Dapagliflozin, inflammation and left ventricular remodelling in patients with type 2 diabetes and left ventricular hypertrophy
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SUBMITTER: Dihoum A
PROVIDER: S-EPMC11241903 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:BackgroundPatients with diabetes have a two to fourfold increased risk for development of and death from cardiovascular disease [CVD]. The current oral hypoglycaemic agents result in limited reduction in this cardiovascular risk. Sodium glucose linked co-transporter type 2 [SGLT2] inhibitors are a relatively new class of antidiabetic agent that have been shown to have potential cardiovascular benefits. In support of this, the EMPA-REG trial showed a striking 38% and 35% reduction in cardiovascular mortality and heart failure [HF] hospitalisation respectively. The exact mechanism (s) responsible for these effects remain (s) unclear. One potential mechanism is regression of Left ventricular hypertrophy (LVH).MethodsThe DAPA-LVH trial is a prospective, double-blind, randomised, placebo-controlled 'proof of concept' single-centre study that has been ongoing since January 2017. It is designed specifically to assess whether the SGLT2 inhibitor dapagliflozin regresses left ventricular [LV] mass in patients with diabetes and left ventricular hypertrophy [LVH]. We are utilising cardiac and abdominal magnetic resonance imaging [MRI] and ambulatory blood pressure monitoring to quantify the cardiovascular and systemic effects of dapagliflozin 10 mg once daily against standard care over a 1 year observation period. The primary endpoint is to detect the changes in LV mass. The secondary outcomes are to assess the changes in, LV volumes, blood pressure, weight, visceral and subcutaneous fat.DiscussionThis trial will be able to determine if SGLT2 inhibitor therapy reduces LV mass in patient with diabetes and LVH thereby strengthening their position as oral hypoglycaemic agents with cardioprotective benefits.Trial registrationClinical Trials.gov: NCT02956811 . Registered November 2016.
| S-EPMC5569551 | biostudies-literature
Project description:AimsHypertensive left ventricular hypertrophy (LVH) is associated with increased cardiovascular events. We previously developed the remodelling index (RI) that incorporated left ventricular (LV) volume and wall-thickness in a single measure of advanced hypertrophy in hypertensive patients. This study examined the prognostic potential of the RI in reference to contemporary LVH classifications.Methods and resultsCardiovascular magnetic resonance was performed in 400 asymptomatic hypertensive patients. The newly derived RI (EDV3t, where EDV is LV end-diastolic volume and t is the maximal wall thickness across 16 myocardial segments) stratified hypertensive patients: no LVH, LVH with normal RI (LVHNormal-RI), and LVH with low RI (LVHLow-RI). The primary outcome was a composite of all-cause mortality, acute coronary syndromes, strokes, and decompensated heart failure. LVHLow-RI was associated with increased LV mass index, fibrosis burden, impaired myocardial function and elevated biochemical markers of myocardial injury (high-sensitive cardiac troponin I), and wall stress. Over 18.3 ± 7.0 months (601.3 patient-years), 14 adverse events occurred (2.2 events/100 patient-years). Patients with LVHLow-RI had more than a five-fold increase in adverse events compared to those with LVHNormal-RI (11.6 events/100 patient-years vs. 2.0 events/100 patient-years, respectively; log-rank P < 0.001). The RI provided incremental prognostic value over and above a model consisting of clinical variables, LVH and concentricity; and predicted adverse events independent of clinical variables, LVH, and other prognostic markers. Concentric and eccentric LVH were associated with adverse prognosis (log-rank P = 0.62) that was similar to the natural history of hypertensive LVH (5.1 events/100 patient-years).ConclusionThe RI provides prognostic value that improves risk stratification of hypertensive LVH.
| S-EPMC8110315 | biostudies-literature
Project description:AimWe tested the hypothesis that dapagliflozin may regress left ventricular hypertrophy (LVH) in people with type 2 diabetes (T2D).Methods and resultsWe randomly assigned 66 people (mean age 67 ± 7 years, 38 males) with T2D, LVH, and controlled blood pressure (BP) to receive dapagliflozin 10 mg once daily or placebo for 12 months. Primary endpoint was change in absolute left ventricular mass (LVM), assessed by cardiac magnetic resonance imaging. In the intention-to-treat analysis, dapagliflozin significantly reduced LVM compared with placebo with an absolute mean change of -2.82g [95% confidence interval (CI): -5.13 to -0.51, P = 0.018]. Additional sensitivity analysis adjusting for baseline LVM, baseline BP, weight, and systolic BP change showed the LVM change to remain statistically significant (mean change -2.92g; 95% CI: -5.45 to -0.38, P = 0.025). Dapagliflozin significantly reduced pre-specified secondary endpoints including ambulatory 24-h systolic BP (P = 0.012), nocturnal systolic BP (P = 0.017), body weight (P < 0.001), visceral adipose tissue (VAT) (P < 0.001), subcutaneous adipose tissue (SCAT) (P = 0.001), insulin resistance, Homeostatic Model Assessment of Insulin Resistance (P = 0.017), and high-sensitivity C-reactive protein (hsCRP) (P = 0.049).ConclusionDapagliflozin treatment significantly reduced LVM in people with T2D and LVH. This reduction in LVM was accompanied by reductions in systolic BP, body weight, visceral and SCAT, insulin resistance, and hsCRP. The regression of LVM suggests dapagliflozin can initiate reverse remodelling and changes in left ventricular structure that may partly contribute to the cardio-protective effects of dapagliflozin.Clinicaltrials.gov identifierNCT02956811.
| S-EPMC8202417 | biostudies-literature
Project description:ObjectiveIn this study, we aimed to estimate the impact of sleep duration on left ventricular hypertrophy (LVH) in type 2 diabetes mellitus (T2DM).MethodsConsecutive patients with T2DM undergoing transthoracic echocardiography (TTE) in our center from October 2017 to February 2021 were analyzed. The association of the risk of LVH in T2DM patients was evaluated using univariable and multivariable logistic regression analyses.ResultsThis study finally included 2689 adult patients (mean age 51.8 ± 12.5 years, 56.2% men, mean sleep duration 7.6 ± 1.4 hours per day). Of all patients, 655 (24.4%) patients were diagnosed with LVH and 2034 did not have LVH. All patients were adults and were diagnosed with T2DM. In the univariate and multivariate regression analyses, gender, sleep duration, body mass index (BMI), waist, hemoglobin (Hb), blood creatinine (Cr), and high-density lipoprotein cholesterol (HDL-c) were associated with LVH. In the restricted cubic spline (RCS) model, the cut-off points of sleep duration given refer to the group of patients with T2DM and LVH were 8 hours per day. With the cut-off points, the multivariable analysis demonstrated that, for diabetic patients, LVH was significantly correlated with a sleep duration of 8 hours per day, hemoglobin, blood urea nitrogen (BUN), and HDL-c.ConclusionFor patients with T2DM, long sleep duration (>8 hours per day), hemoglobin, BUN, and HDL-c were independently associated with LVH. This trial is registered with NCT03811470.
| S-EPMC10735725 | biostudies-literature
Project description:Objective: Psoriasis is an immune mediated disorder associated with T cell activation and cardiovascular disease (CVD). We explored the association of inflammation with left ventricular (LV) remodelling in psoriasis patients receiving treatment with the tumour necrosis factor-α (TNF-α) blocker infliximab. Methods: Psoriasis patients (n = 47, age 47 ± 14 years, 66% men) and 99 control subjects without psoriasis (age 47 ± 11 years, 72% men) were examined by echocardiography in a cross-sectional study. LV remodelling was assessed by LV mass index for height in the allometric power of 2.7. Serum concentrations of C-reactive protein (CRP), serum amyloid A (SAA), neopterin, kynurenine:tryptophan ratio (KTR) and the pyridoxic acid ratio (PAr) index were measured. Results: Serum concentration of neopterin (p = .007) was higher in psoriasis patients, while the other inflammatory biomarkers had similar levels. LV mass index was lower in patients than controls (35.6 ± 9.6 g/m2.7 vs. 40.3 ± 9.8 g/m2.7, p = .008). In the total study population, serum SAA (β = 0.18, p = .02), KTR (β = 0.20, p = .02) and the PAr index (β = 0.26, p = .002) were all associated with higher LV mass index independent of age, sex, body mass index, hypertension, smoking, renal function and psoriasis. Also in psoriasis patients, higher SAA level (β = 0.34, p = .02), KTR (β = 0.32, p = .02) and the PAr index (β = 0.29, p = .05) were associated with higher LV mass index independent of body mass index, hypertension and diabetes. Conclusion: Higher levels of the inflammatory biomarkers SAA, KTR and the PAr index were associated with greater LV mass index in psoriasis patients, indicating a role of chronic inflammation in LV remodelling evident even during treatment with TNF-α blockers.
| S-EPMC9379959 | biostudies-literature
Project description:BackgroundLeft ventricular hypertrophy (LVH), a hallmark of early-stage heart failure (HF), is a common complication in individuals with type 2 diabetes mellitus (T2DM). Metabolic Visceral Fat Score (METS-VF), a novel metric for estimating visceral adiposity, may provide valuable insights into LVH risk. This study explores the association between METS-VF and LVH in T2DM and compare its predictive performance to traditional abdominal obesity indices.MethodsThis cross-sectional study included 4,988 adults with T2DM. Participants were stratified into quartiles based on METS-VF. Logistic regression models assessed the association between METS-VF and LVH. Restricted cubic spline analyses evaluated nonlinear relationships, while stratified analyses explored subgroups effects. Receiver operating characteristic (ROC) curves compared the predictive performance of METS-VF with other indices.ResultsLVH prevalence increased across METS-VF quartiles (Quartile 1: 7.9%; Quartile 2: 13.0%; Quartile 3: 20.0%; Quartile 4: 31.0%; P < 0.001). Higher METS-VF was independently associated with LVH (OR: 9.79; 95% CI: 6.16-15.76; P < 0.001). A nonlinear relationship was observed between METS-VF and LVH, with a steeper risk increase above specific thresholds. Stratified analyses showed that the positive association between METS-VF and LVH was consistent. METS-VF outperformed traditional indices in predicting LVH (AUC: 0.68; 95% CI: 0.66-0.70).ConclusionsMETS-VF is strongly associated with LVH in T2DM, demonstrating superior predictive performance compared to traditional indices. METS-VF is a practical, cost-effective tool for early cardiac risk stratification, facilitating timely interventions to mitigate HF risk in T2DM populations.
| S-EPMC11884144 | biostudies-literature
Project description: Not available
| S-EPMC5478200 | biostudies-literature
Project description:Several studies show that even a level of urine albumin/creatinine ratio (UACR) within the normal range (below 30?mg/g) increases the risk of cardiovascular diseases. We speculate that mildly increased UACR is related to left ventricular hypertrophy (LVH) in patients with type 2 diabetes mellitus (T2DM). In this retrospective study, 317 patients with diabetes with normal UACR, of whom 62 had LVH, were included. The associations between UACR and laboratory indicators, as well as LVH, were examined using multivariate linear regression and logistic regression, respectively. The diagnostic efficiency and the optimal cutoff point of UACR for LVH were evaluated using the area under the receiver operating characteristic curve (AUC) and Youden index. Our results showed that patients with LVH had significantly higher UACR than those without LVH (P < 0.001). The prevalence of LVH presented an upward trend with the elevation of UACR. UACR was independently and positively associated with hemoglobin A1c (P < 0.001). UACR can differentiate LVH (AUC?=?0.682, 95% CI (0.602-0.760), P < 0.001). The optimal cutoff point determined with the Youden index was UACR?=?10.2?mg/g. When categorized by this cutoff point, the odds ratio (OR) for LVH in patients in the higher UACR group (10.2-30?mg/g) was 3.104 (95% CI: 1.557-6.188, P=0.001) compared with patients in the lower UACR group (<10.2?mg/g). When UACR was analyzed as a continuous variable, every double of increased UACR, the OR for LVH was 1.511 (95% CI: 1.047-2.180, P=0.028). Overall, UACR below 30?mg/g is associated with LVH in patients with T2DM. The optimal cutoff value of UACR for identifying LVH in diabetes is 10?mg/g.
| S-EPMC6996706 | biostudies-literature
Project description:BackgroundBeta 2-microglobulin (β2-MG) is a component of the class I major histocompatibility complex (MHCI) and has recently been reported to be involved in type 2 diabetes mellitus (T2DM) and cardiovascular disease. However, the association of β2-MG with left ventricular hypertrophy (LVH) in T2DM patients remains unknown. This study aims to investigate the correlation between serum β2-MG and LVH in T2DM patients.MethodsThe retrospective analysis included 4602 eligible T2DM patients, divided into LVH and non-LVH groups based on echocardiography results. Serum β2-MG levels were measured, and participants were categorized into four groups (Q1-Q4) by their serum β2-MG quartile. The relationship of serum β2-MG level with LVH was evaluated using logistic regression, restricted cubic spline (RCS), subgroup analysis, and machine learning.ResultsThe prevalence of LVH in T2DM patients was 31.12%. Each standard deviation increase in serum β2-MG level corresponded to a 1.17-fold increase in the prevalence of LVH [OR = 1.17, (95% CI: 1.05-1.31); p = 0.006]. When considering β2-MG as a categorical variable (quartile), Q3 [OR = 1.36, (95% CI: 1.09-1.69); p = 0.007] and Q4 [OR = 1.77, (95% CI: 1.36-2.31); p < 0.001] had a significantly higher prevalence of LVH than Q1. RCS analysis found a nonlinear association between β2-MG and LVH prevalence (p for nonlinearity <0.05). Additionally, machine learning results confirmed the importance of β2-MG for LVH in T2DM patients.ConclusionElevated serum β2-MG levels were likely to be associated with an increased prevalence of LVH in T2DM patients, suggesting its potential role in LVH development.
| S-EPMC11331034 | biostudies-literature
Project description:AIMS: Diastolic reserve is the ability of left ventricular filling pressures to remain normal with exercise. Impaired diastolic reserve may be an early sign of diabetic cardiomyopathy. We aimed to determine whether diastolic reserve differs in type 2 diabetes (DM) compared with non-DM, and to identify clinical, anthropological, metabolic and resting echocardiographic correlates of impaired diastolic reserve in patients with DM. METHODS AND RESULTS: 237 patients (aged 53±11 years, 133 DM, ejection fraction 68±9%) underwent rest and exercise echocardiography. Mitral E and septal e' were measured at rest, immediately post, and 10 min into recovery. Analysis of covariance (ANCOVA) and binary regression with continuous outcomes were used to model e' and E/e' changes with exercise to identify impaired diastolic reserve defined as post-exercise E/e' ≥15. After adjusting for baseline differences, patients with DM immediately post-exercise had a lower septal e', a lower Δe' (1.2 vs 2.3 cm/s, p=0.006) and a higher Δ septal E/e' (1.7 vs 0.08, p<0.001) than patients without DM. In patients with normal resting E/e' of ≤8 (n=130), DM had a significantly higher post-exercise septal E/e' and a higher Δseptal E/e' (2.63 vs 0.50, p<0.001). E/e' in patients with DM remained significantly elevated up to 10 min post-exercise. Hypertension, longer duration of insulin therapy, poorer glycaemic control, worse renal function, larger left atrial volume and lower septal e' were independent correlates of impaired diastolic reserve in patients with DM. CONCLUSIONS: Patients with DM have impaired diastolic reserve manifest as a blunted e' response with exercise, persisting into recovery. Clinical, anthropometric, metabolic and echocardiographic correlates of impaired diastolic reserve in patients with DM were identified. An impaired LV diastolic reserve may be the underlying pathophysiological mechanism in patients with DM with unexplained exertional dyspnoea and may allow earlier detection of DM cardiomyopathy.
| S-EPMC4395831 | biostudies-other