Kardiovaskuläre Effekte von SGLT-2-Hemmern

Background

Sodium glucose transporter 2 (SGLT2) inhibitors have been recently approved for the treatment of patients with type 2 diabetes mellitus.

Effects

These new substances result in excretion of glucose via inhibition of the proximal tubular absorption apparatus, thus, eliminating glucose and consequently (with the molecules) calories from the body. Three SGLT2 inhibitors are currently available: dapagliflozin (Forxiga®), empagliflozin (Jardiance®) and canagliflozin (Invokana®). In addition to lowering glucose levels they also result in a decrease of body weight by about 2 kg, systolic blood pressure (by about 4 mmHg) and diastolic blood pressure (by about 2 mmHg). Secondary effects include e.?g. decreasing blood volume and lowering of uric acid concentrations. In a 2015 outcome study, empagliflozin reduced total mortality, cardiovascular mortality, and hospitalizations for congestive heart failure when compared to a standard diabetes regimen combined with placebo. Open questions are whether these effects can also be achieved with other substances of the same class. Moreover the mechanism must still be elucidated, whereby it is possible that many effects play positively together: blood pressure lowering, glucose lowering, weight reduction, plasma volume reduction, improved arterial stiffness, uric acid reduction, etc.

Conclusion

For the practitioner it is important that this new class is well combinable with all other antidiabetic or glucose-lowering drugs. The priority of these drugs in the treatment of diabetes will be established by future guidelines. Decisive is that SGLT2 inhibitors have been approved for mono- and combination therapy.

     

Kardiovaskuläre Effekte oraler Antidiabetika

In the recent years there has been increasing interest in the effects of oral hypoglycemic drugs on the cardiovascular system. This has arisen because of recognitions that thiazolidine-diones, peroxisome proliferators-activated receptor gamma (PPAR-gamma), may have antiatherogenic actions and that sulphonylureas are capable of closing the ATP-dependent potassium channel. PPAR-gamma agonists exert antiatherogenic action by inhibition the production of monocyte inflammatory cytokines, inhibition of expression of adhesion molecules in endothelial cells, inhibition of the proliferation of vascular smooth muscle cells and have antioxidative effects. The United Kingdom Prospective Diabetes Study (UKPDS), published in 1998, found that the use of sulphonylureas had no increase in cardiovascular mortality and that metformin therapy in obese individuals with type 2 diabetes mellitus was associated with reduced cardiovascular death. Recently, the STOP-NIDDM trial has been shown that patients with impaired glucose tolerance treated with the alpha-glucosidase inhibitor acarbose had a significant reduction in the risk of cardiovascular disease.Currently, the results of the UKPDS trial are the only available clinical data on which to base the choice of treatment for type 2 diabetic patients. When a glucose-lowering oral drug is considered necessary and is not contraindicated, the firstline choice is a sulphonylurea or a glinide (repaglinide or nateglinide) for diabetics who are not overweight and metformin for those who are.     

Kardiovaskuläre Effekte der Insulintherapie

Background

The importance of a near normal blood glucose adjustment and insulin therapy for prevention of subsequent microangiopathic diseases is undisputed.

Type 1 diabetes

The important role of intensive insulin therapy for prevention of cardiovascular events in type 1 diabetes has been clearly confirmed by the diabetes control and complications trial (DCCT) of the epidemiology of diabetes interventions and complications (EDIC) research group: in the long term, intensive insulin therapy reduces the risk of non-fatal myocardial infarction, stroke and death from cardiovascular causes by 57?%.

Type 2 diabetes

For patients with type 2 diabetes a cardiovascular benefit of early insulin therapy with near normal blood glucose adjustment was confirmed by the United Kingdom prospective diabetes study (UKPDS) but only becomes apparent in the follow-up period. In insulin therapy of long-standing diabetes mellitus and/or pre-existing cardiovascular diseases, priority is given to avoidance of hypoglycemia in order to prevent acute cardiovascular events. For patients with heart insufficiency the indications are that high insulin dosages should be avoided where possible and the benefit of a near normal blood glucose adjustment has also not been proven.

     

Kardiovaskul?re Effekte inkretinbasierter Therapien

Pharmacological modulation of the glucagon-like peptide-1 (GLP-1) system has emerged as a new therapeutic option for treatment of diabetes mellitus. In addition to the glucose lowering potential GLP-1 was found to have a variety of cardioprotective effects. GLP-1 reduced the size of myocardial infarction during acute ischemia by activation of prosurvival pathways including PI3-kinase, Akt und ERK1/2. In addition, GLP-1 prevented atherosclerotic lesion formation in experimental models and improved endothelial function while acting anti-inflammatory. Furthermore GLP-1 was found to improve chronic heart failure by increasing insulin independent cellular glucose transport. Consequently GLP-1 based therapies might reduce cardiovascular events in diabetic patients which is currently evaluated in clinical endpoint studies.     

Kardiovaskuläre Prävention und Rehabilitation

The distinction between primary and secondary prevention has been abandoned in favor of cardiovascular prevention, mandating individual risk assessment. First, the individual cardiovascular risk of a person is determined by index diseases like myocardial infarction, peripheral arterial disease or other, or, if absent, by a score consisting of a number of conventional risk factors. According to current guidelines, cardiovascular prevention is indicated, as soon as the risk for fatal cardiovascular disease is > or = 5 %, equivalent to a risk for a major cardiovascular event of > or = 20 %. Non-pharmaceutical approaches are: refraining from smoking, mediterranean diet with fatty fish, physical activity and normal body weight. Blood pressure and diabetes mellitus are optimized. In addition, the following agents are used: platelet inhibitors, beta-blockers, ACE-inhibitors, statins and omega-3 fatty acids. A number of structural problems add to individual factors impeding optimal implementation of cardiovascular prevention in Germany.     

Kardiovaskuläre Nebenwirkungen von anabol-androgenen Steroiden

The intake of anabolic-androgenic steroids (AAS) leads to an increase in skeletal muscle mass and is prohibited as a doping measure in sport. AAS abuse is not limited to competitive athletes. It is also prevalent in subjects who do body building or resistance training for cosmetic reasons only. Out of the numerous and partly serious side effects, the cardiovascular ones are presented here. An increase in left ventricular muscle mass is well documented, and some researchers have even reported concentric hypertrophy. By contrast, resistance training without AAS intake does not lead to increased ventricular wall thickness. AAS do not affect the systolic function of the left ventricle, whereas diastolic function might be impaired. Different ultrastructural myocardial alterations have been documented in animal studies. In addition, AAS can induce arterial hypertension. Blood clotting and fibrinolysis are negatively affected, and several case studies of thrombi exist in young strength athletes. Changes in the concentration of blood lipoproteins, particularly a reduction in vessel-protective HDL cholesterol, can lead to early atherosclerosis. Many case reports exist about cardiac deaths in seemingly healthy subjects-most often body builders and other strength athletes. In fatal and nonfatal myocardial infarctions patent coronary arteries were proven frequently. Besides the prothrombotic effects of AAS, an impaired endothelial function and vasospasms are discussed hypothetically as pathomechanisms. Also, cardiomyopathies can occur due to AAS abuse. On the basis of the described possible cardiovascular side effects, it can be concluded that in cases of sudden cardiac deaths in young athletes, a misuse of AS should be excluded.     

Kardiovaskuläre Magnetresonanztomographie

Cardiovascular magnetic resonance imaging (MRI) has the ability to assess the morphology, function, perfusion and evidence of myocardial scar tissue in a single examination. Moreover, cardiovascular MRI can be carried out with no exposure to radiation. Stress MRI can be performed by assessment of dobutamine-induced wall motion abnormalities or by first-pass adenosine perfusion imaging. Compared to stress echocardiography or single photon emission computed tomography, stress MRI is at least as accurate; however, patients with ferromagnetic materials or other contraindications for MRI, such as intolerance of gadolinium contrast agents cannot be examined. The quality of stress MRI depends on where the examination is being performed and should always be regarded in context to other clinical information, such as from patient history and electrocardiography.     

Kardiovaskuläre Pharmakotherapie

Adverse side effects of drugs are a significantly underestimated problem in modern medicine. In this review article, we summarize common adverse side effects of cardiovascular drugs. In particular, we highlight the factors promoting these adverse side effects in patients, including reduced hepatic or renal clearance in elderly patients that often requires dosage adjustment. Pharmacodynamic and pharmacokinetic interactions between drugs (e.g. through the cytochrome P450 system or P-glycoproteins) can modify the plasma concentration of many compounds, thereby also increasing the likelihood of unwanted side effects. The most prominent cardiac side effects include arrhythmias, e.g. atrioventricular (AV) block, drug-induced long-QT syndrome and torsade de pointes and altered inotropy. Non-cardiac side effects are subsequently discussed grouped by drug class. A better understanding of the risks and side effects of cardiovascular drugs is expected to reduce the mortality and morbidity associated with adverse side effects.     

Kardiovaskuläre Rehabilitation

Cardiovascular rehabilitation encompasses the optimization of secondary prevention to reduce morbidity and mortality, the improvement of physical fitness and quality of life as well as the reintegration into social life and employment. This requires a multifactorial intervention on the physical, psychological, educative and social level by a multidisciplinary team. In Germany, cardiac rehabilitation started early after an index event, could demonstrate a significant reduction of total mortality, myocardial infarction and hospitalization during a follow-up of 1–2 years in 4 cohort studies including 10.758 patients with myocardial infarction and bypass surgery. This reduction of clinical events was obtained in addition to rapid revascularization therapy during the acute coronary event and on top of an evidence based secondary preventive medication. By national and international medical societies, cardiac rehabilitation is recommended as well in patients with congestive heart failure, after valve replacement or valve repair, after heart transplantation and cardioverter/defibrillator implantation. In the future, cardiac rehabilitation in Germany should be evaluated by a randomized controlled trial and multifactorial interventions should be tailored individually to specific patient subgroups and medical conditions.     

Kardiovaskuläre Begleiterkrankungen und Komplikationen bei Darmerkrankungen

Vascular diseases are not encountered very often in gastroenterology, though in cases of ischemic colitis a coronary heart disease is often present. In addition, heart diseases such as coronary heart disease, atrial fibrillation, and congestive heart failure are important risk factors for ischemic colitis and should be treated to avoid further ischemic episodes of the gut. The most common extraintestinal manifestations of Crohn's disease and ulcerative colitis are observed in the eye, on the skin, and in the liver region. Involvement of the cardiovascular system does not seem to be very common, though systematic epidemiological data on the significance of these extraintestinal complications--which certainly influence the prognosis--are lacking. Other patients with Crohn's disease or ulcerative colitis suffer from vasculitis, which reflects a further manifestation of inflammatory diseases affecting the cardiovascular system. Another important complication is activation of coagulationfactors, especially during active flare-up of intestinal disease; this can result in thromboembolic events. Systematic studies or investigations on the epidemiology of cardiovascular complications are still lacking, so that an overview of the published data is given. Metastatic tumors of the heart are rare, but there are case reports of cardiac metastases in patients with carcinomas of the colon. Carcinoid heart syndrome, another cardial complication of malignant disease, can prejudice the prognosis of patients with neuroendocrine tumors of the gastrointestinal tract.     

Kardiovaskuläre Magnetresonanztomographie

Board certification in cardiac magnetic resonance imaging can be obtained since 2006 in Germany after a 24-month training period. However, currently only 46 cardiologists in Germany have obtained board certification since 2006 and only 4 cardiologists are authorized to train cardiologists in cardiac magnetic resonance imaging for a 12-month period. A 24-month training period is only granted to radiologists which represents an obstacle for the widespread education of cardiologists in this discipline. This article reviews and compares current recommendations of the European Society of Cardiology, the German Roentgen Society and the Education Curriculum of the German Cardiac Society. Each recommendation proposes three levels of training in cardiac magnetic resonance imaging ranging from 1 month for level 1 and >12 months for professionals corresponding to level 3. Further interdisciplinary efforts are necessary to improve the training in cardiac magnetic resonance imaging.     

Kardiovaskuläre Morbidität und Komorbidität bei Rheumatoider Arthritis und Kollagenosen

Ohne Zusammenfassung     

Kardiovaskuläre Erkrankungen bei Diabetes

Over the past decade, a large number of scientific publications have identified inflammation as a major causal factor in diabetes mellitus and atherosclerosis. Compared to nondiabetic patients, activation of inflammatory cytokines and cells are increased in patients with diabetes. This is partly caused by hyperglycemia and insulin resistance/deficiency.In this review, the key factors of diabetes-associated inflammation are described and potential anti-inflammatory therapies that could potentially reduce the risk of diabetic macroangiopathy are discussed.The multifactorial therapy of diabetes mellitus consisting of blood sugar, cholesterol and high blood pressure control could be supplemented by anti-inflammatory therapies in the future.     

Kardiovaskuläre Pharmakotherapie im Alter

Prevalence of cardiovascular diseases increases with advancing age. Moreover, these patients are getting older and older. Therefore, pharmacotherapy of the elderly becomes a major objective in clinical cardiology. Pharmacodynamic and pharmacokinetic changes in the elderly can interfere with a sufficient treatment of cardiovascular diseases and moreover, multiple drug usage is a considerable risk factor of possible drug-drug interactions. Furthermore, treatment of cardiovascular diseases as hypertension, heart failure or coronary heart disease in the elderly according to the international guidelines is often limited due to co-morbidities restricting usage of the appropriate medication. This review addresses both, the treatment of cardiovascular diseases in the elderly and the pharmacological characteristics of frequently used drugs.     

Kardiovaskuläre Komplikationen nach Nierentransplantation

Cardiovascular diseases are the leading cause of morbidity and mortality after renal transplantation. The highest number of hospitalizations after renal transplantation is due to congestive heart failure in addition to infections. A reduction of traditional and non-traditional risk factors and a critical cardiovascular evaluation of dialysis patients on the waiting list could help to reduce cardiovascular events after renal transplantation. Clinical symptoms and physical activity should be evaluated to differentiate between stable and active cardiac diseases and to decide on further non-invasive and invasive diagnostics and treatment. This article summarizes the prevalence and risk factors of cardiovascular complications after renal transplantation and describes possible preventive strategies.     

Kardiovaskuläre Kalzifikationen bei Niereninsuffizienz

Uremic vascular calcification is still a major challenge in nephrology. Cardiovascular complications contribute substantially to morbidity and mortality of patients with renal replacement therapy. Understanding the development of vascular calcification and enabling the reliable identification of patients at high risk for cardiovascular complications as well as the development of new therapeutic options are of utmost importance. The traditional view of the development of vascular calcification as a passive process has been challenged since results emerged supporting an active, cell-driven pathomechanistic process instead. This review gives an update on the current hypotheses on the development of vascular calcification and a summary of the latest results. In addition new therapeutic strategies for tackling vascular calcification will be discussed.