Daniel Muñoz

2016 ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines: The Task Force for cancer treatments and cardiovascular toxicity of the European Society of Cardiology (ESC)

No abstract available Keywords: European Society of Cardiology; arrhythmias; cancer therapy; cardio-oncology; cardiotoxicity; chemotherapy; early detection; ischaemia; myocardial dysfunction; surveillance.

Anti-inflammatory effect of virgin olive oil in stable coronary disease patients: a randomized, crossover, controlled trial

Objectives:To assess the effect of two similar olive oils, but with differences in their phenolic compounds (powerful antioxidant compounds), on inflammatory markers in stable coronary heart disease patients.Design:Placebo-controlled, crossover, randomized trial.Setting:Cardiology Department of Hospital del Mar and Institut Municipal d’Investigació Mèdica (Barcelona).Subjects:Twenty-eight stable coronary heart disease patients.Interventions:A raw daily dose of 50 ml of virgin and refined olive oil (ROO) was sequentially administered over two periods of 3-weeks, preceded by 2-week washout periods in which ROO was used.Results:Interleukin-6 (P<0.002) and C-reactive protein (P=0.024) decreased after virgin olive oil intervention. No changes were observed in soluble intercellular and vascular adhesion molecules, glucose and lipid profile.Conclusions:Consumption of virgin olive oil, could provide beneficial effects in stable coronary heart disease patients as an additional intervention to the pharmacological treatment.

Intracardiac flow visualization: current status and future directions

Non-invasive cardiovascular imaging initially focused on heart structures, allowing the visualization of their motion and inferring its functional status from it. Colour-Doppler and cardiac magnetic resonance (CMR) have allowed a visual approach to intracardiac flow behaviour, as well as measuring its velocity at single selected spots. Recently, the application of new technologies to medical use and, particularly, to cardiology has allowed, through different algorithms in CMR and applications of ultrasound-related techniques, the description and analysis of flow behaviour in all points and directions of the selected region, creating the opportunity to incorporate new data reflecting cardiac performance to cardiovascular imaging. The following review provides an overview of the currently available imaging techniques that enable flow visualization, as well as its present and future applications based on the available literature and on-going works.

Mononuclear cell transcriptome response after sustained virgin olive oil consumption in humans: an exploratory nutrigenomics study

Virgin olive oil (VOO) is considered to be one of the main components responsible for the health benefits of the Mediterranean diet, particularly against atherosclerosis where peripheral blood mononuclear cells (PBMNCs) play a crucial role in atherosclerosis development and progression. The objective of this article was to identify the PBMNC genes that respond to VOO consumption in order to ascertain the molecular mechanisms underlying the beneficial action of VOO in the prevention of atherosclerosis. Gene expression profiles of PBMNCs from healthy individuals were examined in pooled RNA samples by microarrays after 3 weeks of moderate and regular consumption of VOO, as the main fat source in a diet controlled for antioxidant content. Gene expression was verified by qPCR. The response to VOO consumption was confirmed for individual samples (n = 10) by qPCR for 10 upregulated genes (ADAM17, ALDH1A1, BIRC1, ERCC5, LIAS, OGT, PPARBP, TNFSF10, USP48, and XRCC5). Their putative role in the molecular mechanisms involved in atherosclerosis development and progression is discussed, focusing on a possible relation with VOO consumption. Our data support the hypothesis that 3 weeks of nutritional intervention with VOO supplementation, at doses common in the Mediterranean diet, can alter the expression of genes related to atherosclerosis development and progression.

Assessment of the value of a genetic risk score in improving the estimation of coronary risk

BACKGROUND The American Heart Association has established criteria for the evaluation of novel markers of cardiovascular risk. In accordance with these criteria, we assessed the association between a multi-locus genetic risk score (GRS) and incident coronary heart disease (CHD), and evaluated whether this GRS improves the predictive capacity of the Framingham risk function. METHODS AND RESULTS Using eight genetic variants associated with CHD but not with classical cardiovascular risk factors (CVRFs), we generated a multi-locus GRS, and found it to be linearly associated with CHD in two population based cohorts: The REGICOR Study (n=2351) and The Framingham Heart Study (n=3537) (meta-analyzed HR [95%CI]: ~1.13 [1.01-1.27], per unit). Inclusion of the GRS in the Framingham risk function improved its discriminative capacity in the Framingham sample (c-statistic: 72.81 vs.72.37, p=0.042) but not in the REGICOR sample. According to both the net reclassification improvement (NRI) index and the integrated discrimination index (IDI), the GRS improved re-classification among individuals with intermediate coronary risk (meta-analysis NRI [95%CI]: 17.44 [8.04; 26.83]), but not overall. CONCLUSIONS A multi-locus GRS based on genetic variants unrelated to CVRFs was associated with a linear increase in risk of CHD events in two distinct populations. This GRS improves risk reclassification particularly in the population at intermediate coronary risk. These results indicate the potential value of the inclusion of genetic information in classical functions for risk assessment in the intermediate risk population group.

Identification and validation of seven new loci showing differential DNA methylation related to serum lipid profile: an epigenome-wide approach. The REGICOR study.

Lipid traits (total, low-density and high-density lipoprotein cholesterol, and triglycerides) are risk factors for cardiovascular disease. DNA methylation is not only an inherited but also modifiable epigenetic mark that has been related to cardiovascular risk factors. Our aim was to identify loci showing differential DNA methylation related to serum lipid levels. Blood DNA methylation was assessed using the Illumina Human Methylation 450 BeadChip. A two-stage epigenome-wide association study was performed, with a discovery sample in the REGICOR study (n = 645) and validation in the Framingham Offspring Study (n = 2,542). Fourteen CpG sites located in nine genes (SREBF1, SREBF2, PHOSPHO1, SYNGAP1, ABCG1, CPT1A, MYLIP, TXNIP and SLC7A11) and 2 intergenic regions showed differential methylation in association with lipid traits. Six of these genes and 1 intergenic region were new discoveries showing differential methylation related to total cholesterol (SREBF2), HDL-cholesterol (PHOSPHO1, SYNGAP1 and an intergenic region in chromosome 2) and triglycerides (MYLIP, TXNIP and SLC7A11). These CpGs explained 0.7%, 9.5% and 18.9% of the variability of total cholesterol, HDL cholesterol and triglycerides in the Framingham Offspring Study, respectively. The expression of the genes SREBF2 and SREBF1 was inversely associated with methylation of their corresponding CpGs (P-value = 0.0042 and 0.0045, respectively) in participants of the GOLDN study (n = 98). In turn, SREBF1 expression was directly associated with HDL cholesterol (P-value = 0.0429). Genetic variants in SREBF1, PHOSPHO1, ABCG1 and CPT1A were also associated with lipid profile. Further research is warranted to functionally validate these new loci and assess the causality of new and established associations between these differentially methylated loci and lipid metabolism.

2016 ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines

Authors/Task Force Members: Jose Luis Zamorano* (Chairperson) (Spain), Patrizio Lancellotti* (Co-Chairperson) (Belgium), Daniel Rodriguez Muñoz (Spain), Victor Aboyans (France), Riccardo Asteggiano (Italy), Maurizio Galderisi (Italy), Gilbert Habib (France), Daniel J. Lenihan (USA), Gregory Y. H. Lip (UK), Alexander R. Lyon (UK), Teresa Lopez Fernandez (Spain), Dania Mohty (France), Massimo F. Piepoli (Italy), Juan Tamargo (Spain), Adam Torbicki (Poland), and Thomas M. Suter (Switzerland)

DNA Methylation and High-Density Lipoprotein Functionality—Brief ReportHighlights: The REGICOR Study (Registre Gironi del Cor)

Objective— The function of high-density lipoproteins (HDLs) may better reflect their atheroprotective role, compared with HDL-cholesterol levels. The association between DNA methylation and HDL function has not yet been established. Approach and Results— We designed an epigenome-wide association study including 645 individuals from the REGICOR study (Registre Gironi del Cor). We determined DNA methylation from peripheral blood cells using the HumanMethylation450 array. We analyzed HDL functionality by determining HDL cholesterol efflux capacity and HDL inflammatory index. We discovered 3 methylation sites located in HOXA3, PEX5, and PER3 related to cholesterol efflux capacity and 1 located in GABRR1 related to HDL inflammatory index. Using a candidate gene approach, we also found 2 methylation sites located in CMIP related to cholesterol efflux capacity. Conclusions— We identified 6 potential loci associated with HDL functionality in HOXA3, PEX5, PER3, CMIP, and GABRR1. Additional studies are warranted to validate these findings in other populations.

2017 ESC/EACTS Guidelines for the Management of Valvular Heart Disease

Authors/Task Force Members: Volkmar Falk (EACTS Chairperson) (Germany), Helmut Baumgartner (ESC Chairperson) (Germany), Jeroen J. Bax (The Netherlands), Michele De Bonis (Italy), Christian Hamm (Germany), Per Johan Holm (Sweden), Bernard Iung (France), Patrizio Lancellotti (Belgium), Emmanuel Lansac (France), Daniel Rodriguez Mu~ noz (Spain), Raphael Rosenhek (Austria), Johan Sjögren (Sweden), Pilar Tornos Mas (Spain), Alec Vahanian (France), Thomas Walther (Germany), Olaf Wendler (UK), Stephan Windecker (Switzerland), Jose Luis Zamorano (Spain)

DNA Methylation and High-Density Lipoprotein Functionality

Objective— The function of high-density lipoproteins (HDLs) may better reflect their atheroprotective role, compared with HDL-cholesterol levels. The association between DNA methylation and HDL function has not yet been established. Approach and Results— We designed an epigenome-wide association study including 645 individuals from the REGICOR study (Registre Gironi del Cor). We determined DNA methylation from peripheral blood cells using the HumanMethylation450 array. We analyzed HDL functionality by determining HDL cholesterol efflux capacity and HDL inflammatory index. We discovered 3 methylation sites located in HOXA3, PEX5, and PER3 related to cholesterol efflux capacity and 1 located in GABRR1 related to HDL inflammatory index. Using a candidate gene approach, we also found 2 methylation sites located in CMIP related to cholesterol efflux capacity. Conclusions— We identified 6 potential loci associated with HDL functionality in HOXA3, PEX5, PER3, CMIP, and GABRR1. Additional studies are warranted to validate these findings in other populations.