scholarly journals Combined antiplatelet therapy reduces the pro-inflammatory properties of activated platelets

TH Open ◽  
2021 ◽  
Author(s):  
Alexandra Heinzmann ◽  
Daniëlle Coenen ◽  
Tanja Vajen ◽  
Judith Cosemans ◽  
Rory R Koenen
Keyword(s):  
Myocardial Infarction ◽  
Cardiovascular Events ◽  
Coagulation Factors ◽  
Bioactive Molecules ◽  
Immune Functions ◽  
Atherosclerotic Lesions ◽  
Activated Platelets ◽  
Increased Risk ◽  
Anticoagulant Drugs ◽  
Leukocyte Chemotaxis

The cause of atherothrombosis is rupture or erosion of atherosclerotic lesions, leading to an increased risk on myocardial infarction or stroke. Here, platelet activation plays a major role, leading to the release of bioactive molecules, e.g. chemokines and coagulation factors, and to platelet clot formation. Several antiplatelet therapies have been developed for secondary prevention of cardiovascular events, in which anticoagulant drugs are often combined. Besides playing a role in haemostasis, platelets are also involved in inflammation. However, it is unclear whether current antiplatelet therapies also affect platelet immune functions. In this study, the possible anti-inflammatory effects of antiplatelet medications on chemokine release were investigated using ELISA and on the chemotaxis of THP-1 cells towards platelet releasates. The cause of atherothrombosis is rupture or erosion of atherosclerotic lesions, leading to an increased risk on myocardial infarction or stroke. Here, platelet activation plays a major role, leading to the release of bioactive molecules, e.g. chemokines and coagulation factors, and to platelet clot formation. Several antiplatelet therapies have been developed for secondary prevention of cardiovascular events, in which anticoagulant drugs are often combined. Besides playing a role in haemostasis, platelets are also involved in inflammation. However, it is unclear whether current antiplatelet therapies also affect platelet immune functions. In this study, the possible anti-inflammatory effects of antiplatelet medications on chemokine release were investigated using ELISA and on the chemotaxis of THP-1 cells towards platelet releasates. We found that antiplatelet medication acetylsalicylic acid (ASA) led to reduced chemokine (C-C motif) ligand 5 (CCL5) and chemokine (C-X-C motif) ligand 4 (CXCL4) release from platelets, while leukocyte chemotaxis was not affected. Depending on the agonist, αIIbβ3- and P2Y12-inhibitors also affected CCL5 or CXCL4 release. The combination of ASA with a P2Y12 inhibitor or a phosphodiesterase inhibitor did not lead to an additive reduction on CCL5 or CXCL4 release. Interestingly, these combinations did reduce leukocyte chemotaxis. This study provides evidence that combined therapy of ASA and a P2Y12 or PDE3 inhibitor can decrease the inflammatory leukocyte recruiting potential of the releasate of activated platelets.

Paediatric-onset coronary artery anomalies in pregnancy: a single-centre experience and systematic literature review

2017 ◽  
Vol 27 (8) ◽  
pp. 1529-1537 ◽  
Author(s):  
Michelle Keir ◽  
Catriona Bhagra ◽  
Debra Vatenmakher ◽  
Francisca Arancibia-Galilea ◽  
Katrijn Jansen ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Arrest ◽  
Coronary Artery ◽  
Cardiovascular Events ◽  
Coronary Anomalies ◽  
Coronary Artery Anomalies ◽  
Major Cardiovascular Events ◽  
Coronary Aneurysms ◽  
Increased Risk ◽  
In Pregnancy

AbstractObjectivesIndividuals with childhood-onset coronary artery anomalies are at increased risk of lifelong complications. Although pregnancy is thought to confer additional risk, a few data are available regarding outcomes in this group of women. We sought to define outcomes of pregnancy in this unique population.MethodsWe performed a retrospective survey of women with paediatric-onset coronary anomalies and pregnancy in our institution, combined with a systematic review of published cases. We defined paediatric-onset coronary artery anomalies as congenital coronary anomalies and inflammatory arteriopathies of childhood that cause coronary aneurysms. Major cardiovascular events were defined as pulmonary oedema, sustained arrhythmia requiring treatment, stroke, myocardial infarction, cardiac arrest, or death.ResultsA total of 25 surveys were mailed, and 20 were returned (80% response rate). We included 46 articles from the literature, which described cardiovascular outcomes in 82 women (138 pregnancies). These data were amalgamated for a total of 102 women and 194 pregnancies; 59% of women were known to have paediatric-onset coronary artery anomalies before pregnancy. In 23%, the anomaly was unmasked during or shortly after pregnancy. The remainder, 18%, was diagnosed later in life. Major cardiovascular events occurred in 14 women (14%) and included heart failure (n=5, 5%), myocardial infarction (n=7, 7%), maternal death (n=2, 2%), cardiac arrest secondary to ventricular fibrillation (n=1, 1%), and stroke (n=1, 1%). The majority of maternal events (13/14, 93%) occurred in women with no previous diagnosis of coronary disease.ConclusionsWomen with paediatric-onset coronary artery anomalies have a 14% risk of adverse cardiovascular events in pregnancy, indicating the need for careful assessment and close follow-up. Prospective, multicentre studies are required to better define risk and predictors of complications during pregnancy.

Cannabinoids and myocardial ischemia: Novel insights, updated mechanisms, and implications for myocardial infarction

2021 ◽  
Vol 28 ◽  
Author(s):  
Karim Seif El-Dahan ◽  
Dima Machtoub ◽  
Gaelle Massoud ◽  
Suzanne A. Nasser ◽  
Bassam Hamam ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiovascular Events ◽  
Illicit Drugs ◽  
Supply And Demand ◽  
Health Benefits ◽  
Cell Types ◽  
Cellular Mechanisms ◽  
Potential Health ◽  
Organ Systems ◽  
Increased Risk

: Cannabis is the most widely trafficked and abused illicit drug due to its calming psychoactive properties. It has been increasingly recognized as having potential health benefits and relatively less adverse health effects as compared to other illicit drugs; however, growing evidence clearly indicates that cannabis is associated with considerable adverse cardiovascular events. Recent studies have linked cannabis use to myocardial infarction (MI); yet, very little is known about the underlying mechanisms. A MI is a cardiovascular disease characterized by a mismatch in the oxygen supply and demand of the heart, resulting in ischemia and subsequent necrosis of the myocardium. Since cannabis is increasingly being considered a risk factor for MI, there is a growing need for better appreciating its potential health benefits and consequences. Here, we discuss the cellular mechanisms of cannabis that lead to an increased risk of MI. We provide a thorough and critical analysis of cannabinoids’ actions, which include modulation of adipocyte biology, regional fat distribution, and atherosclerosis, as well as precipitation of hemodynamic stressors relevant in the setting of a MI. By critically dissecting the modulation of signaling pathways in multiple cell types, this paper highlights the mechanisms through which cannabis may trigger life-threatening cardiovascular events. This then provides a framework for future pharmacological studies which can identify targets or develop drugs that modulate cannabis’ effects on the cardiovascular system as well as other organ systems. Cannabis’ impact on the autonomic outflow, vascular smooth muscle cells, myocardium, cortisol levels and other hemodynamic changes are also mechanistically reviewed.

scholarly journals Comparison of In-hospital Major Adverse Cardiovascular Events in Patients of Acute Inferior Myocardial Infarction With or Without Precordial ST Segment Depression

2017 ◽  
pp. 180-9
Author(s):  
Jaya Suganti ◽  
Abdullah Afif Siregar ◽  
Harris Hasan
Keyword(s):  
Myocardial Infarction ◽  
Cardiovascular Events ◽  
Multiple Logistic Regression Analysis ◽  
Major Adverse Cardiovascular Events ◽  
Bivariate Analysis ◽  
P Value ◽  
Inferior Myocardial Infarction ◽  
St Segment ◽  
Increased Risk ◽  
Acute Inferior Myocardial Infarction

Background: The clinical implications of precordial ST segment depression (PSTD) during acute inferior myocardial infarction has been an area of debate, and still under investigation with conflicting results. Based on previous studies, the presence of PSTD defines a high risk subset of patients with acute inferior myocardial infarction due to a more extensive myocardial ischemia that lead to a higher incidence of major adverse cardiovascular events (MACE). Despite of these results, others still considered this ECG finding as a benign electrical phenomenon. The aim of this study is to compare the incidence of in-hospital MACE in patients of acute inferior myocardial infarction with or without PSTD and to know whether PSTD can be used as a predictor of in-hospital MACE in acute inferior myocardial infarction.Methods: A total of 96 acute inferior myocardial infarction patients admitted from December 2013-2015 at Cardiology Department of Haji Adam Malik General Hospital were retrospectively analyzed. Patients were divided into two groups based on the presence of PSTD on admission ECG. Bivariate and multivariate analyses were performed to study the association between PSTD and in-hospital MACE, p value<0.05 was considered statistically significant.Results: The bivariate analysis showed that in-hospital MACE was significantly higher in patients of acute inferior myocardial infarction with PSTD than without PSTD (92% vs 8%, p<0.001). On multiple logistic regression analysis, patients of acute inferior myocardial infarction with PSTD have a 5.4 fold increased risk of in-hospital MACE than patients without PSTD (OR 5.480; 95% CI 1.759-17.067, p=0.003).Conclusion: The presence of precordial ST segment depression on admission ECG in acute inferior myocardial infarction patients was associated with a higher in-hospital MACE and was an independent predictor of in-hospital MACE.

scholarly journals Vital exhaustion and cardiovascular prognosis in myocardial infarction and heart failure: predictive power of different trajectories

2010 ◽  
Vol 41 (4) ◽  
pp. 731-738 ◽  
Author(s):  
O. R. F. Smith ◽  
N. Kupper ◽  
J. Denollet ◽  
P. de Jonge
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Hospital Readmission ◽  
Cardiovascular Events ◽  
Cardiac Patients ◽  
Left Ventricular Ejection ◽  
Vital Exhaustion ◽  
Cardiovascular Prognosis ◽  
Increased Risk

BackgroundWe examined the different trajectories of vital exhaustion (VE) over a 12-month period and their impact on prognosis in a sample of myocardial infarction (MI) and chronic heart failure (CHF) patients.MethodConsecutive MI (n=407) and CHF patients (n=297) were assessed at baseline, and at 3- and 12-month follow-up for symptoms of VE. Latent growth mixture modelling was used to examine the course of VE over time. The combined clinical endpoint was defined as cardiac hospital readmission or death.ResultsFour distinct trajectories for VE were found: low VE, decreasing VE, increasing VE, and severe VE. Sex, marital status, left ventricular ejection fraction, psychotropic medication, sample group (CHF v. MI) and depressive symptoms were associated with VE, varying according to classes. The mean follow-up period was 25.3 months in which 34.7% of the patients experienced an event. Multivariate Cox regression showed that, compared with patients in the low VE class, patients in the increasing VE class [hazard ratio (HR)=1.16, 95% confidence interval (CI) 1.58–3.61, p=0.01], and the severe VE class (HR=1.69, 95% CI 1.31–2.64, p=0.02) had an increased risk for adverse cardiovascular events (i.e. cardiovascular hospital readmission or cardiovascular death). Decreasing VE was not related to adverse cardiovascular events (HR=0.97, 95% CI 0.66–1.69, p=0.81).ConclusionsVE trajectories varied across cardiac patients, and had a differential effect on cardiovascular outcome. Increasing VE and severe VE classes were predictors of poor cardiovascular prognosis. These results suggest that identification of cardiac patients with an increased risk of adverse health outcomes should be based on multiple assessments of VE.

scholarly journals The High-Sensitivity C-Reactive Protein to Prealbumin Ratio Predicts Adverse Cardiovascular Events after ST-Elevation Myocardial Infarction

2021 ◽  
Vol 24 (1) ◽  
pp. E153-E157
Author(s):  
Hongqiang Ren ◽  
Li Zhao ◽  
Yijun Liu ◽  
Zhen Tan ◽  
Guiquan Luo ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Roc Curve ◽  
Cardiovascular Events ◽  
Cox Regression ◽  
High Sensitivity ◽  
St Elevation Myocardial Infarction ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Increased Risk ◽  
St Elevation

Background: This study evaluated the association of the high-sensitivity C-reactive protein to prealbumin ratio (CPR) with adverse cardiovascular events after ST-elevation myocardial infarction (STEMI) in patients undergoing primary percutaneous coronary intervention (PCI). Methods: The study included 682 patients who presented with STEMI and were treated with primary PCI. Patients were divided into 2 groups: high CPR (CPR ≥0.02) and low CPR (CPR <0.02). The primary endpoint of the study was the occurrence of major adverse cardiovascular events (MACE), defined as cardiovascular mortality or admission due to recurrent AMI or heart failure. Multivariate Cox regression models were used to assess the prognostic value of CPR on MACE in patients with STEMI. Results: During a median follow-up of 18 months, the accumulated incidence rate of MACE was significantly higher in the high-CPR group than in the low-CPR group (38.7% versus 12.0%, P < .01). Multivariate analysis revealed that CPR was an independent predictor for increased risk of MACE (hazard ratio = 3.27, 95% confidence interval [CI] 2.14 to 4.49, P < .01). Receiver operating characteristic (ROC) curve analysis showed that the area under the ROC curve for predicting the diagnosis of MACE was higher for CPR (0.82, 95% CI 0.77 to 0.87) than hs-CRP (0.70, 95% CI 0.65 to 0.75). Conclusion: CPR was independently associated with MACE and can be used for risk stratification in patients with STEMI.

Platelet, CD40/CD40L, MPS-Cells: Partners in Crime

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4571-4571
Author(s):  
Giorgio Corinaldesi ◽  
Christian Corinaldesi
Keyword(s):  
Inflammatory Process ◽  
Coagulation Factors ◽  
Nitrogen Species ◽  
Chromosome X ◽  
Platelet Surface ◽  
Activated Platelets ◽  
Tnf Superfamily ◽  
Increased Risk ◽  
Atherothrombotic Disease ◽  
Progression Of Atherosclerosis

Abstract Several suggestions showed a strong correlation of platelet and CD40/40L; CD40/40L is a member of TNF superfamily, the genes is located on chromosome X, and it is expressed on endothelial cells, SMC, fibroblast and activated platelet and plays a pivotal role in inflammatory and expression of adhesion molecules, and it stimulates the release of cytokines. It helps identifing patients with atherosclerosis and an increased risk of thrombosis, peripheral and cardiovascular disease (CAD and CHF). CD40/40L was measured by flow cytometry, and s-CD40L by ELISA. In platelet activation CD40L is translocated to the platelet surface and it is accompanied by the release of sCD40L and RONS (reactive ossigen and nitrogen species) and this contributes to atherothrombotic disease and inflammatory process by forming (CD40-40L/GPIIb-IIIa, CD40-40L/Pselectin- PSGL) complex strictly correlated with levels of ICAM-1 and VCAM-1, induced TF-expression and release of MMPs. Activated platelets release chemokines, enhance adhesion and aggregation cytochine like-factors and coagulation factors. Patients with thrombotic events had more platelet-monocyte aggregate (36.8 +/− 12.4 %) than controls (14.2 +/− 2.1 %) and sCD40L above 4.5 ng/l, ICAM-1 levels 248 +/− 10.8 ng/ml vs 168 +/− 5.4 ng/ml, VCAM-1 764 +/− 18.6 ng/ml vs 532 +/− 8.6 ng/ml. The interaction of platelet and MPS-cells were enhanced by activation of P-Selectin 38.6 +/− 12.4 ng/ml vs 20.4 +/− 4.4 ng/ml, and MCP-1 286 +/−10.4 pg/ ml vs 132 +/− 5.8 pg/ml which are one of the major promoter of inflammation. This finding demonstrated that the development and progression of atherosclerosis is critically dependent on these molecules; this may propose new therapeutic target for future therapies.

Increased Risk of Cardiovascular Events Associated with TKI Treatment in Chronic Phase Chronic Myeloid Leukemia. Data from Swedish Population-Based Registries

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3134-3134 ◽  
Author(s):  
Torsten Dahlén ◽  
Gustaf Edgren ◽  
Martin Höglund ◽  
Mats Lambe ◽  
Magnus Björkholm ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiovascular Events ◽  
Research Funding ◽  
Chronic Phase ◽  
Population Based ◽  
Swedish Population ◽  
2Nd Generation ◽  
Increased Risk ◽  
Tki Treatment

Abstract Introduction: The introduction of continuous tyrosine kinase inhibitor (TKI) treatment has dramatically improved progression-free survival for chronic phase chronic myeloid leukaemia (CML) patients. This success, however, has put the issue of long-term drug toxicity and safety into focus. Recent data from clinical studies have indicated an increased risk of cardiovascular events (CVE), including peripheral arterial occlusive disease, in CML patients receiving treatment with the TKIs nilotinib or ponatinib, as compared to imatinib (Giles et al, Leukemia 2013; Kim et al, Leukemia 2013; Cortes et al, New England Journal of Medicine 2013; FDA communication 2013). This study used data retrieved from Swedish population-based registries to estimate the frequency of CVE in CML patients, particularly those treated with imatinib and the 2nd generation TKIs nilotinib and dasatinib. Methods: We identified all incident cases between 2002 and 2012 in the Nationwide Swedish CML register. All patients who were in blast crisis or accelerated phase at time of diagnosis were excluded. All patients were followed untill death, emigration or 31st December 2012. For all CML patients a comparison cohort was established, matched to be of the same age and sex as the CML cohort, with 5 control subjects per CML patient. By means of record linkage with the nationwide Swedish patient register both cohorts were followed for the occurrence of adverse cardiovascular outcomes. Two sets of relative risks (expressed as incidence rate ratios; IRRs) of cardiovascular and venous thromboembolic disease were computed. In a first step CML patients were compared to the control population. In a second step, restricted to CML patients ever treated with TKIs, CML patients on different TKI treatments were compared. Patients could be treated with several TKIs during their follow-up, and events would only be attributable to the TKI used during the time period. Both analyses were adjusted for age, sex and calendar period. The second analysis was also adjusted for Sokal risk score. Results: A total of 896 CML patients were included and followed during a median of 4.2 years (Table I). The main outcome data are presented in Table II. A total of 23 venous thrombotic events (VTE) and 60 arterial thrombotic events were detected in the CML patient cohort during follow-up. Compared with the general population, this corresponded to significantly increased risks. In particular, deep venous thrombosis and “other arterial thromboses” were more common among CML patients (IRR 2.41 95% CI 1.29-4.52 and IRR 3.50 95% CI 1.36-9.04, respectively). Assessing risks associated with particular TKIs, we noted that treatment with any of the 2nd generation TKIs nilotinib or dasatinib, as compared to imatinib, was associated with a significantly increased occurrence of myocardial infarction (IRR 2.98 95% CI 1.05-8.49 and IRR 2.89 95% CI 1.20-7.00, respectively). Notably, there were no differences in the occurrence of CVE between the different patient groups before CML diagnosis. Conclusion: These data, derived from a large population-based Swedish cohort, provide evidence of an increased risk of both venous and arterial thrombotic events among CML patients and that patients on 2nd generation TKIs, as compared to imatinib, may be at increased risk of myocardial infarction. Further analyses will assess whether these differences may reflect patient selection and characterstics, rather than drug-related factors. Meanwhile, risk factors for CVE should be observed and considered in the TKI treatment of CML. Figure 1 Figure 1. Figure 2 Figure 2. * Footnote: the number of events may not add up because of occurrence of more than one type of vascular event in one subject. The number of events in the analysis within the CML cohort is lower than in the comparison with the general population because of exclusion of patients who were never treated with TKIs in the former analysis. Disclosures Björkholm: Novartis: Research Funding; Shire: Research Funding; Merck: Research Funding; Amgen: Honoraria, Research Funding; Pfizer: Research Funding; Bristol-Myers Squibb: Honoraria; Celgene: Honoraria; Akinon: Honoraria; Nordic Nanovector: Honoraria. Själander:Novartis: Honoraria. Richter:Ariad: Honoraria; Bristol-Myers Squibb: Honoraria; Novartis: Honoraria.

scholarly journals Long-term outcome of patients with invasive electrophysiology procedure-related cardiac tamponade

EP Europace ◽  
2020 ◽  
Vol 22 (10) ◽  
pp. 1547-1557
Author(s):  
Gesa von Olshausen ◽  
Tara Bourke ◽  
Jonas Schwieler ◽  
Nikola Drca ◽  
Hamid Bastani ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Acute Myocardial Infarction ◽  
Cardiac Tamponade ◽  
Cardiovascular Events ◽  
Control Group ◽  
Risk Of Death ◽  
Increased Risk

Abstract Aims Iatrogenic cardiac tamponades are a rare but dreaded complication of invasive electrophysiology procedures (EPs). Their long-term impact on clinical outcomes is unknown. This study analysed the risk of death or serious cardiovascular events in patients suffering from EP-related cardiac tamponade requiring pericardiocentesis during long-term follow-up. Methods and results Out of 19 997 invasive EPs at the Karolinska University Hospital between January 1998 and September 2018, all patients with EP-related periprocedural cardiac tamponade were identified (n = 60) and matched (1:3 ratio) to a control group (n = 180). After a follow-up of 5 years, the composite primary endpoint — death from any cause, acute myocardial infarction, transitory ischaemic attack (TIA)/stroke, and hospitalization for heart failure — occurred in significantly more patients in the tamponade than in the control group [12 patients (20.0%) vs. 19 patients (10.6%); hazard ratio (HR) 2.53 (95% confidence interval, CI 1.15–5.58); P = 0.021]. This was mainly driven by a higher incidence of TIA/stroke in the tamponade than in the control group [HR 3.75 (95% CI 1.01–13.97); P = 0.049]. Death from any cause, acute myocardial infarction, and hospitalization for heart failure did not show a significant difference between the groups. Hospitalization for pericarditis occurred in significantly more patients in the tamponade than in the control group [HR 36.0 (95% CI 4.68–276.86); P = 0.001]. Conclusion Patients with EP-related cardiac tamponade are at higher risk for cerebrovascular events during the first 2 weeks and hospitalization for pericarditis during the first months after index procedure. Despite the increased risk for early complications tamponade patients have a good long-term prognosis without increased risk for mortality or other serious cardiovascular events.

Long-term outcome of patients with invasive electrophysiology procedure related cardiac tamponade

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
G Von Olshausen ◽  
T Bourke ◽  
J Schwieler ◽  
N Drca ◽  
H Bastani ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Acute Myocardial Infarction ◽  
Cardiac Tamponade ◽  
Cardiovascular Events ◽  
Control Group ◽  
Funding Source ◽  
Increased Risk

Abstract Aims Iatrogenic cardiac tamponades are a rare but dreaded complication of invasive electrophysiology procedures (EPs). Their long-term impact on clinical outcomes is unknown. This study analyzed the risk of death or serious cardiovascular events in patients suffering from EP related cardiac tamponade requiring pericardiocentesis during long-term follow-up. Methods and results Out of 19997 invasive EPs at our university hospital between January 1998 and September 2018, all patients with EP related periprocedural cardiac tamponade were identified (n=60) and matched (1:3 ratio) to a control group (n=180). After a follow-up of 5 years, the composite primary end point - death from any cause, acute myocardial infarction, TIA/stroke and hospitalization for heart failure – occurred in significantly more patients in the tamponade than in the control group (12 patients (20.0%) vs 19 patients (10.6%); Hazard ratio (HR) 2.53 (95% CI, 1.15–5.58); p=0.021). This was mainly driven by a higher incidence of TIA/stroke in the tamponade than in the control group (HR 3.75 (95% CI, 1.01–13.97); p=0.049). Death from any cause, acute myocardial infarction and hospitalization for heart failure did not show a significant difference between the groups. Hospitalization for pericarditis occurred in significantly more patients in the tamponade than in the control group (HR 36.0 (95% CI, 4.68–276.86); p=0.001). Conclusion Patients with EP related cardiac tamponade are at higher risk for cerebrovascular events during the first two weeks and hospitalization for pericarditis during the first months after index procedure. Despite the increased risk for early complications tamponade patients have a good long-term prognosis without increased risk for mortality or other serious cardiovascular events. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): German Research Foundation

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