Hypertensive Left Ventricular Hypertrophy Research Articles

Prevalence of Increased QTc Dispersion Among Hypertensive Patients and Its Correlation to Clinical Risk Factors: A Hospital-Based Case-Control Study.

Background In Ghana and other sub-Saharan African countries, hypertension (HTN) prevalence is rapidly increasing. Hypertensive left ventricular hypertrophy (LVH) is associated with excess fibrous tissue deposition throughout the myocardium. This could lead to ventricular arrhythmias and sudden cardiac death. Increased corrected QT dispersion (QTcd) can cause ventricular repolarization and be used to identify patients at risk of ventricular tachyarrhythmia. The measurement of increased QTcd among hypertensive patients is a simple screening tool to stratify patients at cardiovascular risk. Methods A case-control hospital-based study was conducted on 200 consecutive hypertensive patients. Age- and sex-matched control groups of 200 normotensive individuals who gave informed consent were also recruited. The baseline clinical and demographic characteristics of participants were acquired using structured questionnaires. A physical examination and a resting 12-lead ECG were performed. Increased QTcd and LVH were determined. Results The mean age of hypertensive patients was 50.99±6.73 and 48.19±7.17 for the controls (p-value 0.63). The study population was predominantly female (1:2.4 male:female ratio). Higher mean values for QTcd and LVH (Sokolow-Lyon) were observed among hypertensive patients compared to controls. The prevalence of increased QTcd was 45.0% among hypertensive patients compared to 16.5% in controls (χ2=38.14, p-value <0.0000001, odds ratio = 4.14). Conclusion Increased QTcd is prevalent among hypertensive Ghanaians. Its measurement can be an effective non-invasive screening tool to risk-stratify hypertensive patients.

Prevention and treatment of hypertensive left ventricular hypertrophy.

Left ventricular (LV) hypertrophy (LVH) is a well recognized target organ adaptation to longstanding uncontrolled hypertension and other cardiovascular risk factors. It is also a strong and independent predictor of many cardiovascular disorders. This focused review explores the current concepts in screening, diagnosis, prevention, and treatment of LVH in patients with hypertension. Currently, the primary screening and diagnostic tools for LVH are ECG and 2D echocardiography. Implementing machine learning in the diagnostic modalities can improve sensitivity in the detection of LVH. Lifestyle modifications, blood pressure control with antihypertensive therapy, and management of comorbidities aid in preventing and reversing LV remodeling. LVH is a common and often silent complication of hypertension. Prevention and reversal of LV remodeling are crucial for cardiovascular risk reduction in patients with hypertension.

Construction and validation of a nomogram to predict left ventricular hypertrophy in low-risk patients with hypertension.

Electrocardiography (ECG) is an accessible diagnostic tool for screening patients with hypertensive left ventricular hypertrophy (LVH). However, its diagnostic sensitivity is low, with a high probability of false-negatives. Thus, this study aimed to establish a clinically useful nomogram to supplement the assessment of LVH in patients with hypertension and without ECG-LVH based on Cornell product criteria (low-risk hypertensive population). A cross-sectional dataset was used for model construction and divided into development (n=2906) and verification (n=1447) datasets. A multivariable logistic regression risk model and nomogram were developed after screening for risk factors. Of the 4353 low-risk hypertensive patients, 673 (15.4%) had LVH diagnosed by echocardiography (Echo-LVH). Eleven risk factors were identified: hypertension awareness, duration of hypertension, age, sex, high waist-hip ratio, education level, tea consumption, hypochloremia, and other ECG-LVH diagnostic criteria (including Sokolow-Lyon, Sokolow-Lyon products, and Peguero-Lo Presti). For the development and validation datasets, the areas under the curve were 0.724 (sensitivity=0.606) and 0.700 (sensitivity=0.663), respectively. After including blood pressure, the areas under the curve were 0.735 (sensitivity=0.734) and 0.716 (sensitivity=0.718), respectively. This novel nomogram had a good predictive ability and may be used to assess the Echo-LVH risk in patients with hypertension and without ECG-LVH based on Cornell product criteria.

Beta-blockers in Hypertensive Left Ventricular Hypertrophy and Atrial Fibrillation Prevention.

Hypertensive left ventricular hypertrophy (HTN LVH) is a key risk factor for atrial fibrillation (AF). To evaluate the possible role of beta-blockers (BBs) in addition to a renin-angiotensinaldosterone system (RAAS) blocker in AF prevention in patients with HTN LVH. We performed a PubMed, Elsevier, SAGE, Oxford, and Google Scholar search with the search items 'beta blocker hypertension left ventricular hypertrophy patient' from 2013-2023. In the end, a 'snowball search', based on the references of relevant papers as well as from papers that cited them was performed. HTN LVH is a risk factor for AF. In turn, AF substantially complicates HTN LVH and contributes to the genesis of heart failure (HF) with preserved ejection fraction (HFpEF). The prognosis of HFpEF is comparable with that of HF with reduced EF (HFrEF), and, regardless of the type, HF is associated with five-year mortality of 50-75%. The antiarrhythmic properties of BBs are wellrecognized, and BBs as a class of drugs are - in general - recommended to decrease the incidence of AF in HTN. BBs are recommended (as a class) for AF prevention in several contemporary guidelines for HTN. LVH regression in HTN - used as a single criterion for the choice of antihypertensive medication - does not capture this protective effect. Consequently, it is worth studying how meaningful this antiarrhythmic action (to prevent AF) of BBs is in patients with HTN LVH in addition to a RAAS blocker.

Influence of Antihypertensive Drugs on Left Ventricular Hypertrophy Regression in Hypertensive Patients

Background: Hypertension and its effect on heart in the form of left ventricular hypertrophy are the important predictors of heart failure. Hypertension treatment and left ventricular hypertrophy regression is crucial in the prevention of cardiovascular disease. However, the impact of antihypertensive treatment on left ventricular hypertrophy is less studied and which particular class of antihypertensive medicine is more effective is largely unexplored in our population. We designed this study to explore this issue in subjects taking treatment by evaluation initial and after six months echocardiography findings. Methods: One hundred fifty subjects aged 25-75 years, taking antihypertensive medicine were enrolled in the study. Along with basic demographic and epidemiological data, initial and after 6 months echocardiographic findings were analyzed for the presence of LV hypertrophy regression. Choice of medicine and necessary changes for the achievement of blood pressure targets were done on treating physician’s discretion.Results: Out of 150 subjects, data for 130 subjects were available for final analysis. Mean age was 54.4 years with standard deviation of 12.3 years. Apart from age, smoking, overweight and obesity, dyslipidemia, and diabetes were the important risk factors with a prevalence of 28%, 26%, 22% and 20% respectively. Although the decrease in rates of LV hypertrophy over the duration of 6 months were not significant in overall and in subjects treated with various antihypertensive medicines, the reductions in LV mass index (108.76+/-11.3 to 98.46+/-11.23) in overall and in different antihypertensives were significant (p&lt;0.001). The decrease in LV mass index was statistically significant in subjects taking angiotensin converting enzyme inhibitors or angiotensin receptor blockers when compared to subjects taking calcium channel blockers (p&lt;0.05). This decrease in LV mass index was not significant when compared between CCBs and mixed drugs.Conclusion: There was regression in LV hypertrophy among subjects taking antihypertensive treatment. It was more obvious in subjects taking angiotensin converting enzyme inhibitors/angiotensin receptor blockers when compared with subjects taking calcium channel blockers or both.

Epicardial tissue derived leptin promotes myocardial injury in metabolic syndrome rats through PKC/NADPH oxidase/ROS pathway

Abstract Background The epicardial adipose tissue (EAT) of metabolic syndrome (MetS) is abnormally accumulated with dysfunctional secretion of adipokines, closely relating to cardiac dysfunction. The adipokines leptin has been proven to induce cardiac fibroblasts collagen metabolism disorder in hypertensive left ventricular hypertrophy rats. Purpose The study was designed to identify the effects of EAT-derived leptin on the myocardium of MetS rats and explore the potential molecular mechanisms. Methods and results MetS rat model was established in eight-week-old male Wistar rats by 12 week high-fat diet. MetS rats exhibited increased leptin secretion from EAT, cardiac hypertrophy and diastolic dysfunction with preserved systolic function. The myocardium of MetS rats had abnormal structure and mitochondrial morphology, increased oxidative stress injury and inflammatory factors level, especially the subepicardial myocardium, which was correlated with the EAT-derived leptin level, but not the serum leptin (Figure 1). The EAT was separated from each group rats to prepare EAT-Conditioned Medium (EAT-CM). The H9C2 rat cardiomyoblasts were treated with EAT-CM or leptin, plus various signaling pathway inhibitors. EAT derived leptin from MetS rats promoted mitochondrial oxidative stress and dysfunction, induced mitochondrial pathway apoptosis and inhibited cell viability in H9C2 cardiomyoblasts via PKC/NADPH oxidase/ROS pathway. EAT derived leptin from MetS rats stimulated inflammation in H9C2 cardiomyocytes by promoting AP-1 nuclear translocation via PKC/NADPH oxidase/ROS pathway. Leptin promoted the interaction between p-p47phox and gp91phox in H9C2 cardiomyocytes via PKC, activating NADPH oxidase, increasing ROS generation, and inhibiting cell viability. Conclusions EAT derived leptin induces the MetS related myocardial injury though the following two cooperative ways via PKC/NADPH oxidase/ROS pathway: 1. Inducing mitochondrial pathway apoptosis by promoting mitochondrial oxidative stress and dysfunction; 2. Stimulating inflammation by promoting AP-1 nuclear translocation (Figure 2). The results reveal the potential molecular mechanisms of EAT in MetS related myocardial injury, providing novel insights for the further study of MetS related cardiovascular diseases.Figure 1Figure 2

Left atrial mechanics evaluated by two-dimensional strain analysis: alterations in essential hypertension.

Hypertension is a cardiovascular risk factor that predisposes to cardiac structural alterations namely increased left ventricular (LV) wall thickness, reduced LV compliance and diastolic dysfunction, with consequent left atrial (LA) dilation and functional impairment. In this article, we evaluated differences in left atrial structure and function using two-dimensional speckle tracking echocardiography in patients with hypertension compared with controls. This was a retrospective cross-sectional study of 208 hypertensive patients and 157 controls who underwent a comprehensive transthoracic echocardiogram. Patients with hypertension were stratified by the presence of left ventricular hypertrophy (LVH). Non-LVH hypertension patients had lower left atrial reservoir strain (LAS RES ) (34.78 ± 29.78 vs. 29.78 ± 6.08; P = 0.022) and conduit strain (LAS CD ) (19.66 ± 7.29 vs. 14.23 ± 4.59; P = 0.014) vs. controls despite similar left atrial volumes (LAV) . Left atrial contractile strain (LAS CT ) was not significantly different between non-LVH hypertension patients and controls (15.12 ± 3.77 vs. 15.56 ± 3.79; P = 0.601). Left atrial mechanical dispersion was significantly higher in the LVH group compared with the non-LVH hypertension group (42.26 ± 13.01 vs. 50.06 ± 14.95; P = 0.009). In multivariate regression analysis, LVH correlated with left atrial mechanical dispersion ( P = 0.016). An age-hypertension interaction independently correlated with LAS CT ( P < 0.001). Hypertension results in functional left atrial changes even before development of LV hypertrophy and structural left atrial changes with increased left atrial volume. We demonstrate both a likely hypertension-associated left atrial myopathy that prevents age-related compensatory increase in left atrial contractile function, and impact of LVH in hypertension on left atrial dyssynchrony.

Hypertensive Heart Disease: A Narrative Review Series-Part 2: Macrostructural and Functional Abnormalities.

Hypertensive heart disease (HHD) remains a major global public health concern despite the implementation of new approaches for the management of hypertensive patients. The pathological changes occurring during HHD are complex and involve the development of structural and functional cardiac abnormalities. HHD describes a broad spectrum ranging from uncontrolled hypertension and asymptomatic left ventricular hypertrophy (LVH), either a concentric or an eccentric pattern, to the final development of clinical heart failure. Pressure-overload-induced LVH is recognised as the most important predictor of heart failure and sudden death and is associated with an increased risk of cardiac arrhythmias. Cardiac arrhythmias are considered to be one of the most important comorbidities affecting hypertensive patients. This is the second part of a three-part set of review articles. Here, we focus on the macrostructural and functional abnormalities associated with chronic high pressure, their involvement in HHD pathophysiology, and their role in the progression and prognosis of HHD.

Sacubitril/valsartan versus valsartan in regressing myocardial fibrosis in hypertension: a prospective, randomized, open-label, blinded endpoint clinical trial protocol.

Diffuse interstitial myocardial fibrosis is a key common pathological manifestation in hypertensive heart disease (HHD) progressing to heart failure (HF). Angiotensin receptor-neprilysin inhibitors (ARNi), now a front-line treatment for HF, confer benefits independent of blood pressure, signifying a multifactorial mode of action beyond hemodynamic regulation. We aim to test the hypothesis that compared with angiotensin II receptor blockade (ARB) alone, ARNi is more effective in regressing diffuse interstitial myocardial fibrosis in HHD. Role of ARNi in Ventricular Remodeling in Hypertensive LVH (REVERSE-LVH) is a prospective, randomized, open-label, blinded endpoint (PROBE) clinical trial. Adults with hypertension and left ventricular hypertrophy (LVH) according to Asian sex- and age-specific thresholds on cardiovascular magnetic resonance (CMR) imaging are randomized to treatment with either sacubitril/valsartan (an ARNi) or valsartan (an ARB) in 1:1 ratio for a duration of 52 weeks, at the end of which a repeat CMR is performed to assess differential changes from baseline between the two groups. The primary endpoint is the change in CMR-derived diffuse interstitial fibrosis volume. Secondary endpoints include changes in CMR-derived left ventricular mass, volumes, and functional parameters. Serum samples are collected and stored to assess the effects of ARNi, compared with ARB, on circulating biomarkers of cardiac remodeling. The endpoints will be analyzed with reference to the corresponding baseline parameters to evaluate the therapeutic effect of sacubitril/valsartan vs. valsartan. REVERSE-LVH will examine the anti-fibrotic potential of sacubitril/valsartan and will offer mechanistic insights into the clinical benefits of sacubitril/valsartan in hypertension in relation to cardiac remodeling. Advancing the knowledge of the pathophysiology of HHD will consolidate effective risk stratification and personalized treatment through a multimodal manner integrating complementary CMR and biomarkers into the conventional care approach.Clinical Trial Registration: ClinicalTrials.gov, identifier, NCT03553810.

Polymorphic variants at NDUFC2, encoding a mitochondrial complex I subunit, associate with cardiac hypertrophy in human hypertension

BackgroundA dysfunction of NADH dehydrogenase, the mitochondrial Complex I (CI), associated with the development of left ventricular hypertrophy (LVH) in previous experimental studies. A deficiency of Ndufc2 (subunit of CI) impairs CI activity causing severe mitochondrial dysfunction. The T allele at NDUFC2/rs11237379 variant associates with reduced gene expression and impaired mitochondrial function. The present study tested the association of both NDUFC2/rs11237379 and NDUFC2/rs641836 variants with LVH in hypertensive patients. In vitro studies explored the impact of reduced Ndufc2 expression in isolated cardiomyocytes.MethodsTwo-hundred-forty-six subjects (147 male, 59.7%), with a mean age of 59 ± 15 years, were included for the genetic association analysis. Ndufc2 silencing was performed in both H9c2 and rat primary cardiomyocytes to explore the hypertrophy development and the underlying signaling pathway.ResultsThe TT genotype at NDUFC2/rs11237379 associated with significantly reduced gene expression. Multivariate analysis revealed that patients carrying this genotype showed significant differences for septal thickness (p = 0.07), posterior wall thickness (p = 0.008), RWT (p = 0.021), LV mass/BSA (p = 0.03), compared to subjects carrying either CC or CT genotypes. Patients carrying the A allele at NDUFC2/rs641836 showed significant differences for septal thickness (p = 0.017), posterior wall thickness (p = 0.011), LV mass (p = 0.003), LV mass/BSA (p = 0.002) and LV mass/height2.7(p = 0.010) after adjustment for covariates. In-vitro, the Ndufc2 deficiency-dependent mitochondrial dysfunction caused cardiomyocyte hypertrophy, pointing to SIRT3-AMPK-AKT-MnSOD as a major underlying signaling pathway.ConclusionsWe demonstrated for the first time a significant association of NDUFC2 variants with LVH in human hypertension and highlight a key role of Ndufc2 deficiency-dependent CI mitochondrial dysfunction on increased susceptibility to cardiac hypertrophy development.

Pulmonary Hypertension and Left Ventricular Geometric Types in Sickle Cell Anemia

Pulmonary hypertension (PHT) is multifactorial in origin and a major cause of morbidity and mortality in the sickle cell populace. Its correlation with abnormal left ventricular geometric patterns has not been established. Subjects were sickle cell anemic patients of the hematology clinic of a tertiary hospital who gave informed consent. A modified Medical Research Council questionnaire was used to obtain the demographic, anthropometric, and clinical variables of the subjects. Blood samples were taken for hematologic and biochemical analysis. Spirometry, electrocardiography, and echocardiography were done for all subjects. SPSS version 25 was used for analysis. A p ≤0.05 was used for significance. In total 111 subjects with sickle cell anemia were recruited. Male:female ratio was 1:1.4. The prevalence of PHT was 8.1%. Those with PHT were older and had higher blood pressure, lower respiratory rate, higher body mass index, lower estimated glomerular filtration rate, and a higher prevalence of avascular necrosis of the head of femur, stroke, and chest pain. About 2/3 (66.7%) of those with PHT had concentric left ventricular hypertrophy (LVH) whereas none of those with eccentric LVH had PHT. Age, body mass index, systolic blood pressure, aortic root diameter, concentric LVH, serum creatinine, history of stroke, chest pain, and avascular necrosis of the head of femur correlated directly whereas eccentric LVH correlated inversely with PHT. Concentric LVH, relative systemic hypertension, history of chest pain, and respiratory rate were the independent correlates of PHT in subjects with sickle cell anemia. PHT is known to be of poor prognostic significance. Its association with relative systemic hypertension and concentric LVH suggests the need to initiate early treatment to reduce morbidity and mortality in this group.

Association of depression with hypertensive left ventricular hypertrophy in age, sex, and education level-specific differences.

Previous studies have shown that hypertension and depression are associated with worse cardiovascular outcomes and reduced quality of life. Left ventricular hypertrophy (LVH) is strongly linked to increased mortality and cardiovascular disease, and depression may be one of the key factors contributing to hypertensive LVH. The authors consecutively enrolled 353 patients with uncomplicated hypertension between November 2017 and May 2021. All participants completed the Hamilton Depression Scale (HAM-D) to assess their depression status, with depression defined as a HAM-D score of 20 or higher. Linear regression analysis revealed a positive association between HAM-D and LVMI (adjusted β, 1.51, 95% CI, 1.19-1.83, p<.001). Logistic regression models showed that individuals with hypertension and depression had a higher risk of LVH than those with hypertension alone (adjusted OR, 2.51, 95% CI, 1.14-5.52, p=.022). The association between depression and LVH significantly interacted with age, sex, education levels, but not BMI and household income. Following age, sex, and education levels stratification, an independent association of depression and LVH was observed only in age<60 years (age<60 years: OR, 7.36, 95% CI, 2.25-24.13, p<.001), male (male: OR, 16.16, 95% CI, 3.80-68.73, p<.001), and higher education levels (high school and above: OR, 11.09, 95% CI, 2.91-42.22, p<.001). Our findings suggest that depression is a significant risk factor for LVH in hypertensive patients, particularly in those who are under 60 years of age, male, and have higher education levels.

Blood Immune Cell Alterations in Patients with Hypertensive Left Ventricular Hypertrophy and Heart Failure with Preserved Ejection Fraction.

(1) Background: Chronic inflammation and fibrosis are key players in cardiac remodeling associated with left ventricular hypertrophy (LVH) and heart failure with a preserved ejection fraction (HFpEF). Monocytes and T-helpers (Th) are involved in both pro-inflammatory and fibrotic processes, while regulatory T-cells (Treg) could be considered to suppress chronic inflammation in the hypertrophied myocardium. We aimed to estimate the relationship between the frequencies of circulating CD4+ T-cell and monocyte subpopulations and the variables of left ventricular (LV) diastolic function in patients with LVH depending on the presence of HFpEF. (2) Methods: We enrolled 57 patients with asymptomatic hypertensive LVH (n = 21), or LVH associated with HFpEF (n = 36). A clinical assessment and echocardiographs were analyzed. CD4+ Treg, activated Th (Th-act), and monocyte (classical, intermediate, and non-classical) subpopulations were evaluated via direct immunofluorescence and flow cytometry. (3) Results: Patients with HFpEF had a lower Treg/Th-act ratio (p = 0.001). Though asymptomatic patients and patients with HFpEF were comparable in terms of both the total monocyte number and monocyte subsets, there were moderate correlations between intermediate monocyte count and conventional and novel echocardiographic variables of LV diastolic dysfunction in patients with HFpEF. (4) Conclusions: In patients with LVH, the clinical deterioration (transition to HFpEF) and progression of LV diastolic dysfunction are probably associated with T-cell disbalance and an increase in intermediate monocyte counts.

Comprehensive Transcriptomics Profiling of MicroRNA Reveals Plasma Circulating Biomarkers of Hypertrophic Cardiomyopathy and Dysregulated Signaling Pathways.

Hypertrophic cardiomyopathy (HCM) is caused by mutations in genes coding for proteins essential for myocardial contraction. However, it remains unclear through which signaling pathways these gene mutations mediate HCM pathogenesis. Growing evidence indicates that microRNAs (miRNAs) play an important role in the regulation of gene expression. We hypothesized that transcriptomics profiling of plasma miRNAs would reveal circulating biomarkers and dysregulated signaling pathways in HCM. We conducted a multicenter case-control study of cases with HCM and controls with hypertensive left ventricular hypertrophy. We performed plasma transcriptomics profiling of miRNAs using RNA sequencing. We developed a transcriptomics-based discrimination model using samples retrieved during the first two-thirds of the study period at one institution (training set). We prospectively tested its discriminative ability in samples collected thereafter from the same institution (prospective test set). We also externally validated the model by applying it to samples collected from the other institutions (external test set). We executed pathway analysis of dysregulated miRNAs with univariable P<0.05. This study included 555 patients (392 cases and 163 controls). One thousand one hundred forty-one miRNAs passed our quality control filters. The area under the receiver operating characteristic curve of the transcriptomics-based model derived from the training set was 0.86 (95% CI, 0.79-0.93) in the prospective test set and 0.94 (95% CI, 0.90-0.97) in the external test set. Pathway analysis revealed dysregulation of the Ras-MAPK (mitogen-activated protein kinase) pathway and pathways related to inflammation in HCM. This study utilized comprehensive transcriptomics profiling with RNA sequencing in HCM, revealing circulating miRNA biomarkers and dysregulated pathways.

TESTOSTERONE INDUCES POSTMENOPAUSAL HYPERTENSIVE HYPERTROPHY THROUGH INHIBITING THE ACTIVATION OF AMPK- FOXO1/MURF1 SIGNALING PATHWAY

Objective: It has been found that relative elevated level of testosterone could exacerbates postmenopausal hypertensive left ventricular hypertrophy(PM-HTN-LVH), but the mechanisms responsible are unknown. Moreover, MuRF1, a muscle-specific E3 ubiquitin ligase in the ubiquitination process, was newly identified as a negative regulatory factor of myocardial and muscle tissue in exerting a protective functions on the cardiomyocyte hypertrophy. There are little study to certify whether MuRF1 took part in testosterone-induced PM-HTN-LVH. Design and method: Femal spontaneously hypertensive rats (SHR) were ovariectomized (OVX group) or sham-operated (Sham group) at 12 weeks and then the OVX group were intramuscularly injected the testosterone (T 2.85 mg/kg/ quaque omni die im) (OVX+T group) or vehicle (OVX+ vehicle group) for 4 weeks. Futher, Cultured cardiomyocytes were respectively stimulated with different concentration gradients of testosterone for 24h, then measured the expression of myosin heavy chain (MHC) and MuRF1, as well as the phosphorylation levels of AMPK(p-AMPK) and Forkhead box O 1 (p-FOXO1), were separately measured using western blot. Results: After 4 weeks of testosterone supplementation, SHR heart exhibited significant increments in the heart weight/tibial length and the levels of IVST, LVPWT, LVM and the expression of MHC, and have a lower expression of the MuRF1, p-AMPK and p-FOXO1 in the OVX+T group, compared with OVX group and Sham group. Moreover, the expression level of p-AMPK and p-FOXO1 in the heart were at least twice as many as gastrocnemius muscle among the three group, but the MuRF1 was equivalent between heart and gastrocnemius muscle. In vivo, after the treatment of different gradients of testosterone for 24h, the protein expression of MHC showed an S-shaped growth trend and MuRF1, p-AMPK and p-FOXO1 presented with reverse S-shaped reduction along with increasing of testosterone concentration, peaking at 10-6M testosterone. Conclusions: The present study demonstrates that testosterone induces PM-HTN-LVH by modulating the atrophy related AMPK-FOXO1/MuRF1 signaling pathway in vitro and vivo. Increased the heart expression of MuRF1 by activation of AMPK may reverse testosterone-mediated PM-HTN-LVH, which might cause little change of MuRF1 expression in the skeletal muscle resulting in the muscle atrophy.

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.

Urinary proteomics combined with home blood pressure telemonitoring for health care reform trial-First progress report.

High blood pressure (BP) and type-2 diabetes (T2DM) are forerunners of chronic kidney disease and left ventricular dysfunction. Home BP telemonitoring (HTM) and urinary peptidomic profiling (UPP) are technologies enabling risk stratification and personalized prevention. UPRIGHT-HTM (NCT04299529) is an investigator-initiated, multicenter, open-label, randomized trial with blinded endpoint evaluation designed to assess the efficacy of HTM plus UPP (experimental group) over HTM alone (control group) in guiding treatment in asymptomatic patients, aged 55-75 years, with ≥5 cardiovascular risk factors. From screening onwards, HTM data can be freely accessed by all patients and their caregivers; UPP results are communicated early during follow-up to patients and caregivers in the intervention group, but at trial closure in the control group. From May 2021 until January 2023, 235 patients were screened, of whom 53 were still progressing through the run-in period and 144 were randomized. Both groups had similar characteristics, including average age (62.0 years) and the proportions of African Blacks (81.9%), White Europeans (16.7%), women 56.2%, home (31.2%), and office (50.0%) hypertension, T2DM (36.4%), micro-albuminuria (29.4%), and ECG (9.7%) and echocardiographic (11.5%) left ventricular hypertrophy. Home and office BP were 128.8/79.2mmHg and 137.1/82.7mmHg, respectively, resulting in a prevalence of white-coat, masked and sustained hypertension of 40.3%, 11.1%, and 25.7%. HTM persisted after randomization (48 681 readings up to 15 January 2023). In conclusion, results predominantly from low-resource sub-Saharan centers proved the feasibility of this multi-ethnic trial. The COVID-19 pandemic caused delays and differential recruitment rates across centers.

Combination of cardiac color Doppler ultrasound, serum MR-ProANP and NT-ProBNP forecasted hypertensive LVH and LFH

ABSTRACT To analyze the value of the combined test of the cardiac color Doppler ultrasound, the serum middle receptor pro-atrial natriuretic peptide (MR-ProANP) and the N-terminal pro-brain natriuretic peptide (NT-ProBNP) in forecasting the hypertensive left ventricular hypertrophy (LVH) and left heart failure (LHF). All patients were subjected to cardiac color Doppler ultrasound examination to obtain left atrium volume index (LAVI), left ventricular end-diastolic diameter (LVEDD), early-diastolic peak flow velocity (E), early-diastolic mean flow velocity (e’), early-diastolic peak flow velocity/early-diastolic mean flow velocity (E/e’) and left ventricular ejection fraction (LVEF). Biomarkers were performed to obtain serum MR-ProANP and NT-ProBNP concentrations, and statistical analysis was performed. The LVEF was obviously lower than that in the control group (P<0.01). The area under the receiver operating characteristic (ROC) curve (AUC) values of LVEF, E/e’, serum MR-ProANP and NT-ProBNP alone were in the range of 0.7–0.8. The AUC, sensitivity and specificity of LVEF and E/e’ combined with MR-ProANP and NT-ProBNP to diagnose hypertensive LVH and LHF were 0.892, 89.14% and 78.21%, which were higher than those of single diagnosis. In the heart failure group, LVEF was negatively correlated with serum MR-ProANP and NT-ProBNP concentrations (P<0.05), and E/e’ was positively correlated with serum MR-ProANP and NT-ProBNP concentrations (P<0.05). Pump function and ventricular remodeling in patients with hypertensive LVH and LHF are closely related to serum MR-ProANP and NT-ProBNP levels. Combination of the two testing can improve the prediction and diagnostic efficacy of LHF.

Artificial intelligence–enabled classification of hypertrophic heart diseases using electrocardiograms

Differentiating among cardiac diseases associated with left ventricular hypertrophy (LVH) informs diagnosis and clinical care. To evaluate if artificial intelligence-enabled analysis of the 12-lead electrocardiogram (ECG) facilitates automated detection and classification of LVH. We used a pretrained convolutional neural network to derive numerical representations of 12-lead ECG waveforms from patients in a multi-institutional healthcare system who had cardiac diseases associated with LVH (n = 50,709), including cardiac amyloidosis (n = 304), hypertrophic cardiomyopathy (n = 1056), hypertension (n = 20,802), aortic stenosis (n = 446), and other causes (n = 4766). We then regressed LVH etiologies relative to no LVH on age, sex, and the numerical 12-lead representations using logistic regression ("LVH-Net"). To assess deep learning model performance on single-lead data analogous to mobile ECGs, we also developed 2 single-lead deep learning models by training models on lead I ("LVH-Net Lead I") or lead II ("LVH-Net Lead II") from the 12-lead ECG. We compared the performance of the LVH-Net models to alternative models fit on (1) age, sex, and standard ECG measures, and (2) clinical ECG-based rules for diagnosing LVH. The areas under the receiver operator characteristic curve of LVH-Net by specific LVH etiology were cardiac amyloidosis 0.95 [95% CI, 0.93-0.97], hypertrophic cardiomyopathy 0.92 [95% CI, 0.90-0.94], aortic stenosis LVH 0.90 [95% CI, 0.88-0.92], hypertensive LVH 0.76 [95% CI, 0.76-0.77], and other LVH 0.69 [95% CI 0.68-0.71]. The single-lead models also discriminated LVH etiologies well. An artificial intelligence-enabled ECG model is favorable for detection and classification of LVH and outperforms clinical ECG-based rules.

Significance of Beta-Blocker in Patients with Hypertensive Left Ventricular Hypertrophy and Myocardial Ischemia.

Arterial Hypertension (HTN) is a key risk factor for left ventricular hypertrophy (LVH) and a cause of ischemic heart disease (IHD). The association between myocardial ischemia and HTN LVH is strong because myocardial ischemia can occur in HTN LVH even in the absence of significant stenoses of epicardial coronary arteries. To analyze pathophysiological characteristics/co-morbidities precipitating myocardial ischemia in patients with HTN LVH and provide a rationale for recommending beta-blockers (BBs) to prevent/treat ischemia in LVH. We searched PubMed, SCOPUS, PubMed, Elsevier, Springer Verlag, and Google Scholar for review articles and guidelines on hypertension from 01/01/2000 until 01/05/2022. The search was limited to publications written in English. HTN LVH worsens ischemia in coronary artery disease (CAD) patients. Even without obstructive CAD, several pathophysiological mechanisms in HTN LVH can lead to myocardial ischemia. In the same guidelines that recommend BBs for patients with HTN and CAD, we could not find a single recommendation for BBs in patients with HTN LVH but without proven CAD. There are several reasons for the proposal of using some BBs to control ischemia in patients with HTN and LVH (even in the absence of obstructive CAD). Some BBs ought to be considered to prevent/treat ischemia in patients with HTN LVH (even in the absence of obstructive CAD). Furthermore, LVH and ischemic events are important causes of ventricular tachycardia, ventricular fibrillation, and sudden cardiac death; these events are another reason for recommending certain BBs for HTN LVH.