A review on cardiovascular effects of newer hypoglycaemic medications

Cardiovascular disease (CVD) is the most prevalent cause of morbidity and mortality in diabetic patients. Improvement in cardiovascular complications with glycaemic control and managing cardiovascular risk factors is well established. However, the impact of hypoglycaemic medications on CVD is of increasing importance. In 2008, the U.S. Food and Drug Administration issued study regulations for hypoglycaemic agents after rosiglitazone was shown to increase the incidence of myocardial infarction, and the European Medicines Agency provided their own guidance in 2012. As a result, multiple studies have been published evaluating the cardiovascular safety of newer hypoglycaemic medications. Empagliflozin and liraglutide are among the newer agents that have shown cardiovascular benefit and are now recommended for patients with CVD or are at an increased risk of CVD per the 2017 American Diabetes Association Guidelines. Given the influx of new literature and other ongoing studies, it is important to understand the cardiovascular safety of newer hypoglycaemic medications. The purpose of this article is to provide a comprehensive review of clinical trials conducted evaluating cardiovascular outcomes of newer hypoglycaemic medications and their role within diabetic management.

• Key Messages

• With the prevalence of cardiovascular disease in diabetic patients, clinicians should develop a medication regimen that provides both sufficient efficacy for diabetes while also maintaining cardiovascular safety.

• Of the new diabetic classes, empagliflozin, a sodium-glucose co-transporter 2 inhibitor, and liraglutide, a glucagon-like peptide-1 receptor agonist, have shown cardiovascular benefit in diabetic patients with established cardiovascular disease and are now recommended in current guidelines for this population.

• Ongoing trials will give more insight to whether cardiovascular benefit is a class effect with sodium-glucose co-transporter 2 inhibitors and glucagon-like peptide-1 receptor agonists and the cardiovascular safety of dipeptidyl peptidase-4 inhibitors.

     

Effects of antidiabetic drugs on the incidence of macrovascular complications and mortality in type 2 diabetes mellitus: a new perspective on sodium–glucose co-transporter 2 inhibitors

Elevated hemoglobin A_1c (HbA_1c) values correlate with microvascular and macrovascular complications. Thus, patients with type 2 diabetes mellitus (T2DM) are at an increased risk of developing macrovascular events. Treatment of T2DM should be based on a multifactorial approach because of its evidence regarding reduction of macrovascular complications and mortality in T2DM. It is well known that intensive glucose control reduces the risk of microvascular complications in T2DM, but the effects of antidiabetic drugs on macrovascular complications and mortality in T2DM are less clear. The results of recent trials have demonstrated clear evidence that empagliflozin and liraglutide reduce cardiovascular (CV) and all-cause mortality in T2DM, an effect that is absent in other members of antidiabetic drugs. Empagliflozin is a member of a novel class of antidiabetic drugs, the sodium–glucose co-transporter 2 (SGLT2) inhibitors. Two ongoing randomized clinical trials involving other SGLT2 inhibitors, canagliflozin and dapagliflozin, will provide additional evidence of the beneficial effects of SGLT2 inhibitors in T2DM population. The aim of this paper is to systematically present the latest evidence regarding the usage of antidiabetic drugs, and the reduction of macrovascular complications and mortality. A special emphasis is put on the novel class of antidiabetic drugs, of SGLT2 inhibitors.

• Key messages

• Macrovascular complications and mortality are best clinical trial endpoints for evaluating the efficacy of antidiabetic drugs.

• The first antidiabetic drug that demonstrated a reduction in mortality in the treatment of type 2 diabetes mellitus (T2DM) was empagliflozin, a sodium–glucose co-transporter 2 (SGLT2) inhibitor.

• SGLT2 inhibitors are novel class of antidiabetic drugs that play a promising role in the treatment of T2DM.

     

Cardioversion for atrial fibrillation – how to prevent thromboembolic complications?

Abstract

Cardioversion is an essential component of rhythm control strategy for atrial fibrillation. The thromboembolic risk of cardioversion is well established and the mechanisms behind the phenomenon have been comprehensively described. There are several clinical aspects that are important to take into consideration when assessing the safety of cardioversion. Before proceeding to cardioversion, the probability of early treatment failure and antiarrhythmic treatment options to prevent recurrences should be carefully evaluated to avoid the risks of repeated futile cardioversions. Effective periprocedural anticoagulation is the mainstay in thromboembolic complication prevention and the first week after rhythm conversion is the most vulnerable period in this respect. Early timing of cardioversion appears to be another important measure to decrease the risk of thromboembolic complications. Transoesophageal echocardiography is useful in clinical scenarios where early cardioversion is desirable due to debilitating clinical symptoms and a short duration of arrhythmia or the adequacy of preceding anticoagulation is uncertain. However, it does not lessen the need for effective anticoagulation after cardioversion. This review summarizes the recent scientific discoveries to improve the safety of cardioversion for atrial fibrillation.

• Key messages

• Cardioversion for atrial fibrillation entails a significant risk of thromboembolic complications, especially during the first week after the procedure.

• The intensity of periprocedural anticoagulation and the timing of cardioversion appear to be significant determinants of the risk of thromboembolism.

• Awareness of the clinical aspects influencing cardioversion safety should be raised.

     

Depression,antidepressant use,and risk of venous thromboembolism: systematic review and meta-analysis of published observational evidence

Abstract

Purpose: Evidence on the association between depression, antidepressant use and venous thromboembolism (VTE) risk is conflicting. We conducted a systematic review and meta-analysis of published observational studies evaluating the associations of depression and antidepressant use with VTE risk.

Design: Eligible studies were identified in a literature search of MEDLINE, Embase, Web of Science and reference list of relevant studies up to April 2018. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were aggregated using random effects models.

Results: Eight observational studies with data on 960 113 nonoverlapping participants and 9027 VTE cases were included. The pooled RR (95% CI) for VTE comparing antidepressant use with no antidepressant use was 1.27 (1.06–1.51). Tricyclic antidepressants, selective serotonin reuptake inhibitors and other antidepressants were each associated with an increased VTE risk; 1.16 (1.06–1.27), 1.12 (1.02–1.23), and 1.59 (1.21–2.09), respectively. In pooled analysis of three studies that compared patients with depression versus individuals without depression, the RR for VTE was 1.31 (1.13–1.53).

Conclusions: Pooled observational evidence suggests that depression and use of antidepressants are each associated with an increased VTE risk. The effect of antidepressant drugs on VTE may be a class effect. The mechanistic pathways underlying these associations deserve further evaluation.

Systematic review registration: PROSPERO 2018: CRD42018095595

• Key messages

• Emerging evidence suggests that depression and antidepressant use may be associated with venous thromboembolism (VTE) risk, but the evidence is conflicting.

• This first systematic review and meta-analysis of observational studies shows that depression and use of antidepressants are each associated with an increased risk of VTE.

• There may be a class effect of antidepressant drugs on VTE.

     

Six-minute walking test in children

• Implications for Rehabilitation

• Six-minute walking test.

• The six-minute walking test is safe and widely performed in the world because of its easy implementation and low cost.

• Many countries have established normal values to the six-minute walking test in healthy children.

• However, the applicability of this test also gains popularity among children with other disease conditions.

     

Update on extended treatment for venous thromboembolism

Abstract

The importance of assessing the probability of venous thromboembolism recurrence, a condition that includes deep vein thrombosis and pulmonary embolism, lies in the fact that it is the most important factor in deciding the duration of anticoagulant treatment. Risk of recurrence depends mostly on the presence of a risk factor for developing venous thromboembolism, with patients with unprovoked events being at the higher risk of recurrence. The risk of recurrence needs to be balanced with the risk of bleeding and the potential severity of these thrombotic and hemorrhagic events. In patients with an unprovoked venous thromboembolism who complete treatment for the acute (first 10 days) and post-acute phase of the disease (from day 10 to 3–6 months), the decision has to be made regarding prolonged antithrombotic therapy to prevent recurrences. The main goal of extended treatment is preventing recurrences with a safety profile in terms of bleeding risk. Many therapeutic options are now available for these patients, including antiplatelet therapy with aspirin or direct oral anticoagulants. Moreover, apixaban and rivaroxaban at prophylactic doses have demonstrated efficacy in preventing recurrences with a low risk of bleeding.

• Key messages

• Extending treatment (longer than 3–6 months) is challenging in patients with venous thromboembolism (VTE) and depend on the risk of venous thromboembolism recurrence, the bleeding risk and patient and physician preferences.

• Anticoagulation treatment should be stopped in patients with provoked VTE and in those with unprovoked VTE and a high bleeding risk after an initial period of 3–6 months.

• There are some therapeutic alternatives (including Aspirin and low dose of some NOACs) to reduce venous thromboembolism recurrence risk in patients with unprovoked VTE and a low bleeding risk for extended treatment of VTE (after an initial period of 3–6 months).

     

Cardiometabolic diseases of civilization: history and maturation of an evolving global threat. An update and call to action

Despite striking extensions of lifespan, leading causes of death in most countries now constitute chronic, degenerative diseases which outpace the capacity of health systems. Cardiovascular disease is the most common cause of death in both developed and undeveloped countries. In America, nearly half of the adult population has at least one chronic disease, and polypharmacy is commonplace. Prevalence of ideal cardiovascular health has not meaningfully improved over the past two decades. The fall in cardiovascular deaths in Western countries, half due to a fall in risk factors and half due to improved treatments, have plateaued, and this reversal is due to the dual epidemics of obesity and diabetes type 2. High burdens of cardiovascular risk factors are also evident globally. Undeveloped nations bear the burdens of both infectious diseases and high childhood death rates. Unacceptable rates of morbidity and mortality arise from insufficient resources to improve sanitation, pure water, and hygiene, ultimately linked to poverty and disparities. Simultaneously, about 80% of cardiovascular deaths now occur in low- and middle-income nations. For these reasons, risk factors for noncommunicable diseases, including poverty, health illiteracy, and lack of adherence, must be targeted with unprecedented vigor worldwide.

• Key messages

• In developed and relatively wealthy countries, chronic “degenerative” diseases have attained crisis proportions that threaten to reverse health gains made within the past decades.

• Although poverty, disparities, and poor sanitation still cause unnecessary death and despair in developing nations, they are now also burdened with increasing cardiovascular mortality.

• Poor adherence and low levels of health literacy contribute to the high background levels of cardiovascular risk.

     

The association of non-alcoholic fatty liver disease and atrial fibrillation: a review

Non-alcoholic fatty liver disease (NAFLD) is highly prevalent and causes an enormous burden to human health and health-care systems all over the world. A great proportion of this burden results from increased risk of cardiovascular diseases. Atrial fibrillation (AF) is the most common chronic heart arrhythmia globally and it increases the risk of embolic stroke and heart failure. Recent studies have explored the association between NAFLD and AF with somewhat conflicting results. However, ultrasound-verified prospective studies concur that NAFLD is associated with the incidence of AF. According to epidemiological evidence, the greater the prevalence of NALFD in a population, the stronger the association with AF incidence and prevalence. Specifically, diabetic individuals with NAFLD are at the greatest risk of AF. Additionally, the risk of AF may concentrate most in individuals with advanced NAFLD, particularly those with liver fibrosis. The possible mechanistic factors between NAFLD and AF, particularly obesity and systemic inflammation, are diverse and form a complex interplaying network. However, further studies are needed to elucidate whether NAFLD has a causative role in the development of AF. The purpose of this article is to review and discuss the epidemiologic evidence and possible mechanistic links between these two conditions.

• KEY MESSAGES

• Although epidemiologic studies have provided conflicting results on the association of NAFLD and AF, prospective studies with ultrasound-verified NAFLD concur that NAFLD is associated with about 2-fold greater incidence of AF among general population and about 6-fold greater incidence among subjects with type 2 diabetes.

• The risk of AF among individuals with NAFLD is increased by other cardiovascular risk factors, especially type 2 diabetes and advanced age.

• The possible mechanistic links between NALFD and AF are diverse, with obesity and systemic inflammation having a significant role, but further studies are needed until NAFLD can be established as a causal factor in the incidence of AF.

     

Emergency Incident Rehabilitation: Resource Document to the Position Statement of the National Association of EMS Physicians

Position Statement: Emergency Incident Rehabilitation

The National Association of EMS Physicians® believes that:

• Emergency operations and training conducted while wearing protective clothing and respirators is physiologically and cognitively demanding.

• The heat stress and fatigue created by working in protective clothing and respirators creates additional risk of illness/injury for the public safety provider.

• Emergency incident rehabilitation provides a structured rest period for rehydration and correction of abnormal body core temperature following work in protective clothing and respirators.

• Emergency incident rehab should be conducted at incidents (e.g. fireground, hazardous materials, and heavy rescue emergencies) and trainings involving activities that may lead to exceeding safe levels of physical and mental exertion.

• Emergency incident rehabilitation is incident care, not fitness for duty, and meant to reduce physiologic strain and prepare the responder to return to duty at the current incident and for the remainder of the shift.

• EMS should play a role in emergency incident rehabilitation with providers trained to understand the physiologic response of healthy individuals to environmental, exertional, and cognitive stress and implement appropriate mitigation strategies.

• An appropriately qualified physician should have oversight over the creation and implementation of emergency incident rehabilitation protocols and may be separate from the roles and responsibilities of the occupational medicine physician.

• There are no peer-reviewed data related to cold weather rehabilitation. Future studies should address this limitation to the literature.

     

Molecular aspects of hypercholesterolemia treatment: current perspectives and hopes

Hypercholesterolemia is a pathological condition which has been reported in 39% of the worlds’ adult population. We aimed to review molecular aspects of current and novel therapeutic approaches based on low-density lipoprotein cholesterol lowering strategies. Pathogenic mutations in the LDLR, ApoB, PCSK9 and LDLRAP genes cause deficient clearance of circulating low-density lipoprotein cholesterol particles via hepatic LDL receptor. This leads to increased plasma LDL cholesterol levels from birth, which can cause LDL depositions in the arterial walls. Ultimately, it progresses to atherosclerosis and an increased risk of premature cardiovascular diseases. Currently, statins, Ezetimibe, Bile acid sequestrants and PCSK9 inhibitors are the main therapeutic agents for the treatment of hypercholesterolemia. Moreover, novel RNA-based therapy had a strong impact on therapeutic strategies in recent decades. Additional development in understanding of the molecular basis of hypercholesterolemia will provide opportunities for the development of targeted therapy in the near future.

• Key Messages

• The most common genes involved in hypercholesterolemia are LDLR, PCSK9 and ApoB.

• Pharmacogenetic effects are typically constrained to pathways closely related to the pharmacodynamics and pharmacokinetics.

• Change in lifestyle and diet along with treatment of the underlying disease and drug therapy are the current therapeutic strategies.

     

Hereditary and acquired C1-inhibitor-dependent angioedema: from pathophysiology to treatment

Uncontrolled generation of bradykinin (BK) due to insufficient levels of protease inhibitors controlling contact phase (CP) activation, increased activity of CP proteins, and/or inadequate degradation of BK into inactive peptides increases vascular permeability via BK-receptor 2 (BKR2) and results in subcutaneous and submucosal edema formation. Hereditary and acquired angioedema due to C1-inhibitor deficiency (C1-INH-HAE and -AAE) are diseases characterized by serious and potentially fatal attacks of subcutaneous and submucosal edemas of upper airways, facial structures, abdomen, and extremities, due to inadequate control of BK generation. A decreased activity of C1-inhibitor is the hallmark of C1-INH-HAE (types 1 and 2) due to a mutation in the C1-inhibitor gene, whereas the deficiency in C1-inhibitor in C1-INH-AAE is the result of autoimmune phenomena. In HAE with normal C1-inhibitor, a significant percentage of patients have an increased activity of factor XIIa due to a FXII mutation (FXII-HAE). Treatment of C1-inhibitor-dependent angioedema focuses on restoring control of BK generation by inhibition of CP proteases by correcting the balance between CP inhibitors and BK breakdown or by inhibition of BK-mediated effects at the BKR2 on endothelial cells. This review will address the pathophysiology, clinical picture, diagnosis and available treatment in C1-inhibitor-dependent angioedema focusing on BK-release and its regulation.

• Key Messages

• Inadequate control of bradykinin formation results in the formation of characteristic subcutaneous and submucosal edemas of the skin, upper airways, facial structures, abdomen and extremities as seen in hereditary and acquired C1-inhibitor-dependent angioedema.

• Diagnosis of hereditary and acquired C1-inhibitor-dependent angioedema may be troublesome as illustrated by the fact that there is a significant delay in diagnosis; a certain grade of suspicion is therefore crucial for quick diagnosis.

• Submucosal edema formation in hereditary and acquired C1-inhibitor-dependent angioedema is potentially life threatening and can occur at any age.

• To date effective therapies for acute and prophylactic treatment are available.

     

Dental stem cells: recent progresses in tissue engineering and regenerative medicine

Since the disclosure of adult mesenchymal stem cells (MSCs), there have been an intense investigation on the characteristics of these cells and their potentialities. Dental stem cells (DSCs) are MSC-like populations with self-renewal capacity and multidifferentiation potential. Currently, there are five main DSCs, dental pulp stem cells (DPSCs), stem cells from exfoliated deciduous teeth (SHED), stem cells from apical papilla (SCAP), periodontal ligament stem cells (PDLSCs) and dental follicle precursor cells (DFPCs). These cells are extremely accessible, prevail during all life and own an amazing multipotency. In the past decade, DPSCs and SHED have been thoroughly studied in regenerative medicine and tissue engineering as autologous stem cells therapies and have shown amazing therapeutic abilities in oro-facial, neurologic, corneal, cardiovascular, hepatic, diabetic, renal, muscular dystrophy and auto-immune conditions, in both animal and human models, and most recently some of them in human clinical trials. In this review, we focus the characteristics, the multiple roles of DSCs and its potential translation to clinical settings. These new insights of the apparently regenerative aptitude of these DSCs seems quite promising to investigate these cells abilities in a wide variety of pathologies.

• Key messages

• Dental stem cells (DSCs) have a remarkable self-renewal capacity and multidifferentiation potential;

• DSCs are extremely accessible and prevail during all life;

• DSCs, as stem cells therapies, have shown amazing therapeutic abilities in oro-facial, neurologic, corneal, cardiovascular, hepatic, diabetic, renal, muscular dystrophy and autoimmune conditions;

• DSCs are becoming extremely relevant in tissue engineering and regenerative medicine.

     

Cardiac Troponin - diagnostic problems and impact on cardiovascular disease

Abstract

The definition of a high-sensitivity cardiac Troponin (cTn) assay describes the ability to quantify a cardiac biomarker level in at least 50% of healthy individuals. This advance in analytic sensitivity has come with a perceived loss of specificity in the most classic application – chest pain triage and the diagnosis of acute myocardial infarction (AMI). As cardiac Troponin can no longer be used as a dichotomous test, the medical field is increasingly moving towards a more granular interpretation. However, rapid rule-out/rule-in algorithms for AMI still rely on concrete thresholds for efficient triage, irrespective of the patient’s comorbidities. Owing to a slightly elevated cTn value, evermore patients appear to fall into an indeterminate risk zone of diagnostic uncertainty. The reasons are manifold, spanning biological variation, analytical issues, increased plasma membrane permeability and the potential cytosolic release of cTn. This review provides a contemporary overview of the literature concerning the use of cardiac Troponin in chronic and acute cardiovascular care.

• Key messages

• High-sensitivity cardiac Troponin assays have transformed the assessment of cardiovascular disease.

• Rapid rule-out algorithms for chest pain triage have become increasingly complicated, but enable safe rule-out.

• Cardiac Troponin tracks mid- to long-term risk in patients with hyperlipidaemia, heart failure and renal dysfunction.

     

The role of mitochondrial dysfunction in cardiovascular disease: a brief review

Cardiovascular disease (CVD) is a leading cause of mortality worldwide. Proper mitochondrial function is necessary in tissues and organs that are of high energy demand, including the heart. Mitochondria are very sensitive to nutrient and oxygen supply and undergo metabolic adaptation to the changing environment. In CVD, such an adaptation is impaired, which, in turn, leads to a progressive decline of the mitochondrial function associated with abnormalities in the respiratory chain and ATP synthesis, increased oxidative stress, and loss of the structural integrity of mitochondria. Uncoupling of the electron transport chain in dysfunctional mitochondria results in enhanced production of reactive oxygen species, depletion of cell ATP pool, extensive cell damage, and apoptosis of cardiomyocytes. Mitophagy is a process, during which cells clear themselves from dysfunctional and damaged mitochondria using autophagic mechanism. Deregulation of this process in the failing heart, accumulation of dysfunctional mitochondria makes the situation even more adverse. In cardiac pathology, aberrations of the activity of the respiratory chain and ATP production may be considered as a core of mitochondrial dysfunction. Indeed, therapeutic restoration of these key functional properties can be considered as a primary goal for improvement of mitochondrial dysfunction in CVD.

• Key messages

• Mitochondrial dysfunction plays a crucial role in cardiovascular disease pathogenesis.

• Cardiovascular disease is associated with altered mithochondrial biogenesis and clearance.

• In cardiovascular disease, impaired mitochondrial function results in decreased ATP production and enhanced ROS formation.

     

Role of lipids and intraplaque hypoxia in the formation of neovascularization in atherosclerosis

According to the current paradigm, chronic vascular inflammation plays a central role in the pathogenesis of atherosclerosis. The plaque progression is typically completed with rupture and subsequent acute cardiovascular complications. Previously, the role of adventitial vasa vasorum in atherogenesis was underestimated. However, investigators then revealed that vasa vasorum neovascularization can be observed when no clinical manifestation of atherosclerosis is present. Vasa vasorum is involved in various proatherogenic processes such as intimal accumulation of inflammatory leukocytes, intimal thickening, necrotic core formation, intraplaque haemorrhage, lesion rupture and atherothrombosis. Due to the destabilizing action of the intraplaque microenvironment, lesional vasa vasorum neovessels experience serious defects and abnormalities during development that leads to their immaturity, fragility and leakage. Indeed, intraplaque neovessels are a main cause of intraplaque haemorrhage. Visualization techniques showed that presence of neovascularization/haemorrhage can serve as a good indicator of lesion instability and higher risk of rupture. Vasa vasorum density is a strong predictor of acute cardiovascular events such as sudden death, myocardial infarction and stroke. At present, arterial vasa vasorum neovascularization is under intensive investigation along with development of therapeutic tools focused on the control of formation of vasa vasorum neovessels in order to prevent plaque haemorrhage/rupture and thromboembolism.

• KEY MESSAGE

• Neovascularization plays an important role in atherosclerosis, being involved in unstable plaque formation.

• Presence of neovascularization and haemorrhage indicates plaque instability and risk of rupture.

• Various imaging techniques are available to study neovascularization.

     

Childhood obesity in specialist care – searching for a healthy obese child

Abstract

Introduction One in three obese adults is classified as metabolically healthy, but there is less evidence in obese children. We studied the overall clinical presentation of Finnish obese children and the prevalence of cardiometabolic risk factors with child-specific cut-offs.

Material and methods This is a cross-sectional register-based study of 2–18-year-old children (n?=?900) evaluated for obesity in three hospitals in 2005–2012. Clinical and metabolic data were related to sex, age, puberty, and obesity grade and analyzed using chi-square and non-parametric tests.

Results In 80% of cases at least one cardiovascular risk factor was present. Only 3% of subjects for whom complete metabolic data were available (n?=?360) had no metabolic disorder. Systolic blood pressure was hypertensive in 50.2% and diastolic in 14.5% of the children. The youngest children had highest body mass index SD score. Obesity was more severe in boys than girls (p?<?0.001). Hypertensive systolic blood pressure values (p?=?0.012), prediabetes (p?<?0.001), fatty liver (p?<?0.001), and dyslipidemia (p?=?0.025) were more prevalent in 15–18-year-old boys than girls.

Conclusion Most obese children in specialist care have cardiovascular risk factors; this indicates that earlier intervention is needed.

• Key messages

• Most obese children evaluated in specialist care have one or more cardiovascular risk factors, and very few have no metabolic disturbances.

• In late adolescence these risk factors are more common in obese boys than girls.

• Primary care personnel are less likely to intervene in cases of obesity in young children than in adolescents, leading to a delay in treatment.

• Hypertensive blood pressure values require more attention in clinical work.

     

Previous gestational diabetes history is associated with impaired coronary flow reserve

Abstract

Background Gestational diabetes mellitus (GDM) is a prediabetic state that is known to increase the risk of cardiovascular diseases. We have investigated coronary flow velocity reserve (CFVR) and epicardial fat thickness (EFT), and left ventricular diastolic function in patients with a history of previous GDM (p-GDM).

Methods Ninety-three women with GDM history and 95 healthy women without GDM history were recruited. We used transthoracic Doppler echocardiography to assess CFVR, EFT, and left ventricular diastolic function. Insulin resistance of each subject was assessed with homeostasis model assessment insulin resistance (HOMA-IR). Hemoglobin A1c and high-sensitivity C-reactive protein (hsCRP) were also measured in all patients.

Results CFVR values were significantly lower (2.34?±?0.39 versus 2.80?±?0.24, p?<?0.001) and EFT values were significantly higher in patients with p-GDM than the control group (5.5?±?1.3 versus 4.3?±?1.1, p?<?0.001). E/E' ratio (7.21?±?1.77 versus 6.53?±?1.38, p?=?0.003), hemoglobin A1c (5.2?±?0.4 and 5.0?±?0.3, p?=?0.001), HOMA-IR (2.8?±?1.4 versus 1.7?±?0.9, p?=?0.04), and hsCRP levels were significantly higher in the p-GDM group than the control group. Multivariate analysis revealed that gestational diabetes history is independently associated with CFVR.

Conclusion Women with a GDM history may be at more risk regarding coronary microvascular dysfunction compared to the healthy ones.

• Key Messages

• What is already known about this subject?

• Impairment of CFVR reflects coronary microvascular dysfunction and has been shown to be an early manifestation of atherosclerosis and coronary artery disease.

• Several studies have shown an association between p-GDM and atherosclerosis by measuring intima-media thickness.

• What are new findings?

• This preliminary study on coronary microvascular function of patients with p-GDM revealed that CFVR is significantly impaired in p-GDM patients.

• Although the number of patients included in this study is limited, these results suggest that impaired CFVR may be an early manifestation of coronary vascular involvement in patients with p-GDM.

• How might it impact on clinical practice in the foreseeable future?

• In patients with p-GDM, the presence of impaired CFVR should render the clinician aware of the development of coronary artery disease.

     

Targeting vasoactive peptides for managing calcific aortic valve disease

Calcific aortic valve disease (CAVD) represents a spectrum of disease spanning from milder degrees of calcification of valve leaflets, i.e., aortic sclerosis, to severe calcification i.e., aortic stenosis (AS) with hemodynamic instability. The prevalence of CAVD is increasing rapidly due to the aging of the population, being up to 2.8% among patients over 75 years of age. Even without significant aortic valve stenosis, aortic sclerosis is associated with a 50% increased risk of myocardial infarction and death from cardiovascular causes. To date, there is no pharmacological treatment available to reverse or hinder the progression of CAVD. So far, the cholesterol-lowering therapies (statins) and renin–angiotensin system (RAS) blocking drugs have been the major pharmacological agents investigated for treatment of CAVD. Especially angiotensin receptor blockers (ARB)s and angiotensin convertase enzyme inhibitors (ACEI)s, have been under active investigation in clinical trials, but have proven to be unsuccessful in slowing the progression of CAVD. Several studies have suggested that other vasoactive hormones, including endothelin and apelin systems are also associated with development of AS. In the present review, we discuss the role of vasoactive factors in the pathogenesis of CAVD as novel pharmacological targets for the treatment of aortic valve calcification.

• Key messages

• Vasoactive factors are involved in the progression of calcific aortic valve disease.

• Endothelin and renin–angiotensin systems seem to be most prominent targets for therapeutic interventions in the view of valvular pathogenesis.

• Circulating vasoactive factors may provide targets for diagnostic tools of calcified aortic valve disease.