Projected effectiveness of dapagliflozin in heart failure with reduced ejection fraction in clinical practice.

Aim: To estimate the projected effectiveness of dapagliflozin in subjects with heart failure (HF) with reduced ejection fraction in clinical practice in Spain. Materials & methods: This multicenter cohort study included subjects aged 50 years or older consecutively hospitalized for HF in internal medicine departments in Spain. The projected clinical benefits of dapagliflozin were estimated based on results from the DAPA-HF trial. Results: A total of 1595 patients were enrolled, of whom 1199 (75.2%) were eligible for dapagliflozin. Within 1 year after discharge, 21.6% of patients eligible for dapagliflozin were rehospitalized for HF and 20.5% died. Full implementation of dapagliflozin led to an absolute risk reduction of 3.5% for mortality (number needed to treat = 28) and 6.5% (number needed to treat = 15) for HF readmission. Conclusion: Treatment with dapagliflozin in clinical practice may markedly reduce mortality and readmissions for HF.

Heart failure with reduced ejection fraction is a severe disease with a high risk of hospitalization and mortality. With this condition, the heart muscle cannot pump properly. This means that not enough blood is pumped from the heart, reducing the amount of oxygen to the body. Fortunately, there are treatments that reduce this risk, in patients with heart failure. SGLT2 inhibitors, including dapagliflozin, are among the first therapies given to patients with heart failure. In this study, we investigated the potential benefits of adding dapagliflozin to the treatment of patients admitted to the hospital in Spain for heart failure with reduced ejection fraction. Our data showed that dapagliflozin was able to reduce the risk of further events (e.g., heart attack) in these patients.

Recommendations for the care of patients with cardiovascular disease in health emergency situations: a call to action.

COVID-19 has had a negative impact on the health care of patients with cardiovascular disease and patients at high risk of cardiovascular disease. The restrictions affecting access to the health care system have conditioned the care received, resulting in poorer control and a higher risk of events. Taking action to improve the care provided during health emergencies is mandatory. It is important to promote the development of telemedicine and patient empowerment by fostering health literacy and a higher degree of self-care. In addition, primary care and coordination between health care levels should be improved. Moreover, the simplification and optimization of treatment, for example, using the cardiovascular polypill, have led to an improvement in adherence, better control of vascular risk factors, and a reduced risk of events. The present document provides specific recommendations for improving the care provided to patients under a health emergency.

Alirocumab and Coronary Atherosclerosis in Asymptomatic Patients with Familial Hypercholesterolemia: The ARCHITECT Study.

BACKGROUND: The effect of alirocumab, a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor, on coronary plaque burden in patients with familial hypercholesterolemia has not been addressed. Our aim was to assess changes in coronary plaque burden and its characteristics after treatment with alirocumab by quantification and characterization of atherosclerotic plaque throughout the coronary tree on the basis of a noninvasive analysis of coronary computed tomographic angiography in asymptomatic subjects with familial hypercholesterolemia receiving optimized and stable treatment with maximum tolerated statin dose with or without ezetimibe. METHODS: This study is a phase IV, open-label, multicenter, single-arm clinical trial to assess changes in coronary plaque burden and its characteristics after 78 weeks of treatment with alirocumab in patients with familial hypercholesterolemia without clinical atherosclerotic cardiovascular disease. Participants underwent an initial coronary computed tomographic angiography at baseline and another at 78 weeks. Every patient received 150 mg of alirocumab subcutaneiously every 14 days in addition to high-intensity statin therapy. The main outcome was the change on coronary plaque burden and its characteristics by quantification and characterization of atherosclerotic plaque throughout the coronary tree on the basis of analysis of coronary computed tomographic angiography. RESULTS: The study was completed by 104 patients. The median age was 53.3 (46.2-59.4) years. Of these patients, 54 were women (51.9%). Median low-density lipoprotein cholesterol was 138.9 (117.5-175.3) mg/dL at entry and 45.0 (36.0-65.0) mg/dL at follow-up (P<0.001). Coronary plaque burden changed from 34.6% (32.5%-36.8%) at entry to 30.4% (27.4%-33.4%) at follow-up (P<0.001). A significant change in the characteristics of the coronary atherosclerosis was also found: an increase in the proportion of calcified (+0.3%; P<0.001) and mainly fibrous (+6.2%; P<0.001) plaque, accompanied by a decrease in the percentage of fibro-fatty (-3.9%; P<0.001) and necrotic plaque (-0.6%; P<0.001). CONCLUSIONS: Treatment with alirocumab in addition to high-intensity statin therapy resulted in significant regression of coronary plaque burden and plaque stabilization on coronary computed tomographic angiography over 78 weeks in these groups of patients with familial hypercholesterolemia without clinical atherosclerotic cardiovascular disease. ARCHITECT (Effect of Alirocumab on Atherosclerotic Plaque Volume, Architecture and Composition) could link and explain ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) results. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT05465278.

Optimization of Patient Pathway in Heart Failure with Reduced Ejection Fraction and Worsening Heart Failure. Role of Vericiguat.

Heart failure (HF) is a progressive condition with periods of apparent stability and repeated worsening HF events. Over time, unless optimization of HF treatment, worsening HF events become more frequent and patients enter into a cycle of recurrent events with high morbidity and mortality. In patients with HF there is an activation of deleterious neurohormonal pathways, such as the renin angiotensin aldosterone system and the sympathetic system, and an inhibition of protective pathways, including natriuretic peptides and guanylate cyclase. Therefore, HF burden can be reduced only through a holistic approach that targets all neurohormonal systems. In this context, vericiguat may play a key role, as it is the only HF drug that activates the nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate system. On the other hand, it has been described relevant disparities in the management of HF population. Consequently, it is necessary to homogenize the management of these patients, through an integrated patient-care pathway that should be adapted at the local level. In this context, the development of new technologies (ie, video call, specific platforms, remote control devices, etc.) may be very helpful. In this manuscript, a multidisciplinary group of experts analyzed the current evidence and shared their own experience to provide some recommendations about the therapeutic optimization of patients with recent worsening HF, with a particular focus on vericiguat, and also about how the integrated patient-care pathway should be performed.

Demographic, clinical, and functional determinants of antithrombotic treatment in patients with nonvalvular atrial fibrillation.

BACKGROUND: This study assessed the sociodemographic, functional, and clinical determinants of antithrombotic treatment in patients with nonvalvular atrial fibrillation (NVAF) attended in the internal medicine setting. METHODS: A multicenter, cross-sectional study was conducted in NVAF patients who attended internal medicine departments for either a routine visit (outpatients) or hospitalization (inpatients). RESULTS: A total of 961 patients were evaluated. Their antithrombotic management included: no treatment (4.7%), vitamin K antagonists (VKAs) (59.6%), direct oral anticoagulants (DOACs) (21.6%), antiplatelets (6.6%), and antiplatelets plus anticoagulants (7.5%). Permanent NVAF and congestive heart failure were associated with preferential use of oral anticoagulation over antiplatelets, while intermediate-to high-mortality risk according to the PROFUND index was associated with a higher likelihood of using antiplatelet therapy instead of oral anticoagulation. Longer disease duration and institutionalization were identified as determinants of VKA use over DOACs. Female gender, higher education, and having suffered a stroke determined a preferential use of DOACs. CONCLUSIONS: This real-world study showed that most elderly NVAF patients received oral anticoagulation, mainly VKAs, while DOACs remained underused. Antiplatelets were still offered to a proportion of patients. Longer duration of NVAF and institutionalization were identified as determinants of VKA use over DOACs. A poor prognosis according to the PROFUND index was identified as a factor preventing the use of oral anticoagulation.

Epidemiología de la insuficiencia cardiaca con fracción de eyección preservada: resultados del Registro RICA / Epidemiology of heart failure with preserved ejection fraction: Results from the RICA Registry

Introducción y objetivos: La caracterización de los pacientes con insuficiencia cardiaca (IC) con fracción de eyección preservada (IC-FEp) sigue teniendo interés. El objetivo fue conocer la prevalencia, las características clínicas y epidemiológicas de la IC-FEp, y sus cambios en los últimos años.MétodosAnalizamos el Registro RICA, de la Sociedad Española de Medicina Interna; estudio de cohorte multicéntrico y prospectivo de pacientes ingresados por IC, consecutivamente en servicios de medicina interna, durante un periodo de 11 años (2008-2018).ResultadosSe incluyeron 4.752 pacientes, 2957 (62,2%) con IC-FEp, proporción que se mantuvo constante durante todo el periodo. En comparación con los pacientes con IC y fracción de eyección reducida (IC-FEr), los pacientes con IC-FEp tienen: mayor edad, predominio de sexo femenino, etiología hipertensiva y valvular, distinto perfil de comorbilidades y peor capacidad funcional (menor índice de Barthel). La mayoría de pacientes recibía un tratamiento similar al de la IC-FEr (inhibidores del sistema renina-angiotensina-aldosterona y betabloqueantes). La mortalidad global al año de seguimiento fue del 24% en la IC-FEp y del 30% en la IC-FEr. En el análisis multivariante el riesgo de muerte fue superior en los pacientes con IC-FEr (HR: 1,84; IC 95%: [1,43-2,36]); la estancia hospitalaria fue inferior en la IC-FEp y no hubo diferencias en las re-hospitalizaciones. (AU)

Introduction and objectives: There is great interest in better characterizing patients with heart failure (HF) with preserved ejection fraction (HF-PEF). The objective of this study is to determine the prevalence, progression over time and to describe the clinical and epidemiological characteristics of patients with HF-PEF.MethodsFrom the National Registry of Heart Failure (RICA, prospective multicentre cohort study) we analysed patients consecutively admitted for HF in Internal Medicine wards over a period of 11 years (2008-2018).Results4752 patients were included, 2957 (62.2%) with preserved ejection fraction. This prevalence remained constant from 2008 to 2019. Compared to patients with HF and reduced ejection fraction (HF-REF) patients with HF-PEF are older, more are female, there is a higher prevalence of hypertensive and valvular aetiology, they have a profile of different comorbidities and worse functional status. A high proportion of patients receive disease-modifying treatment for IC-REF (renin-angiotensin-aldosterone system inhibitors and beta-blockers). The overall mortality after one-year follow-up was 24% and 30% in the HF-PEF and the HF-REF, respectively. In the multivariate analysis, the risk of death was higher in patients with HF-REF compared to HF-PEF (OR: 1.84; 95% CI: [1.43-2.36]). The length of hospital stay was also lower in the HF-PEF patients but there were no differences in re-hospitalizations. (AU)

Comorbidities and their implications in patients with and without type 2 diabetes mellitus and heart failure with preserved ejection fraction. Findings from the rica registry.

AIM: To determine if patients with heart failure and preserved ejection fraction (HFpEF) and type 2 diabetes mellitus (T2DM) have a higher comorbidity burden than those without T2DM, if other comorbidities are preferentially associated with T2DM and if these conditions confer a worse patient prognosis. METHODS AND RESULTS: Cohort study based on the RICA Spanish Heart Failure Registry, a multicentre, prospective registry that enrols patients admitted for decompensated HF and follows them for 1 year. We selected only patients with HFpEF, classified as having or not having T2DM and performed an agglomerative hierarchical clustering based on variables such as the presence of arrhythmia, chronic obstructive pulmonary disease, dyslipidemia, liver disease, stroke, dementia, body mass index, haemoglobin levels, estimated glomerular filtration rate and systolic blood pressure. A total of 1934 patients were analysed: 907 had T2DM (mean age 78.4 ± 7.6 years) and 1027 did not (mean age 81.4 ± 7.6 years). The analysis resulted in four clusters in patients with T2DM and three in the reminder. All clusters of patients with T2DM showed higher BMI and more kidney disease and anaemia than those without T2DM. Clusters of patients without T2DM had neither significantly better nor worse outcomes. However, among the T2DM patients, clusters 2, 3 and 4 all had significantly poorer outcomes, the worst being cluster 3 (HR 2.0, 95% CI 1.36-2.93, P = .001). CONCLUSIONS: Grouping our patients with HFpEF and T2DM into clusters based on comorbidities revealed a greater disease burden and prognostic implications associated with the T2DM phenotype, compared with those without T2DM.

Epidemiology of heart failure with preserved ejection fraction: Results from the RICA Registry. / Epidemiología de la insuficiencia cardiaca con fracción de eyección preservada: resultados del Registro RICA.

INTRODUCTION AND OBJECTIVES: There is great interest in better characterizing patients with heart failure (HF) with preserved ejection fraction (HF-PEF). The objective of this study is to determine the prevalence, progression over time and to describe the clinical and epidemiological characteristics of patients with HF-PEF. METHODS: From the National Registry of Heart Failure (RICA, prospective multicentre cohort study) we analysed patients consecutively admitted for HF in Internal Medicine wards over a period of 11 years (2008-2018). RESULTS: 4752 patients were included, 2957 (62.2%) with preserved ejection fraction. This prevalence remained constant from 2008 to 2019. Compared to patients with HF and reduced ejection fraction (HF-REF) patients with HF-PEF are older, more are female, there is a higher prevalence of hypertensive and valvular aetiology, they have a profile of different comorbidities and worse functional status. A high proportion of patients receive disease-modifying treatment for IC-REF (renin-angiotensin-aldosterone system inhibitors and beta-blockers). The overall mortality after one-year follow-up was 24% and 30% in the HF-PEF and the HF-REF, respectively. In the multivariate analysis, the risk of death was higher in patients with HF-REF compared to HF-PEF (OR: 1.84; 95% CI: [1.43-2.36]). The length of hospital stay was also lower in the HF-PEF patients but there were no differences in re-hospitalizations. CONCLUSIONS: Sixty percent of patients in the RICA registry have preserved ejection fraction. These patients have a higher comorbidity burden and a worse functional status, but lower mortality compared with HF-REF patients.

Budget impact of ferric carboxymaltose treatment in patients with chronic heart failure and iron deficiency in Spain.

OBJECTIVE: The treatment of iron deficiency (ID) with ferric carboxymaltose (FCM) improves the functional class and quality of life of chronic heart failure (CHF) patients with reduced left ventricular ejection fraction (LVEF), and reduces the rate of hospitalization due to worsening CHF. This study aims to evaluate the budget impact for the Spanish National Health System (SNHS) of treating ID in reduced LVEF CHF with FCM compared to non-iron treatment. METHODS: We simulated a hypothetical cohort of 1000 CHF patients with ID and reduced LVEF based on the Spanish population characteristics. A decision-analytic model was also built using the data from the largest FCM clinical trial (CONFIRM-HF) that lasted for a year. We considered the use of healthcare resources from a national prospective study. A deterministic sensitivity analysis was carried out varying the corresponding baseline data by ±25%. RESULTS: The cost of treating the simulated population with FCM was €2,570,914, while that of the non-iron treatment was €3,105,711, which corresponds to a cost saving of €534,797 per 1,000 patients in one year. Cost savings were mainly due to a decrease in the number of hospitalizations. All sensitivity analysis showed cost savings for the SNHS. CONCLUSIONS: FCM results in an annual cost saving of €534.80 per patient, and would thus be expected to reduce the economic burden of CHF in Spain.

Consenso de expertos sobre la insuficiencia cardiaca con fracción de eyección reducida: más allá de las guías / Expert consensus statement on heart failure with reduced ejection fraction: beyond the guidelines

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Selección del tratamiento anticoagulante óptimo para el paciente con fibrilación auricular y diabetes o enfermedad renal crónica: papel del rivaroxabán / Selecting the best anticoagulant treatment for patients with atrial fibrillation and diabetes or chronic kidney disease: the role of rivaroxaban

Tanto la diabetes mellitus como la enfermedad renal crónica aumentan el riesgo de fibrilación auricular. A su vez, la concomitancia de diabetes mellitus y enfermedad renal crónica incrementa de manera sinérgica el riesgo tromboembólico asociado con la fibrilación auricular, lo que pone al paciente en esta situación en especial riesgo y obliga a no fijar nuestra actuación solo en la reducción del riesgo embólico, sino a buscar una protección general. Aunque todos los anticoagulantes orales reducen eficazmente el riesgo de ictus en el paciente diabético con fibrilación auricular, hay datos que indican que el rivaroxabán podría disminuir además la mortalidad cardiovascular en esta población, ofreciendo una protección adicional. Por otra parte, se ha descrito un empeoramiento de la función renal con el empleo de los antagonistas de la vitamina K (nefropatía por warfarina). En consecuencia, sería deseable que el tratamiento anticoagulante no solo disminuyera el riesgo de complicaciones tromboembólicas, sino que además no se asociara con este deterioro de la función renal. En este sentido, parece que algunos anticoagulantes orales de acción directa, como el dabigatrán y el rivaroxabán, tendrían un menor riesgo de eventos renales adversos en comparación con warfarina

Both diabetes mellitus and chronic kidney disease increase the risk of atrial fibrillation. In turn, the coexistence of diabetes and chronic kidney disease synergistically increases the thromboembolic risk associated with atrial fibrillation, which puts affected patients at a particularly high risk and makes it necessary to focus treatment not only on reducing the risk of embolism but also on providing more general prophylaxis. Although all oral anticoagulants are effective in reducing the risk of stroke in diabetic patients with atrial fibrillation, there are indications that rivaroxaban could also reduce cardiovascular mortality in this population, thereby providing additional benefits. Moreover, it has been reported that renal function deteriorates on vitamin K antagonist treatment (i.e. warfarin-related nephropathy). Consequently, the ideal anticoagulant treatment would decrease the risk of thromboembolic complications without also being associated with impaired renal function. In this context, it appears that some direct oral anticoagulants, such as dabigatran and rivaroxaban, may have a lower risk of adverse renal events than warfarin

Correction to: Influence of frailty on anticoagulant prescription and clinical outcomes after 1­year follow­up in hospitalised older patients with atrial fibrillation.

In the original publication, all the collaborator names were incorrectly tagged and published online. The correct given and family names for the collaborators names should list as follows.

Acute kidney injury is linked to higher mortality in elderly hospitalized patients with non-valvular atrial fibrillation.

AIM: Renal insufficiency is associated with medical complications in patients with non-valvular atrial fibrillation (NVAF). However, data for elderly patients are scarce. Thus, the main objectives of the present study were to analyze the characteristics of elderly patients with NVAF and acute or chronic renal disease, describe their management in real-life conditions, and detect factors associated with complications. METHODS: The NONAVASC registry includes patients > 75 years with NVAF, hospitalized by any cause in 64 Spanish Internal Medicine departments. Patients were categorized into acute kidney injury (AKI), chronic kidney disease (CKD) or preserved renal function (PRF). All variables associated with in-hospital mortality with P < 0.10 in univariate analysis were included to develop a multivariate logistic-regression model. RESULTS: The study included 804 patients (53.9% women), 352 (43.8%) of whom met diagnostic criteria for CKD. AKI was detected in 119 (14.8%) patients. AKI was associated with greater length of stay, higher mortality and an increased rate of patient transfer to nursing homes. After logistic-regression analysis, we found an association between mortality and AKI (OR 2.4, 95% CI 1.03-5.53; P = 0.045). The increase in creatinine values (OR 1.8, 95% CI 1.19-2.73; P = 0.005) and the decrease in albumin values (OR 2.0, 95% CI 1.05-3.73; P = 0.033) were also linked to mortality. CONCLUSIONS: Our study shows the relationship between AKI and creatinine value increase and a higher mortality in elderly patients with NVAF. In light of our findings, the detection of renal function impairment in these patients should alert physicians and consider them as high-risk patients.

Influence of frailty on anticoagulant prescription and clinical outcomes after 1-year follow-up in hospitalised older patients with atrial fibrillation.

Frailty is an important prognostic factor in older adults with cardiovascular diseases. We aim to describe the characteristics of elderly hospitalised frail patients with non-valvular atrial fibrillation (NVAF) and to assess the influence of frailty, along with other functional and health status variables on anticoagulation prescription, 1-year all-cause mortality, and the incidence of ischemic and bleeding complications. An observational, prospective multicentre study was carried out on patients with NVAF over the age of 75, who were admitted to the Internal Medicine departments in Spain. A total of 615 patients were evaluated (mean age 85.23 ± 5.16 years, 54.3% females, 48.3% frail). Frail patients had higher CHA2DS2-VASc and HAS-BLED scores, more comorbidities and worse functional status and cognitive impairment compared to non-frail. During hospitalisation, 58 (9.4%) patients died (12.5% frail, 6.6% non-frail, p = 0.01). Among the participants discharged, 69.8% received anticoagulants, 13% anti-platelets only and 16.9% no anti-thrombotics, with no difference by frailty status. Frailty is not a predictor of anticoagulant prescription at discharge (OR 0.93, 95% CI 0.55-1.57), while functional dependency remains significantly associated (OR for severe dependency 0.44, 95% CI 0.23-0.82). After the 1-year follow-up, frail patients have a higher risk of death (HR 1.99, 95% CI 1.43-2.76). Among patients taking anticoagulants, the incidence of stroke and major bleeding is similar between frailty groups. In our study, frailty is related to worse global health status. It has no impact on antithrombotic prescription, nor is a predictor of AF complications, even though frail subjects have a higher mortality during hospitalisation and after 1-year follow-up.

Rivaroxaban: searching the integral vascular protection.

INTRODUCTION: Residual cardiovascular risk remains high in patients with atherosclerotic cardiovascular disease despite current antithrombotic therapy. On the other hand, patients with atrial fibrillation have an increased risk of myocardial infarction and cardiovascular death. As a result, a new antithrombotic approach appears necessary to reduce this risk. Areas covered: In this article, the role of rivaroxaban on vascular protection in patients with cardiovascular disease and/or atrial fibrillation was reviewed, with a particular focus, but not limited, on clinical trials. Expert commentary: Previous data have shown that factor Xa plays a key role in the etiopathogenesis of atherothrombosis. Experimental data suggest that rivaroxaban exhibits antiinflammatory and antioxidative stress properties, and may improve endothelial dysfunction. The COMPASS trial showed that among patients with stable atherosclerotic vascular disease, the addition of rivaroxaban 2.5 mg twice daily (vascular dose) to aspirin provided a higher cardiovascular protection than aspirin alone. In ROCKET-AF trial, compared with warfarin, rivaroxaban 20 mg once daily (15 mg if moderate renal dysfunction) (anticoagulant dose) was, at least, as effective as warfarin for the prevention of stroke or systemic embolism among patients with nonvalvular atrial fibrillation, with a trend toward a reduction in the risk of cardiovascular outcomes. All these data suggest that rivaroxaban might have a vascular protective effect beyond its stroke/systemic embolism preventive activity.

Factors associated with discontinuing or not starting oral anticoagulant therapy in older hospitalized patients with non-valvular atrial fibrillation.

AIM: To determine the factors associated with discontinuing or not starting oral anticoagulation (OA) therapy in older patients with non-valvular atrial fibrillation (NVAF). METHODS: A prospective, multicenter cohort study was carried out of patients aged >75 years with NVAF hospitalized in internal medicine departments in Spain. For each patient, we recorded creatinine, hemoglobin and platelets levels, as well as CHA2DS2-VASc and HAS-BLED scores and the Charlson Comorbidity Index. We measured the ability to carry out basic activities of daily life with the Barthel Index, and the cognitive state with the Short Portable Mental Status questionnaire. RESULTS: We included 723 patients with NVAF, with a mean age of 84.8 years (SD 5.2 years); 390 (53.9%) of the patients were women. Before admission, 375 (51.9%) patients were treated with OA. Previously diagnosed NVAF (OR 4.099, 95% CI 1.824-9.211, P = 0.001), the number of errors in the Short Portable Mental Status questionnaire (OR 1.180, 95% CI 1.020-1.365, P = 0.026), peripheral arterial disease (OR 0.285, 95% CI 0.114-0.711, P = 0.007) and hemoglobin levels (OR 0.812, 95% CI 0.682-0.966, P = 0.019) were independently associated with not starting OA therapy at discharge. Of the 375 patients treated with OA at admission, 87 (23.2%) had their OA discontinued at discharge. The HAS-BLED score (OR 1.516, 95% CI 1.211-1.897, P < 0.001) and previous acute myocardial infarction (OR 0.327, 95% CI 0.121-0.883, P = 0.027) were associated with the discontinuation of OA. CONCLUSIONS: There are factors associated with discontinuing or not starting OA in older patients with NVAF, which often have no clinical justification. Geriatr Gerontol Int 2018; 18: 1219-1224.

miR-505-3p controls chemokine receptor up-regulation in macrophages: role in familial hypercholesterolemia.

Familial hypercholesterolemia (FH) conveys a high risk of premature atherosclerosis as a result of lifelong exposure to high LDL cholesterol levels that are not fully reduced by standard-of-care lipid-lowering treatment. Inflammatory mediators have played a role in the progression of atherosclerotic lesions. Here, we investigated whether innate immunity cells in patients with FH have a specific proinflammatory phenotype that is distinct from that of cells in normal participants. To this end, miR-505-3p-a microRNA related to chronic inflammation-and its target genes were investigated in monocyte-derived macrophages (MACs) of patients with FH (FH-MACs) and non-FH controls (co-MACs). On the basis of the profiler PCR array analysis of agomiR-505-3p-transfected MACs, we identified the chemokine receptors, CCR3, CCR4, and CXCR1, as genes that are regulated by miR-505-3p via the transcription factor, RUNX1. miR-505-3p was significantly down-regulated, whereas CCR3, CCR4, CXCR, and RUNX1 were increased in FH-MAC compared with co-MAC, with the increase being more evident in the proinflammatory M1-like FH-MAC. Chemokine receptor levels were unrelated to LDL plasma levels at entry, but correlated with age in patients with FH, not in controls. In summary, we demonstrate for first time to our knowledge that MACs from FH-MACs have an inflammatory phenotype that is characterized by the up-regulation of CCR3, CCR4, and CXCR1 under the control of miR-505-3p. These results suggest a chronic inflammatory condition in FH innate immunity cells that is not reverted by standard lipid-lowering treatment.-Escate, R., Mata, P., Cepeda, J. M., Padró, T., Badimon, L. miR-505-3p controls chemokine receptor up-regulation in macrophages: role in familial hypercholesterolemia.

miR-505-3p controls chemokine receptor up-regulation in macrophages: role in familial hypercholesterolemia.

Familial hypercholesterolemia (FH) conveys a high risk of premature atherosclerosis as a result of lifelong exposure to high LDL cholesterol levels that are not fully reduced by standard-of-care lipid-lowering treatment. Inflammatory mediators have played a role in the progression of atherosclerotic lesions. Here, we investigated whether innate immunity cells in patients with FH have a specific proinflammatory phenotype that is distinct from that of cells in normal participants. To this end, miR-505-3p-a microRNA related to chronic inflammation-and its target genes were investigated in monocyte-derived macrophages (MACs) of patients with FH (FH-MACs) and non-FH controls (co-MACs). On the basis of the profiler PCR array analysis of agomiR-505-3p-transfected MACs, we identified the chemokine receptors, CCR3, CCR4, and CXCR1, as genes that are regulated by miR-505-3p via the transcription factor, RUNX1. miR-505-3p was significantly down-regulated, whereas CCR3, CCR4, CXCR, and RUNX1 were increased in FH-MAC compared with co-MAC, with the increase being more evident in the proinflammatory M1-like FH-MAC. Chemokine receptor levels were unrelated to LDL plasma levels at entry, but correlated with age in patients with FH, not in controls. In summary, we demonstrate for first time to our knowledge that MACs from FH-MACs have an inflammatory phenotype that is characterized by the up-regulation of CCR3, CCR4, and CXCR1 under the control of miR-505-3p. These results suggest a chronic inflammatory condition in FH innate immunity cells that is not reverted by standard lipid-lowering treatment.-Escate, R., Mata, P., Cepeda, J.M., Padró, T., Badimon, L. miR-505-3p controls chemokine receptor up-regulation in macrophages: role in familial hypercholesterolemia. FASEB J. 32, 601-612 (2018). www.fasebj.org.

Predicting Cardiovascular Events in Familial Hypercholesterolemia: The SAFEHEART Registry (Spanish Familial Hypercholesterolemia Cohort Study).

BACKGROUND: Although risk factors for atherosclerotic cardiovascular disease (ASCVD) in familial hypercholesterolemia (FH) have been described, models for predicting incident ASCVD have not been reported. Our aim was to use the SAFEHEART registry (Spanish Familial Hypercholesterolemia Cohort Study) to define key risk factors for predicting incident ASCVD in patients with FH. METHODS: SAFEHEART is a multicenter, nationwide, long-term prospective cohort study of a molecularly defined population with FH with or without previous ASCVD. Analyses to define risk factors and to build a risk prediction equation were developed, and the risk prediction equation was tested for its ability to discriminate patients who experience incident ASCVD from those who did not over time. RESULTS: We recruited 2404 adult patients with FH who were followed up for a mean of 5.5 years (SD, 3.2 years), during which 12 (0.5%) and 122 (5.1%) suffered fatal and nonfatal incident ASCVD, respectively. Age, male sex, history of previous ASCVD, high blood pressure, increased body mass index, active smoking, and low-density lipoprotein cholesterol and lipoprotein(a) levels were independent predictors of incident ASCVD from which a risk equation with a Harrell C index of 0.85 was derived. The bootstrap resampling (100 randomized samples) of the original set for internal validation showed a degree of overoptimism of 0.003. Individual risk was estimated for each person without an established diagnosis of ASCVD before enrollment in the registry by use of the SAFEHEART risk equation, the modified Framingham risk equation, and the American College of Cardiology/American Heart Association ASCVD Pooled Cohort Risk Equations. The Harrell C index for these models was 0.81, 0.78, and 0.8, respectively, and differences between the SAFEHEART risk equation and the other 2 were significant (P=0.023 and P=0.045). CONCLUSIONS: The risk of incident ASCVD may be estimated in patients with FH with simple clinical predictors. This finding may improve risk stratification and could be used to guide therapy in patients with FH. CLINICAL TRIAL REGISTRATION: URL: http://clinicaltrials.gov. Unique identifier: NCT02693548.

Características y tratamiento antitrombótico de los pacientes ancianos con fibrilación auricular no valvular hospitalizados en Medicina Interna. Registro NONAVASC / Antithrombotic treatment and characteristics of elderly patients with non-valvular atrial fibrillation hospitalized at Internal Medicine departments. NONAVASC registry

Introducción y objetivos. La prevalencia de fibrilación auricular no valvular (FANV) aumenta con la edad y se asocia a alta morbimortalidad. El objetivo principal fue conocer las características de los pacientes ancianos con FANV hospitalizados y los factores clínico-funcionales que determinan la estrategia antitrombótica utilizada. Pacientes y métodos. Estudio observacional, prospectivo, multicéntrico realizado en pacientes mayores de 75 años con FANV, hospitalizados por cualquier causa en Medicina Interna. Resultados. Se evaluaron 804 pacientes con una edad media de 85 años (rango: 75-101); el 53,9% fueron mujeres. La prevalencia de factores de riesgo y enfermedades vasculares fue elevada: hipertensión (87,6%), insuficiencia cardíaca (65,4%), cardiopatía isquémica (24,4%), enfermedad cerebrovascular (22,4%) e insuficiencia renal (45%). Entre los pacientes con diagnóstico previo al ingreso de FANV el 86,2% recibía tratamiento antitrombótico: anticoagulantes (59,7%), antiagregantes (AAG) (17,8%) y doble terapia (8,7%). Los factores asociados con la utilización del mismo fueron el antecedente de síndrome coronario agudo y la FANV de más de un año de evolución. Se asociaron con el uso de antiagregación la edad avanzada, la FANV de menos de un año de evolución, las puntuaciones superiores de HAS-BLED y el deterioro cognitivo grave. La fibrilación auricular permanente favorecía la prescripción de anticoagulantes. Conclusiones. Los pacientes mayores de 75 años con FANV hospitalizados en Medicina Interna tienen numerosas comorbilidades. El porcentaje de anticoagulación es escaso y un 18% recibe solo antiagregación, influyendo en su selección la edad, el tiempo de evolución de la fibrilación auricular y la gravedad del deterioro cognitivo (AU)

Background and objetives. The prevalence of non-valvular atrial fibrillation (NVAF) increases with the patient's age and is associated with high morbi-mortality rates. The main goal of this study was to describe the characteristics of hospitalized elderly patients with NVAF and to identify the clinical and functional factors which determine the use of different antithrombotic strategies. Patients and methods. Observational, prospective, multicentre study carried out on patients with NVAF over the age of 75, who had been admitted for any medical condition to Internal Medicine departments. Results. We evaluated 804 patients with a mean age of 85 years (range 75-101), of which 53.9% were females. The prevalence of risk factors and cardiovascular disease was high: hypertension (87.6%), heart failure (65.4%), ischemic cardiomyopathy (24.4%), cerebrovascular disease (22.4%) and chronic kidney disease (45%). Among those cases with previous diagnoses of NVAF, antithrombotic treatment was prescribed in 86.2% of patients: anticoagulants (59.7%), antiplatelet medication (17.8%) and double therapy (8.7%). The factors associated with the use of antithrombotic treatment were history of acute coronary syndrome and atrial fibrillation progression longer than one year. Older age, atrial fibrillation for less than one year, higher HAS-BLED scores and severe cognitive impairment were associated with the use of anti-platelet drugs. Permanent atrial fibrillation favoured the use of anticoagulants. Conclusions. Hospitalized patients older than 75 years old with NVAF showed numerous comorbidities. The percentage of anticoagulation was small and 18% received only anti-platelet therapy. The patient's age, atrial fibrillation's progression time and the severity of the cognitive impairment influenced this therapy choice (AU)