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BACKGROUND: Sex differences in atherosclerotic cardiovascular disease (ASCVD) in familial hypercholesterolaemia have been reported but are not fully established. We aimed to assess sex differences in the risk of ASCVD and life-time burden of ASCVD in patients with heterozygous familial hypercholesterolaemia. METHODS: SAFEHEART is a nationwide, multicentre, long-term prospective cohort study conducted in 25 tertiary care hospitals and one regional hospital in Spain. Participants in the SAFEHEART study aged 18 years or older with genetically confirmed familial hypercholesterolaemia were included in our analysis. Data were obtained between Jan 26, 2004, and Nov 30, 2022. ASCVD and age at onset were documented at enrolment and at follow-up. Our aim was to investigate the differences by sex in the risk and burden of ASCVD in patients with heterozygous familial hypercholesterolaemia, over the study follow-up and over the life course. The SAFEHEART study is registered with ClinicalTrials.gov, NCT02693548. FINDINGS: Of the 5262 participants in SAFEHEART at the time of analysis, 3506 (1898 [54·1%] female and 1608 [45·9%] male participants) met the inclusion criteria and were included in the current study. Mean age was 46·1 years (SD 15·5) and median follow-up was 10·3 years (IQR 6·4-13·0). Mean on-treatment LDL-cholesterol at follow-up was 3·1 mmol/L (SD 1·4) in females and 3·0 mmol/L (1·5) in males. LDL-cholesterol reductions over time were similar in both sexes (1·39 mmol/L [95% CI 1·30-1·47] absolute reduction in females vs 1·39 mmol/L [1·29-1·48] in males; p=0·98). At enrolment, 130 (6·8%) females and 304 (18·9%) males (p<0·0001) had cardiovascular disease. During follow-up, 134 (7·1%) females and 222 (13·8%) males (p<0·0001) had incident cardiovascular events. Median age at first ASCVD event (mostly due to coronary artery disease) was 61·6 years (IQR 50·0-71·4) in females and 50·6 years (42·0-58·6) in males (p<0·0001). The adjusted hazard ratio for ASCVD in males compared with females during follow-up was 1·90 (95% CI 1·49-2·42) and for cardiovascular death was 1·74 (1·11-2·73). Major adverse cardiovascular disease event (MACE)-free survival from birth was lower in males than females (hazard ratio 3·52 [95% CI 2·98-4·16]; p<0·0001). Median MACE-free survival time was 90·1 years (95% CI 86·5-not estimable) in females and 71·0 years (69·2-74·6) in males. The age at which 25% of female participants have had a MACE event was 74·9 years, this figure was 55·5 years in male participants. INTERPRETATION: Our findings suggest that the burden and risk of ASCVD are markedly lower in females than males with familial hypercholesterolaemia. The impact of sex needs to be considered to improve risk stratification and personalised management in patients with heterozygous familial hypercholesterolaemia. FUNDING: Fundación Hipercolesterolemia Familiar, the Instituto de Salud Carlos III, and Next Generation EU funds from the Recovery and Resilience Mechanism Program. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.
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Aterosclerose , Hiperlipoproteinemia Tipo II , Humanos , Masculino , Feminino , Hiperlipoproteinemia Tipo II/epidemiologia , Espanha/epidemiologia , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto , Aterosclerose/epidemiologia , Idoso , Fatores Sexuais , Heterozigoto , Fatores de Risco , Doenças Cardiovasculares/epidemiologia , SeguimentosRESUMO
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.
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Insuficiência Cardíaca , Disfunção Ventricular Esquerda , Humanos , Volume Sistólico , Estudos de Coortes , Insuficiência Cardíaca/tratamento farmacológico , Compostos Benzidrílicos/uso terapêuticoRESUMO
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.
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COVID-19 , Doenças Cardiovasculares , Humanos , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/terapia , Fatores de RiscoRESUMO
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.
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Síndrome Coronariana Aguda , Aterosclerose , Doença da Artéria Coronariana , Inibidores de Hidroximetilglutaril-CoA Redutases , Hipercolesterolemia , Hiperlipoproteinemia Tipo II , Placa Aterosclerótica , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Pró-Proteína Convertase 9 , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/tratamento farmacológico , Hipercolesterolemia/tratamento farmacológico , Placa Aterosclerótica/tratamento farmacológico , Hiperlipoproteinemia Tipo II/complicações , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Aterosclerose/tratamento farmacológico , Síndrome Coronariana Aguda/tratamento farmacológico , Resultado do TratamentoRESUMO
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.
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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.
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Anticoagulantes/uso terapêutico , Fibrilação Atrial/complicações , Acidente Vascular Cerebral/prevenção & controle , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Assistência Ambulatorial , Transtornos Cognitivos/complicações , Estudos Transversais , Quimioterapia Combinada , Escolaridade , Inibidores do Fator Xa/uso terapêutico , Feminino , Humanos , Masculino , Inibidores da Agregação Plaquetária/uso terapêutico , Prognóstico , Espanha , Acidente Vascular Cerebral/etiologia , Conduta Expectante/estatística & dados numéricosRESUMO
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.
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Insuficiência Cardíaca , Estudos de Coortes , Feminino , Insuficiência Cardíaca/epidemiologia , Humanos , Prognóstico , Estudos Prospectivos , Sistema de Registros , Volume SistólicoRESUMO
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.
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Diabetes Mellitus Tipo 2 , Insuficiência Cardíaca , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Comorbidade , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Insuficiência Cardíaca/epidemiologia , Humanos , Prognóstico , Sistema de Registros , Volume SistólicoRESUMO
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.
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Anemia Ferropriva , Insuficiência Cardíaca , Anemia Ferropriva/tratamento farmacológico , Compostos Férricos/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Ferro , Maltose/análogos & derivados , Maltose/uso terapêutico , Estudos Prospectivos , Qualidade de Vida , Espanha , Volume Sistólico , Função Ventricular EsquerdaRESUMO
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.
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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.
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Injúria Renal Aguda/mortalidade , Fibrilação Atrial/mortalidade , Mortalidade Hospitalar , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Comorbidade , Creatinina/sangue , Feminino , Humanos , Falência Renal Crônica/mortalidade , Tempo de Internação , Modelos Logísticos , Masculino , Sistema de Registros , Fatores de RiscoRESUMO
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.
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Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Idoso Fragilizado , Hospitalização , Idoso , Idoso de 80 Anos ou mais , Causas de Morte , Comorbidade , Feminino , Avaliação Geriátrica , Humanos , Masculino , Prognóstico , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Espanha , Resultado do TratamentoRESUMO
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.
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Embolia/prevenção & controle , Inibidores do Fator Xa/administração & dosagem , Rivaroxabana/administração & dosagem , Acidente Vascular Cerebral/prevenção & controle , Aterosclerose/complicações , Aterosclerose/tratamento farmacológico , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/tratamento farmacológico , Embolia/etiologia , Humanos , Acidente Vascular Cerebral/etiologiaRESUMO
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.
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Anticoagulantes/uso terapêutico , Fibrilação Atrial/diagnóstico por imagem , Fibrilação Atrial/tratamento farmacológico , Tomada de Decisão Clínica , Hospitalização/estatística & dados numéricos , Administração Oral , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Anticoagulantes/efeitos adversos , Fibrilação Atrial/mortalidade , Estudos de Coortes , Eletrocardiografia/métodos , Feminino , Avaliação Geriátrica , Humanos , Modelos Logísticos , Masculino , Análise Multivariada , Estudos Prospectivos , Medição de Risco , Fatores Sexuais , Espanha , Análise de Sobrevida , Suspensão de TratamentoRESUMO
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.
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Ácidos Cólicos/sangue , Macrófagos/metabolismo , MicroRNAs/metabolismo , Receptores de Quimiocinas/biossíntese , Erros Inatos do Metabolismo de Esteroides/metabolismo , Regulação para Cima , Ácidos Cólicos/imunologia , Ácidos Cólicos/metabolismo , Feminino , Humanos , Macrófagos/imunologia , Macrófagos/patologia , Masculino , MicroRNAs/imunologia , Receptores de Quimiocinas/imunologia , Erros Inatos do Metabolismo de Esteroides/imunologia , Erros Inatos do Metabolismo de Esteroides/patologia , Erros Inatos do Metabolismo de Esteroides/terapiaRESUMO
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.
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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.
Assuntos
Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/epidemiologia , Sistema de Registros , Adulto , Estudos de Coortes , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de Risco , Espanha/epidemiologiaRESUMO
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.