Actividad física y estrés oxidativo

La práctica regular de actividad física (AF) se asocia con una menor mortalidad y morbilidad cardiovascular. Parte de estos efectos beneficiosos están relacionados con los efectos favorables sobre los factores de riesgo cardiovascular clásicos. Sin embargo estos efectos explican sólo una parte de la protección de la AF sobre este tipo de enfermedades. La oxidación de las partículas de LDL colesterol tiene un papel fundamental en el proceso de la arteriosclerosis que es el mecanismo etiopatogénico de gran parte de las enfermedades cardiovasculares. En esta revisión narrativa se presenta el conocimiento actual sobre la relación entre la práctica de AF y la oxidación lipídica

Physical activity and lipid oxidation

Regular physical activity (PA) is associated with lower cardiovascular mortality and morbidity. Part of these benefits is related to the effects over the classic cardiovascular risk factors. These effects, however, only explain part of the protection of PA from these types of diseases. The oxidation of LDL cholesterol particles, which is the aetiopathogenic mechanism of a great part of cardiovascular diseases, plays an important role in the arteriosclerotic process. This narrative review presents current knowledge on the relationship between carrying out physical activity and lipid oxidation

Interrelationship of serum paraoxonase activity and paraoxonase genetic variants on atherosclerosis risk

La paraoxonasa (PON1) és una esterasa calciodepenent estretament associada a les lipoproteïnes d'alta densitat (HDL) que contenen apolipoproteïna AI, i s'ha descrit que dóna capacitat antioxidant a les HDL, amb la qual cosa disminueix l'acumulació dels lipoperòxids. L'activitat PON1 està sota control genètic i ambiental, i varia àmpliament entre individus i poblacions. L'activitat PON1 del paraoxon com a substrat és modulada per diversos polimorfismes en el locus PON1 dels humans. Un d'aquests polimorfismes és el PON1-192, que conté PON1 Q, una isoforma amb baixa activitat per la hidròlisi de paraoxon que té una glutamina a la posició 192, mentre que la isoforma R d'alta activitat conté una arginina a la posició 192. L'associació de l'activitat PON1 amb l'arteriosclerosi en estudis humans, animals i in vitro és prou consistent. Per tant, cal conèixer els factors que poden influenciar la PON1 sèrica. Els estudis genètics d'associació són menys consistents, probablement perquè els polimorfismes de la PON1 tenen només efecte en el risc de malaltia cardíaca coronària en grups particulars d'individus amb la presència de factors addicionals. És particularment important estudiar les interaccions gen-ambient que poden modular l'expressió fenotípica de la PON1 en diferents poblacions.Paraoxonase (PON1) is a calcium-dependent esterase, closely associated with high-density lipoprotein (HDL)-containing apolipoprotein AI, that has been reported to confer antioxidant properties on HDL by decreasing the accumulation of lipid peroxidation products. PON1 activity is under genetic and environmental regulation and appears to vary widely among individuals and populations. PON1 enzyme activity for paraoxon as a substrate is modulated by a number of polymorphisms at the PON1 locus in humans. One of them is the PON1-192 genetic polymorphism that comprises PON1 Q, an isoform which has a glutamine at position 192, and shows a low activity towards paraoxon hydrolysis, while the high paraoxon-activity PON1 R isoform contains an arginine at position 192. The association of PON1 activity levels with atherosclerosis in human, animal and in vitro studies is consistent and exciting. Therefore, there is an obvious need to know whether environmental factors can influence serum PON1. The genetic association studies for PON1 and atherosclerosis are less consistent, since the PON1 polymorphisms probably only produce an effect on coronary heart disease risk in particular subgroups of subjects in the presence of additional factors. It is particularly important to study gene-environmental interactions that may modulate phenotypic expression of PON1 in different populations

Epigenetics of Lipid Phenotypes

Dyslipidemia is a well-established risk factor for cardiovascular disease, the main cause of death worldwide. Blood lipid profiles are patterned by both genetic and environmental factors. In recent years, epigenetics has emerged as a paradigm that unifies these influences. In this review, we have summarized the latest evidence implicating epigenetic mechanisms—DNA methylation, histone modification, and regulation by RNAs—in lipid homeostasis. Key findings have emerged in a number of novel epigenetic loci located in biologically plausible genes (eg, CPT1A, ABCG1, SREBF1, and others), as well as microRNA-33a/b. Evidence from animal and cell culture models suggests a complex interplay between different classes of epigenetic processes in the lipid-related genomic regions. Although epigenetic findings hold the potential to explain the interindividual variability in lipid profiles as well as the underlying mechanisms, they have yet to be translated into effective therapies for dyslipidemia

Evaluation of a Clinical Decision Support System for Dyslipidemia Treatment (HTE-DLPR) by QoE questionnaire

Introduction: Clinical decision support systems (CDSS) are computer systems designed to assist clinicians with patient-related decision making, such as diagnosis and treatment. CDSS have shown to improve both patient outcomes and cost of care.Methods: A multi-center observational prospective study was conducted. Ten physicians agreed to participate. Seventy-seven patients with high or very high cardiovascular risk were included. After using CDSS for dyslipidemia (HTE-DLPR) for a 3 months period, participants were asked to evaluate their experience with HTE-DLPR using a quality of experience questionnaire (QoE) tool for mHealth applications.Results: Total score on the QoE was 3.89 out of 5. The highest scores were received for precision, ease of use and content quality. The lowest scores were given to security, appearance and performance. Physicians were in strong agreement with the 1st HTEDLPR recommendation in 86.1% and the system’s use was described as comfortablein 85% of cases. Users positively evaluated the development of a new version of HTEDLPR in the future receiving a total score of 4.25 out of 5.Conclusions: A CDSS for dyslipidemia (HTE-DLP) has been positively evaluated by physicians using QoE questionnaire

Disentangling the effects of traffic-related noise and air pollution on blood pressure: indoor noise levels and protections

Outdoor road traffic noise levels are associated with hypertension (HT). Studies on blood pressure (BP) are inconsistent and the true indoor traffic noise exposure may differ due to protections against noise. We analysed the effects of long-term exposure to outdoor and indoor traffic noise levels on HT, systolic (SBP) and diastolic BP (DBP, mmHg), adjusting for outdoor annual average concentrations of near-road traffic-related air pollution (nitrogen dioxide, NO2) among 1926 participants (aged 36-82) from the Catalan REGICOR study. Long-term outdoor residential levels of traffic noise at night (Lnight, in A-weighted dB) and annual averages of NO2 (in µg/m3 ) were estimated at the postal addresses’ façades with a city-specific noise model and a land-use regression model, respectively. Indoor traffic noise was calculated from outdoor noise levels subtracting the attenuations in dB according to reported noise protections. Median noise levels were 56.7 dB outdoors and 27.1 dB indoors. Spearman correlations between outdoor and indoor noise with NO2 were 0.75 and 0.23, respectively. Outdoor noise was only associated with HT (OR=1.19, 95%CI: 1.02, 1.40), whereas there was a suggestive association of indoor noise with both HT (OR=1.06, 95%CI: 0.99, 1.13) and SBP (ß=0.38, 95%CI: -0.08, 0.83) per 5 dB increase in outdoor noise levels. NO2 was also associated with both outcomes after adjustment for indoor noise. Findings for indoor traffic noise levels are more plausible than those for outdoor traffic noise. The use of indoor traffic noise estimates help to disentangle the effects from those of traffic-related air pollution.Postprint (author's final draft

The ERICE-score: the new native cardiovascular score for the low-risk and aged mediterranean population of Spain

[Abstract] Introduction and objectives. In Spain, data based on large population-based cohorts adequate to provide an accurate prediction of cardiovascular risk have been scarce. Thus, calibration of the EuroSCORE and Framingham scores has been proposed and done for our population. The aim was to develop a native risk prediction score to accurately estimate the individual cardiovascular risk in the Spanish population. Methods. Seven Spanish population-based cohorts including middle-aged and elderly participants were assembled. There were 11 800 people (6387 women) representing 107 915 person-years of follow-up. A total of 1214 cardiovascular events were identified, of which 633 were fatal. Cox regression analyses were conducted to examine the contributions of the different variables to the 10-year total cardiovascular risk. Results. Age was the strongest cardiovascular risk factor. High systolic blood pressure, diabetes mellitus and smoking were strong predictive factors. The contribution of serum total cholesterol was small. Antihypertensive treatment also had a significant impact on cardiovascular risk, greater in men than in women. The model showed a good discriminative power (C-statistic = 0.789 in men and C = 0.816 in women). Ten-year risk estimations are displayed graphically in risk charts separately for men and women. Conclusions. The ERICE is a new native cardiovascular risk score for the Spanish population derived from the background and contemporaneous risk of several Spanish cohorts. The ERICE score offers the direct and reliable estimation of total cardiovascular risk, taking in consideration the effect of diabetes mellitus and cardiovascular risk factor management. The ERICE score is a practical and useful tool for clinicians to estimate the total individual cardiovascular risk in Spain.[Resumen] Introducción y objetivos. En España no existen unas cohortes poblacionales suficientemente grandes para hacer predicciones precisas del riesgo cardiovascular. Las ecuaciones de Framingham y EuroSCORE calibradas son las más utilizadas en España. El objetivo es desarrollar la primera ecuación de predicción autóctona para estimar con precisión el riesgo cardiovascular individual en España. Métodos. Análisis conjunto de siete cohortes españolas de población de mediana edad y anciana. La población del estudio —11.800 personas (6.387 mujeres)— aportó un total de 107.915 personas-año de seguimiento y 1.214 eventos cardiovasculares (633 de ellos, mortales). Se efectuó un análisis de regresión de Cox para examinar la contribución de los diferentes factores al riesgo de cualquier evento cardiovascular (mortal y no mortal). Resultados. La edad fue el principal factor de riesgo de eventos cardiovasculares. La presión arterial sistólica, la diabetes mellitus, el tabaquismo y el tratamiento antihipertensivo fueron factores predictivos fuertemente asociados con el riesgo cardiovascular. En cambio, la contribución del colesterol total sérico fue pequeña, especialmente en los mayores de 70 años. El modelo final de riesgo mostró un buen poder discriminatorio (estadístico C = 0,789 en varones y C = 0,816 en mujeres). Conclusiones. ERICE es una nueva ecuación de riesgo cardiovascular genuinamente española obtenida a partir del riesgo concurrente individual de los participantes en varias cohortes. La ecuación ERICE ofrece una estimación directa y fiable del riesgo cardiovascular total teniendo en cuenta factores como la diabetes mellitus y el tratamiento farmacológico de los factores de riesgo cardiovascular, habitualmente no incluidos en otras ecuaciones.Instituto de Salud Carlos III; G03/065Instituto de Salud Carlos III; PI05/1464Instituto de Salud Carlos III; RD06/0014/001

Blood DNA methylation signature of diet quality, and association with cardiometabolic traits

BACKGROUND: Diet quality might influence cardiometabolic health through epigenetic changes, but this has been little investigated in adults. Our aim was to identify Cytosine-phosphate-Guanine (CpG) dinucleotides associated with diet quality by conducting an epigenome-wide association study (EWAS) based on blood DNA methylation (DNAm), and to assess how diet-related CpGs associate with inherited susceptibility to cardiometabolic traits: body mass index (BMI), systolic blood pressure (SBP), triglycerides, type 2 diabetes (T2D) and coronary heart disease (CHD). METHODS: Meta-EWAS including 5,274 participants in four cohorts from Spain, the US and the UK. We derived three dietary scores (exposures) to measure adherence to a Mediterranean diet (MMDS), to a healthy plant-based diet (HPDI) and to the Dietary Approaches to Stop Hypertension (DASH). Blood DNAm (outcome) was assessed with the Infinium arrays Human Methylation 450 K BeadChip and MethylationEPIC BeadChip. For each diet score, we performed linear EWAS adjusted for age, sex, blood cells, smoking and technical variables, and BMI in a second set of models. We also conducted Mendelian randomization analyses to assess the potential causal relationship between diet-related CpGs and cardiometabolic traits. RESULTS: We found 18 differentially methylated CpGs associated with dietary scores (p-value < 1.08 × 10-7; Bonferroni correction), of which 12 were previously associated with cardiometabolic traits. Enrichment analysis revealed overrepresentation of diet-associated genes in pathways involved in inflammation and cardiovascular disease. Mendelian randomization analyses suggested that genetically determined methylation levels corresponding to lower diet quality at cg02079413 (SNORA54), cg02107842 (MAST4), and cg23761815 (SLC29A3) were causally associated with higher BMI, and at cg05399785 (WDR8) with greater SBP; and methylation levels associated with higher diet quality at cg00711496 (PRMT1) with lower BMI, T2D risk and CHD risk, and at cg0557921 (AHRR) with lower CHD risk. CONCLUSIONS: Diet quality in adults was related to differential methylation in blood at 18 CpGs, some of which related to cardiometabolic health.Availability: The R code for the analysis is available in the following Github repository: https://github.com/jorgedb98/B64_DIAMETR.git

DNA methylation biomarkers of myocardial infarction and cardiovascular disease

Background: The epigenetic landscape underlying cardiovascular disease (CVD) is not completely understood and the clinical value of the identifed biomarkers is still limited. We aimed to identify diferentially methylated loci associ‑ ated with acute myocardial infarction (AMI) and assess their validity as predictive and causal biomarkers. Results: We designed a case-control, two-stage, epigenome-wide association study on AMI (ndiscovery=391, nvalidation=204). DNA methylation was assessed using the Infnium MethylationEPIC BeadChip. We performed a fxed efects meta-analysis of the two samples. 34 CpGs were associated with AMI. Only 12 of them were available in two independent cohort studies (n~1800 and n~2500) with incident coronary and cardiovascular disease (CHD and CVD, respectively). The Infnium HumanMethylation450 BeadChip was used in those two studies. Four of the 12 CpGs were validated in association with incident CHD: AHRR-mapping cg05575921, PTCD2-mapping cg25769469, intergenic cg21566642 and MPO-mapping cg04988978. We then assessed whether methylation risk scores based on those CpGs improved the predictive capacity of the Framingham risk function, but they did not. Finally, we aimed to study the causality of those associations using a Mendelian randomization approach but only one of the CpGs had a genetic infuence and therefore the results were not conclusive. Conclusions: We have identifed 34 CpGs related to AMI. These loci highlight the relevance of smoking, lipid metab‑ olism, and infammation in the biological mechanisms related to AMI. Four were additionally associated with incident CHD and CVD but did not provide additional predictive informatio