Ceruloplasmina y su implicación en la enfermedad cardiovascular

INTRODUCTION: Inflammation and oxidative stress play a key role in the initiation and maintenance of atherosclerosis and are related to the occurrence of events leading to vessel occlusion, both in the venous system (thromboembolic disease) and in the arterial system (cardiovascular disease). Although there are no clear theories on how these occlusive diseases in both arterial and venous territories are linked, they share the increase of certain inflammatory and oxidative-stress markers. Ceruloplasmin (CP) is a protein involved in copper metabolism that has also been linked to inflammatory responses, whereas the association to occlusive vascular diseases has not been fully characterized. HYPOTHESIS: Our hypothesis is that high levels of CP would be associated with the incidence of cardiovascular events. OBJECTIVES: 1) To evaluate whether high levels of plasma CP are associated with increased incidence of atrial fibrillation. 2) To evaluate whether high levels of plasma CP are associated with increased incidence of venous thromboembolism. 3) To perform a systematic review of the current evidence on whether high levels of plasma CP are associated to a higher risk of coronary heart disease. METHODS: a) We conducted a first analysis evaluating the association of CP with AF incidence in a large cohort, the Atherosclerosis Risk in Communities (ARIC) Study. b) We conducted other investigation to test the association between CP and VTE incidence in the same ARIC study population. c) Finally, to evaluate the influence of CP on CHD, we conducted a systematic review exploring the impact of CP on the risk of CHD over the last three decades. RESULTS: Higher plasma CP levels were associated with incident AF in the ARIC cohort. Regarding VTE, higher concentrations of plasma CP were also associated with greater incident VTE rates. Finally, most of 18 eligible studies reviewed supported a direct relationship between CP elevated levels and incidence of CHD. CONCLUSIONS: We have evaluated the association between CP and three highly prevalent diseases derived from alterations in the cardiovascular system, both venous and arterial location, establishing that high CP levels are related to the occurrence of these conditions.INTRODUCCIÓN: La inflamación y el estrés oxidativo desempeñan un papel fundamental en el inicio y desarrollo del proceso aterosclerótico y están relacionados con la aparición de eventos que conducen a la oclusión de los vasos, tanto en el sistema venoso (enfermedad tromboembólica) como en el arterial (enfermedad cardiovascular). Aunque no hay teorías claras sobre cómo se relacionan estas enfermedades oclusivas en los territorios arteriales y venosos, comparten la elevación de ciertos marcadores inflamatorios y de estrés oxidativo. La ceruloplasmina (CP) es una proteína que actúa en el metabolismo del cobre que se ha relacionado con la respuesta inflamatoria, la cual no se relacionado hasta el momento con las enfermedades vasculares oclusivas. HIPÓTESIS: Nuestra hipótesis es que altos niveles de CP estarían implicados en la aparición de nuevos eventos cardiovasculares. OBJETIVOS: 1) Evaluar si niveles elevados de CP en plasma se asocian a una mayor incidencia de fibrilación auricular. 2) Evaluar si niveles elevados de CP en plasma se asocian a una mayor incidencia de tromboembolismo venoso. 3) Realizar una revisión sistemática de la evidencia actual sobre si niveles elevados de CP en plasma se asocian a un mayor riesgo de enfermedad coronaria. MÉTODOS: a) En un primer análisis, evaluamos la asociación de la CP con la incidencia de FA en el estudio ARIC (Atherosclerosis Risk in Communities), una cohorte comunitaria. b) Realizamos otro trabajo de investigación para comprobar la asociación de CP e incidencia de ETV en la misma población. c) Por último, para evaluar la influencia de la CP en la cardiopatía isquémica, realizamos una revisión sistemática en la que exploramos el impacto de la CP en el riesgo de cardiopatía isquémica en las tres últimas décadas. RESULTADOS: Niveles más altos de CP circulante se asociaron con mayor incidencia de FA en la cohorte ARIC. En relación con la ETV, las mayores concentraciones de CP circulante también se asociaron con mayores tasas de ETV. Por último, la mayoría de los 18 estudios revisados apoyaron una relación directa entre niveles elevados de CP y la incidencia de cardiopatía isquémica. CONCLUSIONES: Tras evaluar la asociación entre la CP y tres enfermedades altamente prevalentes derivadas de alteraciones del sistema cardiovascular, tanto de localización venosa como arterial, podemos concluir que niveles elevados de CP están relacionados con la aparición de estas enfermedades

Different Dietary Approaches, Non-Alcoholic Fatty Liver Disease and Cardiovascular Disease: A Literature Review

Non-alcoholic fatty liver disease (NAFLD) is the first cause of chronic liver disease and is also associated with other harmful entities such as obesity, metabolic syndrome, dyslipidemia, and diabetes. NAFLD is a significant public health concern worldwide, impacting individuals of all ages, and its prevalence is projected to increase in the near future due to its connection with obesity. Intrinsic (genetics) and external (lifestyle) factors may also modulate NAFLD, and, in turn, may partly explain the observed relationship between NAFLD and cardiovascular disease (CVD). Although many drugs are been tested to treat NAFLD, to date, no drug has indication to specifically treat this disorder. Thus, the current management of NAFLD relies on lifestyle modifications and specifically on weight loss, physical activity, and the intake of a healthy diet. In the present narrative review, we will discuss the effects of certain dietary patterns on NAFLD incidence and progression

Ceruloplasmin and Coronary Heart Disease-A Systematic Review

Several studies indicate that oxidative stress might play a central role in the initiation and maintenance of cardiovascular diseases. It remains unclear whether ceruloplasmin acts as a passive marker of inflammation or as a causal mediator. To better understand the impact of ceruloplasmin blood levels on the risk of cardiovascular disease, and paying special attention to coronary heart disease, we conducted a search on the two most commonly used electronic databases (Medline via PubMed and EMBASE) to analyze current assessment using observational studies in the general adult population. Each study was quality rated using criteria developed by the US Preventive Services Task Force. Most of 18 eligible studies reviewed support a direct relationship between ceruloplasmin elevated levels and incidence of coronary heart disease. Our results highlight the importance of promoting clinical trials that determine the functions of ceruloplasmin as a mediator in the development of coronary heart disease and evaluate whether the treatment of elevated ceruloplasmin levels has a role in the prognosis or prevention of this condition

Coenzyme Q10 Supplementation for the Reduction of Oxidative Stress: Clinical Implications in the Treatment of Chronic Diseases

Apart from its main function in the mitochondria as a key element in electron transport, Coenzyme Q10 (CoQ10) has been described as having multiple functions, such as oxidant action in the generation of signals and the control of membrane structure and phospholipid and cellular redox status. Among these, the most relevant and most frequently studied function is the potent antioxidant capability of its coexistent redox forms. Different clinical trials have investigated the effect of CoQ10 supplementation and its ability to reduce oxidative stress. In this review, we focused on recent advances in CoQ10 supplementation, its role as an antioxidant, and the clinical implications that this entails in the treatment of chronic diseases, in particular cardiovascular diseases, kidney disease, chronic obstructive pulmonary disease, non-alcoholic fatty liver disease, and neurodegenerative diseases. As an antioxidant, CoQ10 has proved to be of potential use as a treatment in diseases in which oxidative stress is a hallmark, and beneficial effects of CoQ10 have been reported in the treatment of chronic diseases. However, it is crucial to reach a consensus on the optimal dose and the use of different formulations, which vary from ubiquinol or ubiquinone Ubisol-Q10 or Qter®, to new analogues such as MitoQ, before we can draw a clear conclusion about its clinical use. In addition, a major effort must be made to demonstrate its beneficial effects in clinical trials, with a view to making the implementation of CoQ10 possible in clinical practice

Long-term effect of a dietary intervention with two-healthy dietary approaches on food intake and nutrient density in coronary patients: results from the CORDIOPREV trial

Background: Cardiovascular disease (CVD) is the leading cause of disease burden in the world by non-communicable diseases. Nutritional interventions promoting high-quality dietary patterns with low caloric intake value and high nutrient density (ND) could be linked to a better control of CVD risk and recurrence of coronary disease. This study aims to assess the effects of a dietary intervention based on MedDiet or Low-Fat dietary intervention over changes in ND and food intake after 1 and 7 years of follow-up of the CORDIOPREV study. Methods: We prospectively analyzed the results of the 802 coronary patients randomized to two healthy dietary patterns (MedDiet = 425, Low-Fat Diet = 377) who completed the 7 years of follow-up and had all the dietary data need. Dietary intake information obtained from a validated 137-item Food Frequency Questionnaire was used to calculate 1- and 7-year changes in dietary intake and ND (measured as nutrient intake per 1000 kcal). T test was used to ascertain differences in food intake and ND between groups across follow-up time. Within-subject (dietary allocation group) differences were analyzed with ANOVA repeated measures. Results: From baseline to 7 years of follow-up, significant increases of vegetables, fruits, and whole cereals within groups (p < 0.001) was found. We found a higher increase in dietary intake of certain food groups with MedDiet in comparison with Low-Fat Diet for vegetables (46.1 g/day vs. 18.1 g/day, p < 00.1), fruits (121.3 g/day vs. 72.9 g/day), legumes (4.3 g/day vs. 0.16 g/day) and nuts (7.3 g/day vs. − 3.7 g/day). There was a decrease in energy intake over time in both groups, slightly higher in Low-Fat Diet compared to MedDiet group (− 427.6 kcal/day vs. − 279.8 kcal/day at 1st year, and − 544.6 kcal/day vs. − 215.3 kcal/day after 7 years of follow-up). ND of all the nutrients increased within group across follow-up time, except for Saturated Fatty Acids (SFA), cholesterol and sodium (p < 0.001). Conclusions: A comprehensive dietary intervention improved quality of diet, reducing total energy intake and increasing the intake of healthy food groups and overall ND after 1 year and maintaining this trend after 7 years of follow-up. Our results reinforce the idea of the participation in trials, enhance nutrition literacy and produces better nutritional outcomes in adult patients with established CVD. Clinical trial registry: The trial was registered in 2009 at ClinicalTrials.gov (number NCT00924937)

Quality and Quantity of Protein Intake Influence Incidence of Type 2 Diabetes Mellitus in Coronary Heart Disease Patients: From the CORDIOPREV Study

Evidence suggests that enriching a diet with plant-based proteins could reduce the risk of developing type 2 diabetes mellitus. In the present work, we evaluated the association between the change in plant protein intake (adjusted by energy) and incidence of type 2 diabetes mellitus in patients with coronary heart disease from the CORDIOPREV (coronary diet intervention with olive oil and cardiovascular prevention) study. At baseline and during the follow-up, patients underwent medical examination and blood and oral glucose tolerance tests. Information on patient’s dietary intake was gathered by registered dietitians using a validated food frequency questionnaire. A total of 106 out of 436 nondiabetic patients at baseline developed type 2 diabetes mellitus after a median follow-up of 60 months. Cox regression analyses showed that patients who belonged to the group that increased plant protein intake exhibited a lower risk of developing the disease (HR = 0.64, (0.43–0.96)). Changes in plant protein intake were positively correlated with changes in carbohydrates, fibre, and legumes intake and negatively correlated with changes in saturated fatty acids intake. Results of the present study support the need of improving diet with plant-based proteins to prevent the onset of type 2 diabetes mellitus

Evolution of Metabolic Phenotypes of Obesity in Coronary Patients after 5 Years of Dietary Intervention: From the CORDIOPREV Study

Background: Obesity phenotypes with different metabolic status have been described previously. We analyzed metabolic phenotypes in obese coronary patients during a 5-year follow-up, and examined the factors influencing this evolution. Methods: The CORDIOPREV study is a randomized, long-term secondary prevention study with two healthy diets: Mediterranean and low-fat. All obese patients were classified as either metabolically healthy obese (MHO) or metabolically unhealthy obese (MUO). We evaluated the changes in the metabolic phenotypes and related variables after 5 years of dietary intervention. Results: Initially, 562 out of the 1002 CORDIOPREV patients were obese. After 5 years, 476 obese patients maintained their clinical and dietary visits; 71.8% of MHO patients changed to unhealthy phenotypes (MHO-Progressors), whereas the MHO patients who maintained healthy phenotypes (MHO-Non-Progressors) lost more in terms of their body mass index (BMI) and had a lower fatty liver index (FLI-score) (p < 0.05). Most of the MUO (92%) patients maintained unhealthy phenotypes (MUO-Non-Responders), but 8% became metabolically healthy (MUO-Responders) after a significant decrease in their BMI and FLI-score, with improvement in all metabolic criteria. No differences were found among dietary groups. Conclusions: A greater loss of weight and liver fat is associated with a lower progression of the MHO phenotype to unhealthy phenotypes. Likewise, a marked improvement in these parameters is associated with regression from MUO to healthy phenotypes

Diet and SIRT1 Genotype Interact to Modulate Aging-Related Processes in Patients with Coronary Heart Disease: From the CORDIOPREV Study

We investigated whether long-term consumption of two healthy diets (low-fat (LF) or Mediterranean (Med)) interacts with SIRT1 genotypes to modulate aging-related processes such as leucocyte telomere length (LTL), oxidative stress (OxS) and inflammation in patients with coronary heart disease (CHD). LTL, inflammation, OxS markers (at baseline and after 4 years of follow-up) and SIRT1-Single Nucleotide Polymorphisms (SNPs) (rs7069102 and rs1885472) were determined in patients from the CORDIOPREV study. We analyzed the genotype-marker interactions and the effect of diet on these interactions. Regardless of the diet, we observed LTL maintenance in GG-carriers for the rs7069102, in contrast to carriers of the minor C allele, where it decreased after follow-up (p = 0.001). The GG-carriers showed an increase in reduced/oxidized glutathione (GSH/GSSG) ratio (p = 0.003), lower lipid peroxidation products (LPO) levels (p < 0.001) and a greater decrease in tumor necrosis factor-alpha (TNF-α) levels (p < 0.001) after follow-up. After the LF diet intervention, the GG-carriers showed stabilization in LTL which was significant compared to the C allele subjects (p = 0.037), although the protective effects found for inflammation and OxS markers remained significant after follow-up with the two diets. Patients who are homozygous for the SIRT1-SNP rs7069102 (the most common genotype) may benefit from healthy diets, as suggested by improvements in OxS and inflammation in patients with CHD, which may indicate the slowing-down of the aging process and its related diseases

Effect of a nutritional intervention based on an energy-reduced Mediterranean diet on environmental impact

[EN]To estimate the environmental impact of a dietary intervention based on an energy-reduced Mediterranean diet (MedDiet) after one year of follow-up. Methods Baseline and 1-year follow-up data were used for 5800 participants aged 55–75 years with metabolic syndrome in the PREDIMED-Plus study. Food intake was estimated through a validated semiquantitative food consumption frequency questionnaire, and adherence to the MedDiet was estimated through the Diet Score. Using the EAT-Lancet Commission tables we assessed the influence of dietary intake on environmental impact (through five indicators: greenhouse gas emissions (GHG), land use, energy used, acidification and potential eutrophication). Using multivariable linear regression models, the association between the intervention and changes in each of the environmental factors was assessed. Mediation analyses were carried out to estimate to what extent changes in each of 2 components of the intervention, namely adherence to the MedDiet and caloric reduction, were responsible for the observed reductions in environmental impact. Results We observed a significant reduction in the intervention group compared to the control group in acidification levels (−13.3 vs. -9.9 g SO2-eq), eutrophication (−5.4 vs. -4.0 g PO4-eq) and land use (−2.7 vs. -1.8 m2). Adherence to the MedDiet partially mediated the association between intervention and reduction of acidification by 15 %, eutrophication by 10 % and land use by 10 %. Caloric reduction partially mediated the association with the same factors by 55 %, 51 % and 38 % respectively. In addition, adherence to the MedDiet fully mediated the association between intervention and reduction in GHG emissions by 56 % and energy use by 53 %.SIPublicación en abierto financiada por el Consorcio de Bibliotecas Universitarias de Castilla y León (BUCLE), con cargo al Programa Operativo 2014ES16RFOP009 FEDER 2014-2020 DE CASTILLA Y LEÓN, Actuación:20007-CL - Apoyo Consorcio BUCL

Serum Magnesium is associated with Carotid Atherosclerosis in patients with high cardiovascular risk (CORDIOP REV Study)

This study aimed to ascertain whether there is an independent association between serum magnesium (Mg) and the Carotid Intima-Media Thickness (IMT-CC), a well-accepted atherosclerotic-biomarker surrogate of cardiovascular disease (CVD), in a population with high cardiovascular risk. Serum Mg and traditional atherosclerotic risk factors were recorded in 939 patients (mean age, 59.6 ± 0.3 years, 83.2% men) with coronary heart disease (CHD) enrolled in the CORDIOPREV trial. Serum Mg strongly associated with IMT-CC. Before adjusting for potential confounding factors, IMT-CC decreased by 0.111 ± 0.011 mm per mg/dl increase in serum Mg (p < 0.001). After adjustment, the effect of Mg did not appear mediated through factors related to glucose metabolism, the lipid profile or the mineral metabolism and renal function. Multivariate models showed the lower Mg levels (quartile 1) as a strong independent factor contributing to IMT-CC along with age, sex, SBP, HDL-C, and diuretic use. Logistic regression analysis confirmed the predictive ability of serum Mg to differentiate patients at higher atherosclerotic risk as defined by an IMT-CC ≥ 1.0 mm, yielding a OR for the lower quartile of 10.623 (95%CI 2.311–48.845; P = 0.002) and a ROC-derived cutoff of 1.61 mg/dl. Therefore, our findings outline low serum magnesium as a possible independent risk factor for carotid atherosclerosis.We would like to thank the EASP (Escuela Andaluza de Salud Publica), Granada, Spain, who performed the randomization process for this study. The CORDIOPREV study is supported by Fundacion Patrimonio Comunal Olivarero. CITOLIVA and CEAS, Consejeria de Economia, Innovacion y Ciencia (CVI-7450); Ministerio de Economia (AGL2015-67896-P, PIE14/00005, PIE14/00031); Instituto de Salud Carlos III (FIS 14/00872; FIS 17/01024), co-funded with FEDER (European Regional Development Fund). Y. A. is supported by Nicolas Monardes Programme, Consejeria de Salud-SAS. CIBEROBN is an initiative of Instituto de Salud Carlos III