Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 27
Filtrar
Mais filtros










Intervalo de ano de publicação
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.
Vasc Health Risk Manag ; 16: 11-25, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32021224

RESUMO

Familial hypercholesterolemia (FH) is a frequent disorder associated with premature atherosclerotic cardiovascular disease. Different clinical diagnosis criteria are available, and cost of genetic testing has been reduced in the last years; however, most cases are not diagnosed worldwide. Patients with FH are at high cardiovascular risk and the risk can be reduced with lifelong lifestyle and pharmacological treatment. Statins and ezetimibe are available as generic drugs in most countries reducing the cost of treatment. However, the use of high-intensity statins combined with ezetimibe and PCSK9 inhibitors, if necessary, is low for different reasons that contribute to a high number of patients not reaching LDL-C targets according to guidelines. On the other hand, cardiovascular risk varies greatly in families with FH; therefore, risk stratification strategies including cardiovascular imaging is another element to consider for improving care and management of FH. There are numerous barriers depending on the awareness, knowledge, perception of risk, management and care of patients living with FH that impact in the diagnosis and treatment of the disorder. In this contemporary review, we analyze different barriers in the diagnosis and care of patients to improve patients' care and prevention of atherosclerotic cardiovascular disease and describe recent advances and strategies to improve the gaps in the care of FH, including global collaboration and advocacy.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Colesterol/sangue , Prestação Integrada de Cuidados de Saúde , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/terapia , Programas de Rastreamento , Melhoria de Qualidade , Indicadores de Qualidade em Assistência à Saúde , Biomarcadores/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/etiologia , Diagnóstico Precoce , Predisposição Genética para Doença , Testes Genéticos , Humanos , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/genética , Fenótipo , Valor Preditivo dos Testes , Prognóstico , Medição de Risco , Fatores de Risco
3.
Clin Chim Acta ; 500: 163-171, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31669931

RESUMO

INTRODUCTION: Pathogenic variants in lipoprotein lipase (LPL) and glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) have been described in patients with severe hypertriglyceridaemia. We aimed to optimise high resolution melting (HRM) assays to detect the presence of functional variants in these genes. METHODS: One hundred and sixteen patients with severe hypertriglyceridaemia were studied. HRM assays were optimised to scan exons and splice junctions in LPL and GPIHBP1. Sanger sequencing was the reference method. Next-generation-sequencing (NGS) was performed in five patients, including one with Familial Chylomicronemia syndrome (FCS). RESULTS: We identified 15 different variants in LPL and 6 in GPIHBP1. The variants revealed with NGS were also detected with HRM, including a rare premature stop codon in LPL (p.Trp421*) and two LPL pathogenic variants in the patient with FCS (p.His80Arg + p.Gly215Glu). Having multiple functional variant alleles was associated with pancreatitis onset at younger ages and higher baseline triglycerides. CONCLUSIONS: Our HRM assays detected the presence of functional gene variants that were confirmed with Sanger and NGS sequencing. The presence of multiple functional variant alleles was associated with differences in the clinical profile. Therefore, these assays represent a reliable, cost-effective tool that can be used to complement the NGS approach for gene scanning.

4.
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.

5.
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).

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.
Public Health Nutr ; 22(8): 1433-1443, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30732662

RESUMO

OBJECTIVE: Healthy lifestyle habits are the cornerstone in the management of familial hypercholesterolaemia (FH). Nevertheless, dietary studies on FH-affected populations are scarce. The present study analyses dietary habits, adherence to a Mediterranean diet pattern and physical activity in an adult population with FH and compares them with their non-affected relatives. DESIGN: Cross-sectional study. SETTING: Data came from SAFEHEART, a nationwide study in Spain.ParticipantsIndividuals (n 3714) aged ≥18 years with a genetic diagnosis of FH (n2736) and their non-affected relatives (n 978). Food consumption was evaluated using a validated FFQ. RESULTS: Total energy intake was lower in FH patients v. non-affected relatives (P<0·005). Percentage of energy from fats was also lower in the FH population (35 % in men, 36 % in women) v. those non-affected (38 % in both sexes, P<0·005), due to the lower consumption of saturated fats (12·1 % in FH patients, 13·2 % in non-affected, P<0·005). Consumption of sugars was lower in FH patients v. non-affected relatives (P<0·05). Consumption of vegetables, fish and skimmed milk was higher in the FH population (P<0·005). Patients with FH showed greater adherence to a Mediterranean diet pattern v. non-affected relatives (P<0·005). Active smoking was lower and moderate physical activity was higher in people with FH, especially women (P<0·005). CONCLUSIONS: Adult patients with FH report healthier lifestyles than their non-affected family members. They eat a healthier diet, perform more physical activity and smoke less. However, this patient group's consumption of saturated fats and sugars still exceeds guidelines.

9.
J Clin Lipidol ; 12(5): 1234-1243.e5, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30318066

RESUMO

BACKGROUND: Familial chylomicronemia syndrome (FCS) is a rare metabolic disorder caused by mutations in lipoprotein lipase (LPL) or genes required for LPL functionality and is characterized by hyperchylomicronemia that results in recurrent episodes of acute pancreatitis. Owing to the rarity of FCS, there are few case series describing the phenotypic variability in FCS patients in detail. OBJECTIVE: To provide baseline characteristics in the largest study population to date of patients with FCS. METHODS: We analyzed baseline demographic and clinical characteristics of adult FCS patients in the phase 3 APPROACH study of volanesorsen sodium (antisense inhibitor of apolipoprotein C-III). RESULTS: Sixty-six patients were included in the analysis. Mean (SD) age was 46 (13) years; and mean body mass index was 24.9 (5.7) kg/m2. We identified causal mutations in 79% (52) of patients, with LPL mutations accounting for 62% (41) of cases. Median age at diagnosis was 24 years, 54% were females, and 81% were Caucasian. All patients followed a low-fat diet, 43% received fibrates, 27% fish oils, and 21% statins. Median fasting triglyceride levels (P25, P75) were 1985 (1179, 3047 mg/dL). Overall, 76% of patients reported ≥1 lifetime episode of acute pancreatitis; 23 patients reported a total of 53 pancreatitis events in the 5 years before enrollment. CONCLUSIONS: Our data emphasize the severe hypertriglyceridemia characteristic of FCS patients despite restrictive low-fat diets and frequent use of existing hypolipemic therapies. Acute pancreatitis and recurrent acute pancreatitis are frequent complications of FCS. Diagnosis at an older age suggests likely underdiagnosis and underappreciation of this rare disorder.


Assuntos
Hiperlipoproteinemia Tipo I/tratamento farmacológico , Oligonucleotídeos/uso terapêutico , Adulto , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
10.
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.

11.
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
12.
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
13.
Clín. investig. arterioscler. (Ed. impr.) ; 29(2): 98-102, mar.-abr. 2017. ilus
Artigo em Espanhol | IBECS | ID: ibc-161021

RESUMO

La lipoproteína (a) [Lp(a)] es una lipoproteína definida por presentar una apolipoproteína específica, la apoA, unida a la apoB-100 por diversos tipos de enlaces químicos, entre ellos un puente disulfuro. A pesar de que su mecanismo aterogénico no es completamente conocido, está demostrada su importancia en el desarrollo de ateroesclerosis prematura, mostrando múltiples estudios su papel como factor de riesgo cardiovascular asociado a enfermedad coronaria e ictus. Presentamos el caso de una paciente con diagnóstico de arteritis de Takayasu en la que se detectó una elevación masiva de Lp(a), y abordamos las implicaciones diagnósticas y terapéuticas que tuvo este hallazgo


Lipoprotein (a) [Lp(a)] is a lipoprotein defined by presenting a specific apolipoprotein, ApoA, linked to the ApoB-100 by different types of chemical bonds, including a disulfide bridge. Despite their atherogenic mechanism is not fully understood, its importance has been demonstrated in the development of premature aterosclerosis. Multiple studies have shown its role as a cardiovascular risk factor associated with heart disease and stroke. We report the case of a patient with a diagnosis of Takayasu arteritis in which a massive elevation of Lp(a) was detected. We emphasize its diagnostic and therapeutic implications


Assuntos
Humanos , Feminino , Adulto , Arterite de Takayasu/complicações , Hiperlipoproteinemias/complicações , Arteriosclerose/diagnóstico , Diagnóstico Diferencial , Hipertensão/complicações
14.
Clin Investig Arterioscler ; 29(2): 98-102, 2017.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-28188021

RESUMO

Lipoprotein (a) [Lp(a)] is a lipoprotein defined by presenting a specific apolipoprotein, ApoA, linked to the ApoB-100 by different types of chemical bonds, including a disulfide bridge. Despite their atherogenic mechanism is not fully understood, its importance has been demonstrated in the development of premature aterosclerosis. Multiple studies have shown its role as a cardiovascular risk factor associated with heart disease and stroke. We report the case of a patient with a diagnosis of Takayasu arteritis in which a massive elevation of Lp(a) was detected. We emphasize its diagnostic and therapeutic implications.


Assuntos
Aterosclerose/patologia , Lipoproteína(a)/sangue , Arterite de Takayasu/patologia , Adulto , Aterosclerose/sangue , Aterosclerose/diagnóstico , Doenças Cardiovasculares/etiologia , Angiografia por Tomografia Computadorizada , Feminino , Humanos , Fatores de Risco , Arterite de Takayasu/sangue , Arterite de Takayasu/diagnóstico
15.
Med. clín (Ed. impr.) ; 146(3): 117-120, feb. 2016. tab
Artigo em Espanhol | IBECS | ID: ibc-147824

RESUMO

Fundamento y objetivo: El bexaroteno es un rexinoide sintético selectivo del receptor X aprobado para el tratamiento sistémico del linfoma cutáneo de células T. Durante el tratamiento es muy frecuente la aparición de hipotiroidismo e hiperlipidemia mixta grave, siendo ambos efectos adversos reversibles y dependientes de la dosis. La elevación del colesterol LDL y los triglicéridos (hasta unos niveles aumentados que incluso se han asociado a pancreatitis en algunos casos) está ampliamente descrita (al igual que sucede con otros retinoides), siendo el descenso del colesterol HDL menos conocido. Revisamos nuestra experiencia con el uso de bexaroteno. Material y métodos: Se presenta una serie de 3 casos de pacientes tratados con bexaroteno en los que, además de sufrir los efectos adversos bien conocidos, se observó un grave descenso del colesterol HDL. Resultados: Los 3 pacientes estudiados presentaron complicaciones metabólicas en forma de hipotiroidismo central e hiperlipidemia mixta grave, con especial énfasis en el marcado descenso que experimentaron nuestros pacientes (descenso medio > 83%) en las cifras de colesterol HDL. El tratamiento hipolipidemiante y hormonal sustitutivo con levotiroxina dio lugar a una mejoría de los parámetros, sin llegar a alcanzarse los objetivos. Conclusiones: El bexaroteno produce, como efectos secundarios predecibles, una hiperlipidemia mixta grave con descenso marcado de los niveles de colesterol HDL e hipotiroidismo central, los cuales son reversibles y dependientes de la dosis. Se incluye una reflexión sobre los posibles mecanismos etológicos e implicaciones de este fenómeno (AU)


Background and objective: Bexarotene is a synthetic selective X receptor rexinoide approved for the systemic treatment of cutaneous T-cell lymphoma. During treatment is very frequent the occurrence of hypothyroidism and severe mixed hyperlipidemia, both are reversibles and dose-dependent adverse events. Increase of triglycerides and LDL-cholesterol level (up to even higher levels have been associated with pancreatitis in some cases) is widely described (as is the case with other retinoids) but decrease in HDL-cholesterol is poored know. We review our experience with the use of bexarotene. Material and methods: We present a serie of 3 clinical report of patients treated with bexarotene in whose, in addition to these well-known adverse event, a serious lowering of HDL-cholesterol was observed. Results: The 3 patients studied had metabolic complications like central hypothyroidism and severe mixed hyperlipidemia; with special emphasis on the sharp fall (mean decrease > 83%) in the HDL-cholesterol level. Cholesterol lowering medication and substitutive hormonal replacement with levotiroxine resulted in an improvement of the biochimical parameters without reaching the correct goals. Conclusions: Bexarotene produce as predictable side effects severe mixed hyperlipidemia with marked decrease in HDL-cholesterol levels and central hypothyroidism, being the both reversible and dose-dependent. A reflection on the possible aetiological mechanisms and implications of this phenomenon are included (AU)


Assuntos
Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Idoso , Linfoma Cutâneo de Células T/complicações , Linfoma Cutâneo de Células T/diagnóstico , Tetra-Hidronaftalenos/efeitos adversos , Tetra-Hidronaftalenos/uso terapêutico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/complicações , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , HDL-Colesterol , Tiroxina/uso terapêutico , Hipotireoidismo/induzido quimicamente , Hipotireoidismo/complicações , Hiperlipidemias/induzido quimicamente , Hiperlipidemias/complicações , Testes de Função Tireóidea/tendências
16.
Med Clin (Barc) ; 146(3): 117-20, 2016 Feb 05.
Artigo em Espanhol | MEDLINE | ID: mdl-26688184

RESUMO

BACKGROUND AND OBJECTIVE: Bexarotene is a synthetic selective X receptor rexinoide approved for the systemic treatment of cutaneous T-cell lymphoma. During treatment is very frequent the occurrence of hypothyroidism and severe mixed hyperlipidemia, both are reversibles and dose-dependent adverse events. Increase of triglycerides and LDL-cholesterol level (up to even higher levels have been associated with pancreatitis in some cases) is widely described (as is the case with other retinoids) but decrease in HDL-cholesterol is poored know. We review our experience with the use of bexarotene. MATERIAL AND METHODS: We present a serie of 3 clinical report of patients treated with bexarotene in whose, in addition to these well-known adverse event, a serious lowering of HDL-cholesterol was observed. RESULTS: The 3 patients studied had metabolic complications like central hypothyroidism and severe mixed hyperlipidemia; with special emphasis on the sharp fall (mean decrease>83%) in the HDL-cholesterol level. Cholesterol lowering medication and substitutive hormonal replacement with levotiroxine resulted in an improvement of the biochimical parameters without reaching the correct goals. CONCLUSIONS: Bexarotene produce as predictable side effects severe mixed hyperlipidemia with marked decrease in HDL-cholesterol levels and central hypothyroidism, being the both reversible and dose-dependent. A reflection on the possible aetiological mechanisms and implications of this phenomenon are included.


Assuntos
Antineoplásicos/efeitos adversos , Hiperlipidemias/induzido quimicamente , Hipotireoidismo/induzido quimicamente , Micose Fungoide/tratamento farmacológico , Síndrome de Sézary/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Tetra-Hidronaftalenos/efeitos adversos , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bexaroteno , HDL-Colesterol/sangue , Terapia Combinada , Humanos , Hiperlipidemias/sangue , Hiperlipidemias/tratamento farmacológico , Hipolipemiantes/uso terapêutico , Hipotireoidismo/sangue , Hipotireoidismo/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Transplante de Células-Tronco de Sangue Periférico , Radioterapia Adjuvante , Terapia de Salvação , Neoplasias Cutâneas/radioterapia , Neoplasias Cutâneas/terapia , Tetra-Hidronaftalenos/administração & dosagem , Tiroxina/uso terapêutico
19.
Clín. investig. arterioscler. (Ed. impr.) ; 25(3): 140-145, jul.-ago. 2013.
Artigo em Espanhol | IBECS | ID: ibc-115857

RESUMO

Las estatinas son la base actual del tratamiento hipolipemiante, pese a lo cual pueden tener limitaciones de eficacia y de seguridad. En pacientes de alto riesgo que no alcanzan objetivos terapéuticos, en los que no toleran las estatinas o en los que tienen dislipidemia aterógena podemos combinar 2 o más fármacos de distintas clases terapéuticas, incluyendo, además de las estatinas, ezetimiba, secuestradores de ácidos biliares, fibratos, niacina o ácidos grasos omega 3 de prescripción. No disponemos aún, sin embargo, de evidencias en cuanto a la disminución de episodios cardiovasculares con estas combinaciones (AU)


Statins are the current basis of lipid-lowering therapy, despite which may have limitations on efficacy and safety. In high risk patients who do not achieve current lipid (..) (AU)


Assuntos
Humanos , Hipercolesterolemia/tratamento farmacológico , Terapia Combinada/métodos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Anticolesterolemiantes/uso terapêutico , Fibrina/uso terapêutico , Ácidos Graxos Ômega-3/uso terapêutico
20.
Clin Investig Arterioscler ; 25(3): 140-5, 2013.
Artigo em Espanhol | MEDLINE | ID: mdl-23880257

RESUMO

Statins are the current basis of lipid-lowering therapy, despite which may have limitations on efficacy and safety. In high risk patients who do not achieve current lipid goals, in those intolerant to statins or those with atherogenic dyslipidemia, it is possible combine two or more lipid lowering drugs, including statins, ezetimibe, bile acid sequestrants, fibrates, niacin and prescription omega-3 fatty acids. However, for most of these combination therapies pivotal data on clinical outcomes are still lacking.


Assuntos
Dislipidemias/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipolipemiantes/uso terapêutico , Quimioterapia Combinada , Dislipidemias/fisiopatologia , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Hipolipemiantes/administração & dosagem , Hipolipemiantes/efeitos adversos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA