Sex-specific microRNAs in women with diabetes and left ventricular diastolic dysfunction or HFpEF associate with microvascular injury.
Ontology highlight
ABSTRACT:
SUBMITTER: Florijn BW
PROVIDER: S-EPMC7435264 | biostudies-literature | 2020 Aug
REPOSITORIES: biostudies-literature
Publications
Sex-specific microRNAs in women with diabetes and left ventricular diastolic dysfunction or HFpEF associate with microvascular injury.
Florijn Barend W BW Valstar Gideon B GB Duijs Jacques M G J JMGJ Menken Roxana R Cramer Maarten J MJ Teske Arco J AJ Ghossein-Doha Chahinda C Rutten Frans H FH Spaanderman Marc E A MEA den Ruijter Hester M HM Bijkerk Roel R van Zonneveld Anton Jan AJ
Scientific reports 20200818 1
Left ventricular diastolic dysfunction (LVDD) and heart failure with preserved ejection fraction (HFpEF) are microcirculation defects following diabetes mellitus (DM). Unrecognized HFpEF is more prevalent in women with diabetes compared to men with diabetes and therefore sex-specific diagnostic strategies are needed. Previously, we demonstrated altered plasma miRs in DM patients with microvascular injury [defined by elevated plasma Angiopoietin-2 (Ang-2) levels]. This study hypothesized the pres ...[more]
Similar Datasets
Project description:Aims:More than 50% of patients with heart failure have preserved ejection fraction characterized by diastolic dysfunction. The prevalance of diastolic dysfunction is higher in females and associates with multiple comorbidities such as hypertension (HT), obesity, hypercholesterolemia (HC), and diabetes mellitus (DM). Although its pathophysiology remains incompletely understood, it has been proposed that these comorbidities induce systemic inflammation, coronary microvascular dysfunction, and oxidative stress, leading to myocardial fibrosis, myocyte stiffening and, ultimately, diastolic dysfunction. Here, we tested this hypothesis in a swine model chronically exposed to three common comorbidities. Methods and results:DM (induced by streptozotocin), HC (produced by high fat diet), and HT (resulting from renal artery embolization), were produced in 10 female swine, which were followed for 6?months. Eight female healthy swine on normal pig-chow served as controls. The DM?+?HC?+?HT group showed hyperglycemia, HC, hypertriglyceridemia, renal dysfunction and HT, which were associated with systemic inflammation. Myocardial superoxide production was markedly increased, due to increased NOX activity and eNOS uncoupling, and associated with reduced NO production, and impaired coronary small artery endothelium-dependent vasodilation. These abnormalities were accompanied by increased myocardial collagen content, reduced capillary/fiber ratio, and elevated passive cardiomyocyte stiffness, resulting in an increased left ventricular end-diastolic stiffness (measured by pressure-volume catheter) and a trend towards a reduced E/A ratio (measured by cardiac MRI), while ejection fraction was maintained. Conclusions:The combination of three common comorbidities leads to systemic inflammation, myocardial oxidative stress, and coronary microvascular dysfunction, which associate with myocardial stiffening and LV diastolic dysfunction with preserved ejection fraction.
| S-EPMC5967461 | biostudies-literature
Project description:PurposeTo assess the impact of left ventricular (LV) diastolic dysfunction on left atrial (LA) phasic volume and function using dual-source CT (DSCT) and to find a viable alternative prognostic parameter of CT for LV diastolic dysfunction through quantitative evaluation of LA phasic volume and function in patients with LV diastolic dysfunction.Materials and methodsSeventy-seven patients were examined using DSCT and Doppler echocardiography on the same day. Reservoir, conduit, and contractile function of LA were evaluated by measuring LA volume (LAV) during different cardiac phases and all parameters were normalized to body surface area (BSA). Patients were divided into four groups (normal, impaired relaxation, pseudonormal, and restrictive LV diastolic filling) according to echocardiographic findings. The LA phasic volume and function in different stages of LV diastolic function was compared using one-way ANOVA analysis. The correlations between indexed volume of LA (LAVi) and diastolic function in different stages of LV were evaluated using Spearman correlation analysis.ResultsLA ejection fraction (LAEF), LA contraction, reservoir, and conduit function in patients in impaired relaxation group were not different from those in the normal group, but they were lower in patients in the pseudonormal and restrictive LV diastolic dysfunction groups (P < 0.05). For LA conduit function, there were no significant differences between the patients in the pseudonormal group and restrictive filling group (P = 0.195). There was a strong correlation between the indexed maximal left atrial volume (LAVmax, r = 0.85, P < 0.001), minimal left atrial volume (LAVmin, r = 0.91, P < 0.001), left atrial volume at the onset of P wave (LAVp, r = 0.84, P < 0.001), and different stages of LV diastolic function. The LAVi increased as the severity of LV diastolic dysfunction increased.ConclusionsLA remodeling takes place in patients with LV diastolic dysfunction. At the same time, LA phasic volume and function parameters evaluated by DSCT indicated the severity of the LV diastolic dysfunction. Quantitative analysis of LA phasic volume and function parameters using DSCT could be a viable alternative prognostic parameter of LV diastolic function.
| S-EPMC4436312 | biostudies-literature
Project description:Background and objectivesLeft ventricular diastolic dysfunction is known to be a marker of myocardial damage, in particular myocardial fibrosis resulting from hypertension (HT). However, few studies have shown an association between the grade of diastolic dysfunction and blood pressure classification. We investigated the association between diastolic dysfunction and prehypertension (preHT) in apparently healthy adults who underwent routine health examinations.Subjects and methodsThe study sample included 4261 Koreans, 45 to 64 years of age with no previous history of HT, diabetes mellitus, malignancy, proven coronary artery disease, or valvular heart disease based on echocardiography, who underwent routine health examinations including echocardiography. The subjects were classified into three groups based on resting blood pressure: prehypertensive, hypertensive, and normotensive.ResultsThe prevalence of preHT in our study was 42.1%. After adjusting for age, gender, smoking status, alcohol consumption, fasting blood sugar, serum lipid profile, and body mass index, left ventricular diastolic dysfunction grades 1 and 2 were significantly more frequent in subjects with preHT (odds ratio [OR] 1.66 [95% confidence interval {CI} 1.40-1.96] and 1.37 [95% CI 0.95-1.97], respectively). When analyzed according to gender, the increased OR was especially notable in males.ConclusionLeft ventricular diastolic dysfunction appears to be significantly associated with preHT in Korean middle-aged males.
| S-EPMC4965433 | biostudies-literature
Project description:BackgroundPatients with chronic kidney disease (CKD) and coincident heart failure with preserved ejection fraction (HFpEF) may constitute a distinct HFpEF phenotype. Osteopontin (OPN) is a biomarker of HFpEF and predictive of disease outcome. We recently reported that OPN blockade reversed hypertension, mitochondrial dysfunction, and kidney failure in Col4a3-/- mice, a model of human Alport syndrome.ObjectivesThe purpose of this study was to identify potential OPN targets in biopsies of HF patients, healthy control subjects, and human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs), and to characterize the cardiac phenotype of Col4a3-/- mice, relate this to HFpEF, and investigate possible causative roles for OPN in driving the cardiomyopathy.MethodsOGDHL mRNA and protein were quantified in myocardial samples from patients with HFpEF, heart failure with reduced ejection fraction, and donor control subjects. OGDHL expression was quantified in hiPS-CMs treated with or without anti-OPN antibody. Cardiac parameters were evaluated in Col4a3-/- mice with and without global OPN knockout or AAV9-mediated delivery of 2-oxoglutarate dehydrogenase-like (Ogdhl) to the heart.ResultsOGDHL mRNA and protein displayed abnormal abundances in cardiac biopsies of HFpEF (n = 17) compared with donor control subjects (n = 12; p < 0.01) or heart failure with reduced ejection fraction patients (n = 12; p < 0.05). Blockade of OPN in hiPS-CMs conferred increased OGDHL expression. Col4a3-/- mice demonstrated cardiomyopathy with similarities to HFpEF, including diastolic dysfunction, cardiac hypertrophy and fibrosis, pulmonary edema, and impaired mitochondrial function. The cardiomyopathy was ameliorated by Opn-/- coincident with improved renal function and increased expression of Ogdhl. Heart-specific overexpression of Ogdhl in Col4a3-/- mice also improved cardiac function and cardiomyocyte energy state.ConclusionsCol4a3-/- mice present a model of HFpEF secondary to CKD wherein OPN and OGDHL are intermediates, and possibly therapeutic targets.
| S-EPMC6546303 | biostudies-literature
Project description:The level of Galectin-3 (Gal-3) protein purportedly reflects an ongoing cardiac fibrotic process and has been associated with ventricular remodeling, which is instrumental in the development of heart failure with preserved ejection fraction (HFpEF) syndrome. The aim of this study was to investigate the potential use of Gal-3 in improved characterization of the grades of diastolic dysfunction as defined by echocardiography.Seventy HFpEF patients undergoing routine echocardiography were prospectively enrolled in the present monocentric study. Blood samples for measurements of Gal-3 and amino-terminal pro-brain natriuretic peptide (NT-proBNP) were collected within 24 hours pre- or post-echocardiographic examination. The classification of patients into subgroups based on diastolic dysfunction grade permitted detailed statistical analyses of the derived data.The Gal-3 serum levels of all patients corresponded to echocardiographic indices, suggesting HFpEF (E/A, P=0.03 and E/E', P=0.02). Gal-3 was also associated with progressive diastolic dysfunction, and increased levels corresponded to the course of disease (P=0.012). Detailed analyses of ROC curves suggested that Gal-3 levels could discriminate patients with grade III diastolic dysfunction (area under the curve [AUC]=0.770, P=0.005).Gal-3 demonstrates remarkable effectiveness in the diagnosis of patients suffering from severe grade diastolic dysfunction. Increasing levels of Gal-3 possibly reflect the progressive course of HFpEF, as classified by the echocardiographic grades of diastolic dysfunction.
| S-EPMC5895859 | biostudies-other
Project description:Despite the significant heart failure (HF) burden on society, easily applicable screening techniques, particularly for the early detection of asymptomatic left ventricular (LV) dysfunction, are lacking. The present study aimed to identify and test a set of urinary polypeptides that may indicate early LV diastolic dysfunction as defined by echocardiography in hypertensive patients in a cross-sectional case-control study nested within the FLEMish study on ENvironment, Genes and Health Outcome (FLEMENGHO).To identify potentially discriminating urinary biomarkers for LV diastolic dysfunction, we applied capillary electrophoresis coupled to mass spectrometry. In the discovery set, we compared 19 hypertensive patients with asymptomatic LV diastolic dysfunction with 19 healthy controls. In the absence of adjustment for multiple testing, 85 urinary peptides were different between cases and controls at a P-value of <0.033. With adjustment for multiple testing, three potential biomarkers remained significantly different between cases and controls (P ? 0.02). We combined the 85 potential biomarkers in a high-dimensional model (classifier), which we applied in a blinded manner to an independent test set of 16 hypertensive patients with symptomatic HF and 16 healthy controls. Upon unblinding, the area under the receiver operating characteristic curve (AUC) of the HF classification was 0.84 (95% CI: 0.70-0.98; P= 0.001).In asymptomatic hypertensive patients with LV diastolic dysfunction, we identified a set of urinary polypeptides specific for essential hypertension with LV diastolic dysfunction that subsequently distinguished hypertensive patients with overt HF from healthy controls.
| S-EPMC3705161 | biostudies-literature
Project description:ObjectiveIdentification of echocardiographic, hemodynamic and biochemical predictors of unfavorable prognosis after embolic strokes of undetermined etiology (ESUS) in patients at age <65.Patients and methodsOut of 520 ischemic stroke patients we selected 64 diagnosed with ESUS and additional 36 without stroke but with similar risk profile. All patients underwent echocardiography, non-invasive assessment of hemodynamic parameters using SphygmoCor tonometer and measurements of selected biomarkers. Follow-up time was 12 months.ResultsNine percent of patients died, and recurrent ischemic stroke occurred in 9% of patients only in the ESUS group. Atrial fibrillation (AF) occurred in 10% of patients and the ESUS group had a significantly poorer outcome of AF in the first 2 months after hospitalization. The outcome of re-hospitalization was 28% in the ESUS group and 17% in the control group. In the multivariate analysis mean early diastolic (E') mitral annular velocity (OR 0.75, 95% CI: 0.6-0.94; p=0.01) was significantly associated with cardiovascular hospitalizations. The only independent predictor of recurrent stroke was the ratio of peak velocity of early diastolic transmitral flow to peak velocity of early diastolic mitral annular motion (E/E') (OR 0.75, 95% CI: 0.6-0.94; p=0.01). E/E' was independently associated with composite endpoint (death, hospitalization and recurrent stroke) (OR 1.90, 95% CI 1.1-3.2, p=0.01).ConclusionThe indices of diastolic dysfunction are significantly associated with unfavorable prognosis after ESUS. There is a robust role for outpatient cardiac monitoring especially during the first 2 months after ESUS to detect potential AF.
| S-EPMC7955868 | biostudies-literature
Project description:Background and purposeLeft ventricular (LV) diastolic dysfunction, developed in relation to myocardial dysfunction and remodeling, is documented in 15%-25% of the population. However, its role in functional recovery and recurrent vascular events after acute ischemic stroke has not been thoroughly investigated.MethodsIn this retrospective observational study, we identified 2,827 ischemic stroke cases with adequate echocardiographic evaluations to assess LV diastolic dysfunction within 1 month after the index stroke. The peak transmitral filling velocity/mean mitral annular velocity during early diastole (E/e') was used to estimate LV diastolic dysfunction. We divided patients into 3 groups according to E/e' as follows: <8, 8-15, and ≥15. Recurrent vascular events and functional recovery were prospectively collected at 3 months and 1 year.ResultsAmong included patients, E/e' was 10.6±6.4: E/e' <8 in 993 (35%), 8-15 in 1,444 (51%), and ≥15 in 378 (13%) cases. Functional dependency or death (modified Rankin Scale score ≥2) and composite vascular events were documented in 1,298 (46%) and 187 (7%) patients, respectively, at 3 months. In multivariable analyses, ischemic stroke cases with E/e' ≥15 had increased odds of functional dependence or death at 3 months (adjusted OR [95% CI]: 1.73 [1.27-2.35]) or 1 year (1.47 [1.06-2.06]) and vascular events within 1 year (1.65 [1.08-2.51]). Subgroups with normal ejection fraction or sinus rhythm exhibited a similar overall pattern and direction.ConclusionsLV diastolic dysfunction was associated with poor functional outcomes and composite vascular events up to 1 year.
| S-EPMC4901948 | biostudies-literature
Project description:Diastolic dysfunction is a common pathology occurring in about one third of patients affected by heart failure. This condition may not be associated with a marked decrease in cardiac output or systemic pressure and therefore is more difficult to diagnose than its systolic counterpart. Compromised relaxation or increased stiffness of the left ventricle induces an increase in the upstream pulmonary pressures, and is classified as secondary or group II pulmonary hypertension (2018 Nice classification). This may result in an increase in the right ventricular afterload leading to right ventricular failure. Elevated pulmonary pressures are therefore an important clinical indicator of diastolic heart failure (sometimes referred to as heart failure with preserved ejection fraction, HFpEF), showing significant correlation with associated mortality. However, accurate measurements of this quantity are typically obtained through invasive catheterization and after the onset of symptoms. In this study, we use the hemodynamic consistency of a differential-algebraic circulation model to predict pulmonary pressures in adult patients from other, possibly non-invasive, clinical data. We investigate several aspects of the problem, including the ability of model outputs to represent a sufficiently wide pathologic spectrum, the identifiability of the model's parameters, and the accuracy of the predicted pulmonary pressures. We also find that a classifier using the assimilated model parameters as features is free from the problem of missing data and is able to detect pulmonary hypertension with sufficiently high accuracy. For a cohort of 82 patients suffering from various degrees of heart failure severity, we show that systolic, diastolic, and wedge pulmonary pressures can be estimated on average within 8, 6, and 6 mmHg, respectively. We also show that, in general, increased data availability leads to improved predictions.
| S-EPMC8281259 | biostudies-literature
Project description:Speckle tracking analysis (STE) of the left ventricle offers a new method to assess left ventricular (LV) diastolic function. LV diastolic strain measurements offer a non-invasive, global and direct measure of LV diastolic function. However, there is little data on normal values and the influence of anthropomorphic factors which is crucial in clinical practice for new techniques. The aims of this study were to formulate reference values for LV diastolic strain rate, elucidate effects of age and sex on LV diastolic strain analysis and compare STE measurements with conventional LV diastolic measurements. One-hundred-forty-seven healthy subjects aged 20-72 years (≥ 28 subjects per age decade) were prospectively included (Mean age 44 ± 13.7 years, 50% female) and examined with electrocardiography and 2D-echocardiography, including speckle tracking. Left ventricular peak early diastolic strain rate (Sre) was measured in the apical windows, using STE. Men had significantly lower LV Sre values than women (1.02 ± 0.22 vs. 1.18 ± 0.23, p value < 0.001). Left ventricular Sre was inversely associated with age, with values decreasing with ageing. An inverse relation was also found with blood pressure and body surface area. Linear regression analysis showed that LV Sre was independently associated with both age and sex. A multivariable linear regression analysis for LV Sre with conventional LV diastolic variables accounted for 70.9% of the variation of LV Sre, showing good model performance. Reference values for LV Sre are reported and found to be both age- and sex-dependent. Therefore we recommend age- and sex-specific references values to be used in daily clinical practice.
| S-EPMC6453864 | biostudies-literature