Diabetes Mellitus in Acute Coronary Syndrome.

The global prevalence of diabetes mellitus (DM) has led to a pandemic, with significant microvascular and macrovascular complications including coronary artery disease (CAD), which worsen clinical outcomes and cardiovascular prognosis. Patients with both acute coronary syndrome (ACS) and DM have worse prognosis and several pathophysiologic mechanisms have been implicated including, insulin resistance, hyperglycemia, endothelial dysfunction, platelet activation and aggregations as well as plaque characteristics and extent of coronary lesions. Therefore, regarding reperfusion strategies in the more complex anatomies coronary artery bypass surgery may be the preferred therapeutic strategy over percutaneous coronary intervention while both hyperglycemia and hypoglycemia should be avoided with closed monitoring of glycemic status during the acute phase of myocardial infraction. However, the best treatment strategy remains undefined. Non-insulin therapies, due to the low risk of hypoglycemia concurrently with the multifactorial CV protective effects, may be proved to be the best treatment option in the future. Nevertheless, evidence for the beneficial effects of glucagon like peptide-1 receptor agonists, dipeptidyl-peptidase 4 inhibitors and sodium glycose cotransporter 2 inhibitors, despite accumulating, is not robust and future randomized control trials may provide more definitive data.

Exercise Effects on Left Ventricular Remodeling in Patients with Cardiometabolic Risk Factors.

Left ventricular (LV) remodeling is a dynamic process, which is characterized by changes in ventricular size, shape, and wall thickness, thus altering myocardial geometry and function, and is considered as a negative prognostic factor in patients with heart failure (HF). Hypertension, type 2 diabetes (T2D), and obesity are strongly correlated with the development and the progression of LV remodeling, LV hypertrophy, and LV systolic and/or diastolic dysfunction. Indeed, the beneficial impact of exercise training on primary and secondary prevention of cardiovascular disease (CVD) has been well-established. Recent studies have highlighted that exercise training enhances functional capacity, muscle strength and endurance, cardiac function, and cardiac-related biomarkers among patients with established coronary artery disease (CAD) or HF, thus substantially improving their cardiovascular prognosis, survival rates, and need for rehospitalization. Therefore, in this review article, we discuss the evidence of LV remodeling in patients with cardiometabolic risk factors, such as hypertension, T2D, and obesity, and also highlight the current studies evaluating the effect of exercise training on LV remodeling in these patients.

Antithrombotic Treatment in Coronary Artery Disease.

Coronary artery disease exhibits growing mortality and morbidity worldwide despite the advances in pharmacotherapy and coronary intervention. Coronary artery disease is classified in the acute coronary syndromes and chronic coronary syndromes according to the most recent guidelines of the European Society of Cardiology. Antithrombotic treatment is the cornerstone of therapy in coronary artery disease due to the involvement of atherothrombosis in the pathophysiology of the disease. Administration of antiplatelet agents, anticoagulants and fibrinolytics reduce ischemic risk, which is amplified early post-acute coronary syndromes or post percutaneous coronary intervention; though, antithrombotic treatment increases the risk for bleeding. The balance between ischemic and bleeding risk is difficult to achieve and is affected by patient characteristics, procedural parameters, concomitant medications and pharmacologic characteristics of the antithrombotic agents. Several pharmacological strategies have been evaluated in patients with coronary artery disease, such as the effectiveness and safety of antithrombotic agents, optimal dual antiplatelet treatment schemes and duration, aspirin de-escalation strategies of dual antiplatelet regimens, dual inhibition pathway strategies as well as triple antithrombotic therapy. Future studies are needed in order to investigate the gaps in our knowledge, including special populations.

The prognostic role of galectin-3 and endothelial function in patients with heart failure.

BACKGROUND: Heart failure (HF) is nowadays classified as HF with reduced ejection fraction (HFrEF), HF with mildly reduced EF (HFmrEF), and HF with preserved EF (HFpEF). Endothelial dysfunction (assessed by flow-mediated dilatation [FMD]), increased arterial stiffness (assessed by carotid-femoral pulse-wave velocity [PWV]), and galectin-3, a biomarker of myocardial fibrosis, have been linked to major adverse cardiovascular events (MACE) in patients with ischemic HF. METHODS: In this study we prospectively enrolled 340 patients with stable ischemic HF. We assessed the brachial artery FMD, carotid-femoral PWV, and galectin-3 levels, and patients were followed up for MACE according to HF group. RESULTS: Interestingly, the FMD values exhibited a stepwise improvement according to left ventricular ejection fraction (LVEF) (HFrEF: 4.74 ± 2.35% vs. HFmrEF: 4.97 ± 2.81% vs. HFpEF: 5.94 ± ± 3.46%, p = 0.01), which remained significant after the evaluation of possible confounders including age, sex, cardiovascular risk factors, and number of significantly stenosed epicardial coronary arteries (b coefficient: 0.990, 95% confidence interval: 0.166-1.814, p = 0.019). Single-vessel coronary artery disease was more frequent in the group of HFpEF (HFrEF: 56% vs. HFmrEF: 64% vs. HFpEF: 73%, p = 0.049). PWV did not display any association with LVEF. Patients who presented MACE exhibited worse FMD values (4.51 ± 2.35% vs. 5.32 ± 2.67%, p = 0.02), and the highest tertile of galectin-3 was linked to more MACEs (36% vs. 5.9%, p = 0.01). CONCLUSIONS: Flow-mediated dilatation displayed a linear improvement with LVEF in patients with ischemic HF. Deteriorated values are associated with MACE. Higher levels of galectin-3 might be used for risk stratification of patients with ischemic HF.

Association of Growth Differentiation Factor 15 with Arterial Stiffness and Endothelial Function in Subpopulations of Patients with Coronary Artery Disease: A Proof-of-Concept Study.

BACKGROUND: Growth-differentiation factor-15 (GDF-15) is a biomarker belonging to the transforming growth factor-beta cytokine superfamily, which is linked to many pathological conditions, including inflammation and myocardial injury. Pulse wave velocity (cfPWV) and augmentation index (AIx) are indices of arterial stiffness, which are associated with the severity of coronary artery disease (CAD). Flow-mediated dilatation (FMD) is a well-studied surrogate marker of endothelial-dependent dysfunction and systemic inflammation. OBJECTIVE: In this proof-of-concept study, we aimed to investigate the relationship between circulating GDF-15, endothelial dysfunction, and indices of arterial stiffness in different settings of coronary artery disease and myocardial injury. METHODS: In this cross-sectional single-center study, we enrolled patients (n = 22) after interventional treatment for acute myocardial infarction (AMI), patients (n = 11) admitted with chest pain and elevated cardiac enzymes but without evidence of obstructing CAD (MI-NOCAD) in percutaneous coronary angiography (CAG), and patients (n = 20) who underwent CAG according to indications without evident obstructive CAD in CAG (NOCAD). FMD was assessed at the brachial artery. AIx of the central aortic pressure and cfPWV were estimated by applanation tonometry at the radial and carotid-femoral site, respectively, with a validated acquisition system (Sphygmo- Cor, AtCor Medical, Sydney (NSW), Australia). ELISA was used to determine circulating GDF- 15 serum levels (R&D Systems, Minneapolis, MN). Clinical and demographic data and values of routine biochemical biomarkers were obtained. The highest high-sensitive cardiac Troponin I (hsTpnI) value during hospitalization was also recorded. Left ventricular ejection fraction (LVEF) was assessed with a transthoracic echocardiogram. RESULTS: Patients with AMI were older, had worse LVEF, higher values of hsTpnI and increased circulating GDF-15 levels. Importantly, AMI patients had increased cfPWV values, deteriorated AIx values, blunted FMD and worse serum creatinine levels compared to MI-NOCAD and NOCAD patients, respectively, whereas MI-NOCAD and NOCAD did not differ from each other significantly on these biomarkers. Both AMI and MI-NOCAD patients presented a higher but comparable white blood cell count than NOCAD patients. A strong linear correlation between GDF-15 and cfPWV, hsTpnI, AIx, white blood cell count and creatinine but not with FMD was demonstrated in the general study population. CONCLUSION: This proof-of-concept study showed that higher circulating levels of GDF-15, an inflammatory biomarker, were associated significantly with increased arterial stiffness only in AMI patients, whereas elevated GDF-15 demonstrated a linear relationship with the severity of the myocardial injury.

The effect of allopurinol on cardiovascular outcomes in patients with type 2 diabetes: a systematic review.

BACKGROUND: Cardiovascular disease (CVD) remains the main cause of death in patients with type 2 diabetes (T2D). Although hyperuricemia has been associated with multiple CV complications, it is not officially recognized as a target parameter for CVD risk reduction. AIM: To systematically review the literature in order to determine whether treating hyperuricemia with allopurinol in patients with T2D reduces CVD risk. METHODS: A thorough literature search in the PubMed, CENTRAL, and EMBASE databases from inception to August 2022 was performed. After application of selection criteria, 6 appropriate studies were identified. RESULTS: Detailed analysis of the data derived indicated that there is an association between allopurinol treatment and CV benefits, resulting in a reduced risk of CVD events and mortality rates. This association can be attributed mainly to the reduction of inflammation and oxidative burden, as well as to the improvement of glycemic and lipid profiles. CONCLUSIONS: This systematic review provides evidence that allopurinol may reduce CVD risk in patients with T2D. Randomized, placebo-controlled trials should be performed in order to confirm these findings and identify specific subgroups of patients who will benefit most.

The Role of Cell-derived Microparticles in Cardiovascular Diseases: Current Concepts.

Cardiovascular disease remains the main cause of human morbidity and mortality in developed countries. Microparticles (MPs) are small vesicles originating from the cell membrane as a result of various stimuli and particularly of biological processes that constitute the pathophysiology of atherosclerosis, such as endothelial damage. They form vesicles that can transfer various molecules and signals to remote target cells without direct cell-to-cell interaction. Circulating microparticles have been associated with cardiovascular diseases. Therefore, many studies have been designed to further investigate the role of microparticles as biomarkers for diagnosis, prognosis, and disease monitoring. To this concept, the pro-thrombotic and atherogenic potential of platelets and endothelial-derived MPs have gained research interest, especially concerning accelerated atherosclerosis and triggering as well as prognosis of an acute coronary syndrome. MPs, especially those of endothelial origin, have been investigated in different clinical scenarios of heart failure and in association with left ventricular loading conditions. Finally, most cardiovascular risk factors present unique features in the circulating MPs population, highlighting their pathophysiologic link to cardiovascular disease progression. In this review article, we present a synopsis of the biogenesis and characteristics of microparticles, as well as the most recent data concerning their implication in cardiovascular settings.

Thyroid disorders and cardiovascular manifestations: an update.

Cardiovascular disease (CVD) remains the leading cause of death worldwide, representing a major health, social, and economic issue. Thyroid disorders are very common and affect >10% of the adult population in total. The aim of this review is to describe the physiologic role of thyroid hormones on cardiovascular system, to present cardiovascular manifestations in patients with thyroid disorders, emphasizing in molecular mechanisms and biochemical pathways, and to summarize current knowledge of treatment options. Thyroid hormone receptors are located both in myocardium and vessels, and changes in their concentrations affect cardiovascular function. Hyperthyroidism or hypothyroidism, both clinical and subclinical, without the indicated therapeutical management, may contribute to the progression of CVD. According to recent studies, even middle changes in thyroid hormones levels increase cardiovascular mortality from 20% to 80%. In more details, thyroid disorders seem to have serious effects on the cardiovascular system via plenty mechanisms, including dyslipidemia, hypertension, systolic and diastolic myocardial dysfunction, as well endothelial dysfunction. On top of clinical thyroid disorders management, current therapeutics focus on younger patients with subclinical hypothyroidism and elderly patients with subclinical hyperthyroidism.

Lipoprotein-associated phospholipase A2 levels, endothelial dysfunction and arterial stiffness in patients with stable coronary artery disease.

BACKGROUND: Lipoprotein-associated Phospholipase A2 (Lp-PLA2), can exert proinflammatory as well as proatherogenic properties on the vascular wall. The current study sought to evaluate the influence of high Lp-PLA2 levels on indices of arterial wall properties in patients with stable coronary artery disease (CAD). METHODS: Three hundred seventy-four consecutive patients with stable CAD (mean age 61 ± 11 years, 89% males) were enrolled in this single-center cross-sectional study. Flow-mediated dilation (FMD) was used to assess endothelial function and augmentation index (AIx) of the central aortic pressure was used to assess reflected waves. ELISA was used to determine Lp-PLA2 serum levels. RESULTS: After dividing the participants in 3 equal groups based on the tertiles of circulating Lp-PLA2 values, no significant differences were demonstrated between those in the 3rd tertile with Lp-PLA2 values > 138 µg/L, in the 2nd tertile with Lp-PLA2 values between 101 and 138 µg/L and in the 1st tertile (Lp-PLA2 values < 101 µg/L) regarding age, male gender, smoking habits, family history of CAD or history of a previous myocardial infarction, diabetes mellitus, arterial hypertension, hyperlipidemia, duration of CAD and treatment with relevant medication. Importantly, subjects with Lp-PLA2 values in the highest tertile, had significantly reduced FMD values compared to the middle and lower tertile (4.43 ± 2.37% vs. 4.61 ± 1.97% vs. 5.20 ± 2.52% respectively, P = 0.03). Patients in the highest tertile of Lp-PLA2 values had significantly higher AIx values (24.65 ± 8.69% vs. 23.33 ± 9.65%, P = 0.03), in comparison to the lowest tertile, with Lp-PLA2 values < 101 µg/L. A linear regression analysis showed that Lp-PLA2 values > 138 µg/L negatively correlated to FMD [b = - 0.45 (95% CI: - 0.79 - -0.11), P = 0.01] and AIx values [b = 1.81 (95% CI: 0.57-3.05), P < 0.001] independently of cofounders like gender, age, diabetes mellitus, arterial hypertension, dyslipidemia, smoking habits, family history of CAD, history of previous myocardial infarction, serum glucose, circulating lipid levels, duration of CAD, antihypertensive medication, antidiabetic drugs, statin therapy and treatment with ß-blockers. CONCLUSIONS: Elevated Lp-PLA2 levels relate to endothelial dysfunction and arterial stiffness in patients with stable CAD independently from classical risk factors for CAD, statin use, antihypertensive treatment, and duration of the disease.

MicroRNAs in the Management of Heart Failure.

BACKGROUND: In recent years much research has been devoted to the deployment of biomarkers in the field of heart failure. OBJECTIVES: To study the potential of post-transcriptional regulation by microRNAs on the diagnosis, management and therapy of heart failure. METHODS: Literature search focuses on the role of microRNAs in heart failure. RESULTS: MicroRNAs are expressed and regulated in the course of the pathological manifestations of heart failure (HF). This wide and uncharted area of genetic imprints consisting of small non-coding RNA molecule is upregulated and released into the bloodstream from organs under certain conditions and or stress. The use of genetically based strategies for the management of HF has gained great interest in the field of biomedical science because they can be used as biomarkers providing information regarding cardiac status and function. They also appear as promising tools with therapeutic potential because of their ability to induce changes at the cellular level without creating alterations in the gene sequence. In addition, with the advances in genomic sequencing, quantification and synthesis in technologies of microRNAs identification as well as the growing knowledge of the biology of miRNAs and their involvement in HF, it is expected to favorably affect the prognosis of HF patients. CONCLUSION: MicroRNAs are involved in the regulation of multibiological processes involved in the progress of heart failure. More studies are needed to achieve a clinical valuable implementation of microRNAs in the management of HF.

Novel Antidiabetic Agents: Cardiovascular and Safety Outcomes.

BACKGROUND: Concerns of elevated cardiovascular risk with some anti-diabetic medications warranted trials on the cardiovascular outcome to demonstrate cardiovascular safety of newly marketed anti-diabetic drugs. Although these trials were initially designed to evaluate safety, some of these demonstrated significant cardiovascular benefits. PURPOSE OF REVIEW: We reviewed the cardiovascular and safety outcomes of novel antidiabetic agents in patients with type 2 diabetes and established cardiovascular disease or at high risk of it. We included the outcomes of safety trials, randomized controlled trials, meta-analysis, large cohort studies, and real-world data, which highlighted the cardiovascular profile of DPP-4is, GLP-1RAs and SGLT-2is. CONCLUSION: Although DPP-4is demonstrated non-inferiority to placebo, gaining cardiovascular safety, as well market authorization, SGLT-2is and most of the GLP-1RAs have shown impressive cardiovascular benefits in patients with T2D and established CVD or at high risk of it. These favorable effects of novel antidiabetic agents on cardiovascular parameters provide novel therapeutic approaches in medical management, risk stratification and prevention.

MicroRNAs in cardiovascular disease.

Cardiovascular disease (CVD) remains the predominant cause of human morbidity and mortality in developed countries. Currently, microRNAs have been investigated in many diseases as well-promising biomarkers for diagnosis, prognosis, and disease monitoring. Plenty studies have been designed so as to elucidate the properties of microRNAs in the classification and risk stratification of patients with CVD and also to evaluate their potentials in individualized management and guide treatment decisions. Therefore, in this review article, we aimed to present the most recent data concerning the role of microRNAs as potential novel biomarkers for cardiovascular disease.

Antithrombotic Treatment in Diabetes Mellitus: A Review of the Literature about Antiplatelet and Anticoagulation Strategies Used for Diabetic Patients in Primary and Secondary Prevention.

BACKGROUND: Diabetes mellitus (DM) is on the rise globally. Its prevalence has nearly doubled during the last two decades and it is estimated to affect 8.8% of the global population. Cardiovascular disease (CVD) is the leading cause of death in the diabetic population and despite modern anti-inflammatory and cardioprotective therapeutic strategies, diabetic patients have at least a twice fold risk of cardiovascular events. The prothrombotic state in DM is associated with multiple determinants such as platelet alterations, oxidative stress, endothelial changes, circulating mediators. Thus, proper antithrombotic strategies to reduce the risk of CVD in this population are critical. METHODS: This article reviews the current antiplatelet and anticoagulant agents in the aspect of primary and secondary prevention of CVD in the diabetic population. RESULTS: The use of aspirin may be considered only at high-risk patients in the absence of contraindications. Cangrelor was not inferior to clopidogrel in preventing the composite outcome of CV death, myocardial infarction and revascularization without increasing major bleeding. Triple therapy in the subpopulation with DM significantly reduced the composite primary outcome of CV death, myocardial infarction or repeat target lesion revascularization. That was not the case for stent thrombosis, which was similar in both groups. Importantly, triple therapy did not result in increased bleeding complications, which were similar in both groups. However, cilostazol is linked to various adverse effects (e.g., headache, palpitations, and gastrointestinal disturbances) that drive many patients to withdrawal. CONCLUSION: In conclusion, DM is a rapidly growing disease that increases the risk of CVD, AF, and CV mortality. Proper antithrombotic strategies to reduce CVD risk in DM are a necessity. Moreover, new antithrombotic treatments and combination therapies may play a critical role to overcome antiplatelet resistance in DM patients and reduce morbidity and mortality attributed to CVD.

The Effect of DPP-4i on Endothelial Function and Arterial Stiffness in Patients with Type 2 Diabetes: A Systematic Review of Randomized Placebo-controlled Trials.

We systematically reviewed the literature regarding the impact of dipeptidyl peptidase-4 inhibitors (DPP-4i) on vascular function, including endothelial function and arterial stiffness, as predictors of atherosclerosis progression and cardiovascular disease in patients with type 2 diabetes mellitus (T2DM). We searched PubMed in order to identify clinical trials that investigated the effect of DPP-4i on vascular function in patients with T2DM when compared with placebo. Although 168 articles were initially found, only 6 studies (total 324 patients) investigated the effect of DPP-4i in comparison with placebo, specifically linagliptin and sitagliptin, and satisfied the inclusion criteria. There are scarce data to indicate that linagliptin may enhance endothelial function and exert a slight beneficial effect on arterial wall properties. Sitagliptin seems to have a neutral effect on these variables. Further trials are needed to elucidate the topic. The standards of reporting were in accordance with the PRISMA guidelines.

Endothelial dysfunction and impaired arterial wall properties in patients with retinal vein occlusion.

Retinal vein occlusion (RVO) is a common retinal vascular lesion, and a leading cause of visual impairment. Patients with RVO have an increased risk for cardiovascular disease and share multiple common risk factors. In this study, we investigated the endothelial function and arterial stiffness of patients with RVO compared to healthy-control (CL) subjects. We enrolled 40 consecutive patients with RVO and 40 CL subjects. RVO was diagnosed by an ophthalmologist, endothelial function was evaluated by flow mediated dilation (FMD) in the brachial artery, and carotid-femoral pulse wave velocity (PWV) and augmentation index (AIx) of the radial artery were measured to evaluate arterial stiffness and reflected waves, respectively. No significant differences were detected between the studied groups in sex, age, presence of hypertension or dyslipidemia, body mass index, systolic and diastolic blood pressure levels, total cholesterol levels, and smoking habits (p > 0.05 for all). However, patients with RVO had impaired FMD (p = 0.002) and increased PWV (p = 0.004), even after adjustment for several confounders. Both FMD and PWV were also significantly and independently associated with the development of RVO. Furthermore, a significant and positive correlation between PWV and systolic blood pressure existed only in the CL group. Therefore, we have shown that RVO is associated with significant endothelial dysfunction and increased arterial stiffness. Our results strengthen the vascular theory, according to which, systemic endothelial dysfunction and arteriosclerosis play a significant role in the pathogenesis of RVO.

Coronary Artery Disease and Endothelial Dysfunction: Novel Diagnostic and Therapeutic Approaches.

Coronary artery disease is the leading cause of morbidity and mortality worldwide. The most common pathophysiologic substrate is atherosclerosis which is an inflammatory procedure that starts at childhood and develops throughout life. Endothelial dysfunction is associated with the initiation and progression of atherosclerosis and is characterized by the impaired production of nitric oxide. In general, endothelial dysfunction is linked to poor cardiovascular prognosis and different methods, both invasive and non-invasive, have been developed for its evaluation. Ultrasound evaluation of flow mediated dilatation of the branchial artery is the most commonly used method to assessed endothelial function while intracoronary administration of vasoactive agents may be also be used to test directly endothelial properties of the coronary vasculature. Endothelial dysfunction has also been the subject of therapeutic interventions. This review article summarizes the knowledge about evaluation of endothelial function in acute coronary syndromes and stable coronary artery disease and demonstrates the current therapeutic approaches against endothelial dysfunction.

Mitochondria and cardiovascular diseases-from pathophysiology to treatment.

Mitochondria are the source of cellular energy production and are present in different types of cells. However, their function is especially important for the heart due to the high demands in energy which is achieved through oxidative phosphorylation. Mitochondria form large networks which regulate metabolism and the optimal function is achieved through the balance between mitochondrial fusion and mitochondrial fission. Moreover, mitochondrial function is upon quality control via the process of mitophagy which removes the damaged organelles. Mitochondrial dysfunction is associated with the development of numerous cardiac diseases such as atherosclerosis, ischemia-reperfusion (I/R) injury, hypertension, diabetes, cardiac hypertrophy and heart failure (HF), due to the uncontrolled production of reactive oxygen species (ROS). Therefore, early control of mitochondrial dysfunction is a crucial step in the therapy of cardiac diseases. A number of anti-oxidant molecules and medications have been used but the results are inconsistent among the studies. Eventually, the aim of future research is to design molecules which selectively target mitochondrial dysfunction and restore the capacity of cellular anti-oxidant enzymes.

Effects of Newer Antidiabetic Drugs on Endothelial Function and Arterial Stiffness: A Systematic Review and Meta-Analysis.

BACKGROUND: Newer antidiabetic drugs, i.e., dipeptidyl peptidase-4 (DPP-4) inhibitors, sodium-glucose cotransporter-2 (SGLT-2) inhibitors, and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may exert distinct cardiovascular effects. We sought to explore their impact on vascular function. METHODS: Published literature was systematically searched up to January 2018 for clinical studies assessing the effects of DPP-4 inhibitors, GLP-1 RAs, and SGLT-2 inhibitors on endothelial function and arterial stiffness, assessed by flow-mediated dilation (FMD) of the brachial artery and pulse wave velocity (PWV), respectively. For each eligible study, we used the mean difference (MD) with 95% confidence intervals (CIs) for FMD and PWV. The pooled MD for FMD and PWV were calculated by using a random-effect model. The presence of heterogeneity among studies was evaluated by the I 2 statistic. RESULTS: A total of 26 eligible studies (n = 668 patients) were included in the present meta-analysis. Among newer antidiabetic drugs, only SGLT-2 inhibitors significantly improved FMD (pooled MD 1.14%, 95% CI: 0.18 to 1.73, p = 0.016), but not DPP-4 inhibitors (pooled MD = 0.86%, 95% CI: -0.15 to 1.86, p = 0.095) or GLP-1 RA (pooled MD = 2.37%, 95% CI: -0.51 to 5.25, p = 0.107). Both GLP-1 RA (pooled MD = -1.97, 95% CI: -2.65 to -1.30, p < 0.001) and, to a lesser extent, DPP-4 inhibitors (pooled MD = -0.18, 95% CI: -0.30 to -0.07, p = 0.002) significantly decreased PWV. CONCLUSIONS: Newer antidiabetic drugs differentially affect endothelial function and arterial stiffness, as assessed by FMD and PWV, respectively. These findings could explain the distinct effects of these drugs on cardiovascular risk of patients with type 2 diabetes.