evaluation for secondary arterial hypertension. Design and method: 32 patients underwent routine evaluation for secondary hypertension and target organ damage. Patients were divided into two groups, one with MRAs and the other without MRAs. Data were presented as mean +standard deviation and compared by the Indipendent-Sample t-test. Results: The mean age was 38 years, and 13 patients were diagnosed with MRAs. There were more men in the MRAs group, otherwise, there were no significant differences in baseline characteristics between the groups (BMI, smoking, family history). None of them were diagnosed with secondary endocrine hypertension or renal artery stenosis. MRAs group showed significantly higher values of office SBP/DBP (p &lt; 0,012) and 24-hour SBP/DBP (p &lt; 0,001), and nonsignificantly higher values of heart rate. Although nonsignificant, direct renin concentrations were slightly higher in the MRAs group, while insulin levels were higher in the non-MRAs group. Dyslipidemia was diagnosed in most patients, without significant differences between groups. Electrocardiographic and echocardiographic changes suggesting hypertensive heart remodeling were found in 55% of patients in MRAs compared to 32% in non-MRAs, there were no significant differences in NTproBNP levels. A nonsignificant reduction in glomerular filtration rate was noticed in the MRAs group, while there were no significant differences in 24-hour albuminuria (p 0,308; p 0,614). Conclusions: The significance of MRAs in arterial hypertension is a matter of debate. In our study of young patients with arterial hypertension and MRAs, we observed features of more severe hypertension with already existing hypertensive target organ damages. Proper medical treatment with antihypertensive agents is crucial. Future studies will answer the question about interventional therapeutic procedures’ role in preventing cardiovascular complications.

Metabolic syndrome as risk factor for left ventricular hypertrophy in children with chronic kidney disease.

The metabolic syndrome (MS), a cluster of clinical and biochemical abnormalities including insulin resistance, dyslipidemia and hypertension, is often diagnosed in chronic kidney disease (CKD) children. Left ventricular hypertrophy (LVH) is a major target organ damage in hypertension and an important cardiovascular risk factor in CKD patients. We aimed to identify the most significant risk factors of LVH in children with CKD. Children with CKD stage 1-5 were enrolled in the study. MS was diagnosed according to De Ferranti (DF) as ≥3 from 5 criteria. Ambulatory blood pressure measurements (ABPM) and echocardiographic evaluation were performed. LVH was defined as ≥95th percentile of LV mass index related to height and age. Clinical and laboratory parameters included: serum albumin, Ca, HCT, cystatin C, creatinine, estimated glomerular filtration rate (eGFR) based on Schwartz formula, triglycerides, high-density lipoprotein (HDL), proteinuria, BMI standard deviation score (SDS), height SDS, waist circumference, ABPM data. 71 children (28 girls/43 boys) with median age 14.05 (25%-75%:10.03-16.30) years and median eGFR 66.75 (32.76-92.32) ml/min/1.73m2 were evaluated. CKD stage 5 was diagnosed in 11 pts (15.5%). MS (DF) was diagnosed in 20 pts (28.2%). Glucose ≥ 110 mg/dL was present in 3 pts (4.2%); waist circumference ≥75th pc in 16 pts (22.5%); triglycerides ≥ 100 mg/dL in 35 pts (49.3%); HDL < 50mg/dL in 31 pts (43.7%) and BP ≥ 90th pc in 29 pts (40.8%), respectively. LVH was detected in 21 (29.6%) children. In univariate regression the strongest risk factor for LVH was CKD stage 5 (OR 4.9, p=0.0019) and low height SDS (OR 0.43,p=0.0009). In stepwise multiple logistic regression analysis (logit model) of the most important risk factors for LVH in CKD children, only three were statistically significant predictors: 1)MS diagnosis based on DF criteria (OR=24.11; 95%CI 1.1-528.7; p=0.043; Chi2=8.38,p=0.0038); 2), high mean arterial pressure (MAP SDS) in ABPM (OR=2.812; 95%CI 1.057-7.48; p=0.038;Chi2=5.91, p=0.015) and 3) low height SDS (OR=0.078; 95%CI 0.013-0.486;p=0.006; Chi2=25.01, p<0.001). In children with chronic kidney disease LVH is associated with the cluster of multiple factors, among them the components of MS, hypertension, stage 5 CKD and growth deficit were the most significant.

Deficiency of Tregs in hypertension-associated left ventricular hypertrophy.

Left ventricular hypertrophy (LVH) is the most common target organ damage in hypertension. Abnormal numbers or functions of CD4+ CD25+ Foxp3+ regulatory T lymphocytes (Tregs) can cause immune disorders, which participates in LVH. This study aimed to explore the role of Tregs in LVH by investigating circulating Tregs and associated cytokine levels in hypertensive patients with or without LVH. Blood samples were collected from 83 hypertensive patients without LVH (essential hypertension group, EH), 91 hypertensive patients with LVH (left ventricular hypertrophy group, LVH), and 69 normotensive controls without LVH (control group, CG). Tregs and cytokines were measured by flow cytometry and enzyme-linked immunosorbent assays. We found that circulating Tregs were significantly lower in hypertensive patients than in CG subjects. It was lower in LVH than in EH patients. No correlation between blood pressure regulation and Tregs was found in EH or LVH patients. Furthermore, Tregs in older females were lower than those in older males among LVH patients. Additionally, serum interleukin-10 (IL-10) and transforming growth factor beta 1 (TGFβ1) decreased in hypertensive patients, and interleukin-6 (IL-6) increased in LVH patients. Tregs were negatively correlated with creatine kinase, low-density lipoprotein cholesterol, apoprotein B, high-sensitivity C-reactive protein, and left ventricular mass index (LVMI) values. In general, our study demonstrates significantly decreased circulating Tregs in hypertensive LVH patients. Decreased circulating Tregs in LVH is independent of blood pressure regulation. IL-6, IL-10, and TGF-β1 are related with LVH in hypertension.

Prediction of pulse wave of target organ damage in hypertension based on multiple feature fusion

With respect to less efficiency and low accuracy of predicting on hypertensive target organ damage, this article proposes a fusion prediction model combining pulse-taking with inquiry diagnosis of traditional Chinese medicine to accomplish the efficient and non-invasive diagnosis. Regarding the class imbalance of inquiry diagnosis samples, an Eliminated random forest algorithm is proposed to select efficient features and reduce the impact of class imbalance on classification performance via cluster-based under-sampling algorithm. As to low discriminability of hypertensive time-domain pulse wave samples, time-domain pulse wave is transformed to the frequency-domain MFCC feature maps, and fuse feature maps of inquiry diagnosis scale for predicting hypertension target organ damage. In the article, the clinical 608 cases of hypertensive target organ damage are from Longhua Hospital affiliated to Shanghai University of Chinese Medicine and Hospital of Integrated Traditional Chinese and Western Medicine concerning pulse-taking and inquiry diagnosis. The evaluation indicators of 5-Fold cross-validation classification, i.e. F1-score, Accuracy, Precision, Sensitivity, AUC, are 97.31%, 98.72%, 97.71%, 97.04%, 99.13% respectively, which are higher than those of the other typical models. In addition, this article also studies the correlation between classification of pulse-taking or inquiry diagnosis and its features, and analyzes the feature importance ranking on pulse-taking and inquiry diagnosis, which aids clinicians to seek the occurrence mechanisms of hypertensive target organ damage, and find the effective measurements for timely prevention and treatment.