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1.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-32201274

RESUMO

INTRODUCTION AND OBJECTIVES: The SAFEHEART study was designed to analyze the situation of familial heterozygous hypercholesterolemia (FHH) and improve knowledge of this disease in Spain. Our objective was to determine the incidence rate of cardiovascular events, the estimated risk of developing an event and its modification, the use of lipid-lowering treatment, and the achievement of low-density lipoprotein cholesterol targets in patients with FHH. METHODS: SAFEHEART is a prospective, open, multicenter, nationwide cohort study, with long-term protocol-based follow-up in a population of individuals with molecularly-characterized FHH. We analyzed patients older than 18 years with complete follow-up. RESULTS: We included 2648 patients with FHH. The median follow-up was 6.6 (4.8-9.7) years. The overall incidence rate of cardiovascular events was 1.3 events/100 patient-years. After the follow-up, the 10-year estimated risk of developing a cardiovascular event was reduced from 1.6% to 1.3% (P <.001). In the last follow-up, 20.6% and 22.2% of the patients in primary and secondary prevention achieved low-density lipoprotein cholesterol values <100mg/dL and <70mg/dL, respectively. CONCLUSIONS: This study was performed in the largest population of patients with FHH in Spain. We identified the incidence rate of cardiovascular events, the estimated risk of developing a cardiovascular event and its modification, the achievement of low-density lipoprotein cholesterol targets, and the therapeutic management in this population. Although the cardiovascular risk of FHH is high, appropriate treatment reduces the likelihood of an event. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Identifier: NCT02693548.

2.
Cardiovasc Res ; 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-32061123

RESUMO

AIMS: Presentation of acute events in patients with atherosclerosis remains unpredictable even after controlling for classical risk factors. MicroRNAs (miRNAs) measured in liquid biopsies could be good candidate biomarkers to improve risk prediction. Here, we hypothesized that miRNAs could predict atherosclerotic plaque progression and clinical event presentation in familial hypercholesterolemia (FH) patients. METHODS AND RESULTS: Circulating miRNAs (plasma, exosomes, microvesicles) were investigated by TaqMan Array and RT-qPCR assays. Patients with genetic diagnosis of FH and healthy relatives from the SAFEHEART cohort were included. A differential signature of 10 miRNA was obtained by comparing two extreme phenotypes consisting of FH-patients suffering a cardiovascular event (CVE) within a 8-year follow-up period (FH-CVE, N=42) and non-FH hypercholesterolemic relatives from the same cohort, matched for age and treatment, without CVE during the same period (nFH-nCVE, N=30). The validation studies included two independent groups of patients with FH-background (Discovery-Group, N=89, Validation-Group N=196), developing a future CVE (FH-CVE) or not (FH-nCVE) within the same time period of follow-up. Of the 10 miRNAs initially selected, miR-133a was significantly higher in FH-CVE than in FH-nCVE patients. ROC-analysis confirmed miR-133a as the best microRNA for predicting CVE in FH-patients (0.76±0.054; P<0.001). Furthermore, Kaplan-Meier and COX-analysis showed that high plasma miR-133a levels associated to the higher risk of presenting a CVE within the next 8 years (HR: 3.89 [95%CI: 1.88-8.07], P<0.001). In silico analysis of curate biological interactions related miR-133a with target genes involved in regulation of the cell-membrane lipid-receptor LRP6 and inflammatory cytokines (CXCL8, IL6, TNF). These predictions were experimentally proven in human macrophages and endothelial cells transfected with agomiR-133a. CONCLUSION: Elevated levels of miR-133a in the circulation anticipate those FH-patients that are going to present a clinical CVE within the next 2 years (average). Mechanistically, miR-133a is directly related with lipid- and inflammatory-signalling in key cells for atherosclerosis progression. TRANSLATIONAL PERSPECTIVE: The present study in patients with familial hypercholesterolemia shows that epigenetic markers can allow the identification of those patients that are going to present an acute clinical event within the next two years (average). There are currently few prognostic biomarkers able to identify subjects at risk of developing major acute cardiovascular events. Here, by using a non-targeted approach of miRNA-discovery, we show for first time that plasma levels of miR-133a have prognostic value to predict incident cardiovascular events in patients with familial hypercholesterolemia treated as per guidelines. Future studies with larger independent cohorts are needed to validate the prognostic value of miR-133a in the general population.

3.
J Clin Lipidol ; 13(6): 989-996, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31706904

RESUMO

BACKGROUND: Maximal doses of potent statins are the basement of treatment of familial hypercholesterolemia (FH). Little is known about the use of different statin regimens in FH. OBJECTIVES: The objectives of the study were to describe the treatment changes and low-density lipoprotein cholesterol (LDL-C) goal achievement with atorvastatin (ATV) and rosuvastatin (RV) in the SAFEHEART cohort, as well as to analyze the incidence of atherosclerotic cardiovascular events (ACVEs) and changes in the cardiovascular risk. METHODS: SAFEHEART is a prospective follow-up nationwide cohort study in a molecularly defined FH population. The patients were contacted on a yearly basis to obtain relevant changes in life habits, medication, and ACVEs. RESULTS: A total of 1939 patients were analyzed. Median follow-up was 6.6 years (5-10). The estimated 10-year risk according the SAFEHEART risk equation was 1.61 (0.67-3.39) and 1.22 (0.54-2.93) at enrollment for ATV and RV, respectively (P < .001). There were no significant differences at the follow-up: 1.29 (0.54-2.82) and 1.22 (0.54-2.76) in the ATV and RV groups, respectively (P = .51). Sixteen percent of patients in primary prevention with ATV and 18% with RV achieved an LDL-C <100 mg/dL and 4% in secondary prevention with ATV and 5% with RV achieved an LDL-C <70 mg/dL. The use of ezetimibe was marginally greater in the RV group. One hundred sixty ACVEs occurred during follow-up, being its incidence rate 1.1 events/100 patient-years in the ATV group and 1.2 in the RV group (P = .58). CONCLUSION: ATV and RV are 2 high-potency statins widely used in FH. Although the reduction in LDL-C levels was greater with RV than with ATV, the superiority of RV for reducing ACVEs was not demonstrated.

4.
Eur J Clin Nutr ; 73(12): 1622-1625, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31695140

RESUMO

The association of components of a low saturated fat (SFA) and of a Mediterranean diet was tested with atherosclerosis biomarkers in 190 familial hypercholesterolemia adults (FH) from Brazil (BR) and Spain (SP). Median blood LDL-C, Apolipoprotein B (apoB), and C reactive protein (hs-CRP) concentrations were higher in BR than in SP: 179.0 vs.161 mg/dL; 141 vs. 103 mg/dL; and 1.6 vs. 0.8 mg/L respectively (all p < 0.001). In BR there was lower median total fat (22.3 vs. 38.3%) and SFA (8.1 vs. 12.5%) but higher cholesterol (283.3 mg vs.188.9 mg) and carbohydrate (57.1 vs. 42.5%) consumption (all p < 0.001). Inverse associations were encountered between fibers, mono, and polyunsaturated fats and their ratios to SFA with LDL-C and ApoB (all p < 0.001). There was a direct association respectively of cholesterol with lipid biomarkers and of carbohydrates and trans-fatty acids with hs-CRP while other fats showed inverse relations with the latter (p < 0.001).

5.
Sci Rep ; 9(1): 17184, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31748628

RESUMO

Cardiovascular disease is an important cause of morbidity and mortality in people living with HIV (PLWH), who commonly experience lipid disturbances. The aim of this study was to determine whether the plasma lipidomic profile differs between PLWH receiving a darunavir-based ART and those receiving integrase inhibitor-based ART. This was a cross-sectional study of unselected patients for whom metabolomic analysis was performed using ultra-high-performance liquid chromatography coupled to mass spectrometry. Data for the two subgroups were compared by calculating the log2 of the fold change for each metabolite and then grouping these into the main lipid families. Sixty-two PLWH aged 49.3 ± 8.6 years (82% men) were included: 12 patients (19.4%) had hypertension, 8 (12.9%) had type 2 diabetes, 25 (41.0%) had dyslipidaemia and 9 (14.5%) were taking statins, without significant differences in all these variables between the two groups. Twenty-five (40.3%) received darunavir-based ART and 37 (59.7%) integrase inhibitor-based ART. Although the differences were not statistically significant, patients treated with darunavir-based ART had higher concentrations of total cholesterol (211 mg/dL vs 194 mg/dL), LDL-cholesterol (132 mg/dL vs 117 mg/dL) and triglycerides (155 mg/dL vs 122 mg/dL), and lower HDL-cholesterol concentration (50 mg/dL vs 52 mg/dL). The main lipid families and metabolites differed slightly between groups (log2-fold change; P-value): ceramides (-0.07; 0.49), phosphatidylinositols (-0.05; 0.63), diacylglycerols (0.10; 0.64), phosphatidylethanolamines (0.03; 0.78), triacylglycerols (0.27; 0.18) and lysophosphatidylethanolamines (0.03; 0.83). In the integrase inhibitor-based group, the use of tenofovir alafenamide fumarate significantly increases the majority of lipid fractions, when compared with tenofovir disoproxil fumarate. The lipidomic profile did not differ between PLWH treated with darunavir-based or integrase inhibitor-based ART. This was especially true for ceramides, which are involved in cardiovascular disease. Further studies are needed to study the impact of ART in lipidomic profile.

6.
Atherosclerosis ; 286: 40-45, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31100618

RESUMO

BACKGROUND AND AIMS: Patients with familial hypercholesterolaemia (FH) may require proprotein convertase subtilisin/kexin-type 9 (PCSK9) mAb as add-on therapy to achieve LDL-cholesterol (LDL-C) goals. However, the current cost of these therapies means that choosing suitable patients is based on consensus or clinical judgement rather than a quantitative risk assessment. We used the SAFEHEART Risk Equation (RE) to estimate the number needed to treat (NNT) at different risk thresholds and baseline LDL-C to identify those FH patients more likely to derive the greatest benefit from PCSK9 mAb. METHODS: Five-year event rates were calculated using the SAFEHEART-RE for every patient, overall and across LDL-C strata. A 60% reduction of LDL-C after theoretical treatment with PCSK9 mAb was assumed. Individual absolute risk simulating the effects of PCSK9 inhibition was calculated using the SAFEHEART-RE and, in a similar way, by using the Cholesterol Treatment Trialists' (CTT) Collaboration criteria. Absolute risk reduction and NNTs were calculated. RESULTS: Of the total SAFEHEART population, 2,153 were FH cases aged 18 years or older, on maximum tolerated lipid lowering treatment. NNTs were dependent of both baseline predicted risk and baseline LDL-C level ranging from 44 to 17 for those with 5-year risk of ≥1 to ≥5. The smallest NNT (12) was observed among those with 5-year risk of ≥5% and LDL-C ≥160 mg/dl. Using the CTT criteria produced similar results. CONCLUSIONS: The SAFEHEART-RE may provide a useful quantitative tool for rationalising the selection of FH patients who might derive greater absolute benefits from PCSK9 mAb.

7.
Atherosclerosis ; 285: 17-22, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30991288

RESUMO

BACKGROUND AND AIMS: Heterozygous familial hypercholesterolemia (FH) is a genetic disorder characterized by high levels of low-density lipoprotein cholesterol (LDL-C). The magnitude of atherosclerotic cardiovascular disease (ASCVD) risk in FH patients is highly variable, and this can result from genetic factors. The aim of our study was to characterize whether polymorphisms in VEGFR2 and OPG genes could influence the expression of ASCVD in FH patients. METHODS: We studied 318 FH patients from the SAFEHEART registry, without clinical diagnosis of ASCVD. A coronary tomographic angiography (CTA) was performed to determine and evaluate the presence of coronary stenosis and coronary artery calcium, as measured by coronary calcium score (CCS). Genotyping of OPG rs2073618 and VEGFR2 rs2071559 polymorphisms was performed using TaqMan 5'-exonuclease allelic discrimination assays. RESULTS: Homozygous GG genotype and G allele of VEGFR2 rs2071559 polymorphism were associated with decreased risk of developing coronary artery stenosis. In the analysis of OPG rs2073618 and VEGFR2 rs2071559 polymorphisms, according to the presence of coronary artery calcium, we found significant differences in both polymorphisms. Homozygous GG genotype and G allele of VEGFR2 rs2071559 polymorphism were associated with decreased risk of accumulation of coronary artery calcium measured by CCS in CTA. Moreover, being a carrier of the GG genotype and G allele of the OPG rs2073618 polymorphism increased the risk of the presence of coronary artery calcium measured by CCS in CTA. CONCLUSIONS: Polymorphisms in VEGFR2 and OPG genes modify the risk of ASCVD in FH patients.

8.
Eur Cardiol ; 13(1): 14-20, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30310464

RESUMO

Familial hypercholesterolaemia is the most common monogenic disorder associated with premature coronary artery disease. Mutations are most frequently found in the LDL receptor gene. Clinical criteria can be used to make the diagnosis; however, genetic testing will confirm the disorder and is very useful for cascade screening. Early identification and adequate treatment can improve prognosis, reducing negative clinical cardiovascular outcomes. Patients with familial hypercholesterolaemia are considered at high cardiovascular risk and the treatment target is LDL cholesterol <2.6 mmol/l or at least a 50 % reduction in LDL cholesterol. Patients require intensive treatment with statins and ezetimibe and/or colesevelam. Recently, proprotein convertase subtilisin/kexin type 9 inhibitors have been approved for the management of familial hypercholesterolaemia on top of statins.

9.
J Clin Lipidol ; 12(6): 1482-1492.e3, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30150141

RESUMO

BACKGROUND: Familial chylomicronemia syndrome (FCS) is an extremely rare lipoprotein disorder caused by mutations in at least 5 genes of the lipoprotein lipase (LPL) complex. OBJECTIVE: This work shows the molecular analysis of patients diagnosed with FCS, who attended the Spanish Arteriosclerosis Society lipid units and were included in the National Dyslipidemia Registry. METHODS: Among the 238 patients registered with severe hypertriglyceridemia (fasting triglycerides >1000 mg/dL), 26 were diagnosed with FCS as they had confirmed postheparin plasma LPL activity deficiency and/or homozygosity for loss-of-function mutations in LPL, GPIHBP1, APOC2, LMF1, or Apolipoprotein A5 (APOA5). RESULTS: Among the 26 FCS cases, 23 had mutations in the homozygous state: 19 in LPL and 4 in the GPIHBP1 gene. The molecular analysis revealed 3 novel mutations: 2 in LPL, in 2 unrelated patients (c.312delA; p.Asp105Thrfs*66 and c.629A>G; p.His210Arg), and 1 in GPHIBP1 in a third patient (c.502delC; p.Leu168Serfs*83). These 3 patients had confirmed lack of LPL activity. Three additional patients with confirmed LPL activity deficiency were heterozygous carriers of mutations in the genes analyzed. Among these, we found 2 novel mutations in APOA5 (c.50-1G>A and c.326_327insC; p.Tyr110Leufs*158). CONCLUSION: We have identified 5 novel pathogenic mutations: 2 in LPL, 1 in GPIHBP1, and 2 in the APOA5 gene. The genetic defaults accounting for the LPL activity deficiency of 23 of them have been clearly identified and 3 patients, who harbored mutations in heterozygosity, were diagnosed based on LPL activity deficiency, which raises the question of the involvement of new genes in the manifestation of FCS.


Assuntos
Aterosclerose , Hiperlipoproteinemia Tipo I/genética , Hiperlipoproteinemia Tipo I/metabolismo , Sistema de Registros/estatística & dados numéricos , Sociedades Médicas , Adulto , Feminino , Humanos , Hiperlipoproteinemia Tipo I/epidemiologia , Lipase Lipoproteica/genética , Lipase Lipoproteica/metabolismo , Masculino , Pessoa de Meia-Idade , Mutação , Espanha , Triglicerídeos/sangue
10.
Med. clín (Ed. impr.) ; 151(1): 8-15, jul. 2018. tab
Artigo em Espanhol | IBECS | ID: ibc-173743

RESUMO

Fundamento y objetivo: Evaluar en la práctica clínica el cumplimiento de las recomendaciones del Informe de Posicionamiento Terapéutico (IPT) de la Agencia Española de Medicamentos y Productos Sanitarios sobre el tratamiento con anticoagulantes orales en pacientes≥75 años con fibrilación auricular no valvular (FANV) atendidos en unidades de Medicina Interna en España. Pacientes y métodos: Estudio observacional, transversal y multicéntrico, en el que se incluyeron 837 pacientes≥75 años con FANV en tratamiento estable con anticoagulantes orales durante los 3 meses previos a la inclusión y que hubiesen iniciado dicho tratamiento antes de comenzar el período de inclusión. Resultados: La edad media fue de 83,0±5,0 años, el CHADS2 medio 3,2±1,2, el CHA2DS2-VASc 5,0±1,4 y el HAS-BLED 2,1±0,9. El 70,8% de los pacientes estaba en tratamiento con antagonistas de la vitamina K (AVK) y el resto con anticoagulantes orales de acción directa (ACOD). El 65,6% de los pacientes con AVK no siguieron las recomendaciones del IPT frente al 43,0% de los pacientes con ACOD (p<0,0001). En el caso de los pacientes con AVK, el motivo principal para ser considerado como no adecuado fue presentar un mal control de la anticoagulación y no cambiar a un ACOD, mientras que en el caso de los ACOD fue recibir una dosis inadecuada según el IPT. Conclusiones: En un porcentaje elevado de pacientes ancianos con FANV anticoagulados en España no se siguen las recomendaciones realizadas por el IPT, especialmente con los AVK, al no realizarse el cambio a ACOD a pesar de un tiempo en rango terapéutico inadecuado


Background and objective: To evaluate the adherence to the recommendations in clinical practice performed by the Therapeutic Positioning Report (TPR) of the Spanish Agency of Medicines and Sanitary Products about the treatment with oral anticoagulants in patients aged≥75 years old with nonvalvular atrial fibrillation (NVAF) treated in Internal Medicine departments in Spain. Patients and methods: Observational, cross-sectional and multicenter study in which 837 patients aged≥75 years old with NVAF, with stable treatment with oral anticoagulants at least 3 months before inclusion, and that had started treatment with oral anticoagulants before the inclusion period were included. Results: Mean age was 83.0±5.0 years old, mean CHADS2 score 3.2±1.2, mean CHA2DS2-VASc score 5.0±1.4, and mean HAS-BLED score 2.1±0.9. A percentage of 70.8 of patients were treated with vitamin K antagonists (VKA) and the rest of patients with direct oral anticoagulants (DOACs). A percentage of 65.6 of patients treated with VKA did not follow the recommendations made by the TPR compared with 43.0% of patients treated with DOACs (P<.0001). In the case of VKA, the main reason for being considered as not appropriate according to the TPR was having poor control of anticoagulation and not switching to DOACs, whereas in the case of DOACs, it was not receiving the adequate dose according to the TPR. Conclusions: In a high proportion of anticoagulated elderly patients with NVAF in Spain, the recommendations performed by the TPR are not followed, particularly with VKA, since patients are not switched to DOACs despite time in therapeutic range


Assuntos
Humanos , Masculino , Feminino , Idoso , Idoso de 80 Anos ou mais , Vitamina K/antagonistas & inibidores , Antifibrinolíticos/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Estudo Observacional , Estudos Transversais , Anticoagulantes/uso terapêutico , Anticoagulantes/administração & dosagem , Idoso
11.
J Clin Lipidol ; 12(4): 948-957, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29753733

RESUMO

BACKGROUND: Familial hypercholesterolemia (FH) confers an increased risk of premature atherosclerotic disease. Coronary computed tomographic angiography (CTA) can assess preclinical coronary atherosclerosis. OBJECTIVES: To describe coronary CTA findings in asymptomatic molecularly defined FH individuals, to identify those factors related to its presence and extension, and to assess the impact of these results in patients' care and estimated risk. METHODS: Four hundred and forty individuals with FH, without clinical cardiovascular disease, were consecutively enrolled and underwent a coronary CTA that was used to analyze coronary atherosclerosis based on coronary calcium score (CCS), sum of stenosis severity, and plaque composition sum (PCS). For FH patients, cardiovascular risk was estimated using the specific SAFEHEART risk equation. Follow-up was performed using a standardized protocol. RESULTS: Mean age was 46.4 years (231 women, 52%). Coronary calcium was present in 55%, mean CCS was 130.9, 46% had a plaque with lumen involvement, and mean PCS was 1.1. During follow-up, there were 17 (4%) nonfatal events and 2 (1%) fatal events. CCS was independently associated to the estimated risk and low-density lipoprotein-cholesterol life-years, sum of stenosis severity to the estimated risk, and PCS to the estimated risk and low-density lipoprotein-cholesterol life-years. CTA findings induced a positive change in patients' care and in their estimated risk. CONCLUSION: Coronary artery atherosclerosis is highly prevalent in asymptomatic patients with FH and it is independently associated to cardiovascular risk. More advanced disease on CTA was associated with subsequent intensification of therapy and reduction of estimated risk. Further longitudinal studies are required to know if these findings might improve the risk stratification in patients with FH.


Assuntos
Angiografia Coronária , Hiperlipoproteinemia Tipo II/diagnóstico , Adulto , Idoso , Cálcio/metabolismo , LDL-Colesterol/sangue , Constrição Patológica , Feminino , Seguimentos , Humanos , Hiperlipoproteinemia Tipo II/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/complicações , Placa Aterosclerótica/diagnóstico , Fatores de Risco , Tomografia Computadorizada por Raios X , Adulto Jovem
12.
Patient Prefer Adherence ; 12: 267-274, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29497282

RESUMO

Background: Although, by itself, atrial fibrillation is associated with an impairment of quality of life antithrombotic therapy may play a role. Objective: To evaluate the satisfaction with anticoagulant treatment in patients with nonvalvular atrial fibrillation who attended internal medicine departments in Spain. Methods: Patients from two different cross-sectional studies were combined. To measure the satisfaction with anticoagulant treatment, the Anti-Clot-Treatment Scale (ACTS) questionnaire was completed by every patient. A multivariate analysis was performed to determine the variables associated with satisfaction of patients receiving oral anticoagulants. Results: A total of 1,309 patients (mean age 78.5±8.4 years; 49.3% men; CHA2DS2VASC 4.9±1.5; HAS-BLED 2.0±0.9) were included in the study, of whom 902 (68.9%) were taking vitamin K antagonists (VKA) and 407 (31.1%) direct oral anticoagulants (DOACs). Overall, satisfaction with oral anticoagulation was high (ACTS Burdens scale 49.69±9.45; ACTS Benefits scale 11.35±2.61). The perceived burdens with anticoagulant treatment were lower in men, as well as in patients with no dependency, normal renal function, who were not polymedicated, or who had moderate bleeding risk. Among patients taking VKA, those subjects with a lower number of International Normalized Ratio (INR) determinations in the last 6 months or with an optimal time in the therapeutic range exhibited a lower perceived burden. Patients taking DOACs (vs VKA) showed a lower perceived burden with anticoagulation. Benefits with anti-coagulation were higher in men, younger patients, those with no dependency, or low bleeding risk. Perceived benefits were higher in patients taking DOACs (vs VKA). Conclusion: Satisfaction with oral anticoagulation was high in patients with nonvalvular atrial fibrillation, who were attending internal medicine departments daily in Spain. Among patients taking VKA, those subjects with a lower number of INR determinations in the last 6 months or with an optimal time in the therapeutic range exhibited a lower perceived burden with anticoagulant therapy. Patients taking DOACs (vs VKA) showed lower perceived burdens and higher perceived benefits with anticoagulation.

13.
J Comp Eff Res ; 7(3): 223-232, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29465254

RESUMO

AIM: To analyze the use of oral anticoagulants in elderly patients with atrial fibrillation in clinical practice. PATIENTS & METHODS: Cross-sectional and multicenter study performed in atrial fibrillation patients ≥75 years treated with oral anticoagulants ≥3 months. RESULTS: 837 patients (83.0 ± 5.0 years; CHA2DS2-VASc 5.0 ± 1.4; HAS-BLED 2.1 ± 0.9; 70.8% vitamin K antagonists; 29.2% direct oral anticoagulants [DOACs]) were included. Poor adherence was observed in 27.9% of patients. Higher scores in the Pfeiffer's test and FRAIL scale were associated with poorer adherence. Among patients treated with DOACs, 62.3% received the lower doses. Having high CHADS2 score and being older were associated with the use of low doses. CONCLUSION: 28% of patients had a poor adherence to anticoagulant treatment. 62% of patients were treated with the lower doses of DOACs.


Assuntos
Anticoagulantes/administração & dosagem , Fibrilação Atrial/tratamento farmacológico , Administração Oral , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Adesão à Medicação , Polimedicação , Acidente Vascular Cerebral/prevenção & controle
14.
Med Clin (Barc) ; 151(1): 8-15, 2018 07 13.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-28992980

RESUMO

BACKGROUND AND OBJECTIVE: To evaluate the adherence to the recommendations in clinical practice performed by the Therapeutic Positioning Report (TPR) of the Spanish Agency of Medicines and Sanitary Products about the treatment with oral anticoagulants in patients aged≥75 years old with nonvalvular atrial fibrillation (NVAF) treated in Internal Medicine departments in Spain. PATIENTS AND METHODS: Observational, cross-sectional and multicenter study in which 837 patients aged≥75 years old with NVAF, with stable treatment with oral anticoagulants at least 3 months before inclusion, and that had started treatment with oral anticoagulants before the inclusion period were included. RESULTS: Mean age was 83.0±5.0 years old, mean CHADS2 score 3.2±1.2, mean CHA2DS2-VASc score 5.0±1.4, and mean HAS-BLED score 2.1±0.9. A percentage of 70.8 of patients were treated with vitamin K antagonists (VKA) and the rest of patients with direct oral anticoagulants (DOACs). A percentage of 65.6 of patients treated with VKA did not follow the recommendations made by the TPR compared with 43.0% of patients treated with DOACs (P<.0001). In the case of VKA, the main reason for being considered as not appropriate according to the TPR was having poor control of anticoagulation and not switching to DOACs, whereas in the case of DOACs, it was not receiving the adequate dose according to the TPR. CONCLUSIONS: In a high proportion of anticoagulated elderly patients with NVAF in Spain, the recommendations performed by the TPR are not followed, particularly with VKA, since patients are not switched to DOACs despite time in therapeutic range.


Assuntos
Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Fidelidade a Diretrizes/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Masculino , Guias de Prática Clínica como Assunto , Espanha
15.
Rev. esp. cardiol. (Ed. impr.) ; 70(6): 444-450, jun. 2017. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-163301

RESUMO

Introducción y objetivos: Poco se conoce acerca de las características de los sujetos con hipercolesterolemia familiar (HF) menores de 18 años, así como del tratamiento hipolipemiante empleado en estos pacientes y la consecución de objetivos lipídicos en la vida real. Nuestro objetivo es valorar la consecución de objetivos de colesterol unido a lipoproteínas de baja densidad (cLDL) en pacientes con HF menores de 18 años incluidos en un gran registro nacional. Métodos: Se analizó a los pacientes menores de 18 años incluidos en un gran registro en marcha de pacientes con diagnóstico genético de HF en España. Se analizó la consecución de los objetivos recomendados de cLDL en plasma a la inclusión y en el seguimiento en relación con el uso de terapia hipolipemiante. Resultados: Se incluyó a 392 individuos menores de 18 años, de los que 217 obtuvieron diagnóstico genético de HF y seguimiento completo. El tiempo de seguimiento medio fue 4,69 [intervalo intercuartílico, 2,48-6,38] años; el 68,2% de los casos con HF tomaban estatinas y el 41,5% de los pacientes tenían el cLDL < 130 mg/dl. El uso de estatinas fue el único predictor de consecución de objetivos de cLDL. Conclusiones: Este estudio demostró que una alta proporción de pacientes con HF menores de 18 años tenía altas concentraciones de cLDL y no lograron alcanzar los objetivos de cLDL recomendados. El uso de estatinas fue el único predictor independiente asociado a conseguir el objetivo de cLDL recomendado. No se detectó ningún problema de seguridad durante el seguimiento. Estos resultados enfatizan que muchos pacientes con HF no están suficientemente controlados y aún es posible mejorar del tratamiento (AU)


Introduction and objectives: Little is known about the characteristics of persons with familial hypercholesterolemia (FH) younger than 18 years, the lipid-lowering therapy used in these patients, and the lipid goals reached in real life. Our aim was to evaluate the achievement of low-density lipoprotein cholesterol (LDL-C) treatment goals in FH patients younger than 18 years enrolled in a large national registry. Methods: We analyzed patients younger than 18 years enrolled in a large ongoing registry of molecularly-defined patients with FH in Spain. The attainment of guideline-recommended plasma LDL-C goals at entry and follow-up was analyzed in relation to the use of lipid-lowering therapy. Results: We enrolled 392 individuals younger than 18 years. Of these, 217 were molecularly-diagnosed FH patients and had a complete follow-up. The median follow-up time was 4.69 years (interquartile range, 2.48-6.38 years), 68.2% of FH patients were on statins, and 41.5% patients had LDL-C < 130 mg/dL. Statin use was the only predictor of LDL-C goal attainment. Conclusions: This study shows that a high proportion of FH patients younger than 18 years have high LDL-C levels and fail to achieve recommended LDL-C targets. Statin use was the only independent predictor of LDL-C goal achievement. No safety concerns were detected during follow-up. These results indicate that many FH patients are not adequately controlled and that there is still room for treatment improvement (AU)


Assuntos
Humanos , Criança , Adolescente , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Anticolesterolemiantes/uso terapêutico , Doenças Cardiovasculares/epidemiologia , Arteriosclerose/epidemiologia , Marcadores Genéticos
16.
J Clin Lipidol ; 11(1): 260-271, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28391894

RESUMO

BACKGROUND: Although familial hypercholesterolemia (FH) confers a high risk of coronary artery disease, most patients are undiagnosed, and little is known about the efficiency of genetic cascade screening programs at national level. OBJECTIVE: The aim of the study was to estimate the cost-effectiveness of a national genetic cascade screening program in Spain. METHODS: An economic evaluation was performed using a decision tree analysis. The choice in the decision tree was between implementation of the national program for FH (NPFH) or keeping the usual clinical care. The NPFH detects FH patients through total cholesterol measurement at primary care level and use of genetic testing in index cases and relatives. The payer (National Health System) and social (including the productivity lost) perspectives were considered. The outcome variables were coronary events avoided, deaths avoided, and quality-adjusted life years (QALYs) gained. RESULTS: From the payer perspective, the application of the NPFH during 1 year prevents 847 coronary events and 203 deaths in the 9000 FH patients cohort during a 10-year follow-up, yielding an extra 767 QALYs, at a cost of €29,608 per QALY gained. From the social perspective, the NPFH is dominant over the control (the cost decreases and the effectiveness increases). The sensitivity analysis confirms the robustness of the findings. CONCLUSION: The NPFH based on molecular testing is a cost-effective diagnostic and management strategy that supports government expenditure aimed at preventing coronary artery disease in FH patients in Spain. Implementation of such a strategy is likely to be also cost-effective in countries with similar developed healthcare systems.


Assuntos
Análise Custo-Benefício , Hiperlipoproteinemia Tipo II/diagnóstico , Programas de Rastreamento/economia , Adulto , Diagnóstico Precoce , Feminino , Humanos , Masculino
17.
Circulation ; 135(22): 2133-2144, 2017 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-28275165

RESUMO

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/epidemiologia
18.
Rev Esp Cardiol (Engl Ed) ; 70(6): 444-450, 2017 Jun.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-27913073

RESUMO

INTRODUCTION AND OBJECTIVES: Little is known about the characteristics of persons with familial hypercholesterolemia (FH) younger than 18 years, the lipid-lowering therapy used in these patients, and the lipid goals reached in real life. Our aim was to evaluate the achievement of low-density lipoprotein cholesterol (LDL-C) treatment goals in FH patients younger than 18 years enrolled in a large national registry. METHODS: We analyzed patients younger than 18 years enrolled in a large ongoing registry of molecularly-defined patients with FH in Spain. The attainment of guideline-recommended plasma LDL-C goals at entry and follow-up was analyzed in relation to the use of lipid-lowering therapy. RESULTS: We enrolled 392 individuals younger than 18 years. Of these, 217 were molecularly-diagnosed FH patients and had a complete follow-up. The median follow-up time was 4.69 years (interquartile range, 2.48-6.38 years), 68.2% of FH patients were on statins, and 41.5% patients had LDL-C < 130mg/dL. Statin use was the only predictor of LDL-C goal attainment. CONCLUSIONS: This study shows that a high proportion of FH patients younger than 18 years have high LDL-C levels and fail to achieve recommended LDL-C targets. Statin use was the only independent predictor of LDL-C goal achievement. No safety concerns were detected during follow-up. These results indicate that many FH patients are not adequately controlled and that there is still room for treatment improvement.


Assuntos
Anticolesterolemiantes/uso terapêutico , LDL-Colesterol/sangue , Fidelidade a Diretrizes , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Sistema de Registros , Adolescente , Criança , LDL-Colesterol/efeitos dos fármacos , Feminino , Seguimentos , Humanos , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/epidemiologia , Incidência , Masculino , Estudos Prospectivos , Espanha/epidemiologia , Resultado do Tratamento
19.
J Clin Lipidol ; 10(4): 953-961, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27578128

RESUMO

BACKGROUND: Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder associated with very high levels of cholesterol, accelerated atherosclerosis and very premature death, often secondary to occlusion of the coronary ostia by supravalvular atheroma in untreated individuals. OBJECTIVE: To describe molecular and clinical characteristics of HoFH enrolled at SAFEHEART registry and to evaluate the role of the type of mutation in clinical expression. METHODS: SAFEHEART is a registry of molecularly defined familial hypercholesterolemia patients. A standardized phone call is made every year for the follow-up. Patients with confirmed HoFH were selected. Molecular and clinical characteristics were analyzed. RESULTS: Thirty-four HoFH patients (27 true HoFH, 4 compound heterozygous familial hypercholesterolemia, and 3 autosomal recessive hypercholesterolemia) have been enrolled in the period 2004-2015. Twenty different mutations in LDLR gene have been detected. Sixteen patients carry defective mutations (DMs), and 15 carry null mutations (NMs). Only patients with NMs met low-density lipoprotein cholesterol (LDL-C) criteria for clinical diagnosis. Patients with NMs had higher untreated LDL-C levels (P < .0001), more aortic valve stenosis (P < .05), and lower age at first cardiovascular event (P < .05) compared to patients with DMs. In the follow-up, 1 liver transplant patient died and 3 cases underwent revascularization procedures. Eight cases started LDL apheresis and 1 case had a liver transplant. CONCLUSIONS: HoFH phenotypic expression is highly variable. These patients have high atherosclerotic coronary artery disease risk including aortic valve stenosis and do not achieve the LDL-C treatment goals with standard therapy.


Assuntos
Hiperlipoproteinemia Tipo II/epidemiologia , Hiperlipoproteinemia Tipo II/genética , Sistema de Registros/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Seguimentos , Humanos , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Hipolipemiantes/farmacologia , Hipolipemiantes/uso terapêutico , Lactente , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Mutação , Fenótipo , Receptores de LDL/genética , Espanha/epidemiologia , Adulto Jovem
20.
J Am Coll Cardiol ; 67(11): 1278-85, 2016 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-26988947

RESUMO

BACKGROUND: Familial hypercholesterolemia (FH) is the most common genetic disorder associated with premature atherosclerotic cardiovascular disease (ASCVD). There are sparse data on attainment of treatment targets; large registries that reflect real-life clinical practice can uniquely provide this information. OBJECTIVES: We sought to evaluate the achievement of low-density lipoprotein cholesterol (LDL-C) treatment goals in FH patients enrolled in a large national registry. METHODS: The SAFEHEART study (Spanish Familial Hypercholesterolemia Cohort Study) is a large, ongoing registry of molecularly defined patients with heterozygous FH treated in Spain. The attainment of guideline-recommended plasma LDL-C goals at entry and follow-up was investigated in relation to use of lipid-lowering therapy (LLT). RESULTS: The study recruited 4,132 individuals (3,745 of whom were ≥18 years of age); 2,752 of those enrolled were molecularly diagnosed FH cases. Mean follow-up was 5.1 ± 3.1 years; 71.8% of FH cases were on maximal LLT, and an LDL-C treatment target <100 mg/dl was reached by only 11.2% of patients. At follow-up, there was a significant increase in the use of ezetimibe, drug combinations with statins, and maximal LLT. The presence of type 2 diabetes mellitus, a defective allele mutation, ezetimibe use, and the absence of previous ASCVD were predictors of the attainment of LDL-C goals. CONCLUSIONS: Despite the use of intensified LLT, many FH patients continue to experience high plasma LDL-C levels and, consequently, do not achieve recommended treatment targets. Type of LDL-receptor mutation, use of ezetimibe, coexistent diabetes, and ASCVD status can bear significantly on the likelihood of attaining LDL-C treatment goals.


Assuntos
Anticolesterolemiantes/uso terapêutico , Atorvastatina/administração & dosagem , LDL-Colesterol/sangue , Ezetimiba/administração & dosagem , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Sistema de Registros , Rosuvastatina Cálcica/administração & dosagem , Adolescente , Adulto , Biomarcadores/sangue , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Espanha/epidemiologia , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
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