The Year in Cardiology 2013: cardiovascular disease prevention

The decline in cardiovascular mortality in Europe by nearly 50% over the last three decades resulted in particular from improved risk factor control and prevention interventions in addition to improved treatment. This review provides an overview of key studies in epidemiology, hypertension control, lipidology, diabetology, and lifestyle changes published in 2013. EXAMINE in diabetology and AIM-High and HPS-2-THRIVE in lipidology failed to demonstrate an event reduction. According to EUROASPIRE IV clinical implementation of secondary prevention treatments is still suboptimal. The 2013 study highlights in prevention prove the dynamic progress of knowledge in the field;, however, knowledge alone is futile without implementatio

Stamm- und progenitorzellbasierte Therapieansätze: Aktuelle Entwicklungen zur Behandlung des akuten Myokardinfarkts und der chronischen ischämischen Kardiomyopathie

Zusammenfassung: Die perkutane koronare Revaskularisation sowie eine optimierte medikamentöse Therapie können bei Patienten mit akutem Myokardinfarkt das linksventrikuläre (LV) Remodeling und die LV-Dysfunktion reduzieren. Trotz dieser modernen Therapiestrategien entwickelt ein nicht unerheblicher Teil dieser Patienten ein ungünstiges kardiales Remodeling, das mit einer schlechten Prognose einhergeht. Stamm- und progenitorzellbasierte Ansätze für die Behandlung des akuten Myokardinfarkts und der chronischen ischämischen Kardiomyopathie werden als potenzielle neue therapeutische Optionen intensiv untersucht. Diese Übersicht fasst die aktuellen Entwicklungen in der stamm- und progenitorzellbasierten Therapie bei ischämischer Herzerkrankung zusammen. Dabei erfolgt eine Einschätzung der Reparatur- und Regenerationsfähigkeit verschiedener Stamm- und Progenitorzellpopulationen. Darüber hinaus werden die Vor- und Nachteile der verschiedenen kardialen Applikationsformen der Zellen und mögliche neue Strategien zur Funktionsverbesserung von Stamm- und Progenitorzellen für den Einsatz der zellbasierten kardiovaskulären Therapie dargestell

Potential novel pharmacological therapies for myocardial remodelling

Left ventricular (LV) remodelling remains an important treatment target in patients after myocardial infarction (MI) and chronic heart failure (CHF). Accumulating evidence has supported the concept that beneficial effects of current pharmacological treatment strategies to improve the prognosis in these patients, such as angiotensin-converting enzyme (ACE) inhibition, angiotensin type 1 receptor blocker therapy, and beta-blocker therapy, are related, at least in part, to their effects on LV remodelling and dysfunction. However, despite modern reperfusion therapy after MI and optimized treatment of patients with CHF, LV remodelling is observed in a substantial proportion of patients and is associated with an adverse clinical outcome. These observations call for novel therapeutic strategies to prevent or even reverse cardiac remodelling. Recent insights from experimental studies have provided new targets for interventions to prevent or reverse LV remodelling, i.e. reduced endothelial nitric oxide (NO) synthase-derived NO availability, activation of cardiac and leukocyte-dependent oxidant stress pathways, inflammatory pathway activation, matrix-metalloproteinase activation, or stem cell transfer and delivery of novel paracrine factors. An important challenge in translating these observations from preclinical studies into clinical treatment strategies relates to the fact that clinical studies are designed on top of established pharmacological therapy, whereas most experimental studies have tested novel interventions without concomitant drug regimens such as ACE inhibitors or beta-blockers. Therefore, animal studies may overestimate the effect of potential novel treatment strategies on LV remodelling and dysfunction, since established pharmacological therapies may act, in part, via identical or similar signalling pathways. Nevertheless, preclinical studies provide essential information for identifying potential novel targets, and their potential drawbacks, and are required for developing novel clinical treatment strategies to prevent or reverse LV remodelling and dysfunctio

The year in cardiology: cardiovascular prevention. The year in cardiology 2019.

No abstract available

537Microparticles and exosomes differentially impact on endothelial cell function in coronary artery disease

Background and Purpose: Microparticles (MPs) and exosomes are released by cells using different mechanisms. Thus, quantitative as well as qualitative changes of both particle populations, MPs and exosomes, in patients with coronary artery disease (CAD) might reflect an altered activation status of the endothelium, platelets and leukocytes. Moreover, they might exert differential effects on the target organs, such as the endothelium. Yet, alterations in both populations have not been studied side-by-side so far. The aim of the study was to compare the impact of MPs and exosomes from healthy subjects and CAD patients on endothelial cell (EC) functional characteristics. Methods: MPs and exosomes were isolated by stepwise filtration and ultracentrifugation from citrate-plasma and verified by electron microscopy and dynamic light scattering. MP and exosome fractions, as well as the vehicle (PBS), were added to human arterial ECs and EC apoptosis, number, size, capacity for in vitro-reendothelialisation after scratching, expression of adhesion molecules ICAM-1 and VCAM-1 were assessed. In parallel, platelet-, endothelial- and leukocyte-derived MPs were quantified. In a separate sub-study, the same parameters were assessed in plasma of CAD patients undergoing standard medical rehabilitation or an exercise-based cardiac rehabilitation programme. Results: MPs of healthy, but not of CAD patients supported in vitro re-endothelialisation, while exosomes had no influence. Exercise, but not standard rehabilitation improved CAD MP capacity to support in vitro rehabilitation. This was negatively correlated to the number of leukocyte- and endothelial-derived MPs, but not total or platelet MPs. EC number was negatively affected by exposure to CAD MPs. ANCOVA analysis identified disease, but not the particle type as influencing factor. Instead, apoptotic cell death was influenced by particle type, but not by the disease, and was not altered in rehabilitation. Similarly, ICAM-1 and VCAM-1 expression were enhanced on ECs after incubation with exosomes, but not with MPs, with no effect of disease or rehabilitation. Conclusion: MPs and exosomes differentially affect endothelial cell function and underlie differential modulation in disease and rehabilitation. Those findings might in the future help to optimize and monitor cardiovascular therap

Accuracy of low-dose computed tomography coronary angiography using prospective electrocardiogram-triggering: first clinical experience

AIMS: To evaluate the accuracy of low-dose computed tomography coronary angiography (CTCA) using prospective ECG-triggering for the assessment of coronary artery disease (CAD). METHODS AND RESULTS: A total of 30 patients (19 males, 11 females, mean age 58.8 +/- 9.9 years) underwent low-dose CTCA and invasive coronary angiography (CA) [median 2 days (0, 41)]. Before CT scanning, intravenous beta-blocker was administered in 18 of 30 patients as heart rate (HR) was >65 b.p.m., achieving a mean HR of 55.7 +/- 7.9 b.p.m. CAD was defined as coronary artery narrowing > or =50%, using CA as standard of reference. The estimated mean effective radiation dose was 2.1 +/- 0.7 mSv (range: 1.0-3.3), yielding 96.0% (383/399) of evaluable segments. On an intention-to-diagnose-base, all non-evaluative segments were included in the analysis. Vessels with a non-evaluative segment and no further finding were censored as false positive. Patient-based analysis revealed sensitivity, specificity, positive predictive value, and negative predictive value of 100, 83.3, 90.0, and 100%, respectively. The respective values per vessel were 100, 88.9, 85.7, and 100%, respectively. CONCLUSION: Prospective ECG-triggering allows low-dose CTCA and provides high diagnostic accuracy in the assessment of CAD in patients with stable sinus rhythm and a low heart rat

Anti-inflammatory treatment improves high-density lipoprotein function in rheumatoid arthritis

OBJECTIVE: Patients with rheumatoid arthritis (RA) are at increased cardiovascular risk. Recent studies suggest that high-density lipoprotein (HDL) may lose its protective vascular phenotype in inflammatory conditions. However, the effects of common anti-inflammatory treatments on HDL function are not yet known. METHODS: We compared the function of HDL in 18 patients with RA and 18 matched healthy controls. Subsequently, patients were randomised to (methotrexate+infliximab (M+I) (5 mg/kg)) or methotrexate+placebo (M+P) infusions for 54 weeks. At week 54 and thereafter, all patients received infliximab therapy until completion of the trial (110 weeks), enabling assessment of the impact of 1 year of infliximab therapy in all patients. HDL functional properties were assessed at baseline, 54 weeks and 110 weeks by measuring the impact on endothelial nitric oxide (NO) bioavailability and superoxide production (SO), paraoxonase activity (PON-1) and cholesterol efflux. RESULTS: All HDL vascular assays were impaired in patients compared with controls. After 54 weeks, NO in response to HDL was significantly greater in patients who received M+I compared with those who received M+P. Endothelial SO in response to HDL was reduced in both groups, but PON-1 and cholesterol efflux remained unchanged. All vascular measures improved compared with baseline after ≥1 infliximab therapy in the analysis at 110 weeks. No significant trend was noted for cholesterol efflux. CONCLUSIONS: HDL function can be improved with anti-inflammatory treatment in patients with RA. The M+I combination was superior to the M+P alone, suggesting that the tumour necrosis factor-α pathway may have a role in HDL vascular properties

Exposure to Ambient Air Fine Particulate Matter Prevents VEGF-Induced Mobilization of Endothelial Progenitor Cells from the Bone Marrow

Background: Exposure to ambient fine particulate matter air pollution (PM2.5; < 2.5 µm in aerodynamic diameter) induces endothelial dysfunction and increases the risk for cardiovascular disease. Endothelial progenitor cells (EPCs) contribute to postnatal endothelial repair and regeneration. In humans and mice, EPC levels are decreased upon exposure to elevated levels of PM2.5

Neural network-based integration of polygenic and clinical information: development and validation of a prediction model for 10-year risk of major adverse cardiac events in the UK Biobank cohort

Background: In primary cardiovascular disease prevention, early identification of high-risk individuals is crucial. Genetic information allows for the stratification of genetic predispositions and lifetime risk of cardiovascular disease. However, towards clinical application, the added value over clinical predictors later in life is crucial. Currently, this genotype–phenotype relationship and implications for overall cardiovascular risk are unclear. Methods: In this study, we developed and validated a neural network-based risk model (NeuralCVD) integrating polygenic and clinical predictors in 395 713 cardiovascular disease-free participants from the UK Biobank cohort. The primary outcome was the first record of a major adverse cardiac event (MACE) within 10 years. We compared the NeuralCVD model with both established clinical scores (SCORE, ASCVD, and QRISK3 recalibrated to the UK Biobank cohort) and a linear Cox-Model, assessing risk discrimination, net reclassification, and calibration over 22 spatially distinct recruitment centres. Findings: The NeuralCVD score was well calibrated and improved on the best clinical baseline, QRISK3 (ΔConcordance index [C-index] 0·01, 95% CI 0·009–0·011; net reclassification improvement (NRI) 0·0488, 95% CI 0·0442–0·0534) and a Cox model (ΔC-index 0·003, 95% CI 0·002–0·004; NRI 0·0469, 95% CI 0·0429–0·0511) in risk discrimination and net reclassification. After adding polygenic scores we found further improvements on population level (ΔC-index 0·006, 95% CI 0·005–0·007; NRI 0·0116, 95% CI 0·0066–0·0159). Additionally, we identified an interaction of genetic information with the pre-existing clinical phenotype, not captured by conventional models. Additional high polygenic risk increased overall risk most in individuals with low to intermediate clinical risk, and age younger than 50 years. Interpretation: Our results demonstrated that the NeuralCVD score can estimate cardiovascular risk trajectories for primary prevention. NeuralCVD learns the transition of predictive information from genotype to phenotype and identifies individuals with high genetic predisposition before developing a severe clinical phenotype. This finding could improve the reprioritisation of otherwise low-risk individuals with a high genetic cardiovascular predisposition for preventive interventions. Funding: Charité–Universitätsmedizin Berlin, Einstein Foundation Berlin, and the Medical Informatics Initiative