Evaluación del riesgo cardiovascular en pacientes con disrupción del ritmo circadiano en prevención secundaria, en pacientes sometidos a una intervención dietéticas (dieta mediterránea o dieta baja en grasas)

Background: Cardiovascular disease continues to be a major cause of morbidity and mortality. Despite several efforts to control and management traditional risk factor by physicians, researchers and governments it is not enough to reduce the cardiovascular burden. Chronodisruption has emerged as a novel risk factor linked for cardiovascular diseases. In this order, certain population have demonstrated to be prone to suffer chronodisruption such as shift workers or evening subjects. Thus, evening subjects have showed to have unhealthy lifestyle habits with later meal timing, activity and sleep timing, potential mechanisms associated with the high cardiometabolic risk linked to evening subjects. Our hypothesis was demonstrated that those patients prone to suffer circadian rhythm disruption (i.e. evening chronotype) with unhealthy lifestyle habits, present higher cardiometabolic risk based in greater endothelial dysfunction and increased cardiometabolic and inflammatory markers. Objectives: Main objective: - To investigate whether patients in secondary prevention with a disruption of the circadian rhythm (unregulated sleep pattern, physical activity and an unusual meal schedule) have, at baseline, greater endothelial dysfunction as measured by flow-mediated vasodilation (FMD) of the brachial artery. Secondary objectives: - To determine whether participants following a Mediterranean diet with 35% of daily calories from fat (22% monounsaturated fat) or a low-fat diet with 28% of daily calories from fat (12% monounsaturated fat) for three years will improve endothelial function in participants with disruption of circadian rhythm. - To determine whether the disruption of the circadian rhythm is associated with increased inflammatory markers (C-reactive protein (CRP), Interleukins). - To investigate whether whose participants with a disruption of the circadian rhythm show a higher oxidative stress. Material and methods: The CORDIOPREV study is a randomized single-blind, controlled dietary intervention trial in coronary heart diseases (CHD) patients. The models of diet intervention included in the CORDIOPREV study were: the Mediterranean diet, with a minimum 35% of calories as fat (22% monounsaturated fatty acids (MUFA)) and a maximum of 50% carbohydrates and the low-fat diet comprising of <30% total fat (12%-14% MUFA fat), and a minimum 55% carbohydrates. The chronotype was assessed using the Morningness-Eveningness questionnaire in 857 participants from the CORDIOPREV study. At the beginning of the CORDIOPREV study and after 1,5 years, the flow mediated vasodilation in the brachial artery was assessed. Lifestyle habits were obtained through questionnaire at baseline of the study and yearly. Meal and sleep timing of one-week duration were collected during first years of the study. Baseline and annual visits included blood samples, blood pressure and anthropometric measures. In a sub-set of participants (n=168) ambulatory circadian monitoring were recorded and non-parametric analyses were used to calculate circadian-related parameters. Results: There were no significant differences in endothelial dysfunction according to chronotype at baseline either after 1.5 years of a healthy dietary intervention. No differences were found between the two models of diet. However, evening subjects demonstrated high cardiovascular risk with higher cardiometabolic and inflammatory markers such as HDL-C (p 0.04), homocysteine (p<0.01), hs-CRP (p 0.01) and triglycerides (p<0.01) at baseline of the study and during the four first year of the follow-up despite a healthy dietary intervention compared to morning subjects. Also, evening subjects had a higher prevalence of MetS (OR 1.58 IC 95% [1.10-2.28], p 0.01). Differences in several lifestyle habits according to chronotype were found. Thus, evening subjects were less active (p 0.01) and more sedentary (p<0.01), evening subjects had later meal timing of three main meals (p<0.01) and later sleep timing (p 0.01) and longer sleep duration (p 0.02) than morning subjects. In the sub-set of participants that the ambulatory circadian monitoring was performed, evening subjects showed lower amplitude (p=0.04), greater fragmentation (p=0.04), less stable pattern day to day (p<0.01), and lower robustness (p<0.01) of the TAP rhythms and lower regular habits (p<0.01) compared to morning subjects. A correlation of the lifestyle factors and circadian-related parameters with cardiometabolic and inflammatory markers were demonstrated. Conclusions: Our findings showed that evening individuals with preexisting CHD had a higher cardiometabolic risk due to their propensity for chronodisruption. Evening subjects has worse lifestyles factors and circadian health compared to morning subjects that could influence as potential mechanism of the high cardiometabolic risk found. Our finding support to assess chronotype in high-risk population to target personalized and tailoring recommendations and reduce their cardiovascular burden.Introducción: Las enfermedades cardiovasculares continúan siendo la principal causa de morbilidad y mortalidad. A pesar de numerosos esfuerzos para controlar y manejar los factores de riesgo tradicional por los médicos, investigadores y políticos, esto no es suficiente para reducir la carga cardiovascular. La cronodisrupción ha emergido como un novedoso factor de riesgo ligado a las enfermedades cardiovasculares. En este sentido, cierta población ha demostrado ser propensa a sufrir cronodisrupción tanto como trabajadores por turnos o sujetos vespertinos. Así, los sujetos vespertinos han mostrado tener unos hábitos de vida no saludables con un horario de alimentación, actividad y sueño más tardío, mecanismos potencialmente asociados con un elevado riesgo cardiometabólico. Nuestra hipótesis era demostrar que aquellos pacientes propensos a sufrir disrupción del ritmo circadiano (es decir cronotipo vespertino) con hábitos de vida no saludable, presenta un mayor riesgo cardiometabólico basado en una mayor disfunción endotelial y un incremento en los marcadores cardiometabólico e inflamatorios. Objetivos: Objetivo principal: - Investigar si pacientes en prevención secundaria con una disrupción del ritmo circadiano (patrón del sueño no regulado, actividad física y un horario fuera de lo habitual de comidas) tienen en una situación basal, mayor disfunción endotelial medida mediante VMF de la arteria braquial. - Analizar si en aquellos pacientes con una disrupción del ritmo circadiano, el seguimiento de dos dietas cardiosaludables durante 3 años, una dieta mediterránea con un 35% de calorías en forma de grasa (22% de grasa monoinsaturada), o una dieta baja en grasa con un 28% de calorías en forma de grasa (12% de grasa monoinsaturada) mejoran la función endotelial. - Investigar si la disrupción del ritmo circadiano lleva apareado un aumento de marcadores inflamatorios (PCR, Interleucinas). - Analizar si aquellos pacientes con una disrupción del ritmo circadiano presentan mayor estrés oxidativo. Material y métodos: El estudio CORDIOPREV es un estudio aleatorizado simple ciego, con una intervención dietética controlada en pacientes con enfermedad coronaria establecida. Los modelos de dieta incluidos en el estudio CORDIOPREV fueron: la dieta mediterránea, con un mínimo de 35% de calorías como grasa (22% ácidos grasos monoinsaturados) y un máximo de 50% de carbohidratos y la dieta baja en grasa compuesta de <30% total de grasa (12-14% ácidos grasos monoinsaturados), y un mínimo de 55% de carbohidratos. El cronotipo fue evaluado usando el cuestionario de matutinidad-vespertinidad en 857 participantes del estudio CORDIOPREV. Al comienzo del estudio CORDIOPREV y al 1,5 año, fue evaluado la vasodilatación mediada por flujo en la arteria braquial. Los hábitos de vida fueron obtenidos a través de cuestionarios en el basal y cada año del estudio. El horario de alimentación y sueño de una semana fueron recogidos a lo largo de los primeros años del estudio. Las visitas basales y anuales incluyeron muestras sanguíneas, toma de presión arterial y medidas antropométricas. En un subconjunto de participantes (n=168) se realizó una monitorización circadiana ambulatoria, y análisis no paramétricos fueron usados para calcular parámetros de salud circadianos. Resultados: No hubo diferencias significativas en la disfunción endotelial en función del cronotipo ni basalmente ni tras 1,5 años de una intervención dietética saludable. No hubo diferencias entre ambos modelos de dietas. Sin embrago, los sujetos vespertinos comparado con los sujetos matutinos demostraron un alto riesgo cardiovascular con mayores niveles de marcadores cardiometabólico e inflamatorios como HDL- colesterol (p 0.04), homocisteína (p<0.01), hs-CRP (p 0.01) y triglicéridos (<0.01) basalmente en el estudio y durante los primeros cuatro años de seguimiento a pesar de una intervención dietética saludable. También, los sujetos vespertinos tuvieron una mayor prevalencia de síndrome metabólico (OR 1.58 IC 95% [1.10-2.28], p 0.01). Hubo diferencias en multitud de hábitos de vida de acuerdo al cronotipo. Así, los sujetos vespertinos comparado con los sujetos matutinos fueron menos activos (p 0.01) y más sedentarios (p<0.01), los sujetos vespertinos tuvieron horarios más tardíos de las tres principales comidas (p<0,01) y de sueño (p 0.01), y una duración del sueño mayor (p 0.02). En el subconjunto de participantes en el que se realizó la monitorización circadiana continua, los sujetos vespertinos mostraron en comparación a los sujetos matutinos una menor amplitud (p=0.04), una mayor fragmentación (p=0.04), un patrón menos estable día a día (p<0.01), y una menor robustez de los ritmos de TAP, así como unos hábitos menos regulares (p<0.01). Se demostró que existía una correlación de los factores de estilo de vida y los parámetros de salud circadiana con los marcadores cardiometabólico e inflamatorios. Conclusiones: Nuestros hallazgos muestran que los sujetos vespertinos con antecedentes de enfermedad coronaria tienen un mayor riesgo cardiometabólico debido a su propensión a la cronodisrupción. Los sujetos vespertinos tienen peores factores de estilo de vida y salud circadiana que los sujetos matutinos, que podría influir como un mecanismo potencial del alto riesgo cardiometabólico que muestran. Nuestros hallazgos apoyan evaluar el cronotipo en una población de alto riesgo para realizar recomendaciones personalizadas y ajustadas y reducir su carga cardiovascular

Daylight Saving Time transitions and Cardiovascular Disease in Andalusia: Time Series Modeling and Analysis Using Visibility Graphs

The present study aimed to determine whether transitions both to and from daylight saving time (DST) led to an increase in the incidence of hospital admissions for major acute cardiovascular events (MACE). To support the analysis, natural visibility graphs (NVGs) were used with data from Andalusian public hospitals between 2009 and 2019. We calculated the incidence rates of hospital admissions for MACE, and specifically acute myocardial infarction and ischemic stroke during the 2 weeks leading up to, and 2 weeks after, the DST transition. NVG were applied to identify dynamic patterns. The study included 157 221 patients diagnosed with MACE, 71 992 with AMI (42 975 ST-elevation myocardial infarction (STEMI) and 26 752 non-ST-elevation myocardial infarction (NSTEMI)), and 51 420 with ischemic stroke. Observed/expected ratios shown an increased risk of AMI (1.06; 95% CI (1.00–1.11); P = .044), NSTEMI (1.12; 95% CI (1.02–1.22); P = .013), and acute coronary syndrome (1.05; 95% CI (1.00–1.10); P = .04) around the autumn DST. The NVG showed slight variations in the daily pattern of pre-DST and post-DST hospitalization admissions for all pathologies, but indicated that the increase in the incidence of hospital admissions after the DST is not sufficient to change the normal pattern significantly

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

COVID-19 pandemic on coronary artery and cerebrovascular diseases in Southern Spain: interrupted time series analysis

OBJECTIVE: Healthcare systems have been put under intense pressure by the COVID-19 pandemic, although some studies have shown a decline in hospital admissions for cardiovascular and cerebrovascular diseases during the first and second wave of the pandemic. In addition, studies analyzing gender and procedural differences are scarce. The present study aimed to determine the impact of the pandemic on hospital admissions for acute myocardial infarction (AMI) and cerebrovascular disease (CVD) in Andalusia (Spain) and analyzed differences by gender and by percutaneous coronary interventions performed. PATIENTS AND METHODS: An interrupted time series analysis of AMI and CVD hospital admissions in Andalusia (Spain) was carried out to measure the impact of the COVID-19 outbreak. AMI and CVD cases admitted daily in public hospitals of Andalusia between January 2018 and December 2020 were included. RESULTS: During the pandemic, significant reductions in AMI [-19%; 95% confidence interval (CI): (-29%, -9%), p<0.001] and CVD [-17%; 95% CI: (-26%, -9%); p<0.01] in daily hospital admissions were observed. Differences were also produced according to the diagnosis (ST-Elevation Myocardial Infarction, Non-ST-Elevation Myocardial Infarction, other AMI and stroke), with a greater reduction in females for AMI and in males for CVD. Although there were more percutaneous coronary interventions during the pandemic, no significant reductions were observed

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

A plasma fatty acid profile associated to type 2 diabetes development: from the CORDIOPREV study

Purpose: The prevalence of type 2 diabetes mellitus (T2DM) is increasing worldwide. For this reason, it is essential to identify biomarkers for the early detection of T2DM risk and/or for a better prognosis of T2DM. We aimed to identify a plasma fatty acid (FA) profile associated with T2DM development. Methods: We included 462 coronary heart disease patients from the CORDIOPREV study without T2DM at baseline. Of these, 107 patients developed T2DM according to the American Diabetes Association (ADA) diagnosis criteria after a median follow-up of 60 months. We performed a random classification of patients in a training set, used to build a FA Score, and a Validation set, in which we tested the FA Score. Results: FA selection with the highest prediction power was performed by random survival forest in the Training set, which yielded 4 out of the 24 FA: myristic, petroselinic, α-linolenic and arachidonic acids. We built a FA Score with the selected FA and observed that patients with a higher score presented a greater risk of T2DM development, with an HR of 3.15 (95% CI 2.04–3.37) in the Training set, and an HR of 2.14 (95% CI 1.50–2.84) in the Validation set, per standard deviation (SD) increase. Moreover, patients with a higher FA Score presented lower insulin sensitivity and higher hepatic insulin resistance (p < 0.05). Conclusión: Our results suggest that a detrimental FA plasma profile precedes the development of T2DM in patients with coronary heart disease, and that this FA profile can, therefore, be used as a predictive biomarker

Recensiones [Revista de Historia Económica, Año IV, Otoño 1986, n. 3 pp. 653-684]

Alberto e Branislava Tenenti. Il prezzo del rischio. L'assicurazione mediterránea vista da Ragusa (1563-1591) (Por Carlos Martínez Shaw).-- Henry George. Progreso y Miseria (Por Lucas Beltrán).-- Jean-Francois Bergier. Histoire économique de la Suisse (Por Gregorio Núñez Romero-Balmas).-- José Barrientos García. Un siglo de moral económica en Salamanca (1526-1629). I. Francisco de Vitoria y Domingo de Soto (Por Luis Perdices Blas).-- Colin M. Winston. Workers and the Right in Spain, 1900-1936 (Por Mercedes Cabrera).-- Pedro Carasa Soto. El sistema hospitalario español en el siglo XIX (Por Alicia Eva Kaufmann).-- María Teresa Pérez Picazo y Guy Lemeunier. El proceso de modernización en la región murciana (siglos XVI-XIX) (Por Juan A. Sánchez Belén).-- Pablo Campos Palacín. Economía y energía en la dehesa extremeña (Por Santiago Zapata Blanco).-- José Antonio Biescas Ferrer. El proceso de industrialización en la región aragonesa en el periodo 1900-1920 (Por Luis Germán Zubero).-- Dolores García Cantús. El gremio de plateros de Valencia en los siglos XVIII y XIX (Por Enrique Mateu Tortosa).-- Josep M.ª Llobet Portella. La «Taula de Canvi» de Cervera y su entorno socioeconómico (1599-1715) (Por Gaspar Feliú)Publicad

Changes in quantity plant‑based protein intake on type 2 diabetes remission in coronary heart disease patients: from the CORDIOPREV study

Purpose: Diabetes remission is a phenomenon described in the context of drastic weight loss due to bariatric surgery or low-calorie diets. Evidence suggests that increasing the intake of plant protein could reduce the risk of type 2 diabetes. We sought for association between changes in plant protein intake in the context of 2 healthy diets without weight loss nor glucose-lowering medication, and diabetes remission in coronary heart disease patients from the CORDIOPREV study. Methods: Newly diagnosed type 2 diabetes participants without glucose-lowering treatment were randomized to consume a Mediterranean or a low-fat diet. Type 2 diabetes remission was assessed with a median follow-up of 60 months according to the ADA recommendation. Information on patient's dietary intake was collected using food-frequency questionnaires. At first year of intervention, 177 patients were classified according to changes in plant protein consumption into those who increased or decreased its intake, in order to perform an observational analysis on the association between protein intake and diabetes remission. Results: Cox regression showed that patients increasing plant protein intake were more likely to remit from diabetes than those who decreased its intake (HR = 1.71(1.05–2.77)). The remission occurred mainly at first and second year of follow-up with diminished number of patients achieving remission in the third year onwards. The increase in plant protein was associated with lower intake of animal protein, cholesterol, saturated fatty acids, and fat, and with higher intake of whole grains, fibre, carbohydrates, legumes, and tree nuts. Conclusión: These results support the need to increase protein intake of vegetal origin as dietary therapy to reverse type 2 diabetes in the context of healthy diets without weight loss

Prevalence of bleeding secondary to anticoagulation and mortality in patients with atrial fibrillation admitted with SARS-CoV-2 infection.

Atrial fibrillation (AF) is common in patients admitted with severe COVID-19. However, there is limited data about the management of chronic anticoagulation therapy in these patients. We assessed the anticoagulation and incidence of major cardiovascular events in hospitalized patients with AF and COVID-19. We retrospectively investigated all consecutive patients with AF admitted with COVID-19 between March and May 2020 in 9 Spanish hospitals. We selected a control group of non-AF patients consecutively admitted with COVID-19. We compared baseline characteristics, incidence of major bleeding, thrombotic events and mortality. We used propensity score matching (PSM) to minimize potential confounding variables, as well as a multivariate analysis to predict major bleeding and death. 305 patients admitted with AF and COVID-19 were included. After PSM, 151 AF patients were matched with 151 control group patients. During admission, low-molecular-weight heparin was the principal anticoagulant and the incidence of major bleeding and mortality were higher in the AF group [16 (10.6%) vs 3 (2%), p=0.003; 52 (34.4%) vs 35 (23.2%), p=0.03, respectively]. The multivariate analysis showed the presence of AF as independent predictor of in-hospital major bleeding and mortality in COVID-19 patients. In AF group, a secondary multivariate analysis identified high levels of D-dimer as independent predictor of in-hospital major bleeding. AF patients admitted with COVID-19 represent a population at high risk for bleeding and mortality during admission. It seems advisable to individualize anticoagulation therapy during admission, considering patient specific bleeding and thrombotic risk.S

Effects of a healthy lifestyle intervention and COVID-19-adjusted training curriculum on firefighter recruits

There are knowledge gaps regarding healthy lifestyle (HLS) interventions in fire academy settings and also concerning the impacts of the pandemic on training. We enrolled fire recruits from two fire academies (A and B) in New England in early 2019 as the historical control group, and recruits from academies in New England (B) and Florida (C), respectively, during the pandemic as the intervention group. The three academies have similar training environments and curricula. The exposures of interest were a combination of (1) an HLS intervention and (2) impacts of the pandemic on training curricula and environs (i.e. social distancing, masking, reduced class size, etc.). We examined the health/fitness changes throughout training. The follow-up rate was 78%, leaving 92 recruits in the historical control group and 55 in the intervention group. The results show an HLS intervention improved the effects of fire academy training on recruits healthy behaviors (MEDI-lifestyle score, 0.5 ± 1.4 vs. - 0.3 ± 1.7), systolic blood pressure (- 7.2 ± 10.0 vs. 2.9 ± 12.9 mmHg), and mental health (Beck Depression score, - 0.45 ± 1.14 vs. - 0.01 ± 1.05) (all P < 0.05). The associations remained significant after multivariable adjustments. Moreover, a 1-point MEDI-lifestyle increment during academy training is associated with about 2% decrement in blood pressures over time, after multivariable adjustments (P < 0.05). Nonetheless, the impacts of pandemic restrictions on academy procedures compromised physical fitness training, namely in percent body fat, push-ups, and pull-ups