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Statins in Non-alcoholic Steatohepatitis.
Torres-Peña, JD, Martín-Piedra, L, Fuentes-Jiménez, F
Frontiers in cardiovascular medicine. 2021;:777131
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the primary cause of chronic liver disease. The range is extensive, including hepatocellular carcinoma, cirrhosis, fibrosis, fatty liver, and non-alcoholic steatohepatitis (NASH). NASH is a condition related to obesity, overweight, metabolic syndrome, diabetes, and dyslipidemia. It is a dynamic condition that can regress to isolated steatosis or progress to fibrosis and cirrhosis. Statins exert anti-inflammatory, proapoptotic, and antifibrotic effects. It has been proposed that these drugs could have a relevant role in NASH. In this review, we provide an overview of current evidence, from mechanisms of statins involved in the modulation of NASH to human trials about the use of statins to treat or attenuate NASH.
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Prior Treatment with Statins is Associated with Improved Outcomes of Patients with COVID-19: Data from the SEMI-COVID-19 Registry.
Torres-Peña, JD, Pérez-Belmonte, LM, Fuentes-Jiménez, F, López Carmona, MD, Pérez-Martinez, P, López-Miranda, J, Carrasco Sánchez, FJ, Vargas Núñez, JA, Del Corral Beamonte, E, Magallanes Gamboa, JO, et al
Drugs. 2021;(6):685-695
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Abstract
BACKGROUND The impact of statins on COVID-19 outcomes is important given the high prevalence of their use among individuals at risk for severe COVID-19. Our aim is to assess whether patients receiving chronic statin treatment who are hospitalized with COVID-19 have reduced in-hospital mortality if statin therapy is maintained during hospitalization. METHODS This work is a cross-sectional, observational, retrospective multicenter study that analyzed 2921 patients who required hospital admission at 150 Spanish centers included in the nationwide SEMI-COVID-19 Network. We compared the clinical characteristics and COVID-19 disease outcomes between patients receiving chronic statin therapy who maintained this therapy during hospitalization versus those who did not. Propensity score matching was used to match each statin user whose therapy was maintained during hospitalization to a statin user whose therapy was withdrawn during hospitalization. RESULTS After propensity score matching, continuation of statin therapy was associated with lower all-cause mortality (OR 0.67, 0.54-0.83, p < 0.001); lower incidence of acute kidney injury (AKI) (OR 0.76,0.6-0.97, p = 0.025), acute respiratory distress syndrome (ARDS) (OR 0.78, 0.69- 0.89, p < 0.001), and sepsis (4.82% vs 9.85%, p = 0.008); and less need for invasive mechanical ventilation (IMV) (5.35% vs 8.57, p < 0.001) compared to patients whose statin therapy was withdrawn during hospitalization. CONCLUSIONS Patients previously treated with statins who are hospitalized for COVID-19 and maintain statin therapy during hospitalization have a lower mortality rate than those in whom therapy is withdrawn. In addition, statin therapy was associated with a decreased probability that patients with COVID-19 will develop AKI, ARDS, or sepsis and decreases the need for IMV.
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Mortality and other adverse outcomes in patients with type 2 diabetes mellitus admitted for COVID-19 in association with glucose-lowering drugs: a nationwide cohort study.
Pérez-Belmonte, LM, Torres-Peña, JD, López-Carmona, MD, Ayala-Gutiérrez, MM, Fuentes-Jiménez, F, Jorge Huerta, L, Muñoz, JA, Rubio-Rivas, M, Madrazo, M, Garcia, MG, et al
BMC medicine. 2020;(1):359
Abstract
BACKGROUND Limited evidence exists on the role of glucose-lowering drugs in patients with COVID-19. Our main objective was to examine the association between in-hospital death and each routine at-home glucose-lowering drug both individually and in combination with metformin in patients with type 2 diabetes mellitus admitted for COVID-19. We also evaluated their association with the composite outcome of the need for ICU admission, invasive and non-invasive mechanical ventilation, or in-hospital death as well as on the development of in-hospital complications and a long-time hospital stay. METHODS We selected all patients with type 2 diabetes mellitus in the Spanish Society of Internal Medicine's registry of COVID-19 patients (SEMI-COVID-19 Registry). It is an ongoing, observational, multicenter, nationwide cohort of patients admitted for COVID-19 in Spain from March 1, 2020. Each glucose-lowering drug user was matched with a user of other glucose-lowering drugs in a 1:1 manner by propensity scores. In order to assess the adequacy of propensity score matching, we used the standardized mean difference found in patient characteristics after matching. There was considered to be a significant imbalance in the group if a standardized mean difference > 10% was found. To evaluate the association between treatment and study outcomes, both conditional logit and mixed effect logistic regressions were used when the sample size was ≥ 100. RESULTS A total of 2666 patients were found in the SEMI-COVID-19 Registry, 1297 on glucose-lowering drugs in monotherapy and 465 in combination with metformin. After propensity matching, 249 patients on metformin, 105 on dipeptidyl peptidase-4 inhibitors, 129 on insulin, 127 on metformin/dipeptidyl peptidase-4 inhibitors, 34 on metformin/sodium-glucose cotransporter 2 inhibitor, and 67 on metformin/insulin were selected. No at-home glucose-lowering drugs showed a significant association with in-hospital death; the composite outcome of the need of intensive care unit admission, mechanical ventilation, or in-hospital death; in-hospital complications; or long-time hospital stays. CONCLUSIONS In patients with type 2 diabetes mellitus admitted for COVID-19, at-home glucose-lowering drugs showed no significant association with mortality and adverse outcomes. Given the close relationship between diabetes and COVID-19 and the limited evidence on the role of glucose-lowering drugs, prospective studies are needed.
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[Diagnosis and treatment of familial hypercholesterolemia in Spain: consensus document].
Mata, P, Alonso, R, Ruiz, A, Gonzalez-Juanatey, JR, Badimón, L, Díaz-Díaz, JL, Muñoz, MT, Muñiz, O, Galve, E, Irigoyen, L, et al
Atencion primaria. 2015;(1):56-65
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Abstract
Familial hypercholesterolemia (FH) is a common genetic disorder, clinically manifested since birth, and associated with very high levels of plasma LDL-cholesterol (LDL-c), xanthomas, and premature coronary heart disease. Its early detection and treatment reduces coronary morbidity and mortality. Despite effective treatment being available, FH is under-diagnosed and under-treated. Identification of index cases and cascade screening using LDL-c levels and genetic testing are the most cost-effective strategies for detecting new cases and starting early treatment. Long-term treatment with statins has decreased the vascular risk to the levels of the general population. LDL-c targets are < 130 mg/dL for children and young adults, <100mg/dL for adults, and < 70 mg/dL for adults with known coronary heart disease or diabetes. Most patients do not to reach these goals, and combined treatments with ezetimibe or other drugs may be necessary. When the goals are not achieved with the maximum tolerated drug treatment, a reduction ≥ 50% in LDL-c levels can be acceptable. Lipoprotein apheresis can be useful in homozygous, and in treatment-resistant severe heterozygous, cases. This Consensus Paper gives recommendations on the diagnosis, screening, and treatment of FH in children and adults, and specific advice to specialists and general practitioners with the objective of improving the clinical management of these patients, in order to reduce the high burden of coronary heart disease.
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Lipoprotein(a) levels in familial hypercholesterolemia: an important predictor of cardiovascular disease independent of the type of LDL receptor mutation.
Alonso, R, Andres, E, Mata, N, Fuentes-Jiménez, F, Badimón, L, López-Miranda, J, Padró, T, Muñiz, O, Díaz-Díaz, JL, Mauri, M, et al
Journal of the American College of Cardiology. 2014;(19):1982-9
Abstract
OBJECTIVES The aim of this study was to determine the relationship between lipoprotein(a) [Lp(a)] and cardiovascular disease (CVD) in a large cohort of patients with heterozygous familial hypercholesterolemia (FH). BACKGROUND Lp(a) is considered a cardiovascular risk factor. Nevertheless, the role of Lp(a) as a predictor of CVD in patients with FH has been a controversial issue. METHODS A cross-sectional analysis of 1,960 patients with FH and 957 non-FH relatives recruited for SAFEHEART (Spanish Familial Hypercholesterolemia Cohort Study), a long-term observational cohort study of a molecularly well-defined FH study group, was performed. Lp(a) concentrations were measured in plasma using an immunoturbidimetric method. RESULTS Patients with FH, especially those with CVD, had higher Lp(a) plasma levels compared with their unaffected relatives (p < 0.001). A significant difference in Lp(a) levels was observed when the most frequent null and defective mutations in LDLR mutations were analyzed (p < 0.0016). On multivariate analysis, Lp(a) was an independent predictor of cardiovascular disease. Patients carrying null mutations and Lp(a) levels >50 mg/dl showed the highest cardiovascular risk compared with patients carrying the same mutations and Lp(a) levels <50 mg/dl. CONCLUSIONS Lp(a) is an independent predictor of CVD in men and women with FH. The risk of CVD is higher in those patients with an Lp(a) level >50 mg/dl and carrying a receptor-negative mutation in the LDLR gene compared with other less severe mutations.
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Early diagnosis and treatment of familial hypercholesterolemia: improving patient outcomes.
Alonso, R, Mata, P, Zambón, D, Mata, N, Fuentes-Jiménez, F
Expert review of cardiovascular therapy. 2013;(3):327-42
Abstract
Familial hypercholesterolemia (FH) is the most frequent inherited disorder associated with premature coronary artery disease. Early identification and treatment of patients will reduce cardiovascular outcomes. Identification of index cases and then cascade testing in first-degree relatives using lipid levels and genetic test is the most cost-effective strategy implemented in some countries. FH patients are considered at high cardiovascular risk. Imaging techniques such as coronary computed tomography angiography could identify subjects that will require more intensive treatments. Recent guidelines recommend an LDL-C below 100 mg/dl or at least 50% LDL-C reduction if the first goal is not attained as treatment targets in heterozygous FH. Statins are the first-line agents in almost all patients, and several options exist to obtain larger LDL-C reductions like the addition of ezetimibe and/or colesevelam. Novel agents like microsomal triglyceride transfer protein inhibitors, apolipoprotein B100 antisense or PCSK9-specific monoclonal antibodies, if approved by regulatory agencies, will reduce LDL-C levels and potentially reduce cardiovascular risk in homozygous and severe heterozygous FH patients.
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Mediterranean diet, moderate-to-high intensity training, and health-related quality of life in adults with metabolic syndrome.
Landaeta-Díaz, L, Fernández, JM, Da Silva-Grigoletto, M, Rosado-Alvarez, D, Gómez-Garduño, A, Gómez-Delgado, F, López-Miranda, J, Pérez-Jiménez, F, Fuentes-Jiménez, F
European journal of preventive cardiology. 2013;(4):555-64
Abstract
BACKGROUND Much recent research has focused on the benefits of the Mediterranean diet on risk factors of metabolic syndrome (MetS). In addition numerous investigations have also demonstrated that moderate and high-intensity endurance training may induce greater beneficial adaptations in body composition and cardiometabolic risk than low-intensity endurance training. How a model of Mediterranean diet with and without moderate-to-high intensity training influences health-related quality of life (HRQoL) and physical fitness in MetS patients is unknown. DESIGN AND METHODS A total of 45 sedentary MetS males and females (50⊟66 years) were randomly divided into two groups: (a) hypocaloric, normoproteic Mediterranean diet (MeD); and (b) the same diet plus periodized moderate-to-high intensity training (MeDE) for 12 weeks. HRQoL (EuroQol and SF-36 questionnaires), fitness, response to submaximal exercise, and risk factors of MetS were determined before and after treatment. RESULTS MeD improved some physical and mental domains of HRQoL (physical function, vitality, general physical health, emotional role, and self-perception of health) and resulted in weight loss and improvement of MetS risk factors (intra-group p < 0.05). Moreover, the MeDE intervention resulted in greater improvement in these domains and the improvement of other HRQoL components (physical role, bodily pain, social function, and health profile). MeDE increased physical fitness, resulted in a better physiological response to submaximal effort and caused a greater weight loss (intra-group and inter-group, p < 0.05). CONCLUSIONS A model of hypocaloric Mediterranean diet combined with periodized moderate-to-high intensity training may lead to greater improvement in HRQoL through a greater effect on physical and functional fitness, bodyweight, and risk factors than diet alone.
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Moderate-to-high-intensity training and a hypocaloric Mediterranean diet enhance endothelial progenitor cells and fitness in subjects with the metabolic syndrome.
Fernández, JM, Rosado-Álvarez, D, Da Silva Grigoletto, ME, Rangel-Zúñiga, OA, Landaeta-Díaz, LL, Caballero-Villarraso, J, López-Miranda, J, Pérez-Jiménez, F, Fuentes-Jiménez, F
Clinical science (London, England : 1979). 2012;(6):361-73
Abstract
A reduction in EPC (endothelial progenitor cell) number could explain the development and progression of atherosclerosis in the MetS (metabolic syndrome). Although much research in recent years has focused on the Mediterranean dietary pattern and the MetS, the effect of this diet with/without moderate-to-high-intensity endurance training on EPCs levels and CrF (cardiorespiratory fitness) remains unclear. In the present study, the objective was to assess the effect of a Mediterranean diet hypocaloric model with and without moderate-to-high-intensity endurance training on EPC number and CrF of MetS patients. Thus 45 MetS patients (50-66 years) were randomized to a 12-week intervention with the hypocaloric MeD (Mediterranean diet) or the MeDE (MeD plus moderate-to-high-intensity endurance training). Training included two weekly supervised sessions [80% MaxHR (maximum heart rate); leg and arm pedalling] and one at-home session (65-75% MaxHR; walking controlled by heart rate monitors). Changes in: (i) EPC number [CD34(+)KDR(+) (kinase insert domain-containing receptor)], (ii) CrF variables and (iii) MetS components and IRH (ischaemic reactive hyperaemia) were determined at the end of the study. A total of 40 subjects completed all 12 weeks of the study, with 20 in each group. The MeDE led to a greater increase in EPC numbers and CrF than did the MeD intervention (P ≤ 0.001). In addition, a positive correlation was observed between the increase in EPCs and fitness in the MeDE group (r=0.72; r(2)=0.52; P ≤ 0.001). Body weight loss, insulin sensitivity, TAGs (triacylglycerols) and blood pressure showed a greater decrease in the MeDE than MeD groups. Furthermore, IRH was only improved after the MeDE intervention. In conclusion, compliance with moderate-to-high-intensity endurance training enhances the positive effects of a model of MeD on the regenerative capacity of endothelium and on the fitness of MetS patients.