This study aimed to assess the effect of dapagliflozin on the no-reflow phenomenon in patients with type II diabetes mellitus (T2DM) and acute myocardial infarction (AMI) who underwent percutaneous coronary intervention (PCI).

This single-center, observational cohort study included a total of 829 consecutive T2DM patients who were diagnosed with AMI and underwent PCI within 24 h of the onset of symptoms. Only patients using dapagliflozin (10 mg per day) for more than one year were considered as patients using dapagliflozin. The no-reflow phenomenon was defined as inadequate myocardial perfusion within a segment of the coronary circulation without angiographic evidence of mechanical vessel obstruction, dissection, or residual stenosis after PCI.

Four hundred and thirty-four patients were diagnosed with ST-segment elevation myocardial infarction (STEMI), and 395 patients were diagnosed with non-ST-segment elevation myocardial infarction (NSTEMI). Forward conditional logistic regression analysis demonstrated that the estimated glomerular filtration rate (OR = 0.940, 95% CI: 0.900 to 0.982, p = 0.006), SYNTAX score I (OR = 1.338, 95% CI: 1.179 to 1.520, p < 0.001), and dapagliflozin use (OR = 0.030, 95% CI: 0.004 to 0.228, p = 0.001) were independent predictors of the no-reflow phenomenon in STEMI. However, dapagliflozin use (OR = 0.112, 95% CI: 0.013 to 0.933, p = 0.043) was the only independent predictor of the no-reflow phenomenon in NSTEMI.

Lower rates of the no-reflow phenomenon were observed in T2DM patients taking dapagliflozin, diagnosed with AMI, and underwent PCI. However, this finding requires further investigation.

The purpose of this systematic review and meta-analysis is to investigate the association of metabolic dysfunction-associated steatotic liver disease (MASLD) with arterial stiffness and enlighten on potential cardiometabolic co-factors.

A literature search in PubMed/Medline, Embase, Scopus, and Web of Science databases was conducted. All the observational studies comparing arterial stiffness indices between adults with Non-alcoholic Fatty Liver Disease (NAFLD), Metabolic Dysfunction Associated-Fatty Liver Disease (MAFLD), or MASLD and apparently healthy individuals with normal liver function were included. Pulse wave velocity (PWV) and augmentation index (AIx) were mainly used as arterial stiffness indices.

Fourty one unique studies were included in the systematic review, with 27 deemed eligible for meta-analysis. Patients with MASLD had increased carotid-femoral PWV (14 studies, Mean difference (MD): 0.96 m/s, 95% confidence interval (CI) 0.65-1.27, p < 0.001) compared with healthy individuals. This finding was independent from body mass index, triglycerides, high-density lipoprotein, systolic blood pressure, and fasting plasma glucose. Moreover, patients with MASLD had higher brachial-ankle PWV (13 studies, MD: 78.14 cm/s, 95% CI 60.37-95.90, p < 0.001) and AIx (7 studies, MD: 3.85%, 95% CI 0.87-6.82, p = 0.0195) compared with controls.

MASLD is correlated with increased arterial stiffness. This relation is unaffected by common cardiometabolic risk factors.

PROSPERO (ID: CRD42023468258).

Endothelial cells regulate vascular tone, blood flow, coagulation, and inflammation, with heterogeneous populations serving specific roles throughout the body. In the kidney, endothelial cells maintain vascular integrity and function, contribute to filtration, and support other renal structures. Nitric oxide (NO) is a key signaling molecule that maintains vascular tone and endothelial function. It is synthesized by nitric oxide synthase (NOS) isoforms, with endothelial NOS playing a central role in vascular health. Chronic kidney disease (CKD) is characterized by reduced NO bioavailability, driven by the accumulation of endogenous NOS inhibitors such as asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA). Uremic toxins, oxidative stress, and proinflammatory cytokines contribute to a prothrombotic and proinflammatory state, contributing to endothelial dysfunction and exacerbating cardiovascular (CV) risks in CKD. Biomarkers such as ADMA, SDMA, endothelial microparticles, and soluble adhesion molecules offer insights into vascular health, while invasive or noninvasive diagnostic techniques can assess endothelial function in CKD. Effective management strategies focus on enhancing NO bioavailability, controlling oxidative stress, reducing inflammation, and optimizing dialysis to minimize uremic toxin levels. Emerging therapeutic approaches, including antioxidant therapies and endothelial progenitor cell-based interventions, show promise in preserving vascular function. A multifaceted approach to managing endothelial dysfunction is critical for mitigating CV complications and improving patient outcomes in CKD.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have shown benefits in improving cardiovascular (CV) outcomes in patients with heart failure (HF) and may mitigate symptom progression in myocardial infarction (MI). However, their effectiveness in patients with type 2 diabetes and MI undergoing percutaneous coronary intervention (PCI) is unclear.

To identify eligible studies, a comprehensive search of electronic databases, PubMed, Cochrane Library, Scopus and Embase, was conducted from inception until May 2024. Results were presented as risk ratios (RR) and their corresponding 95 % confidence intervals (CIs).

Our analysis included 8 observational studies comprising 24,229 patients. The results indicated that SGLT2i with PCI was associated with a significantly reduced risk of all-cause death (RR=0.61; 95 % CI=0.54 to 0.68), CV death (RR=0.46; 95 % CI=0.22 to 0.94), major adverse cardiovascular events (RR=0.80;95 % CI: 0.66 to 0.96), HF-related hospitalizations (RR=0.63; 95 % CI=0.44 to 0.90), stroke (RR=0.77; 95 % CI: 0.62 to 0.96) and acute kidney injury (RR=0.46; 95 % CI: 0.25 to 0.84) compared to PCI without SGLT2i use. However, the risk of revascularization remained comparable between the groups.

Our study demonstrates that SGLT2i with PCI in patients with type 2 diabetes and MI are associated with improved CV outcomes compared to PCI without SGLT2i use. Randomized controlled trials are required to confirm the improvement in outcomes with SGLT2i therapy combined with PCI in patients with MI and diabetes.

Vascular endothelium is integral to the regulation of vascular homeostasis and maintenance of normal arterial function in healthy individuals. Endothelial dysfunction is a significant contributor to the advancement of atherosclerosis, which can precipitate cardiovascular complications. A notable correlation exists between diabetes and endothelial dysfunction, wherein chronic hyperglycemia and acute fluctuations in glucose levels exacerbate oxidative stress. This results in diminished nitric oxide synthesis and heightened production of endothelin-1, ultimately leading to endothelial impairment. In clinical settings, it is imperative to implement appropriate therapeutic strategies aimed at enhancing endothelial function to prevent and manage diabetes-associated vascular complications. Various antidiabetic agents, including insulin, GLP-1 receptor agonists, sulfonylureas, DPP-4 inhibitors, SGLT2 inhibitors, α-glucosidase inhibitors, thiazolidinediones (TZDs), and metformin, are effective in mitigating blood glucose variability and improving insulin sensitivity by lowering postprandial glucose levels. Additionally, traditional Chinese medicinal compounds, such as turmeric extract, resveratrol, matrine alkaloids, tanshinone, puerarin, tanshinol, paeonol, astragaloside, berberine, and quercetin, exhibit hypoglycemic properties and enhance vascular function through diverse mechanisms. Consequently, larger randomized controlled trials involving both pharmacological and herbal interventions are essential to elucidate their impact on endothelial dysfunction in patients with diabetes. This article aims to explore a comprehensive approach to the treatment of diabetic endothelial dysfunction based on an understanding of its pathophysiology.

This systematic review and meta-analysis assesses the association of arterial stiffness with age-related macular degeneration (AMD), glaucoma, retinal vein occlusion (RVO) and retinopathy (diabetic and hypertensive).

Medline and Embase were systematically searched for observational studies of arterial stiffness and eye disease. Cohort studies were included if they estimated arterial stiffness using any measures based on the arterial waveform, with cross-sectional and case-control studies limited to measures of pulse wave velocity. We assessed the certainty of evidence using Grading of Recommendations, Assessment, Development and Evaluation.

The systematic review of 61 studies (six for AMD, ten for glaucoma, six for RVO and 39 for retinopathy) showed that arterial stiffness overall was higher in people with eye disease than people without eye disease. Forty-four cross-sectional and case-control studies were included in the meta-analysis. Arterial stiffness estimated by way of pulse wave velocity was associated with AMD (mean difference: 0.92 m/s, 95% CI 0.37 to 1.46; 2 studies; n=381; low certainty evidence), glaucoma (mean difference: 0.97 m/s, 95% CI 0.31 to 1.64; 7 studies; n=3418; low certainty evidence), RVO (mean difference: 2.79 m/s, 95% CI 2.02 to 3.55; 5 studies; n=414; very low certainty evidence) and retinopathy (1.48 m/s, 95% CI 0.1.16 to 1.81; 22 studies; n=10 074; low certainty evidence). The 19 cohort studies identified (five for AMD, three for glaucoma, one for RVO and 10 for retinopathy) indicated overall that increased arterial stiffness was associated with the future development of eye disease.

Higher arterial stiffness is associated with AMD, glaucoma, RVO and retinopathy PROSPERO REGISTRATION NUMBER: CRD42019129563.

Vascular aging refers to the degenerative changes in vascular wall structure and vasodilatory function, forming the pathophysiological basis for the onset and progression of cardiovascular disease (CVD). Pulse wave velocity (PWV), a non-invasive method for evaluating and detecting early vascular aging, has achieved significant results in predicting CVD risk and evaluating the efficacy of pharmacological treatments. PWV can effectively predict CVD risk across various populations, including healthy individuals, patients with hypertension, diabetes, and chronic inflammatory diseases. In patients with comorbidities such as hypertension, pharmacological interventions, such as anti-inflammatory, lipid-lowering, anti-hypertensive, and anti-diabetic treatments, can effectively reduce PWV and thus slow down vascular aging. Therefore, PWV is not only a vital tool for assessing early vascular aging but also an important indicator for evaluating treatment outcomes. Regular monitoring of PWV levels is of great significance in predicting CVD risk, evaluating therapeutic efficacy, and guiding clinical decision-making.

Background: The association between diabetic nephropathy and arterial elasticity and endothelial function is well established. In this study, we compared the effect of the combination of dulaglutide and dapagliflozin versus DPP-4 inhibitors on the endothelial glycocalyx, arterial stiffness, myocardial function, and albuminuria. Methods: Overall, 60 patients were randomized to combined dulaglutide and dapagliflozin treatment (n = 30) or DPP-4 inhibitors (DPP-4i, n = 30) (ClinicalTrials.gov: NCT06611904). We measured at baseline and 4 and 12 months post-treatment: (i) the perfused boundary region of the sublingual arterial microvessels, (ii) pulse wave velocity (PWV) and central systolic blood pressure (cSBP), (iii) global left ventricular longitudinal strain (GLS), and (iv) urine albumin-to-creatinine ratio (UACR). Results: After twelve months, dual therapy showed greater improvements vs. DPP-4i in PBR (2.10 ± 0.31 to 1.93 ± 0.23 μm vs. 2.11 ± 0.31 to 2.08 ± 0.28 μm, p < 0.001), UACR (326 ± 61 to 142 ± 47 mg/g vs. 345 ± 48 to 306 ± 60 mg/g, p < 0.01), and PWV (11.77 ± 2.37 to 10.7 ± 2.29 m/s vs. 10.64 ± 2.44 to 10.54 ± 2.84 m/s, p < 0.001), while only dual therapy showed improvement in cSBP (130.21 ± 17.23 to 123.36 ± 18.42 mmHg). These effects were independent of glycemic control. Both treatments improved GLS, but the effect of dual therapy was significantly higher compared to DPP-4i (18.19% vs. 6.01%, respectively). Conclusions: Twelve-month treatment with dulaglutide and dapagliflozin showed a greater improvement in arterial stiffness, endothelial function, myocardial function, and albuminuria than DPP-4is. Early initiation of combined therapy as an add-on to metformin should be considered in these patients.

Little is known about the effects of sodium-glucose co-transporter 2 inhibitors (SGLT2i) on atherosclerosis. We aimed to determine if a 90-day intake of Dapagliflozin could improve atherosclerosis biomarkers (namely endothelial function assessed by flow-mediated dilatation [FMD] and carotid intima-media thickness [CIMT]) in diabetic and non-diabetic acute coronary syndrome (ACS) patients when initiated in the early in-hospital phase. ATH-SGLT2i was a prospective, single-center, observational trial that included 113 SGLT2i naive patients who were admitted for ACS and who were prescribed Dapagliflozin at a fixed dose of 10 mg during their hospital stay for either type 2 diabetes or for heart failure. After 90 days of follow-up, subjects who had a continuous intake of Dapagliflozin formed the SGLT2i group, while patients who did not take Dapagliflozin formed the non-SGLT2i group. In each of these main study groups, we considered diabetic and non-diabetic subgroups. The primary endpoint was the difference in between baseline and 90 days in FMD (∆FMD) and in FMD rate (∆FMD%). The secondary outcome was change in CIMT (∆CIMT). We enrolled 54 patients in the SGLT2i group aged 59 ± 9 years (70.4% males) which 30 were diabetics, and 59 in the non-SGLT2i group aged 63 ± 11 years (78% males) which 34 were diabetics. After 90 days, ∆FMD and ∆ FMD% were higher in the SGLT2i group in comparison with the non-SGLT2i group (0.05 ± 0.15 vs -0.05 ± 0.11, P < .001 and 1.78 ± 3.63 vs -0.88 ± 4, P < .001). Within the SGLT2i group, the improvement of FMD% was higher in non-diabetic patients (2.85 ± 3.46 vs 0.9 ± 3.59, P = .05). Multivariate analysis showed that Dapagliflozin intake was independently associated with FMD% improvement (HR = 2.24). After 90 days, CIMT showed no significant difference between the SGLT2i and the non-SGLT2i groups. In this pilot study, a 90-day intake of Dapagliflozin at the fixed dose of 10 mg started in the acute phase of an ACS, was associated with endothelial function improvement in diabetic and non-diabetic patients.

Flow-mediated dilation (FMD) is a noninvasive method to evaluate vascular endothelial function, which manifests the vascular inflammatory response, cell proliferation, and autoregulation. Since FMD is noninvasive and assesses commonly in the brachial artery by ultrasound, compared to other invasive methods such as optical coherence tomography (OCT) and intravascular ultrasound (IVUS), it is widely used to evaluate endothelial function and allows serial assessment. In this review, we present the currently accepted mechanisms and methods of FMD measurement with the studies applied in the current clinical practice using FMD. After all, the association with cardiovascular diseases is of substance, and so we introduce clinical studies of FMD related to cardiovascular disease such as diabetes, hyperlipidemia, chronic kidney disease, coronary artery disease, and peripheral vascular disease. In addition, studies related to pregnancy and COVID-19 were also inspected. Yet, endothelial examination is not endorsed as a cardiovascular prevention measure, for the lack of a clear standardized value methodology. Still, many studies recommend practicable FMD and would be a better prognostic value in the cardiovascular prognosis in future clinical research.

Pulse wave velocity (PWV) is as a reliable marker of arterial stiffness and vascular aging, surpassing traditional risk factors in predicting detrimental cardiovascular events. The present meta-analysis aims to investigate PWV thresholds and assess its prognostic value in outcomes of acute ischemic stroke (AIS). A search was conducted in PubMed, Cochrane, Web of Science, and Scopus for studies published up to January 2024, focusing on patients admitted with AIS, wherein arterial stiffness was assessed through PWV measurements during hospitalization. Identified studies reported PWV values in individuals with both favorable and unfavorable outcomes at the end of follow-up. Initially, 35 eligible studies provided data for weighted mean baPWV (11,953 AIS patients) and cfPWV (2,197 AIS patients) calculations. The average age was 67 years, with approximately 60% male, 67% hypertensive, 30% diabetic and 30% smoker participants. The weighted mean systolic blood pressure was approximately 150 mmHg. In AIS patients, the mean PWV was 10 m/s for standard cfPWV and 20 m/s for baPWV. Nine cohort studies (6,006 AIS patients) were included in the quantitative analysis of clinical outcomes. Higher PWV levels were associated with poorer functional outcomes (2.3 m/s higher, 95%CI:1.2-3.4, p < 0.001; I2 = 87.4%). AIS patients with arterial stiffness/vascular aging (higher PWV) had approximately 46.2% increased risk of poor functional outcome, 12.7% higher risk of mortality, 13.9% greater risk of major adverse cardiovascular events, and 13.9% greater risk of stroke recurrence over the long term compared to those without arterial stiffness. Advanced vascular aging, as indicated by PWV, significantly predicts adverse outcomes in AIS patients. Integrating the assessment of vascular aging into clinical practice can improve risk perception in these patients.

Sodium-glucose cotransporter 2 inhibitors (SGLT-2i) are now recommended in the current European Society of Cardiology/American College of Cardiology guidelines for the treatment of heart failure (HF) across the spectrum of left ventricular ejection fraction (LVEF) and several large trials have documented the beneficial effects of this drug class on cardiovascular outcomes. Although the clinical efficacy of SGLT-2 inhibition in HF is now well recognised, research is still ongoing to better understand the underlying mechanistic effects of this drug class. In this paper we assess the haemodynamic effects following SGLT-2i treatment in HF patients by reviewing the current literature. We focus our review on preload of the LV in terms of filling pressure and pulmonary artery pressure, cardiac output and afterload. We discuss these variables stratified according to HF with reduced LVEF (HFrEF) and HF with preserved LVEF (HFpEF). Finally, we examine the evidence of LV remodelling in the setting of SGLT-2i-related changes in haemodynamics.

Arterial hypertension (AH) is a significant risk factor for cardiovascular disease and is associated with increased arterial stiffness, particularly as measured by pulse wave velocity (PWV). This study aims to explore the relationships between age groups, antihypertensive and new oral antidiabetic drugs, body composition, and arterial stiffness parameters in hypertensive patients.

A single-center cross-sectional study was conducted including 584 participants who underwent 24 h ambulatory blood pressure monitoring (including central blood pressure (BP) and PWV measurement), body composition analysis, and provided medical history and current pharmacotherapy data.

The study found that PWV was significantly higher in patients with poorly regulated BP in those aged 65 years and older. Significant PWV predictors included systolic BP, heart rate, peripheral mean arterial pressure, peripheral pulse pressure, augmentation index, calcium channel blockers, moxonidine, sodium-glucose co-transporter 2 inhibitors, urapidil, and statin prescription. Also, statistically significant negative correlations were found between PWV and visceral fat level, fat-free mass, and the percentage of muscle mass.

The findings suggest that arterial stiffness is interconnected with peripheral and central blood pressure parameters, body composition parameters, and prescribed hypertensive and new antidiabetic drugs.

While arterial stiffening is a known risk factor for cardiovascular diseases, it remains unclear whether there is an early vascular aging (EVA) in patients who have experienced acute ischemic stroke (AIS). This systematic review and meta-analysis aims to investigate whether patients with AIS exhibit EVA through pulse wave velocity (PWV) measurements shortly after the stroke onset, shedding light on the relationship between arterial stiffness, hypertension, and stroke.

Thirteen case-control studies were included, comparing PWV measurements between AIS patients and non-AIS individuals. A meta-analysis was performed to compare PWV levels, age, blood pressure, and the prevalence of different cardiovascular risk factors among 1711 AIS patients and 1551 controls.

Despite AIS patients showing higher PWV compared to controls (mean difference: 1.72 m/s, 95 % CI: 1.05-2.38, p < 0.001; I2 = 88.3 %), their age did not significantly differ (95 % CI: -0.47-0.94, p = 0.519; I2 = 0 %), suggesting EVA in AIS patients. Moreover, AIS patients exhibited elevated systolic and diastolic blood pressure and had higher odds of smoking, hypertension, diabetes, and male gender compared to controls.

This study's findings underscore the presence of EVA in AIS patients, evident through increased PWV measurements shortly after stroke onset. Notably, smoking, hypertension, and diabetes mellitus emerge as substantial factors contributing to accelerated arterial stiffness within this population.

The cardiovascular benefits of semaglutide are established; however, its effects on surrogate vascular markers and liver function are not known.

To investigate the effects of semaglutide on vascular, endothelial, and liver function in patients with type 2 diabetes (T2DM) and nonalcoholic fatty liver disease (NAFLD).

Overall, 75 consecutive subjects with T2DM and NAFLD were enrolled: 50 patients received semaglutide 1 mg (treatment group) and 25 patients received dipeptidyl peptidase 4 inhibitors (control group). All patients underwent a clinical, vascular, and hepatic examination with Fibroscan elastography at 4 and 12 months after inclusion in the study.

Treatment with semaglutide resulted in a reduction of Controlled Attenuation Parameter (CAP) score, E fibrosis score, NAFLD fibrosis score, Fibrosis-4 (FIB-4) score and perfused boundary region (PBR) at 4 and at 12 months (P < .05), contrary to controls. Patients treated with semaglutide showed a greater decrease of central systolic blood pressure (SBP) (-6% vs -4%, P = .048 and -11% vs -9%, P = .039), augmentation index (AIx) (-59% vs -52%, P = .041 and -70% vs -57%, P = .022), and pulse wave velocity (PWV) (-6% vs -3.5%, P = .019 and -12% vs -10%, P = .036) at 4 and at 12 months, respectively. In all patients, ΔPWV and ΔPBR were correlated with a corresponding reduction of CAP, E fibrosis, NAFLD fibrosis, and FIB-4 scores.

Twelve-month treatment with semaglutide simultaneously improves arterial stiffness, endothelial function, and liver steatosis and fibrosis in patients with T2DM and NAFLD.

After acute myocardial infarction, patients are at increased risk for adverse outcomes, including heart failure and death. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have shown promising cardiovascular benefits, but their efficacy in patients after myocardial infarction is not well established. This study aimed to evaluate the efficacy of SGLT2i in preventing cardiovascular outcomes in patients after myocardial infarction through a systematic review and meta-analysis. We conducted a comprehensive literature search of PubMed, Cochrane, EMBASE, and Web of Science for randomized controlled trials (RCTs) and retrospective and prospective studies evaluating SGLT2i in patients after myocardial infarction. The primary outcomes were major adverse cardiovascular events (MACEs) and all-cause mortality. Secondary outcomes included cardiovascular mortality, recurrent myocardial infarction, revascularization, and rehospitalization. Data were pooled using a random-effects model, and risk ratios (RRs) with 95% confidence intervals (CIs) were calculated. The meta-analysis included eight studies (three RCTs and five observational studies) with a follow-up duration ranging from 4 to 24 months. SGLT2i were associated with a significantly lower risk of MACE (RR: 0.71, 95% CI: 0.52-0.97, p = 0.03) and rehospitalization (RR: 0.64, 95% CI: 0.51-0.82, p<0.01) compared to controls. Although not statistically significant, the risk of all-cause mortality (RR: 0.79, 95% CI: 0.53-1.18, p = 0.25) and cardiovascular mortality was lower in the SGLT2i group. This meta-analysis suggests that SGLT2i may improve cardiovascular outcomes in patients after myocardial infarction, particularly by reducing the risk of MACEs and rehospitalization. However, larger trials with high-risk populations are needed to confirm these findings and elucidate the underlying mechanisms.

In chronic kidney disease (CKD) patients, several risk factors contribute to the development of endothelial dysfunction (ED), which can be described as an alteration in the cell structure or in the function of the endothelium. Among the well-known CKD-related risk factors capable of altering the production of endothelium-derived relaxing factors, we include asymmetric dimethylarginine increase, reduced dimethylarginine dimethylamine hydrolase enzyme activity, low-grade chronic systemic inflammation, hyperhomocysteinemia, oxidative stress, insulin resistance, alteration of calcium phosphorus metabolism, and early aging. In this review, we also examined the most important techniques useful for studying ED in humans, which are divided into indirect and direct methods. The direct study of coronary endothelial function is considered the gold standard technique to evaluate if ED is present. In addition to the discussion of the main pharmacological treatments useful to counteract ED in CKD patients (namely sodium-glucose cotransporter 2 inhibitors and mineralocorticoid receptor antagonist), we elucidate innovative non-pharmacological treatments that are successful in accompanying the pharmacological ones. Among them, the most important are the consumption of extra virgin olive oil with high intake of minor polar compounds, adherence to a plant-dominant, low-protein diet (LPD), an adaptive physical activity program and, finally, ketoanalogue administration in combination with the LPD or the very low-protein diet.

The present meta-analysis aimed to examine the effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors on the prognosis of diabetes patients who experienced acute myocardial infarction (AMI). This investigation encompassed an array of clinical endpoints, comprising cardiovascular death, myocardial reinfarction, all-cause mortality, major adverse cardiovascular events (MACEs), and rehospitalization.

The study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The PubMed, Cochrane Library, Embase, and Web of Science databases were searched up to October 2023. Studies reporting clinical outcomes in diabetic patients who experienced AMI and were treated with SGLT2 inhibitors (SGLT2-I) were included. Two researchers independently selected the studies and assessed the risk of bias in the included studies using the Cochrane risk of bias tool for Risk for Bias In Non-randomized Studies-of Interventions (ROBINS-I).

A total of 2450 publications were initially retrieved; ultimately, five studies involving 5398 patients were included in the meta-analysis. The analysis revealed that SGLT2-I were associated with significantly lower risks of cardiovascular death (odds ratio (OR), 0.34; 95% CI, 0.14-0.82) and all-cause mortality (OR, 0.54; 95% CI, 0.38-0.76). However, SGLT2-I did not lead to a significant decrease in the rate of myocardial reinfarction (OR, 0.91; 95% CI, 0.65-1.29). SGLT2-I did lead to a significant reduction in MACEs (OR, 0.59; 95% CI, 0.35-1.0), but there was significant heterogeneity among the included studies. SGLT2-I also led to a significant reduction in rehospitalizations (OR, 0.45; 95% CI, 0.26-0.76). There was significant heterogeneity in the analysis of rehospitalization, but the effect remained significant when we excluded the main sources of heterogeneity (OR, 0.35; 95% CI, 0.24-0.52).

The pooled analyses revealed that SGLT2-I were associated with reductions in all-cause mortality, cardiovascular death, and rehospitalization. In the future, prospective studies with larger sample sizes are needed to confirm and refine these findings.

Diabetes is a metabolic disorder whose prevalence has become a worrying condition in recent decades. Chronic diabetes can result in serious health conditions such as impaired kidney function, stroke, blindness, and myocardial infarction. Despite a variety of currently available treatments, cases of diabetes and its complications are on the rise. This review article provides a comprehensive account of the ameliorative effect of prebiotics and probiotics individually or in combination i.e. synbiotics on health complications induced by Type 2 Diabetes Mellitus (T2DM). Recent advances in the field underscore encouraging outcomes suggesting the consumption of synbiotics leads to favorable changes in the gut microbiota. These changes result in the production of bioactive metabolites such as short-chain fatty acids (crucial for lowering blood sugar levels), reducing inflammation, preventing insulin resistance, and encouraging the release of glucagon-like peptide-1 in the host. Notably, novel strategies supplementing synbiotics to support gut microbiota are gaining attraction as pivotal interventions in mitigating T2DM-induced health complications. Thus, by nurturing a symbiotic relationship between prebiotics and probiotics i.e. synbiotics, these interventions hold promise in reshaping the microbial landscape of the gut thereby offering a multifaceted approach to managing T2DM and its associated morbidities. Supporting the potential of synbiotics underscores a paradigm shift toward holistic and targeted interventions in diabetes management, offering prospects for improved outcomes and enhanced quality of life for affected individuals. Nevertheless, more research needs to be done to better understand the single and multispecies pre/pro and synbiotics in the prevention and management of T2DM-induced health complications.

Despite accumulating evidence on the potential of glucose-lowering agents (GLAs) to prevent cardiovascular events, the comparative effects of GLAs on vascular function remain unclear. This study utilized validated indicators such as flow-mediated dilation (FMD; positive value favors) and pulse wave velocity (PWV; negative value favors) to uncover the comparative effects of GLAs on vascular function.

Randomized controlled trials (RCTs) comparing the effects of GLAs on FMD or PWV with placebo or other GLAs in patients with type 2 diabetes (T2DM) were searched through PubMed and Embase. The frequentist method of network meta-analysis (NMA) was conducted using a random effects model, and standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated.

The NMA included 38 RCTs with 2,065 patients. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium glucose cotransporter-2 inhibitors (SGLT-2Is) had significantly more positive effects on FMD improvement and PWV reduction than placebo. Thiazolidinedione (TZD) treatment resulted in significantly improved FMD compared to other GLAs as well as placebo (SMD: 1.14; 95% CI: 0.84 to 1.43). Both pioglitazone and rosiglitazone were discovered to have considerably more favorable effects on improving FMD and reducing PWV compared to placebo and other GLAs, as a result of the analysis incorporating each drug in the TZD class. The sensitivity analysis results corroborated the main findings.

This NMA showed more favorable effects of GLP-1RAs and SGLT-2Is than placebo in improving both arterial stiffness and endothelial function in patients with T2DM. In addition, TZDs showed superior effects in improving endothelial function as compared with the other GLAs and placebo.

The elastic properties of conductance arteries are one of the most important hemodynamic functions in the body, and data continue to emerge regarding the importance of their dysfunction in vascular aging and a range of cardiovascular diseases. Here, we provide new insight into the integrative physiology of arterial stiffening and its clinical consequence. We also comprehensively review progress made on pathways/molecules that appear today as important basic determinants of arterial stiffness, particularly those mediating the vascular smooth muscle cell (VSMC) contractility, plasticity and stiffness. We focus on membrane and nuclear mechanotransduction, clearance function of the vascular wall, phenotypic switching of VSMCs, immunoinflammatory stimuli and epigenetic mechanisms. Finally, we discuss the most important advances of the latest clinical studies that revisit the classical therapeutic concepts of arterial stiffness and lead to a patient-by-patient strategy according to cardiovascular risk exposure and underlying disease.

Age is a key risk factor for cardiovascular disease, including atherosclerosis. However, pathophysiological disease processes in the arteries are not an inevitable feature of aging. Large cohort studies with arterial phenotyping along with clinical and demographic data are essential to better understand factors related to the susceptibility or resilience to age-related vascular pathophysiology in humans. This review explores the mechanisms by which vascular structure and function alters with age, and how these changes relate to cardiovascular pathophysiology and disease. Features of vascular aging in the coronary arteries have historically been difficult to quantify pre-mortem due to their size and location. However, non-invasive imaging modalities including CT Coronary Angiogram are now being used to assess coronary vascular age, and further advances in imaging analysis such as the CT Fat Attenuation Index will help provide further measurement of features associated with coronary vascular aging. Currently, markers of vascular aging are not used as therapeutic targets in routine clinical practice, but non-pharmacological interventions including aerobic exercise and low salt diet, as well as anti-hypertensives have been demonstrated to reduce arterial stiffness. Advances in imaging technology, both in acquisition and advanced analysis, as well as harmonisation of measurements for researchers across the globe will be invaluable in understanding what constitutes healthy vascular aging and in identifying features of vascular aging that are associated with coronary artery disease and its adverse outcomes. Assessing such images in large cohorts can facilitate improved definitions of resilient and susceptible phenotypes to vascular aging in the coronary arteries. This is a critical step in identifying further risk factors and biomarkers within these groups and driving forward the development of novel therapies aimed at slowing or stopping age-related vascular changes in the coronary arteries.

Results from large placebo-controlled randomized trials in patients with heart failure with mid-range ejection fraction (HFmrEF) and HF with preserved EF (HFpEF) have become available recently. This article discusses results of these clinical trials.

Peer-reviewed articles were identified from MEDLINE (1966 to December 31, 2022) using search terms dapagliflozin, empagliflozin, SGLT-2Is, HFmrEF, and HFpEF.

Eight completed, pertinent clinical trials were included.

EMPEROR-Preserved, and DELIVER demonstrated that empagliflozin and dapagliflozin reduce CV death and heart failure hospitalization (HHF) in patients with HFmrEF and HFpEF, with/without diabetes when added to a standard heart failure (HF) regimen. The benefit is primarily due to reduction in HHF. Additional data from post hoc analyses of trials of dapagliflozin, ertugliflozin, and sotagliflozin suggest that these benefits may be a class effect. Benefits appear greatest in patients with left ventricular ejection fraction 41% up to about 65%.

While many pharmacologic treatments have been proven to reduce mortality and improve cardiovascular (CV) outcomes in people with HFmrEF and HF with reduced EF (HFrEF), there are few therapy which improve CV outcome in people with HFpEF. SGLT-2I become one of the first class of pharmacologic agent that can be used to reduce HHF and CV mortality.

Studies showed that empagliflozin and dapagliflozin reduce the combined risk of CV death or HHF in patients with HFmrEF and HFpEF when added to a standard HF regimen. Given that benefit has now been demonstrated across the spectrum of HF, SGLT-2Is should be considered one of the standard HF pharmacotherapy.

Estimated pulse wave velocity (ePWV) measurements have good agreement with PWV measurements. However, the relationship between ePWV and the risk of new-onset diabetes remains unclear. Therefore, this study aimed to investigate whether ePWV was associated with new-onset diabetes.

Based on a secondary analysis of the Chinese Rich Health Care Group's cohort study, 211,809 participants who met the criteria were enrolled and divided into four groups based on the ePWV quartiles. Diabetes events are of interest as a result of the study. Over a mean follow-up of 3.12 years, 3000 male (1.41%) and 1173 female (0.55%) patients were diagnosed with new-onset diabetes. The cumulative incidence curves based on quartile subgroups showed that the Q4 group had a significantly higher overall incidence of diabetes than the other subgroups. A multivariate Cox regression analysis showed that ePWV was an independent predictor of new-onset diabetes (hazard ratio, 1.233; 95% confidence interval, 1.198-1.269; P < 0.001). The receiver operating characteristic curve showed that the predictive value was higher than for age and blood pressure. The ePWV was treated as a continuous variable using MaxStat, which identified that the best cut-off point for diabetes risk was 8.47 m/s. A stratified analysis showed that the association between ePWV and the risk of diabetes remained significant in multiple strata.

An elevated ePWV was independently associated with an increased risk of developing diabetes in Chinese adults. Thus, ePWV may be a reliable indicator of the risk of early diabetes.

Prevention of cardiovascular disease (CVD) remains one of the largest public health challenges of our time. Identifying individuals at increased cardiovascular risk at an asymptomatic, sub-clinical stage is of paramount importance for minimizing disease progression as well as the substantial health and economic burden associated with overt CVD. Vascular ageing (VA) involves the deterioration in vascular structure and function over time and ultimately leads to damage in the heart, brain, kidney, and other organs. Vascular ageing encompasses the cumulative effect of all cardiovascular risk factors on the arterial wall over the life course and thus may help identify those at elevated cardiovascular risk, early in disease development. Although the concept of VA is gaining interest clinically, it is seldom measured in routine clinical practice due to lack of consensus on how to characterize VA as physiological vs. pathological and various practical issues. In this state-of-the-art review and as a network of scientists, clinicians, engineers, and industry partners with expertise in VA, we address six questions related to VA in an attempt to increase knowledge among the broader medical community and move the routine measurement of VA a little closer from bench towards bedside.

Changes in vascular function are closely associated with the development of cardiovascular disease (CVD). Pulse wave velocity (PWV) is a potential indicator of vascular dysfunction; it allows noninvasive assessment of arterial stiffness. Currently, evidence for the effects of different classes of antidiabetic drugs on arterial stiffness remains limited. In this study, a network meta-analysis (NMA) was performed to explore the associations between changes in arterial stiffness and first-line antidiabetic drugs by evaluating PWV in patients with different metabolic abnormalities.

We systematically searched several electronic databases for randomized controlled trials (RCTs) published from inception until 25 August 2022, without language restrictions. The primary outcome was the change in PWV (ΔPWV) in all included studies; subgroup analysis was performed for patients with abnormal glucose metabolism, including prediabetes and diabetes mellitus. NMA was performed to calculate the mean differences (MDs) with 95% confidence intervals (CIs) as effect sizes to evaluate the ΔPWV.

Among the 2257 candidate articles identified in the initial search, 18 RCTs were eventually included in the analysis. In all studies, two classes of new antidiabetic drugs, glucagon-like peptide-1 receptor (GLP-1R) agonists and sSodium-glucose co-transporter 2 (SGLT-2) inhibitors, improved arterial stiffness by decreasing PWV compared with placebo (MD = -1.11, 95% CI: -1.94 to 0.28) and (MD = -0.76, 95% CI: -1.45 to -0.08). A conventional antidiabetic drug, metformin, also showed similar efficacy compared with placebo (MD = -0.73, 95% CI: -1.33 to -0.12). Finally, in subgroup studies of patients with abnormal glucose metabolism diseases, GLP-1R agonists (MD = -1.06, 95% CI: -2.05 to -0.10) significantly decreased PWV compared with placebo.

Three classes of antidiabetic drugs-GLP-1R agonists, SGLT-2 inhibitors, and metformin-have the potential to improve arterial stiffness. Among the six classes of antidiabetic drugs analyzed, GLP-1R agonists constitute the only class of drugs that improves arterial stiffness in patients with abnormal glucose metabolism diseases.

We investigated the effect of additional treatment with newer antidiabetic drugs on endothelium function and arterial stiffness in subjects with type 1 diabetes mellitus (T1DM) without cardiovascular diseases. A total of 89 participants, all users of CGMS (continuous monitoring glucose system), were randomized into three comparable groups, receiving empagliflozin (E; n = 30), receiving semaglutide (S; n = 30), and a control group (C; n = 29). At baseline and 12 weeks post treatment, we measured FMD (brachial artery flow-mediated dilation) and FBF (forearm blood flow as reactive hyperemia assessed with strain gauge plethysmography) as parameters of endothelial function, as well as pulse wave velocity (PWV) and peripheral resistance as parameters of arterial stiffness. Improvement in FMD was significant in both intervention groups compared to controls (E group 2.0-fold, p = 0.000 and S group 1.9-fold, p = 0.000), with no changes between those two groups (p = 0.745). During the evaluation of FBF, there were statistically insignificant improvements in both therapeutic groups compared to controls (E group 1.39-fold, p = 0.074 and S group 1.22-fold, p = 0.701). In arterial stiffness parameters, improvements were seen only in the semaglutide group, with a decline in peripheral resistance by 5.1% (p = 0.046). We can conclude that, for arterial stiffness, semaglutide seems better, but both drugs positively impact endothelial function and, thus, could also have a protective role in T1DM.

The aorta and aortic wall have a complex biological system of structural, biochemical, biomolecular, and hemodynamic elements. Arterial stiffness could be considered a manifestation of wall structural and functional variations, and it has been revealed to have a strong connection with aortopathies and be a predictor of cardiovascular risk, especially in patients affected by hypertension, diabetes mellitus, and nephropathy. Stiffness affects the function of different organs, especially the brain, kidneys, and heart, promoting remodeling of small arteries and endothelial dysfunction. This parameter could be easily evaluated using different methods, but pulse-wave velocity (PWV), the speed of transmission of arterial pressure waves, is considered the gold standard for a good and precise assessment. An increased PWV value indicates an elevated level of aortic stiffness because of the decline in elastin synthesis and activation of proteolysis and the increase in fibrosis that contributes to parietal rigidity. Higher values of PWV could also be found in some genetic diseases, such as Marfan syndrome (MFS) or Loeys-Dietz syndrome (LDS). Aortic stiffness has emerged as a major new cardiovascular disease (CVD) risk factor, and its evaluation using PWV could be very useful to identify patients with a high cardiovascular risk, giving some important prognostic information but also being used to value the benefits of therapeutic strategies.

Beyond lowering plasma glucose levels, sodium-glucose cotransporter 2 inhibitors (SGLT2is) significantly reduce hospitalization for heart failure (HF) and retard the progression of chronic kidney disease (CKD) in patients with type 2 diabetes. Endothelial dysfunction is not only involved in the development and progression of cardiovascular disease (CVD), but is also associated with the progression of CKD. In patients with type 2 diabetes, hyperglycemia, insulin resistance, hyperinsulinemia and dyslipidemia induce the development of endothelial dysfunction. SGLT2is have been shown to improve endothelial dysfunction, as assessed by flow-mediated vasodilation, in individuals at high risk of CVD. Along with an improvement in endothelial dysfunction, SGLT2is have been shown to improve oxidative stress, inflammation, mitochondrial dysfunction, glucotoxicity, such as the advanced signaling of glycation end products, and nitric oxide bioavailability. The improvements in endothelial dysfunction and such endothelium-derived factors may play an important role in preventing the development of coronary artery disease, coronary microvascular dysfunction and diabetic cardiomyopathy, which cause HF, and play a role in retarding CKD. The suppression of the development of HF and the progression of CKD achieved by SGLT2is might have been largely induced by their capacity to improve vascular endothelial function.

To test the hypothesis that glucagon-like peptide-1 receptor (GLP-1R) agonists have beneficial effects on vascular endothelial function, fibrinolysis and inflammation through weight loss-independent mechanisms.

Individuals with obesity and prediabetes were randomized to 14 weeks of the GLP-1R agonist liraglutide, hypocaloric diet or the dipeptidyl peptidase-4 inhibitor sitagliptin in a 2:1:1 ratio. Treatment with drug was double blind and placebo-controlled. Measurements were made at baseline, after 2 weeks prior to significant weight loss and after 14 weeks. The primary outcomes were measures of endothelial function: flow-mediated vasodilation (FMD), plasminogen activator inhibitor-1 (PAI-1) and urine albumin-to-creatinine ratio (UACR).

Eighty-eight individuals were studied (liraglutide N = 44, diet N = 22, sitagliptin N = 22). Liraglutide and diet reduced weight, insulin resistance and PAI-1, while sitagliptin did not. There was no significant effect of any treatment on endothelial vasodilator function measured by FMD. Post hoc subgroup analyses in individuals with baseline FMD below the median, indicative of greater endothelial dysfunction, showed an improvement in FMD by all three treatments. GLP-1R antagonism with exendin (9-39) increased fasting blood glucose but did not change FMD or PAI-1. There was no effect of treatment on UACR. Finally, liraglutide, but not sitagliptin or diet, reduced the chemokine monocyte chemoattractant protein-1 (MCP-1).

Liraglutide and diet reduce weight, insulin resistance and PAI-1. Liraglutide, sitagliptin and diet do not change FMD in obese individuals with prediabetes with normal endothelial function. Liraglutide alone lowers the pro-inflammatory and pro-atherosclerotic chemokine MCP-1, indicating that this beneficial effect is independent of weight loss.

Type 2 diabetes (T2D) is a widely prevalent disease with substantial economic and social impact for which multiple conventional and novel pharmacotherapies are currently available; however, the landscape of T2D treatment is constantly changing as new therapies emerge and the understanding of currently available agents deepens. This review aims to provide an updated summary of the pharmacotherapeutic approach to T2D. Each class of agents is presented by mechanism of action, details of administration, side effect profile, cost, and use in certain populations including heart failure, non-alcoholic fatty liver disease, obesity, chronic kidney disease, and older individuals. We also review targets of novel therapeutic T2D agent development. Finally, we outline an up-to-date treatment approach that starts with identification of an individualized goal for glycemic control then selection, initiation, and further intensification of a personalized therapeutic plan for T2D.

Obstructive sleep apnea (OSA) is a common but largely undiagnosed clinical condition, which is turning into a serious public health issue. Of note is that its prevalence is gradually increasing in parallel with the obesity and type 2 diabetes mellitus (T2DM) epidemics. The aim of this article is to comprehensively review the literature in order to evaluate the cardiovascular (CV) risk among patients with OSA and prediabetes or T2DM. OSA seems to be an independent risk factor for the development as well as the progression of T2DM, whereas it is associated with T2DM-related macrovascular and microvascular complications. OSA may also act as a potential risk factor for the presentation and development of CV disease, such as hypertension, coronary artery disease, heart failure, pulmonary hypertension, atrial fibrillation and other cardiac arrythmias, as well as stroke. OSA and T2DM also share common pathophysiological mechanisms leading to atherosclerosis. Considering that the coexistence of OSA and T2DM is an independent and cumulative risk factor for CV mortality, more so than the two diseases separately, clinicians and healthcare professionals should be aware of and screen for OSA in patients with T2DM. Notably, targeted therapy for both conditions seems to substantially improve CV prognosis.

Sodium−glucose co-transporter-2 inhibitors or gliflozins, the newest anti-hyperglycemic class, induce cardioprotective benefits in patients with type 2 diabetes (T2D). As platelet activation and oxidative stress play a key role in atherothrombotic-related complications, we hypothesized that gliflozins might modulate oxidative stress, platelet activation and thrombus formation. We performed an interventional open-label single-arm before-after study in 32 T2D patients on top of their ongoing metformin therapy. The population was divided into two groups: treatment with GLP-1 receptor agonists (GLP-1RA, Group A) and gliflozins (Group B). Oxidative stress, platelet activation and thrombus growth were assessed before and after 15 days of treatment. Compared to the baseline, gliflozins treatment significantly decreased sNOX2-dp (−45.2%, p < 0.001), H2O2 production (−53.4%, p < 0.001), TxB2 (−33.1%, p < 0.001), sP-selectin (−49.3%, p < 0.001) and sCD40L levels (−62.3%, p < 0.001) as well as thrombus formation (−32%, p < 0.001), whereas it potentiated anti-oxidant power (HBA, +30.8%, p < 0.001). Moreover, a significant difference in oxidative stress, platelet activation and thrombus formation across groups A and B was found. In addition, an in vitro study on stimulated platelets treated with gliflozins (10−30 μM) showed a reduction in oxidative stress, platelet activation and thrombus growth. Our results showed that gliflozins have antiplatelet and antithrombic activity related to an NOX2 down-regulation, suggesting a new mechanism responsible for cardiovascular protection.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve endothelial dysfunction and reduce cardiovascular events in individuals with type 2 diabetes (T2D). Proprotein convertase subtilisin/kexin 9 (PCSK9i) inhibitors reduce cardiovascular events in high-risk patients. Whether the addition of PCSK9i to SGLT2i treatment adds benefits is not known.

To assess the PCSK9-i effect on the endothelial function of T2D individuals under treatment with SGLT2-i.

Individuals with T2D were randomized in a 1:1 ratio to a 16-week treatment with either empagliflozin (E) or empagliflozin plus evolocumab (EE). The primary endpoint was post-treatment change from baseline in flow-mediated dilation (FMD) at 1-min. Secondary outcomes included changes in plasma levels of nitric oxide metabolites and isoprostane.

A total of 110 patients were enrolled, the mean age was 58 years, and 71% were men. The median post-treatment change in FMD at 1-min was 2.7% (interquartile range [IQR]: 0.9%) and 0.4% (IQR: 0.9%) in the EE and E groups, respectively (p < 0.001). There was a greater increase in plasma levels of nitrate [5.9 (16.5) vs. 2.6 (11.8); p = 0.001] and nitrite [0.14 (0.72) vs. 0.02 (0.74); p = 0.025] in the EE group than in the E group, respectively. Isoprostane reduction was more pronounced in the EE group when compared to the E group [-1.7 (5.9) vs. -1.1 (5.3); p < 0.001).

In individuals with T2D, the addition of evolocumab on top of empagliflozin improves endothelial function.

The adipocyte fatty-acid binding protein (A-FABP) is predominantly expressed in macrophages and adipocytes and is an essential mediator of inflammation and atherosclerosis pathogenesis. Atherosclerosis is an aggravating factor for peripheral arterial disease (PAD). Our study intended to study the association between PAD and serum A-FABP levels in type-2 diabetes mellitus (T2DM) patients. One hundred and twenty T2DM subjects were enrolled in the study. Fasting blood samples were collected to determine biochemical data and A-FABP levels. By the automatic oscillometric method, the ankle−brachial index (ABI) was measured. Low ABI was defined as any value < 0.9. Twenty participants with T2DM (16.7%) were included in the low ABI group. Low ABI T2DM participants had an increased mean body mass index, body fat mass, systolic blood pressure, C-reactive protein, urine albumin−creatinine ratio, and A-FABP levels compared to those in the normal ABI group. After variables significantly associated with PAD were adjusted by multivariate logistic regression analyses, circulating A-FABP levels (odds ratio [OR]: 1.138; 95 percent confidence interval [CI]: 1.023−1.266; p = 0.017) were identified as the independent marker of PAD. In conclusion, fasting serum A-FABP value has positive association with PAD in T2DM patients.

Myocardial infarction (MI) is the leading cause of death and morbidity worldwide, with an incidence relatively high in developed countries and rapidly growing in developing countries. The most common cause of MI is the rupture of an atherosclerotic plaque with subsequent thrombotic occlusion in the coronary circulation. This causes cardiomyocyte death and myocardial necrosis, with subsequent inflammation and fibrosis. Current therapies aim to restore coronary flow by thrombus dissolution with pharmaceutical treatment and/or intravascular stent implantation and to counteract neurohormonal activation. Despite these therapies, the injury caused by myocardial ischemia leads to left ventricular remodeling; this process involves changes in cardiac geometry, dimension and function and eventually progression to heart failure (HF). This review describes the pathophysiological mechanism that leads to cardiac remodeling and the therapeutic strategies with a role in slowing the progression of remodeling and improving cardiac structure and function.