Hypertensive Left Ventricular Hypertrophy Research Articles

Value of Monocyte to High-Density Lipoprotein Cholesterol Ratio in Screening of Left Ventricular Hypertrophy in Young and Middle-Aged Patients With Essential Hypertension

Abstract Background To investigate the relationships of monocyte to high-density lipoprotein cholesterol (HDL-C) ratio (MHR) with left ventricular hypertrophy (LVH) in young and middle-aged patients with essential hypertension (EH). Methods A retrospective analysis was performed on clinical data of 294 young and middle-aged patients with EH (aged from 18 to 65 years old). According to the left ventricular mass index (LVMI), the patients were divided into LVH (n = 98) and non-LVH (n = 196) groups. The data on echocardiography, routine blood test, biochemical examination, and so on were collected in all subjects, then LVMI and MHR were calculated. The association between MHR and hypertensive LVH was analyzed by correlation and binary logistic regression analyses. The receiver operating characteristic curve (ROC) was used to determine the predict value of MHR. Results MHR was higher while HDL-C was lower in the LVH group compared with the non-LVH group (MHR: 0.47 ± 0.11 vs. 0.33 ± 0.12, P < 0.001; HDL-C: 1.05 [0.94–1.22] vs. 1.27 [1.07–1.47] mmol/l, P < 0.001). Correlation analysis showed that LVMI was positively correlated with MHR (r = 0.381, P < 0.001). Multivariate logistic regression analysis showed that MHR was an independent risk factor for LVH in young and middle-aged EH patients (odds ratio = 2.914, 95% confidence interval [CI] 2.084–4.068, P < 0.001) after adjusting for body mass index, smoking, HDL-C, and other confounding factors. The area under the ROC curve of MHR for predict LVH was 0.831 (95% CI 0.782–0.880), and the optimal cutoff value of MHR was 0.37, with a sensitivity of 93.9% and a specificity of 75.5%. Conclusions MHR is positively correlated with LVH in young and middle-aged patients with EH. MHR is an independent risk factor for LVH in this population, and can be used for LVH risk screening.

The Correlation Between ABPM Parameters and Left Ventricular Hypertrophy in Pediatric Essential Hypertension.

ObjectiveTo explore the association of dipping pattern and blood pressure load with left ventricular hypertrophy (LVH) in pediatric essential hypertension.Materials and MethodsThrough an echocardiography monitor and an ambulatory blood pressure monitor of 425 children and adolescents diagnosed with essential hypertension with no treatment received, we identified 140 cases of LVH. Grouping patients according to LVH (LVH, N = 140; n-LVH, N = 285), we further evaluated their ambulatory blood pressure monitoring (ABPM) parameters by comparing dipping patterns between groups. A multivariable logistic regression analysis was used to determine the effect of blood pressure load on LVH.ResultsNo significant difference was found in systolic or diastolic blood pressure dipping patterns between groups (P = 0.161, P = 0.139). However, compared to the n-LVH group, the LVH group presented significant elevated nighttime systolic blood pressure (SBP) (P < 0.05), while nighttime DBP remained stable (P = 0.391), resulting in higher daytime and nighttime SBP loads, higher nighttime DBP load, and higher 24-h SBP load (P < 0.05). Notably, our multivariable logistic regression has shown that this trend of 24-h SBP load acts independently as a critical risk factor for LVH.ConclusionCollectively, we observed a correlation between BP load and LVH in pediatric hypertension. Our data demonstrated that SBP load has a more significant weight in LVH progression, and 24-h SBP load, in particular, acts as a critical early prognostic parameter for LVH in pediatric hypertension.

ASSOCIATION OF NDUFC2 POLYMORPHIC VARIANTS WITH LEFT VENTRICULAR HYPERTROPHY IN HUMAN HYPERTENSION

Objective: Previous experimental studies showed that a dysfunction of the NADH dehydrogenase (ubiquinone), the mitochondrial Complex I (CI), is associated with the development of left ventricular hypertrophy (LVH). A deficiency of Ndufc2 (a subunit of CI) impairs CI activity and causes severe mitochondrial dysfunction. The NDUFC2/rs11237379 polymorphic variant is associated with reduced gene expression and impaired mitochondrial function, contributing to increased susceptibility to vascular diseases. We examined the association of NDUFC2/rs11237379 and another NDUFC2 polymorphic variant (rs641836) with the development of LVH in hypertensive patients. Design and method: Two-hundred-fourty-six hypertensive subjects (147 male, 59.7%) with a mean age of 59 ± 15 years were studied. Seventy-nine individuals (32%) presented LVH. Results: The association analysis for both SNPs showed that hypertensive patients carrying the TT genotype at the NDUFC2/rs11237379 had a significant increase of echocardiographically assessed septal thickness (p = 0.001), posterior wall thickness (p = 0.003), relative wall thickness (RWT) (p = 0.01), LV mass/ body surface area (BSA) (p = 0.012) and LV mass/height2.(p = 0.0033) compared to subjects carrying either CC or CT genotypes. To better dissect the genetic effect, a covariate ANOVA was performed for each cardiac variable, considering age, gender, body mass index (BMI), office blood pressure (BP), antihypertensive treatment with a combination of 2 or more drugs and the number of BP-lowering agents as covariates. The adjustment for covariates revealed significant differences for septal thickness (p = 0.07), posterior wall thickness (p = 0.008), RWT (p = 0.021), LV mass/BSA (p = 0.03). With regard to NDUFC2/rs641836, hypertensive subjects carrying the mutant A allele had a significant increase of septal thickness (p = 0.001), posterior wall thickness (p = 0.001), RWT (p = 0.005), LV mass (p = 0.001), LV mass/BSA(p = 0.001), LV mass/height2.7(p = 0.002) compared to wild-type homozygotes. After adjustment for covariates, the results were significant 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). Conclusions: Our results demonstrate for the first time a significant association of NDUFC2 variants with LVH in hypertensives and highlight a novel role of CI dependent mitochondrial dysfunction on increased susceptibility to cardiac damage in human hypertension. This study paves the way of a new pathophysiological mechanism of LVH which may lead to new clinical strategies.

Cardiovascular implications in adolescent and young adult hypertension.

Hypertension is one of the most prevalent diseases in the United States, affecting an estimated 3.5% of children and adolescents. It can be adversely affect most organ systems but is particularly detrimental to the heart and vascular systems. The repercussions can be gauged through well-established measures of cardiovascular function including left ventricular mass index (LVMI), left ventricular hypertrophy (LVH), carotid intima media thickness (cIMT), and aortic stiffness. Cardiovascular function is also affected by underlying etiologies of hypertension including chronic kidney disease, polycystic kidney disease, coarctation of the aorta, adrenal disorders, renal artery stenosis, obstructive sleep apnea, as well as various drugs and medications (decongestants, stimulants, Non-steroidal Anti-inflammatory Drugs (NSAIDs), and steroids). An exhaustive literature search was conducted for clinical data regarding pediatric hypertension. Sixty-seven articles were incorporated with data on 189,477 subjects total. The data was then extracted and categorized as relating to hypertension incidence, LVMI, LVH, cIMT, and/or aortic stiffness. The prevalence of pediatric ( 18 years) hypertension extracted from 47 studies from 1994 to 2018 averaged 4%. The LVMI assessed over 7 studies (n = 661) averaged 39.3 g/ in the hypertensive cohort and 30.1 g/ in the control cohort. The cIMT assessed over 7 studies (n = 580) averaged 0.55 mm in the hypertensive cohort and 0.49 mm in the control cohort. Ambulatory arterial stiffness parameters assessed over 5 studies (n = 573) in the normotensive cohort averaged 99.73 mmHg, 69.81 mmHg, 76.85 mmHg, and 46.90 mmHg, for SBP, DBP, MAP, and PP respectively. Ambulatory arterial stiffness parameters assessed over 5 studies (n = 573) in the hypertensive cohort averaged 129.56 mmHg, 73.69 mmHg, 95.08 mmHg, and 56.80 mmHg, for SBP, DBP, MAP, and PP respectively. The significance of pediatric hypertension is emphasized by evidence of early cardiovascular disease as demonstrated by non-invasive measures including cIMT and arterial stiffness parameters, and target organ damage and including LVH and LVMI factors. Thus, early diagnosis and treatment of high blood pressure is paramount for improving long term cardiovascular health and preventing long term morbidity and mortality.

Discussion on Significance of Cardiac Ultrasound on the Diagnosis of Hypertensive Left Ventricular Hypertrophy with Left Heart Failure

Discussion on Significance of Cardiac Ultrasound on the Diagnosis of Hypertensive Left Ventricular Hypertrophy with Left Heart Failure

Network Meta-analysis of oral blood-activating and stasis-removing Chinese patent medicines in treatment of hypertensive left ventricular hypertrophy

This study was designed to assess the clinical efficacy of oral blood-activating and stasis-removing Chinese patent medicines in treating hypertensive left ventricular hypertrophy(LVH) based on network Meta-analysis. The clinical randomized controlled trials(RCTs) concerning the treatment of hypertensive LVH with oral blood-activating and stasis-removing Chinese patent medicines were retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, Web of Science, and Cochrane Library from their inception to September 2021. Two researchers independently completed the literature screening, data extraction, and quality evaluation. The data were then analyzed by RevMan 5.3, Stata 15.1, and ADDIS 1.16.8. Finally, a total of 31 RCTs were included, involving 3 001 patients and four oral blood-activating and stasis-removing Chinese patent medicines. In terms of the alleviation of heart damage, the Chinese patent medicines combined with conventional western medicine groups were superior to the conventional western medicine groups in lo-wering the left ventricular mass index(LVMI). There was no significant difference in LVMI, left ventricular ejection fraction(LVEF), or the ratio of early diastolic peak flow velocity to late diastolic peak flow velocity(E/A) between different Chinese patent medicines combined with conventional western medicine groups. Xinnao Shutong Capsules/Tablets combined with conventional western medicine had the best efficacy in reducing LVMI and elevating LVEF, while Xinkeshu Capsules/Tablets combined with conventional western medicine had the best effect in improving E/A. In the control of blood pressure, when all Chinese patent medicines except for Xinnao Shutong Capsules/Tablets were combined with conventional western medicine, the resulting systolic blood pressure(SBP) and diastolic blood pressure(DBP) were significantly lower than those in the conventional western medicine group. Xinkeshu Capsules/Tablets combined with conventional western medicine produced the best effect in reducing SBP and DBP, followed by Xinnao Shutong Capsules/Tablets. In terms of safety, no serious adverse reactions occurred in all trials. The four oral blood-activating and stasis-removing Chinese patent medicines included in this study exhibited obvious advantages in the treatment of hypertensive LVH when they were combined with conventional western medicine, with the best effects observed in the Xinnao Shutong Capsules/Tablets combined with conventional western medicine group. However, due to the limitation of the quantity and quality of the included articles, the conclusion of this study still needs to be verified by more high-quality, multi-center, and large-sample RCTs.

Abstract EP29: Sex Differences In Anxiety Associated With Left Ventricular Hypertrophy And Transmural Dispersion Of Repolarization In Hypertensive Patients

Background: Previous studies showed that hypertensive with anxiety have a higher mean left ventricular mass index (LVMI) and QTc dispersion. This study explores the associations between anxiety and left ventricular hypertrophy (LVH) as well as transmural dispersion of repolarization (TDR) (as detected by T peak-T end interval/QT interval, Tp-Te/QT ratio) in hypertensive patients. Methods: A total of 353 uncomplicated hypertensive patients were enrolled at Shaanxi Provincial People’s Hospital from 2017 to 2021. All enrolled subjects completed the Hamilton Anxiety Scale (HAMA). HAM-A score ≥14 was defined as the presence of anxiety. The association between HAM-A and hypertensive LVH was estimated with logistic regression models. The association between HAM-A score and Tp-Te/QT was estimated with linear regression model (adjusted for age, sex, body mass index, smoking, creatinine, uric acid, triglyceride, total cholesterol, low density lipoprotein cholesterol, and high-density lipoprotein cholesterol). This study was approved by the Ethics Committee of Shaanxi Provincial People’s Hospital and performed in keeping with the requirements of the Declaration of Helsinki. Results: Participants were divided into two groups according to anxiety or not. The LVMI was significantly higher in hypertensive patients with anxiety than hypertensive patients without anxiety (no anxiety: 84.36±23.82, anxiety: 105.75±25.45, g/m 2 , P &lt;0.001). The HAM-A score was positive correlated with LVMI (r=0.578, P &lt;0.001) and Tp-Te/QT (r=0.252, P &lt;0.001). In logistic regression models, hypertensive patients with anxiety had a higher risk of hypertensive LVH than hypertensive patients without anxiety (unadjusted OR, 2.86, 95% CI, 1.65-4.93, P &lt;0.001; adjusted OR, 2.62, 95% CI, 1.49-4.64, P &lt;0.001). Linear regression analysis also showed that HAM-A score was associated with Tp-Te/QT ratio (unadjusted β, 0.002, 95% CI, 0.001-0.002, P &lt;0.001; adjusted β, 0.002, 95% CI, 0.001-0.002, P &lt;0.001). There was an interaction between sex and anxiety in regard to LVH risk ( P for interaction = 0.035) and increased Tp-Te/QT ( P for interaction = 0.014). After stratification by sex, the anxiety group had a higher risk of hypertensive LVH than no anxiety group in male (unadjusted OR, 5.73, 95% CI, 2.43-13.50, P &lt;0.001; adjusted OR, 5.39, 95% CI, 2.13-13.66, P &lt;0.001) but not in female (unadjusted OR, 1.70, 95% CI, 0.82-3.53, P =0.152; adjusted: OR, 1.62, 95% CI, 0.76-3.45, P =0.209) hypertensive patients. HAM-A score was also associated with Tp-Te/QT ratio in male (unadjusted β, 0.003, 95% CI, 0.002-0.004, P &lt;0.001; adjusted β, 0.003, 95% CI, 0.001-0.004, P &lt;0.001) but not in female (unadjusted β, 0.001, 95% CI, -0.0001-0.002, P =0.061; adjusted β, 0.001, 95% CI, -0.0001-0.002, P =0.086). Conclusion: Our data indicated that anxiety is associated with LVH and increased TDR in male but not female hypertensive patients.

Comprehensive bioinformatics analysis identifies LAPTM5 as a potential blood biomarker for hypertensive patients with left ventricular hypertrophy.

Left ventricular hypertrophy (LVH) is a pivotal manifestation of hypertensive organ damage associated with an increased cardiovascular risk. However, early diagnostic biomarkers for assessing LVH in patients with hypertension (HT) remain indefinite. Here, multiple bioinformatics tools combined with an experimental verification strategy were used to identify blood biomarkers for hypertensive LVH. GSE74144 mRNA expression profiles were downloaded from the Gene Expression Omnibus (GEO) database to screen candidate biomarkers, which were used to perform weighted gene co-expression network analysis (WGCNA) and establish the least absolute shrinkage and selection operator (LASSO) regression model, combined with support vector machine-recursive feature elimination (SVM-RFE) algorithms. Finally, the potential blood biomarkers were verified in an animal model. A total of 142 hub genes in peripheral blood leukocytes were identified between HT with LVH and HT without LVH, which were mainly involved in the ATP metabolic process, oxidative phosphorylation, and mitochondrial structure and function. Notably, lysosomal associated transmembrane protein 5 (LAPTM5) was identified as the potential diagnostic marker of hypertensive LVH, which showed strong correlations with diverse marker sets of reactive oxygen species (ROS) and autophagy. RT-PCR validation of blood samples and cardiac magnetic resonance imaging (CMRI) showed that the expression of LAPTM5 was significantly higher in the HT with LVH model than in normal controls, LAPTM5 demonstrated a positive association with the left ventricle wall thickness as well as electrocardiogram (ECG) parameters widths of the QRS complex and QTc interval. In conclusion, LAPTM5 may be a potential biomarker for the diagnosis of LVH in patients with HT, and it can provide new insights for future studies on the occurrence and the molecular mechanisms of hypertensive LVH.

Magnetic Resonance for Differential Diagnosis of Left Ventricular Hypertrophy: Diagnostic and Prognostic Implications.

Background: Left ventricular hypertrophy (LVH) may be due to different causes, ranging from benign secondary forms to severe cardiomyopathies. Transthoracic Echocardiography (TTE) and ECG are the first-level examinations for LVH diagnosis. Cardiac magnetic resonance (CMR) accurately defines LVH type, extent and severity. Objectives: to evaluate the diagnostic and prognostic role of CMR in patients with TTE and/or ECG evidence of LVH. Methods: We performed CMR in 300 consecutive patients with echocardiographic and/or ECG signs of LVH. Results: Overall, 275 patients had TTE evidence of LVH, with initial suspicion of hypertrophic cardiomyopathy (HCM) in 132 (44%), cardiac amyloidosis in 41 (14%), hypertensive LVH in 48 (16%), aortic stenosis in 4 (1%), and undetermined LVH in 50 (16%). The initial echocardiographic diagnostic suspicion of LVH was confirmed in 172 patients (57.3%) and changed in 128 patients (42.7%, p < 0.0001): the diagnosis of HCM increased from 44% to 71% of patients; hypertensive and undetermined LVH decreased significantly (respectively to 4% and 5%). CMR allowed for a diagnosis in 41 out of 50 (82%) patients with undetermined LVH at TTE. CMR also identified HCM in 17 out of 25 patients with apparently normal echocardiography but with ECG criteria for LVH. Finally, the reclassification of the diagnosis by CMR was associated with a change in survival risk of patients: after CMR reclassification, no events occurred in patients with undetermined or hypertensive LVH. Conclusions: CMR changed echocardiographic suspicion in almost half of patients with LVH. In the subgroup of patients with abnormal ECG, CMR identified LVH (particularly HCM) in 80% of patients. This study highlights the indication of CMR to better characterize the type, extent and severity of LVH detected at echocardiography and suspected with ECG.

Elevated plasma macrophage migration inhibitor factor is associated with hypertension and hypertensive left ventricular hypertrophy.

Previous studies have found that the macrophage migration inhibitor factor is associated with endothelial dysfunction and ventricular remodelling. The aim of this study was to explore the potential relationship between plasma macrophage migration inhibitor factor levels and hypertension and hypertensive left ventricular hypertrophy. A total of 308 participants (including 187 uncomplicated hypertensive patients and 121 healthy controls) were enroled from 2017 to 2019. The association between macrophage migration inhibitor factors and hypertension and hypertensive left ventricular hypertrophy was estimated with univariate and multivariate logistic regression models. Elevated macrophage migration inhibitor factor was associated with the development of hypertension (second tertile: adjusted OR, 2.27, 95% CI, 1.24-4.16, P = 0.008; third tertile: adjusted OR, 5.43, 95% CI, 2.75-10.71, P < 0.001; compared with the first tertile). In addition, we assessed the association between macrophage migration inhibitor factor and left ventricular hypertrophy in hypertensive patients (n = 187). Plasma macrophage migration inhibitor factor was significantly correlated with hypertensive left ventricular mass index (r = 0.580, P < 0.001). In patients with hypertension, an elevated macrophage migration inhibitor factor was significantly associated with hypertensive left ventricular hypertrophy (second tertile: adjusted OR, 3.20, 95% CI, 1.17-8.78, P = 0.024; third tertile: adjusted OR, 24.95, 95% CI, 8.72-71.41, P < 0.001; compared with the first tertile). Receiver operating characteristic analysis indicated that macrophage migration inhibitor factor had reasonable predictive accuracy for the development of hypertensive left ventricular hypertrophy (area under curve 0.84, 95% CI 0.78-0.90, P < 0.001). Our data indicated that elevated macrophage migration inhibitor factor is associated with hypertension and hypertensive left ventricular hypertrophy.

Comparative Study of Electrocardiographic and Echocardiographic Evidence of Left Ventricular Hypertrophy in Systemic Hypertension

Background and Aims: Hypertension is a common health problem. Left ventricular hypertrophy, a condition in hypertension is a risk factor for myocardial infarction, stroke and heart failure. This study aims to detect left ventricular hypertrophy in hypertensive patients using Electrocardiography and echocardiography. Methods: In this descriptive cross-sectional study; 143 patients of Hypertension from February 2019 to August 2019 were enrolled. They were evaluated for left ventricular hypertrophy using electrocardiography and echocardiography. Sokolow-Lyon and Cornell Voltage electrocardiographic criteria were used and their sensitivities and specificities to detect left ventricular hypertrophy were calculated taking echocardiography as a gold standard method. Results: The mean age of the study population was 58.69 ± 11.33 years. Mean duration of hypertension was 4.72 ±3.2 years. The mean systolic and diastolic blood pressure were 137 ± 15.42 mmHg and 84 ± 10.5 mmHg respectively. Out of 143 study population, 30(21%) of them had left ventricular hypertrophy on electrocardiography as defined by Sokolow-Lyon criteria, and 29(20.3%) had left ventricular hypertrophy on electrocardiography as per Cornell Voltage criteria. On combining both Sokolow-Lyon and Cornell Voltage criteria, 37(25.9%) of the study population had left ventricular hypertrophy on electrocardiography (either as per Sokolow-Lyon or Cornell Voltage criteria). On echocardiography, 62(43.4%) of them were found to have left ventricular hypertrophy. Conclusions: Electrocardiography is a less sensitive tool to diagnose Left Ventricular Hypertrophy in hypertension but its specificity is high (&gt;95%). Investigation of choice to detect Left Ventricular Hypertrophy in hypertensive people is still the echocardiography.

Reversal of hypertensive heart disease: a multiple linear regression model.

Background: The development of left ventricular hypertrophy in primary hypertension increases cardiovascular mortality and morbidity. Reversal of left ventricular hypertrophy through therapeutic control of blood pressure reduces the risk of adverse cardiovascular incidents. Objective: In our study, we explored for the determinants of left ventricular hypertrophy regression. Methods: A cohort (n=217) of patients with hypertensive left ventricular hypertrophy was identified by screening consecutive patients in medical outpatient unit. The primary inclusion criteria were (i) Blood pressure more than140/90 mm of Hg (ii) Left Ventricular Mass Index more than 115 and 95 gm/m2 for males and females respectively. Left Ventricular Mass Index was determined by echocardiography at the time of recruitment and after 24 weeks of standard pharmacotherapy. The change in Left Ventricular Mass Index was modelled using multiple linear regression with both categorical and continuous explanatory variables. The effect of drug therapy on change in Left Ventricular Mass Index was tested in the model with dummy coded variables for the treatment categories. Results: In simple linear regression, the variables significantly correlating with change in Left Ventricular Mass Index were baseline Left Ventricular Mass Index (r=0.62, p<0.001), change in systolic blood pressure (r=0.22, p=0.001), change in mean blood pressure (r=0.16, p=0.02), baseline systolic blood pressure (r=0.15, p=0.02), age (r=0.12, p=0.09) and diabetes (r=0.12, p=0.09). The best fit model (r2=0.408) retained baseline Left Ventricular Mass Index (β=0.59, p<0.001), change in systolic blood pressure (β=0.14, p=0.01) and diabetes (β=-0.104, p=0.05) as the significant predictors. Introduction of treatment effect into the model non-significantly increased the fit of the model (r2=0.414, p=0.27-0.98). Conclusions: Pre-treatment Left Ventricular Mass Index and reduction in systolic blood pressure were the major determinants of left ventricular hypertrophy regression. We also observed that there is lesser left ventricular hypertrophy regression in diabetic patients, warranting future research to explore glycaemic control as a modifiable factor in left ventricular hypertrophy reversal.

Efficacy of shear wave elasticity for evaluating myocardial hypertrophy in hypertensive rats

Shear wave (SW) imaging is a novel ultrasound-based technique for assessing tissue characteristics. SW elasticity may be useful to assess the severity of hypertensive left ventricular (LV) hypertrophy. This study aimed to evaluate the efficacy of SW elasticity for assessing the degree of myocardial hypertrophy using hypertensive rats. Rats were divided into hypertension group and control group. SW elasticity was measured on the excised heart. Myocardial hypertrophy was assessed histologically. LV weight was greater in hypertension group. An increase in interventricular septum and LV free wall thicknesses was observed in hypertension group. SW elasticity was significantly higher in hypertension group than in control group (14.6 ± 4.3 kPa vs. 6.5 ± 1.1 kPa, P < 0.01). The cross-sectional area of cardiomyocytes was larger in hypertension group than in control group (397 ± 50 μm2 vs. 243 ± 14 μm2, P < 0.01), and SW elasticity was positively correlated with the cross-sectional area of cardiomyocytes (R = 0.96, P < 0.01). This study showed that SW elasticity was higher in hypertensive rats and was closely correlated with the degree of myocardial hypertrophy, suggesting the efficacy of SW elasticity for estimating the severity of hypertensive LV hypertrophy.

Abstract 13312: Comprehensive Sequencing of Small Non-Coding RNA Reveals Plasma Circulating Biomarkers of Hypertrophic Cardiomyopathy and Dysregulated Signaling Pathways

Background: Hypertrophic cardiomyopathy (HCM) is caused by mutations in the genes essential in normal myocardial contraction. However, it remains unclear through which signaling pathways gene mutations mediate the development of HCM. Growing evidence indicates that small non-coding RNAs (snRNAs) play important roles in post-transcriptional regulation of gene expression. Hypothesis: Comprehensive sequencing of snRNAs in plasma reveals circulating HCM biomarkers and differentially regulated signaling pathways. Methods: We conducted a multicenter case-control study of cases with HCM and age-, sex-, and body mass index-matched controls with hypertensive left ventricular hypertrophy. We carried out RNA-seq of 3293 snRNAs in plasma. We performed a sparse partial least squares discriminant analysis to develop snRNA-based discrimination model using samples retrieved during the first two-thirds of the study period (the training set). We prospectively tested the discriminative ability in independent samples that were collected thereafter (the test set). We also identified signaling pathways associated with snRNAs that were significantly dysregulated in HCM with Bonferroni-adjusted P&lt;0.05. Results: The study included 324 patients (165 cases and 159 controls; n=224 in the training set, n=100 in the test set). Using the transcriptomics-based model derived from the training set, the area under the receiver-operating-characteristic curve in the test set was 0.89 (95%CI 0.81-0.96; Figure ). Pathway analysis revealed that the Ras-MAPK pathway was upregulated in HCM (false discovery rate [FDR]=0.000002). Pathways involved in inflammation and fibrosis - e.g., TNF (FDR=0.000003) and TGF-β (FDR=0.002) - were also upregulated. Conclusions: This study serves as the largest-scale investigation to reveal circulating snRNA biomarkers of HCM and exhibits both novel (e.g., Ras-MAPK) and known (e.g., TNF, TGF-β) pathways that are differentially regulated in HCM.

Comparing echocardiographic characteristics in genotype positive-phenotype positive hypertrophic cardiomyopathy and hypertensive left ventricular hypertrophy.

There is little information about hypertrophic cardiomyopathy (HCM) with pathologic genetic mutations and concurrent hypertension (HTN). Hypertensive left ventricular hypertrophy (LVH) does not exclude an underlying genetic aetiology. This was a single-centre case-control study of 39 adults with pathologic HCM mutations, confirmed by genetic testing, compared to 39 age- and gender-matched patients with hypertensive LVH. The gene-positive HCM cohort was further stratified by the coexisting presence or absence of HTN. Clinical and echocardiographic characteristics were compared. Of 39 gene-positive HCM, 43.6% (17/39) had concurrent HTN. The gene-positive HCM cohort had larger left atrial (LA) area (22.1 cm2 vs. 18.9 cm2, P = 0.002), more diastolic predominant pulmonary vein flow (38.5% vs. 7.7%, P = 0.001), and more moderate diastolic dysfunction (33.3% vs. 12.8%, P = 0.032) when compared with the hypertensive LVH cohort. Greater left ventricular (LV) mass (277.7 g vs. 207.7 g, P = 0.025), increased frequency of severe LVH (58.8% vs. 27.3%, P = 0.047), and more abnormal global longitudinal strain (GLS) (-14.1% vs. -16.9%, P = 0.049) was observed in the gene-positive HCM cohort with concurrent HTN. Gene-positive HCM, compared to hypertensive LVH, is characterized by more advanced diastolic dysfunction and larger LA size. Gene-positive HCM patients with concomitant HTN had greater LV mass, more severe LVH, and more abnormal GLS, suggesting HTN may negatively affect the progression of myocardial dysfunction in genetic HCM. LVH out-of-proportion to pressure burden in HTN patients should raise suspicion of underlying genetic HCM.

Comprehensive proteomics profiling reveals molecular pathways that are differentially regulated in hypertrophic cardiomyopathy and correlate with clinical markers of disease severity

Abstract Background Hypertrophic cardiomyopathy (HCM) is caused by mutations in the genes coding for proteins essential in normal myocardial contraction. However, it remains unclear through which molecular pathways gene mutations mediate the development and progression of HCM. Purpose To determine protein biomarkers and molecular pathways that are differentially regulated in HCM and correlated with disease severity. Methods We conducted a multicenter case-control study of cases with HCM and controls with hypertensive left ventricular hypertrophy. We carried out plasma proteomics profiling of 1681 proteins using the SOMAscan assay. We performed a sparse partial least squares discriminant analysis to develop a proteomics-based discrimination model with data from 1 institution (i.e., the training set). We tested the discriminative ability in independent samples from the other institutions (i.e., the test set). We executed pathway analysis using significantly dysregulated proteins with Bonferroni-corrected p&amp;lt;0.05. Pathways with false discovery rate (FDR) &amp;lt;0.05 and dysregulation of ≥5 member proteins were declared positive. In HCM, we also identified proteins with significant correlation with clinical markers of disease severity (e.g., New York Heart Association [NYHA] class, left atrial diameter) and performed pathway analysis. Results The study included 266 cases and 167 controls (n=308 in the training set; n=125 in the test set). Using the proteomics-based model derived from the training set, the area under the receiver-operating-characteristic curve was 0.89 (95% confidence interval [CI] 0.83–0.94, p&amp;lt;0.001) in the test set (Figure). The sensitivity was 0.84 (95% CI 0.76–0.92) and the specificity was 0.78 (95% CI 0.66–0.90). A total of 508 proteins were significantly associated with the disease status. As shown in the Table, pathway analysis revealed that the Ras-MAPK pathway, along with its upstream and downstream (e.g., Rap1, PI3K-Akt) pathways, was upregulated in HCM (FDR &amp;lt;0.001). Pathways involved in inflammation and fibrosis – e.g., the TGF-β pathway – were also found to be upregulated in HCM. In patients with HCM, 207 out of the 1681 proteins were significantly correlated with NYHA functional class. This number is more than twice as large as what would be expected by chance (i.e., 84 proteins at α=0.05 level). Pathway analysis of these 207 proteins showed upregulation of the Ras-MAPK and related pathways – e.g., PI3K-Akt, Rap1, and TNF. Similarly, 264 of the 1681 proteins were correlated with left atrial diameter in HCM. Pathway analysis of the 264 proteins revealed upregulation of the MAPK and the PI3K-Akt pathways. Conclusions This multicenter case-control study with independent validation serves as the largest-scale investigation with the most comprehensive proteomics profiling in HCM, exhibiting both novel (e.g., Ras-MAPK) and known (e.g., TGF-β) pathways that are differentially regulated in HCM and correlated with disease severity. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Institute of Health and American Heart Association Figure 1. ROC curveTable 1. Differentially regulated pathways

ANALYSIS OF ECHOCARDIOGRAPHIC AND MRI ANATOMICAL CHARACTERISTICS AND HEMODYNAMIC CHARACTERISTICS OF LEFT VENTRICULAR OUTFLOW TRACT STENOSIS

Objective: To analyze the anatomical morphological and hemodynamic characteristics of left ventricular outflow tract stenosis (LVOTS) by echocardiography and MRI. Methods: The Echocardiography data of 112 patients with LVOTS were retrospectively analyzed by measuring the basal interventricular septal thickness (IVST-b), the left ventricle posterior wall thickness (LVPWT), and the peak pressure gradient of LVOTS, as well as by observing the characteristics of spectral pattern and the presence of systolic anterior motion of mitral valve leaflets. A Siemens 3.0T MRI scanner was used to scan the contrast-enhanced left ventricular (LV) volume of all cases. The obtained end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV) and ejection fraction (EF) of LV were compared with the Echocardiography results. Results: The 112 patients were divided into four groups: hypertrophic obstructive cardiomyopathy (Group I, 42 cases), hypertensive left ventricular hypertrophy (Group II, 40 cases), basal septal hypertrophy in the elderly (Group III, 21 cases), and the subaortic membrane (Group IV, 9 cases). The continuous wave (CW) Doppler characteristic of Groups I, II, and III was broadsword-shaped jet, and that of Group IV was equilateral triangle-like spectrum. The IVST-b, IVST-b/LVPWT ratio and peak pressure gradient of LVOTS of Group I was significantly higher than those in Groups II and III ([Formula: see text]). The LVPWT of the first three groups was slightly correlated with the LVOTS peak pressure gradient ([Formula: see text], respectively, [Formula: see text]). There were no statistically significant differences between Echocardiography and MRI results regarding the LV EDV, ESV, SV, and EF ([Formula: see text]), and no statistically significant differences were found between Echocardiography and MRI results regarding the myocardial thicknesses of septal, anterior, lateral, and inferior walls ([Formula: see text]). The Pearson’s correlation analysis demonstrated correlations between MRI and Echocardiography results for LV EDV, ESV, SV, and EF ([Formula: see text], 0.002, 0.009, and [Formula: see text], respectively). The MRI enhancement was shown as delayed enhancement in 52 cases, localized enhancement in 8 cases, diffuse enhancement in 6 cases, and transmural enhancement in 3 cases, with abnormal enhancement lesions distributed in the area of ventricular septum free wall junctions and ventricular septum. Conclusion: Using MRI to evaluate LV function of hypertrophic cardiomyopathy is reliable and accurate. MRI enhancement can be used for the quantitative measurement of myocardial fibrosis. Echocardiography can distinguish the stenosis types of LVOTS. The IVST-b and existence of SAM may be important anatomical characteristics determining the degree of dynamic stenosis, and MRI combined with Echocardiography can provide important detailed information.

The high normal ankle brachial index is associated with left ventricular hypertrophy in hypertension patients among the Han Chinese

Left ventricular hypertrophy (LVH) is the most common target organs damage in the hypertension patients. Abnormal low (≤0.9) or high (≥1.40) ankle brachial index (ABI) are associated with an increased risk of cardiovascular events. However, the relationships between a high ABI in the normal range (0.9–1.4) and LVH in Han Chinese hypertension are not entirely elucidated. This study included 3953 hypertension patients aged 40–75 years among Han Chinese. Hypertension was defined as systolic blood pressure≥140 mm Hg, diastolic blood pressure≥90 mm Hg, or history of antihypertensive drug use. Left ventricular mass (LVM) was measured by transthoracic echocardiography. LVH was diagnosed by using the criteria of LVM ≥49.2 g/m2.7 for men and 46.7 g/m2.7 for women. Our study suggested that the ABI was higher in patients with LVH than in those without (1.13±0.11, 1.11±0.11, p < 0.001). The prevalence of LVH in patients with the lowest (0.9 < ABI≤1.03), second (1.04≤ABI≤1.11), the third (1.12≤ABI≤1.20), and the highest quartile (1.21≤ABI < 1.40) of ABI was 37.2%, 38.2%, 45.5%, 45.7%, respectively. Logistic regression analysis suggested that the highest and third quartile of ABI were significantly associated with increased LVH risk (multivariate‐adjusted OR of highest group:1.83; third group:1.61). The association of ABI at second quartile with LVH was nonsignificant. Similar results were observed in less than 60 years and without coronary heart disease or diabetes group. Our observations in Chinese patients with hypertension indicated high ABI may be an important risk factor for LVH in hypertension patients among Han Chinese, even in the normal range.

Comprehensive Proteomics Profiling Reveals Circulating Biomarkers of Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is caused by mutations in the genes coding for proteins essential in normal myocardial contraction. However, it remains unclear through which molecular pathways gene mutations mediate the development of HCM. The objectives were to determine plasma protein biomarkers of HCM and to reveal molecular pathways differentially regulated in HCM. We conducted a multicenter case-control study of cases with HCM and controls with hypertensive left ventricular hypertrophy. We performed plasma proteomics profiling of 1681 proteins. We performed a sparse partial least squares discriminant analysis to develop a proteomics-based discrimination model with data from 1 institution (ie, the training set). We tested the discriminative ability in independent samples from the other institution (ie, the test set). As an exploratory analysis, we executed pathway analysis of significantly dysregulated proteins. Pathways with false discovery rate <0.05 were declared positive. The study included 266 cases and 167 controls (n=308 in the training set; n=125 in the test set). Using the proteomics-based model derived from the training set, the area under the receiver operating characteristic curve was 0.89 (95% CI, 0.83-0.94) in the test set. Pathway analysis revealed that the Ras-MAPK (mitogen-activated protein kinase) pathway, along with its upstream and downstream pathways, was upregulated in HCM. Pathways involved in inflammation and fibrosis-for example, the TGF (transforming growth factor)-β pathway-were also upregulated. This study serves as the largest-scale investigation with the most comprehensive proteomics profiling in HCM, revealing circulating biomarkers and exhibiting both novel (eg, Ras-MAPK) and known (eg, TGF-β) pathways differentially regulated in HCM.

Neutrophil to Lymphocyte Ratio Is Increased and Associated With Left Ventricular Diastolic Function in Newly Diagnosed Essential Hypertension Children.

Aim: Hypertension is associated with cardiac structural and functional changes, including left ventricular hypertrophy (LVH) and LV systolic dysfunction diastolic dysfunction. Neutrophil-to-lymphocyte ratio (NLR) is a novel inflammatory biomarker associated with cardiovascular diseases. The current study aimed to evaluate NLR in children with newly diagnosed essential hypertension and its relationship between blood pressure and cardiac changes.Methods and Subjects: Sixty-five children with newly diagnosed essential hypertension and 54 healthy children were included. Clinical characteristics, blood cell counts, and biochemical parameters were collected. LVH was assessed by calculation of LV mass index (LVMI), and LV systolic function was evaluated by measuring LV ejection fraction and fractional shortening. LV diastolic function was primarily assessed with E/E′ ratio by Doppler and echocardiography.Results: The hypertension children had significantly higher LVMI and E/E′ ratio than the controls, whereas there was no difference in LV systolic function between the two groups. The NLR was significantly higher in the hypertension group than the control group. Moreover, NLR was positively correlated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels in the hypertension group. Additionally, a significantly positive correlation between NLR and E/E′ ratio was found in the hypertension group. However, NLR was not related to LVH and LV systolic function indicators in hypertension children.Conclusion: NLR is elevated in hypertension children, and it is associated positively with office blood pressure levels. Moreover, NLR may help assess LV diastolic function in hypertension children.