[Cardiac involvement in storage diseases : Role of genetic diagnostics]. / Kardiale Speichererkrankungen : Stellenwert der genetischen Diagnostik.

In clinical practice cardiac involvement in patients with storage disorders is often diagnosed at a late and advanced stage of the disease with pronounced organ damage. As the currently available targeted therapies can only stop the progress of the disease, a timely diagnosis is of particular relevance. Genetic testing has become increasingly more important in cases of suspected cardiac manifestation in storage disorders. Thereby, diagnostic genetic testing can help to confirm the diagnosis and may also be relevant for therapeutic decision making. In relatives of affected patients predictive genetic testing provides the opportunity for an early therapeutic intervention.

[Comments on the guidelines (2018) of the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH) on the management of arterial hypertension]. / Kommentar zu den Leitlinien (2018) der Europäischen Gesellschaft für Kardiologie (ESC) und der Europäischen Gesellschaft für Hypertonie (ESH) für das Management der arteriellen Hypertonie.

Arterial hypertension represents one of the most frequent chronic diseases that can lead to complications, such as stroke, dementia, heart attack, heart failure and renal failure. By 2025 the number of hypertensive patients will increase to approximately 1.6 billion people worldwide. The new guidelines of the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH) on the management of arterial hypertension replace the guidelines of the ESC/ESH from 2013. The 2018 guidelines of the ESC/ESH were adopted by the German Cardiac Society and the German Hypertension League. In these comments national characteristics are worked out and the essential new aspects of the guidelines are critically discussed. These include, for example, the definition of hypertension, the importance of out of office blood pressure measurements, revised blood pressure targets, the modified algorithm for drug treatment and the relevance of device-based hypertension treatments. Important aspects for the management of hypertensive emergencies are also presented.

A comparison of gamma-glutamyl transferase and alkaline phosphatase as prognostic markers in patients with coronary heart disease.

BACKGROUND AND AIMS: Whether gamma-glutamyl transferase (GGT) or alkaline phosphatase (ALP) is a better prognostic marker in patients with coronary heart disease (CHD) remains unknown. The aim of this study was to compare the prognostic value of GGT and ALP in patients with CHD. METHODS AND RESULTS: This study included 3768 patients with CHD. The main study outcome was 3-year all-cause mortality. The median values of GGT and ALP were 36.2 U/L and 69.3 U/L. Patients were divided into subgroups according to GGT or ALP activity > or ≤median. Overall, there were 304 deaths: 195 deaths occurred in patients with GGT >median (n = 1882) and 109 deaths occurred in patients with GGT ≤median (n = 1886); Kaplan-Meier [KM] estimates of all-cause mortality were 11.9% and 6.4% (unadjusted hazard ratio [HR] = 1.85, 95% confidence interval [CI], 1.46 to 2.34]; P < 0.001). According to ALP activity, 186 deaths occurred in patients with ALP >median (n = 1883) and 118 deaths occurred in patients with ALP ≤median (n = 1885); KM estimates of all-cause mortality were 11.4% and 7.1% (unadjusted HR = 1.64 [1.30-2.06]; P < 0.001). After adjustment, GGT (adjusted HR = 1.32 [1.11-1.58]; P = 0.002) but not ALP (adjusted HR = 1.20 [1.00-1.43]; P = 0.051, with both HR calculated per 1 unit increment in logarithmic GGT or ALP scale) remained significantly associated with the risk for mortality. The C statistic of the mortality model with GGT was greater than the C statistic of the model with ALP (0.831 [0.802-0.859] vs. 0.826 [0.793-0.855]; P < 0.001). CONCLUSIONS: In patients with CHD, GGT was a stronger correlate of all-cause mortality than ALP.

[Management of arterial hypertension : ESC/ESH guidelines 2018]. / Management der arteriellen Hypertonie : ESC/ESH-Leitlinien 2018.

The ESC/ESH guidelines 2018 for the treatment of arterial hypertension are designed for adults with hypertension, i. e. ≥18 years. The guidelines reflect new findings and assess them for the recommendations. The specific objectives of these guidelines were to develop pragmatic guidance on how to improve the detection and treatment of hypertension and to improve poor blood pressure control rates by promoting simple and effective treatment strategies. This overview also presents the differences to the last guidelines on hypertension from the year 2013.

[Management of arterial hypertension]. / Management der arteriellen Hypertonie.

Arterial hypertension has a high prevalence and is a major risk factor for the development of cardiovascular diseases. It is a major contributor to worldwide morbidity and mortality and hence poses a huge socioeconomic burden. Despite great progress in perception, diagnosis and treatment of hypertension, blood pressure control is inadequate in less than half of the hypertensive patients (<140/90 mm Hg). The diagnosis of arterial hypertension starts in most patients with the conventional office blood pressure measurement. Out-of-office blood pressure measurement is an important adjunct, especially to unmask white-coat hypertension. To reach the right target blood pressure many effective antihypertensive drugs are available. By how much the blood pressure should be lowered is currently a matter of controversy. The 2013 European and the identical German national guidelines recommend a target blood pressure of <140/90 mm Hg for most patients. The recent SPRINT study revealed that some patients may benefit from an even lower blood pressure. This CME-article summarizes recent developments in the management of arterial hypertension and provides tips for daily practice based on these aims.

[Genetic testing in polygenic diseases : Atrial fibrillation, arterial hypertension and coronary artery disease]. / Genetische Diagnostik polygener Erkrankungen : Vorhofflimmern, Hypertonie und koronare Herzerkrankung.

Genetic testing plays an increasing role in cardiovascular medicine. Advances in technology and the development of novel and more affordable (high throughput) methods have led to the identification of genetic risk factors in research and clinical practice. Also, this progress has simplified the screening of patients and individuals at risk. In case of rare monogenic diseases, diagnostics, risk stratification, and, in some cases, treatment decisions have become easier. For common, polygenic cardiovascular diseases, the situation is more complex due to interaction of modifiable external risk factors and nonmodifiable factors like genetic predisposition. Over the last few years, it has been shown that multiple genes are involved in the pathophysiology of these cardiovascular diseases rather than one single gene. In the following article, we give an overview of the genetic risk factors in polygenic cardiovascular diseases as atrial fibrillation, arterial hypertension and coronary artery disease. Furthermore, we aim to illustrate in which cases genetic testing is recommended in these diseases.

[Practical guidelines for genetic testing in cardiovascular diseases]. / Praktische Durchführung der genetischen Diagnostik in der Kardiologie.

In the last decade, genetic testing for cardiovascular disorders has become more and more relevant. Progress in molecular genetics has led to new opportunities for diagnostics, improved risk prediction and could lead to novel therapeutic approaches. Genetic diagnostic testing is relevant for both confirming a diagnosis as well as deciding on therapeutic consequences, if applicable. Furthermore, predictive testing in family members for specific cardiovascular diseases is now a standard procedure in holistic patient management. The process of genetic testing as well as documentation requirements and discussion of test results with patients are subject to legal regulations. These regulations might be confusing for clinical practitioners/cardiologists. The aim of this article is to provide a clinical framework for genetic testing. First, we explain the legal and ethical background. Second, we illustrate the process of genetic testing step by step and present updates on remuneration. Finally, we discuss the significance of genetic testing and specific disease indications in cardiology.

Angiographic and clinical outcomes of patients treated with everolimus-eluting bioresorbable stents in routine clinical practice: Results of the ISAR-ABSORB registry.

OBJECTIVES: We aimed to analyze angiographic and clinical results of patients undergoing BRS implantation in a real-world setting. BACKGROUND: Angiographic and clinical outcome data from patients undergoing implantation of drug-eluting bioresorbable stents (BRS) in routine clinical practice is scant. METHODS: Consecutive patients undergoing implantation of everolimus-eluting BRS at two high-volume centers in Munich, Germany were enrolled. Data were collected prospectively. All patients were scheduled for angiographic surveillance 6-8 months after stent implantation. Quantitative coronary angiographic analysis was performed in a core laboratory. Clinical follow-up was performed to 12 months and events were adjudicated by independent assessors. RESULTS: A total of 419 patients were studied. Mean age was 66.6 ± 10.9 years, 31.5% had diabetes mellitus, 76.1% had multivessel disease, and 39.0% presented with acute coronary syndrome; 49.0% of lesions were AHA/ACC type B2/C, 13.1% had treatment of bifurcation lesions. Mean reference vessel diameter was 2.89 ± 0.46 mm. At angiographic follow-up in-stent late loss was 0.26 ± 0.51 mm, in-segment diameter stenosis was 27.5 ± 16.1, and binary angiographic restenosis was 7.5%. At 12 months, the rate of death, myocardial infarction, or target lesion revascularization was 13.1%. Definite stent thrombosis occurred in 2.6%. CONCLUSIONS: The use of everolimus-eluting BRS in routine clinical practice is associated with high antirestenotic efficacy in patients undergoing angiographic surveillance. Overall clinical outcomes at 12 months are satisfactory though stent thrombosis rates are not insignificant. Further study with longer term follow-up and larger numbers of treated patients is required before we can be sure of the role of these devices in clinical practice.

[Management of arterial hypertension]. / Management der arteriellen Hypertonie.

Arterial hypertension is one of the most frequent diseases in the western world and is one of the three most important risk factors for heart diseases. The 2013 guidelines of the European Societies of Hypertension and Cardiology (ESH/ESC) provide a clear action plan for evidence-based diagnostics and therapeutic measures in hypertensive subjects and simplify target blood pressures across various patient groups. Non-pharmacological options play a central role in the treatment of arterial hypertension. The indications for drug therapy arise from three criteria including the level of hypertension, risk profile of the patient, as well as response to non-pharmacological therapy. For the first choice monotherapy five substance groups are available: diuretics, beta blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin (AT) 1 receptor antagonists and calcium antagonists. By combination therapy, the responder rate can be significantly increased with respect to a normalization of blood pressure. A true treatment resistance, in which the therapeutic goal is not reached in spite of a triple combination with maximum dosage, is extremely rare. Further treatment options are combinations of four drug classes and changes of medication. Hypertensive emergencies require a rapid intervention; nevertheless, the magnitude of blood pressure lowering can greatly vary depending on the individual clinical picture.

[New ESH/ESC guidelines on arterial hypertension : what is new and what indications remain for renal denervation?]. / Neue ESH/ESC-Leitlinien für die arterielle Hypertonie : Was ist neu, und welche Indikation bleibt für die renale Denervierung?

Arterial hypertension is one of the most common diseases in the western world and one of the most important risk factors for other cardiovascular diseases. Despite widespread therapeutic options, there is still a large proportion of patients with uncontrolled hypertension. The new European guidelines on hypertension give clear lines of action for diagnosis and treatment sorted into appropriate evidence levels based on current scientific data. Such evidence is still unclear for renal denervation so that no clear recommendations can be given.

[Genetic analyses as basis for a personalized medicine in patients with coronary artery disease]. / Genetische Analysen als Basis einer individualisierten Medizin bei koronarer Herzkrankheit.

Knowledge about the etiology of coronary artery disease (CAD) entered new dimensions using genome-wide association studies. The current situation is that 46 chromosomal loci have been identified to be associated with CAD with genome-wide significance, i.e. p<5×10(-8), in Western Europeans. As the individual DNA sequence remains unchanged after fertilization, the risk variants cannot occur due to confounders, such as secondary disease processes. Thus, it can be proposed that these variants are directly affecting a primary and thereby causal pathophysiological process in CAD. Interestingly, only 20% of the effects mediated by the identified loci can be explained by the influence of traditional risk factors. This implies that yet unknown mechanisms and, as a consequence, new therapeutic targets play an important role in the pathophysiology of CAD. However, the high allele frequency of risk loci was also surprising. In the diploid chromosome set Western European individuals carry on average 30-50 risk variants at the 46 loci. Considering this, every individual in the population carries a larger or smaller genetic predisposition for CAD. On the other hand it is remarkable that many risk allele carriers seem to be able to compensate the genetic risk: even in old age not everyone suffers from CAD. This indicates yet unknown gene-gene and gene-environment interactions and limits the current possibilities in individual risk prediction.

[Importance of modern genome-wide studies for the risk of myocardial infarction]. / Bedeutung moderner Genomstudien für das Herzinfarktrisiko.

The individual genetic susceptibility is a cornerstone in the pathogenesis of coronary artery disease (CAD). The search for the genetic background and the subsequently altered molecular mechanisms has been ineffective for several years. The increase in genome-wide association studies in recent years has changed the scenario and more than 40 variants have so far been identified to be highly significantly associated with CAD and the risk of myocardial infarction (MI). Whereas most of these findings affect frequent polymorphisms, exome-wide sequencing in families with a high prevalence of CAD revealed mutations with a high penetrance and as a consequence a high risk of suffering from MI. The findings allow a deeper insight into functional mechanisms involved in the pathogenesis of atherosclerosis. Furthermore, the data enables validation of the numerous epidemiologically identified risk markers with respect to the causal role in the development of CAD, making the genetic architecture of CAD much more transparent. Nevertheless, individual risk prediction has only made weak progress in the face of the new findings. Every individual without exception carries numerous risk alleles even when the number and effect strength shows individual differences. Thus, a varying degree of genetic susceptibility is shared by all of us. Current research is therefore focusing on the functional integration of genetic information to discover new approaches to prevention and therapy.

[Arterial hypertension in patients with coronary artery disease]. / Arterielle Hypertonie bei Patienten mit koronarer Herzerkrankung.

Arterial hypertension is the most important risk factor for coronary artery disease (CAD). There is a high coincidence of both diseases, whereby both impair coronary microcirculatory function synergistically, which can be measured functionally by decreased coronary flow reserve. This dysfunction leads to permanent damage to the left ventricular myocardium. Lifestyle changes play a central role in the primary and secondary prevention of CAD. Additionally, there are well-established options for antihypertensive drug therapy, which should be combined with aspirin and statins. Pharmacological treatment should follow distinctive blood pressure goals in relation to the severity of CAD. Particular attention is paid in this context to the relation between diastolic blood pressure values and cardiovascular endpoints, which displays a j-shaped curve with the lowest risk at levels between 70 and 90 mmHg.

[Risk factor "smoking" : smoking cessation in patients with cardiovascular diseases]. / Risikofaktor "Rauchen" : Wege aus der Nikotinsucht bei Patienten mit kardiovaskulären Erkrankungen.

Smoking is the most frequent cause of avoidable premature death. Annually, almost 6 million people die due to nicotine consumption. Comparing modifiable cardiovascular risk factors, smoking has the strongest impact on cardiovascular mortality. More than 50% of all premature myocardial infarctions are related to nicotine consumption. Even in patients with known coronary disease receiving optimal medical therapy, there is a remarkable additional preventive effect of smoking cessation detectable. Therefore, smoking cessation is an essential component of primary and secondary prevention strategies. Smoking cessation programs applying a combination of behavior therapy and supporting medical treatment have been demonstrated to be the most effective.

Implications of prevalent and incident diabetes mellitus on left ventricular geometry and function in the ageing heart: the MONICA/KORA Augsburg cohort study.

BACKGROUND AND AIM: It is unclear to what extent diabetes modulates the ageing-related adaptations of cardiac geometry and function. METHODS AND RESULTS: We examined 1005 adults, aged 25-74 years, from a population-based survey at baseline in 1994/5 and at follow-up in 2004/5. We compared persistently non-diabetic individuals (ND; no diabetes at baseline and at follow-up, n=833) with incident (ID; non-diabetic at baseline and diabetic at follow-up, n=36) and with prevalent diabetics (PD; diabetes at baseline and follow-up examination, n=21). Left ventricular (LV) geometry and function were evaluated by echocardiography. Statistical analyses were performed with multivariate linear regression models. Over ten years the PD group displayed a significantly stronger relative increase of LV mass (+9.34% vs. +23.7%) that was mediated by a more pronounced increase of LV end-diastolic diameter (+0% vs. +6.95%) compared to the ND group. In parallel, LA diameter increased (+4.50% vs. +12.7%), whereas ejection fraction decreased (+3.02% vs. -4.92%) more significantly in the PD group. Moreover, at the follow-up examination the PD and ID groups showed a significantly worse diastolic function, indicated by a higher E/EM ratio compared with the ND group (11.6 and 11.8 vs. 9.79, respectively). CONCLUSIONS: Long-standing diabetes was associated with an acceleration of age-related changes of left ventricular geometry accumulating in an eccentric remodelling of the left ventricle. Likewise, echocardiographic measures of systolic and diastolic ventricular function deteriorated more rapidly in individuals with diabetes.

Large scale association analysis of novel genetic loci for coronary artery disease.

BACKGROUND: Combined analysis of 2 genome-wide association studies in cases enriched for family history recently identified 7 loci (on 1p13.3, 1q41, 2q36.3, 6q25.1, 9p21, 10q11.21, and 15q22.33) that may affect risk of coronary artery disease (CAD). Apart from the 9p21 locus, the other loci await substantive replication. Furthermore, the effect of these loci on CAD risk in a broader range of individuals remains to be determined. METHODS AND RESULTS: We undertook association analysis of single nucleotide polymorphisms at each locus with CAD risk in 11,550 cases and 11,205 controls from 9 European studies. The 9p21.3 locus showed unequivocal association (rs1333049, combined odds ratio [OR]=1.20, 95% CI [1.16 to 1.25], probability value=2.81 x 10(-21)). We also confirmed association signals at 1p13.3 (rs599839, OR=1.13 [1.08 to 1.19], P=1.44 x 10(-7)), 1q41 (rs3008621, OR=1.10 [1.04 to 1.17], P=1.02 x 10(-3)), and 10q11.21 (rs501120, OR=1.11 [1.05 to 1.18], P=4.34 x 10(-4)). The associations with 6q25.1 (rs6922269, P=0.020) and 2q36.3 (rs2943634, P=0.032) were borderline and not statistically significant after correction for multiple testing. The 15q22.33 locus did not replicate. The 10q11.21 locus showed a possible sex interaction (P=0.015), with a significant effect in women (OR=1.29 [1.15 to 1.45], P=1.86 x 10(-5)) but not men (OR=1.03 [0.96 to 1.11], P=0.387). There were no other strong interactions of any of the loci with other traditional risk factors. The loci at 9p21, 1p13.3, 2q36.3, and 10q11.21 acted independently and cumulatively increased CAD risk by 15% (12% to 18%), per additional risk allele. CONCLUSIONS: The findings provide strong evidence for association between at least 4 genetic loci and CAD risk. Cumulatively, these novel loci have a significant impact on risk of CAD at least in European populations.

[Patient care in the acute phase of stress induced cardiomyopathy (Tako-Tsubo cardiomyopathy)--and thereafter?]. / Patientenversorgung in der akuten Phase der stressinduzierten Kardiomyopathie (Tako-Tsubo-Kardiomyopathie)--und danach?

The prognosis of patients presenting with Tako-Tsubo cardiomyopathy (TTC) is generally considered to be favorable. However, in the acute phase of the disorder complications are not infrequent and, therefore, continuous monitoring and consistent therapy in an intensive care unit is essential. Typical complications in patients with TTC are cardiogenic shock, obstruction of the left ventricular outflow tract (LVOT), occasionally accompanied by acute mitral regurgitation, arrhythmias, predominantly torsade de pointes tachycardias due to QT prolongation, left ventricular (LV) thrombus formation with or without consecutive thromboembolic events, and LV rupture. After confirmation of TTC by coronary angiography, repeat echocardiography should be performed. A standardized therapy for patients with TTC has so far not been established. Recommendations for the acute phase include the administration of anxiolytic agents for patients who present with preceding emotional stress, consistent therapy of physical stressors (such as pain or asthma) and avoidance of catecholamine therapy. Shock due to LVOT obstruction is treated by administration of volume and ß-blockers. With respect to the occurrence of torsade de pointes tachycardias, drugs which might cause QT prolongation should not be given. The notable incidence of LV thrombus formation justifies therapeutic anticoagulation. Systematic studies and treatment recommendations for the prophylaxis of recurrent TTC do not exist. The recently reported association between TTC and malignant disorders should prompt tumor screening and subsequent preventive medical checkups in patients affected by TTC.

[Identification of risk genes for myocardial infarction by genome wide association studies]. / Identifizierung von Risikogenen für den Herzinfarkt durch genomweite Assoziationsstudien.

Myocardial infarction (MI) shows a strong heritability. For a long time the identification of responsible genes has been rather unsuccessful. However, with the advent of genome wide association studies (GWAS) using DNA-array technology a number of significant loci for MI have been identified which were widely replicated. Interestingly, only a small fraction of the hitherto identified genes is also associated with classical risk factors for MI such as hypercholesterolemia or diabetes. Therefore it can be concluded that the MI risk mediated by the newly identified genes involves a number of novel pathophysiological mechanisms. This review summarizes the present state of knowledge in the field and tries to give a perspective on how these findings can be translated into clinical practice and further scientific discovery. Special consideration is given to the association of MI risk with genetic variants in the hemostatic system.

Prevalence of undiagnosed Type-2-diabetes mellitus and impaired fasting glucose in German primary care: data from the German Metabolic and Cardiovascular Risk Project (GEMCAS).

AIMS: Primary care physicians are gatekeepers of the healthcare system and thus responsible for screening, prevention and treatment of diabetes. Little is known about the prevalence of diabetes, impaired fasting glucose and factors that are associated with the risk of future development of diabetes and subsequent cardiovascular disease in unselected patients presenting to general practitioners. RESEARCH DESIGN AND METHODS: A nationwide sample of 35,869 primary care patients screened in 2005 was used to estimate the prevalence of detected and undetected diabetes as well as of impaired fasting glucose. Logistic regressions were used to assess the prevalence, cardiovascular morbidity and the factors associated with undetected diabetes and impaired fasting glucose. RESULTS: 1) Using a blood glucose screening algorithm the prevalence of known type 1 and type 2 diabetes mellitus was found to be 0.6 and 12.2%, respectively. Another 2.9% (23% of the diagnosed) had either undiagnosed diabetes (0.9%) or impaired fasting glucose (2.0%). 2) Undiagnosed patients had a more unfavourable cardiovascular risk profile compared to non-diabetic patients. 3) Moreover, higher age, male gender, low HDL-cholesterol and elevated triglycerides as well as a family history of diabetes were associated with unknown diabetes or impaired fasting glucose. CONCLUSIONS: Approximately 15.7% of individuals in Germany consulting a primary care physician are affected from either diabetes (known and unknown) or impaired fasting glucose and face a substantially elevated cardiovascular risk score. This study demonstrated that using a simplified blood glucose screening algorithm considering risk markers like higher age, male gender, low HDL-cholesterol, high triglycerides and a family history of diabetes may well serve as a suitable screening approach for undiagnosed diabetes and impaired fasting glucose in primary care practice.