RESUMEN
PURPOSE OF REVIEW: The purpose of this review was to summarize important and updated information on sitosterolemia. Sitosterolemia is an inherited lipid disorder consisting of high levels of plasma plant sterols. This sterol storage condition is caused by biallelic loss-of-function genetic variants in either ABCG5 or ABCG8, leading to increased intestinal absorption and decreased hepatic excretion of plant sterols. Clinically, patients with sitosterolemia usually exhibit xanthomatosis, high levels of plasma cholesterol, and premature atherosclerotic disease, but presentation can be highly heterogeneous. Therefore, recognition of this condition requires a high level of suspicion, with confirmation upon genetic diagnosis or through measurement of plasma phytosterols. Treatment of sitosterolemia with both a plant sterol-restricted diet and the intestinal cholesterol absorption inhibitor ezetimibe can reduce efficiently the levels of plasma plant sterols, consisting in the first-line therapy for this disease. RECENT FINDINGS: Since hypercholesterolemia is often present in individuals with sitosterolemia, it is important to search for genetic variants in ABCG5 and ABCG8 in patients with clinical criteria for familial hypercholesterolemia (FH), but no variants in FH implicated genes. Indeed, recent studies have suggested that genetic variants in ABCG5/ABCG8 can mimic FH, and even when in heterozygosis, they may potentially exacerbate the phenotype of patients with severe dyslipidemia. Sitosterolemia is a genetic lipid disorder characterized by increased circulating levels of plant sterols and clinically manifested by xanthomatosis, hematologic disorders, and early atherosclerosis. Awareness about this condition, a rare, but commonly underdiagnosed and yet treatable cause of premature atherosclerotic disease, is imperative.
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Aterosclerosis , Hipercolesterolemia , Hiperlipoproteinemia Tipo II , Enfermedades Intestinales , Errores Innatos del Metabolismo Lipídico , Fitosteroles , Xantomatosis , Humanos , Hipercolesterolemia/tratamiento farmacológico , Fitosteroles/efectos adversos , Fitosteroles/genética , Errores Innatos del Metabolismo Lipídico/diagnóstico , Errores Innatos del Metabolismo Lipídico/genética , Errores Innatos del Metabolismo Lipídico/terapia , Enfermedades Intestinales/diagnóstico , Enfermedades Intestinales/genética , Enfermedades Intestinales/tratamiento farmacológico , Hiperlipoproteinemia Tipo II/complicaciones , Colesterol , Xantomatosis/etiología , Aterosclerosis/genética , Aterosclerosis/complicacionesAsunto(s)
Aterosclerosis , Enfermedades Cardiovasculares , Hiperlipoproteinemia Tipo II , Aterosclerosis/epidemiología , Aterosclerosis/genética , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/genética , Humanos , Hiperlipoproteinemia Tipo II/complicaciones , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/epidemiologíaRESUMEN
PURPOSE OF REVIEW: Familial hypercholesterolemia is a high cardiovascular risk disorder. We will review the role of lipoprotein(a) in cardiovascular risk and in aortic valve stenosis in familial hypercholesterolemia, as well as its association with their phenotype, and strategies to identify this high-risk population. RECENT FINDINGS: Patients with familial hypercholesterolemia have higher lipoprotein(a) levels mainly due to an increased frequency of LPA variants, and the cardiovascular risk is increased twofolds when both conditions coexist. Also, an increased risk for aortic valve stenosis and valve replacement has been observed with high lipoprotein(a) levels. Assessment of lipoprotein(a) during the cascade screening for familial hypercholesterolemia is a good opportunity to identify this high-risk population. High cardiovascular risk in familial hypercholesterolemia is increased even more when lipoprotein(a) is also elevated. Measurement of lipoprotein(a) in these patients is crucial to identify those subjects who need to intensify LDL-cholesterol reduction pending availability of lipoprotein(a)-specific treatments.
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Estenosis de la Válvula Aórtica , Hiperlipoproteinemia Tipo II , Lipoproteína(a)/sangre , Estenosis de la Válvula Aórtica/complicaciones , LDL-Colesterol , Crimen , Humanos , Hiperlipoproteinemia Tipo II/complicaciones , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/genéticaRESUMEN
PURPOSE OF REVIEW: Familial hypercholesterolemia (FH) is a relatively common genetic disorder associated with elevated atherosclerotic risk. Dietary interventions can modulate processes associated with cardiovascular risk and potentiate the impact of pharmacological lipid-lowering therapies. This review evaluates recent findings of dietary patterns and their components on risk biomarkers in people with FH. RECENT FINDINGS: Diets lower in saturated fatty acids (SFA) may reduce low-density lipoprotein-cholesterol (LDL-C); however, their effects seem to be modest. A Mediterranean style diet apparently exerts more robust effects on plasma LDL-C, apolipoprotein B and C reactive protein concentrations than one restricted in SFA. Supplementation of plant sterols and stanols reduces LDL-C especially in children with FH. Caloric restricted diets may reduce weight and improve triglyceride levels in individuals with FH and excess body weight. SUMMARY: Despite the strong impact of genetic variants, dietary patterns mostly low in SFA and especially the Mediterranean diet may influence risk biomarkers in FH. However, most available studies are limited by cross-sectional design, small number of study subjects and short-term follow-ups. Robust interventional studies are necessary to test the impact of dietary patterns in people with FH.
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Aterosclerosis , Dieta Mediterránea , Hiperlipoproteinemia Tipo II , Aterosclerosis/epidemiología , Biomarcadores , Niño , LDL-Colesterol , Estudios Transversales , Humanos , Hiperlipoproteinemia Tipo II/complicaciones , Hiperlipoproteinemia Tipo II/genéticaAsunto(s)
Aterosclerosis , Enfermedades Cardiovasculares , Hiperlipoproteinemia Tipo II , Anciano , Aterosclerosis/epidemiología , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/prevención & control , Estudios de Casos y Controles , Estudios de Seguimiento , Humanos , Hiperlipoproteinemia Tipo II/complicaciones , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/genéticaRESUMEN
RATIONALE: Familial Hypercholesterolemia (FH) is a genetic condition that predisposes patients to substantially increased risk of early-onset atherosclerotic cardiovascular disease. FH risks can be minimized through regular participation in three self-management. BEHAVIORS: physical activity, healthy eating, and taking cholesterol lowering medication. OBJECTIVE: The present study tested the effectiveness of an integrated social cognition model in predicting intention to participate in the self-management behaviors in FH patients from seven countries. METHOD: Consecutive patients in FH clinics from Australia, Hong Kong, Brazil, Malaysia, Taiwan, China, and UK (total Nâ¯=â¯726) completed measures of social cognitive beliefs about illness from the common sense model of self-regulation, beliefs about behaviors from the theory of planned behavior, and past behavior for the three self-management behaviors. RESULTS: Structural equation models indicated that beliefs about behaviors from the theory of planned behavior, namely, attitudes, subjective norms, and perceived behavioral control, were consistent predictors of intention across samples and behaviors. By comparison, effects of beliefs about illness from the common sense model were smaller and trivial in size. Beliefs partially mediated past behavior effects on intention, although indirect effects of past behavior on intention were larger for physical activity relative to taking medication and healthy eating. Model constructs did not fully account for past behavior effects on intentions. Variability in the strength of the beliefs about behaviors was observed across samples and behaviors. CONCLUSION: Current findings outline the importance of beliefs about behaviors as predictors of FH self-management behaviors. Variability in the relative contribution of the beliefs across samples and behaviors highlights the imperative of identifying sample- and behavior-specific correlates of FH self-management behaviors.
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Conocimientos, Actitudes y Práctica en Salud , Hiperlipoproteinemia Tipo II/psicología , Intención , Participación del Paciente/psicología , Automanejo/psicología , Australia , Brasil , China , Estudios Transversales , Femenino , Hong Kong , Humanos , Hiperlipoproteinemia Tipo II/complicaciones , Hiperlipoproteinemia Tipo II/terapia , Malasia , Masculino , Participación del Paciente/métodos , Participación del Paciente/estadística & datos numéricos , Automanejo/métodos , Automanejo/estadística & datos numéricos , Encuestas y Cuestionarios , Taiwán , Reino UnidoRESUMEN
A literature review about depression, anxiety, illness perception and neurocognitive impairment in adults with familial hypercholesterolemia (FH) was performed. Through PubMed and PsycINFO published studies from 1980 until March 2017 were searched. Two papers assessed depression and anxiety. Four papers explored illness perception. Five studies assessed cognitive impairment. Mean depression and anxiety scores were within normal range. From the reviewed research, it can be concluded that deficits in executive functioning and memory appear in FH patients between 18 and 40 years old, and mild cognitive impairment in older than 50. The research in the field of the present review is relatively recent: all the studies have been published in the current century. Further research should be done using complete standardized neuropsychological assessment and brain imaging techniques. Studies exploring the possible influence of cognitive deficits on adherence should be conducted also.
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Trastornos de Ansiedad/psicología , Trastornos del Conocimiento/psicología , Depresión/psicología , Hiperlipoproteinemia Tipo II/complicaciones , Humanos , Hiperlipoproteinemia Tipo II/genética , Pruebas NeuropsicológicasRESUMEN
BACKGROUND AND AIMS: Achilles tendon xanthomas (ATX) are a sign of long-term exposure to high blood cholesterol in familial hypercholesterolemia (FH) patients, which have been associated with cardiovascular disease. We evaluated the ATX association with the presence and extent of subclinical coronary atherosclerosis in heterozygous FH patients. METHODS: 102 FH patients diagnosed by US-MEDPED criteria (67% with genetically proven FH), with median LDL-C 279 mg/dL (interquartile range: 240; 313), asymptomatic for cardiovascular disease, underwent computed tomography angiography and coronary artery calcium (CAC) quantification. Subclinical coronary atherosclerosis was quantified by CAC, segment-stenosis (SSS) and segment-involvement (SIS) scores. Adjusted Poisson regression was used to assess the association of ATX with subclinical atherosclerosis burden as continuous variables. RESULTS: Patients with ATX (n = 21, 21%) had higher LDL-C and lipoprotein(a) [Lp(a)] concentrations as well as greater CAC scores, SIS and SSS (p < 0.05). After adjusting for age, sex, smoking, hypertension, previous statin use, HDL-C, LDL-C and Lp(a) concentrations, there was an independent positive association of ATX presence with CAC scores (ß = 1.017, p < 0.001), SSS (ß = 0.809, p < 0.001) and SIS (ß = 0.640, p < 0.001). CONCLUSIONS: ATX are independently associated with the extension of subclinical coronary atherosclerosis quantified by tomographic scores in FH patients.
Asunto(s)
Tendón Calcáneo , Apolipoproteína B-100/genética , Enfermedad de la Arteria Coronaria/etiología , Heterocigoto , Hiperlipoproteinemia Tipo II/genética , Mutación , Receptores de LDL/genética , Xantomatosis/etiología , Tendón Calcáneo/diagnóstico por imagen , Adulto , Enfermedades Asintomáticas , Biomarcadores/sangre , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Angiografía por Tomografía Computarizada , Angiografía Coronaria/métodos , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Estudios Transversales , Femenino , Predisposición Genética a la Enfermedad , Humanos , Hiperlipoproteinemia Tipo II/sangre , Hiperlipoproteinemia Tipo II/complicaciones , Hiperlipoproteinemia Tipo II/diagnóstico , Lipoproteína(a)/sangre , Masculino , Persona de Mediana Edad , Fenotipo , Proyectos Piloto , Índice de Severidad de la Enfermedad , Xantomatosis/diagnóstico por imagenRESUMEN
BACKGROUND: There is little information about familial hypercholesterolemia (FH) epidemiology and care in Ibero-American countries. The Ibero-American FH network aims at reducing the gap on diagnosis and treatment of this disease in the region. OBJECTIVE: To describe clinical, molecular, and organizational characteristics of FH diagnosis in Argentina, Brazil, Chile, Colombia, Mexico, Portugal, Spain, and Uruguay. METHODS: Descriptive analysis of country data related to FH cascade screening, molecular diagnosis, clinical practice guidelines, and patient organization presence in Ibero-America. RESULTS: From a conservative estimation of an FH prevalence of 1 of 500 individuals, there should be 1.2 million heterozygous FH individuals in Ibero-America and roughly 27,400 were diagnosed so far. Only Spain, Brazil, Portugal, and Uruguay have active cascade screening programs. The prevalence of cardiovascular disease ranged from 10% to 42% in member countries, and the highest molecular identification rates are seen in Spain, 8.3%, followed by Portugal, 3.8%, and Uruguay with 2.5%. In the 3 countries with more FH patients identified (Spain, Portugal, and Brazil) between 10 and 15 mutations are responsible for 30% to 47% of all FH cases. Spain and Portugal share 5 of the 10 most common mutations (4 in low density lipoprotein receptor [LDLR] and the APOB3527). Spain and Spanish-speaking Latin American countries share 6 of the most common LDLR mutations and the APOB3527. LDL apheresis is available only in Spain and Portugal and not all countries have specific FH diagnostic and treatment guidelines as well as patient organizations. CONCLUSIONS: Ibero-American countries share similar mutations and gaps in FH care.
Asunto(s)
Hiperlipoproteinemia Tipo II/epidemiología , Enfermedades Cardiovasculares/complicaciones , Humanos , Hiperlipoproteinemia Tipo II/complicaciones , Portugal/epidemiología , América del Sur/epidemiología , España/epidemiologíaRESUMEN
PURPOSE OF REVIEW: Familial hypercholesterolemia is associated with a high lifetime risk of atherosclerotic cardiovascular disease (ASCVD). However, this risk is variable. This review evaluates recent evidence related to ASCVD risk stratification in familial hypercholesterolemia considering aspects of phenotype and genotype. RECENT FINDINGS: The heterogeneity in clinical, laboratory characteristics, and in ASCVD risk in both homozygous and heterozygous familial hypercholesterolemia individuals in part can be attributed to the type of molecular defect. In most individuals with LDL cholesterol more than 190âmg/dl, a familial hypercholesterolemia-causing variant is not encountered, however, when present, a variant implicates an even higher ASCVD risk for such individuals. Previous ASCVD events, elevated blood lipoprotein(a), cutaneous markers of cholesterol deposit are among other factors that indicate a higher ASCVD risk in familial hypercholesterolemia individuals underlying a more severe form of the phenotype. SUMMARY: Both clinical and genetic parameters help identify higher ASCVD risk among severe familial hypercholesterolemia individuals.
Asunto(s)
Genotipo , Personal de Salud , Hiperlipoproteinemia Tipo II/genética , Fenotipo , Humanos , Hiperlipoproteinemia Tipo II/complicaciones , Mutación , RiesgoRESUMEN
BACKGROUND AND AIMS: Familial hypercholesterolemia (FH) is a common genetic disorder characterized by elevated blood cholesterol, increased prevalence of subclinical atherosclerosis and high risk of premature coronary heart disease. However, this risk is not explained solely by elevated LDL-cholesterol concentrations, and other factors may influence atherosclerosis development. There is evidence that increased adiposity may predispose to atherosclerosis in FH. Epicardial fat has been associated with subclinical coronary atherosclerosis in the general population. This study evaluated the association of epicardial fat (EFV) volume with the presence and extent of subclinical coronary atherosclerosis detected by computed tomography angiography in FH patients. METHODS: Ninety-seven FH subjects (35% male, mean age 45 ± 13 years, LDL-C 281 ± 56 mg/dL, 67% with proven molecular defects) underwent computed tomography angiography and coronary artery calcium (CAC) scoring. EFV was measured in non-contrast images using a semi-automated method. Segment-stenosis score (SSS) and segment-involvement score (SIS) were calculated. Multivariate Poisson regression was utilized to assess an independent association of EFV with coronary atherosclerotic burden. RESULTS: EFV was positively associated with age, body mass index, waist circumference, blood glucose, the presence of the metabolic syndrome components, but not with LDL-C. After adjusting for confounders and abdominal circumference, an independent association (shown as ß coefficients and 95% confidence intervals) of EVF with CAC scores [ß = 0.263 (0.234; 0.292), p=0.000], SIS [ß = 0.304 (0.141; 0.465) p=0.000] and SSS [ß = 0.296 (0.121; 0.471), p=0.001] was found. CONCLUSIONS: In FH, EFV was independently associated with coronary atherosclerotic presence and severity.
Asunto(s)
Adiposidad , Enfermedad de la Arteria Coronaria/complicaciones , Hiperlipoproteinemia Tipo II/complicaciones , Pericardio/patología , Tejido Adiposo/patología , Adulto , Aterosclerosis/sangre , Colesterol/sangre , LDL-Colesterol/sangre , Estudios de Cohortes , Femenino , Corazón/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Mutación , Encuestas y Cuestionarios , Tomografía Computarizada por Rayos XRESUMEN
A hipercolesterolemia familiar (HF) é uma doença genética relativamente comum caracterizada por níveis elevados de LDL-colesterol (LDL-C) e, por conseguinte, associada a risco de desenvolvimento prematuro de doença cardiovascular aterosclerótica. O tratamento hipolipemiante reduz significativamente o risco cardiovascular desses pacientes, tornando fundamental a identificação precoce desses indivíduos, seguida de tratamento adequado assim que possível. Para tanto, existem escores diagnósticos de HF, como o escore holandês Dutch Lipid Clinic Network, que avalia níveis de LDL-C, antecedente familiar e/ou pessoal de evento cardiovascular isquêmico e a presença de sinais físicos, como xantomas. Uma vez feito o diagnóstico de HF, torna-se muito importante a estratificação de risco desses pacientes. A identificação de fatores de risco associados (como tabagismo,diabetes mellitus, hipertensão arterial, aumento de Lp(a), entre outros) aliada ao uso de métodos para detecção de doença aterosclerótica subclínica em indivíduos com HF pode auxiliar na identificação daqueles que têm maior risco cardiovascular e são candidatos a estratégias mais agressivas de redução de LDL-C. Nesse artigo, revisamos os principais critérios diagnósticos de HF e a estratificação de risco desses pacientes
Familial hypercholesterolemia (FH) is a relatively common genetic disease that is characterized by elevated LDL-cholesterol (LDL-C) levels. As a consequence, it is associated with the risk of premature development of atherosclerotic cardiovascular disease.Lipid-lowering therapies significantly reduces the cardiovascular risk in these patients, making early identification of these individuals essential, followed by adequate treatment as soon as possible. There are diagnostic scores of FH for this purpose, such as the Dutch Lipid Clinic Network score, which evaluates LDL-C levels, family history and/or personal history of ischemic cardiovascular event and the presence of physical signs, such as xanthomas. Once FH has been diagnosed, it is very important to stratify the risk in these patients. The identification of associated risk factors (such as smoking, diabetes mellitus, high blood pressure, elevated Lp(a), among others), together with the use of methods to detect subclinical atherosclerotic disease in individuals with FH, can assist in the identification of those with a higher cardiovascular risk, and who are therefore candidates for more aggressive strategies to reduce LDL-C. This article gives a review of the main diagnostic criteria of FH, and the risk stratification in these patients
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Humanos , Masculino , Femenino , Niño , Adolescente , Enfermedades Cardiovasculares/fisiopatología , Factores de Riesgo , Técnicas y Procedimientos Diagnósticos , Hiperlipoproteinemia Tipo II/complicaciones , Hiperlipoproteinemia Tipo II/diagnóstico , LDL-Colesterol/genética , LDL-Colesterol/sangre , Enfermedad de la Arteria Coronaria/complicaciones , Xantomatosis/complicaciones , Xantomatosis/diagnóstico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Aterosclerosis/fisiopatología , Lipoproteínas LDLAsunto(s)
Trastornos del Conocimiento/tratamiento farmacológico , Hiperlipoproteinemia Tipo II/tratamiento farmacológico , Indanos/farmacología , Nootrópicos/farmacología , Piperidinas/farmacología , Animales , Inhibidores de la Colinesterasa/farmacología , Trastornos del Conocimiento/etiología , Discriminación en Psicología/efectos de los fármacos , Modelos Animales de Enfermedad , Donepezilo , Evaluación Preclínica de Medicamentos , Conducta Exploratoria/efectos de los fármacos , Hiperlipoproteinemia Tipo II/complicaciones , Hiperlipoproteinemia Tipo II/psicología , Aprendizaje/efectos de los fármacos , Memoria/efectos de los fármacos , Ratones Endogámicos C57BL , Ratones Noqueados , Pruebas Psicológicas , Receptores de LDL/genética , Receptores de LDL/metabolismo , Percepción Espacial/efectos de los fármacosRESUMEN
A MTP (Microsomal Triglyceride Transfer Protein - Proteína Microsomal de Transferência de Triglicérides) é uma proteína chave envolvida na formação e secreção das lipoproteínas que contêm apo B no fígado e intestino. Mutações no gene que codifica a MTP são a base molecular da a betalipoproteinemiae da hipobetalipoproteinemia, doenças caracterizadas,respectivamente, pela ausência total ou parcial de lipoproteínas que contêm apo B de origem intestinal e hepática. Após a descoberta da causa molecular da a betalipoproteinemia no início dos anos 90, a MTP tornou-se potencial alvo terapêutico tanto para a hipercolesterolemia como para a quilomicronemia. Entre os vários fármacos desenvolvidos com esse propósito,apenas a lomitapida chegou ao mercado, tendo sido aprovada,até o momento, para uso exclusivo na hipercolesterol emiafamiliar homozigótica. A restrição de seu uso a esse grupo de pacientes se deve aos efeitos colaterais que dela decorrem: esteatose hepática, diarreia, elevações das transaminases.Estudos de fase 2 e 3 mostraram sua capacidade de reduzir o LDL-colesterol em uso isolado ou em associação com outras terapias hipolipemiantes. Espera-se que sua utilização emportadores de hipercolesterolemia familiar homozigótica possa produzir, paralelamente à melhora do perfil lipídico, os eventos cardiovasculares graves e precoces a que esta população de pacientes está sujeita. São necessários mais estudos para que eventualmente o emprego da lomitapida possa ser estendido para outros grupos, como os intolerantes às estatinas ou os que não atingem as metas terapêuticas apesar de doses máximas dos medicamentos ora disponíveis.
The microsomal triglyceride transfer protein (MTP) is a keyprotein in the assembly and secretion of apolipoprotein (apo)B-containing lipoproteins in the liver and intestine. Mutationsin the gene encoding for MTP are the molecular basis ofabetalipoproteinemia and hipobetalipoproteinemia, diseasescharacterized, respectively, by the complete and partial absenceof apo B containing lipoproteins from hepatic or intestinalorigin. Following the discovery of the molecular cause ofabetalipoproteinemia in the early 1990s, MTP became a potentialtherapeutic target for the treatment of both hypercholesterolemia aswell as chylomicronemia. Among the various products developedfor this purpose, only lomitapide reached the market, having beenapproved, till the present moment for exclusive use in homozygousfamilial hypercholesterolemic patients. The restriction of its usefor this group of patients is due to the side effects caused by it:hepatic steatosis, diarrhea, transaminasis elevations. Phase 2 and3 studies showed its capability of reducing LDL-cholesterol levelsin isolated use or in combination with other therapies commonlyused to reduce cholesterol levels. It is awaited that its use inhomozygous familial hypercholesterolemic patients can produce,in parallel to the improved lipid profile, reduction of the severe andprecocious cardiovascular events that this population is exposed.More studies are needed to eventually extend the lomitapide usefor other groups of patients, as the statins intolerants or those whodo not reach therapeutic targets despite maximal doses of todaysavailable medications.
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Humanos , Hiperlipoproteinemia Tipo II/complicaciones , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/tratamiento farmacológico , Ensayos Clínicos como Asunto , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Interacciones FarmacológicasRESUMEN
Background: Familial hypercholesterolemia (FH) is an autosomal dominant genetic disease characterized by an elevation in the serum levels of total cholesterol and of low-density lipoproteins (LDL- c). Known to be closely related to the atherosclerotic process, FH can determine the development of early obstructive lesions in different arterial beds. In this context, FH has also been proposed to be a risk factor for peripheral arterial disease (PAD). Objective: This observational cross-sectional study assessed the association of PAD with other manifestations of cardiovascular disease (CVD), such as coronary artery and cerebrovascular disease, in patients with heterozygous FH. Methods: The diagnosis of PAD was established by ankle-brachial index (ABI) values ≤ 0.90. This study assessed 202 patients (35% of men) with heterozygous FH (90.6% with LDL receptor mutations), mean age of 51 ± 14 years and total cholesterol levels of 342 ± 86 mg /dL. Results: The prevalences of PAD and previous CVD were 17% and 28.2 %, respectively. On multivariate analysis, an independent association between CVD and the diagnosis of PAD was observed (OR = 2.50; 95% CI: 1.004 - 6.230; p = 0.049). Conclusion: Systematic screening for PAD by use of ABI is feasible to assess patients with FH, and it might indicate an increased risk for CVD. However, further studies are required to determine the role of ABI as a tool to assess the cardiovascular risk of those patients. .
Fundamento: A hipercolesterolemia familiar (HF) é uma doença de herança genética autossômica dominante caracterizada pela elevação dos valores séricos de colesterol total e das lipoproteínas de baixa densidade (LDL-c). Conhecida por estar estreitamente relacionada ao processo aterosclerótico, a HF pode determinar o desenvolvimento de lesões obstrutivas precoces em distintos leitos arteriais. Nesse contexto, a HF também tem sido proposta como fator de risco para a doença arterial periférica (DAP). Objetivo: Avaliamos, por meio de um estudo transversal e observacional, a associação da DAP com outras manifestações de doença cardiovascular (DCV), isto é, doença arterial coronária e cerebrovascular em portadores de HF heterozigótica. Métodos: diagnóstico de DAP foi estabelecido pela medida do índice tornozelo-braquial (ITB) com valores ≤ 0,90. Foram estudados 202 pacientes com HF (90,6% apresentando mutações no receptor da LDL), idade 51 ± 14 anos, colesterol total 342 ± 86 mg/dL e 35% do sexo masculino. Resultados: As prevalências de DAP e de DCV prévia foram 17% e 28,2%, respectivamente. Houve associação independente da DAP com a DCV (OR = 2,50, IC 95% 1,004-6,230, p = 0,049) após análise multivariada. Conclusão: A pesquisa sistemática da DAP por meio do ITB é factível na avaliação de portadores de HF e pode sinalizar aumento no risco de DCV. Contudo, mais estudos são necessários para determinar o papel do uso do ITB como ferramenta para avaliação do risco cardiovascular nessa população. (Arq Bras Cardiol. 2014; 103(2):118-123) .
Asunto(s)
Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedades Cardiovasculares/etiología , Hiperlipoproteinemia Tipo II/complicaciones , Enfermedad Arterial Periférica/etiología , Índice Tobillo Braquial , Presión Sanguínea/fisiología , Estudios Transversales , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/fisiopatología , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Hiperlipoproteinemia Tipo II/fisiopatología , Enfermedad Arterial Periférica/sangre , Enfermedad Arterial Periférica/fisiopatología , Factores de Riesgo , Estadísticas no Paramétricas , Encuestas y Cuestionarios , Triglicéridos/sangreRESUMEN
BACKGROUND: Familial hypercholesterolemia (FH) is an autosomal dominant genetic disease characterized by an elevation in the serum levels of total cholesterol and of low-density lipoproteins (LDL- c). Known to be closely related to the atherosclerotic process, FH can determine the development of early obstructive lesions in different arterial beds. In this context, FH has also been proposed to be a risk factor for peripheral arterial disease (PAD). OBJECTIVE: This observational cross-sectional study assessed the association of PAD with other manifestations of cardiovascular disease (CVD), such as coronary artery and cerebrovascular disease, in patients with heterozygous FH. METHODS: The diagnosis of PAD was established by ankle-brachial index (ABI) values ≤ 0.90. This study assessed 202 patients (35% of men) with heterozygous FH (90.6% with LDL receptor mutations), mean age of 51 ± 14 years and total cholesterol levels of 342 ± 86 mg /dL. RESULTS: The prevalences of PAD and previous CVD were 17% and 28.2 %, respectively. On multivariate analysis, an independent association between CVD and the diagnosis of PAD was observed (OR = 2.50; 95% CI: 1.004 - 6.230; p = 0.049). CONCLUSION: Systematic screening for PAD by use of ABI is feasible to assess patients with FH, and it might indicate an increased risk for CVD. However, further studies are required to determine the role of ABI as a tool to assess the cardiovascular risk of those patients.
Asunto(s)
Enfermedades Cardiovasculares/etiología , Hiperlipoproteinemia Tipo II/complicaciones , Enfermedad Arterial Periférica/etiología , Adulto , Anciano , Índice Tobillo Braquial , Presión Sanguínea/fisiología , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/fisiopatología , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Estudios Transversales , Femenino , Humanos , Hiperlipoproteinemia Tipo II/fisiopatología , Masculino , Persona de Mediana Edad , Enfermedad Arterial Periférica/sangre , Enfermedad Arterial Periférica/fisiopatología , Factores de Riesgo , Estadísticas no Paramétricas , Encuestas y Cuestionarios , Triglicéridos/sangreRESUMEN
Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder of low-density lipoprotein cholesterol (LDL-C) metabolism resulting in extremely elevated serum levels of LDL-C and premature atherosclerotic cardiovascular disease. Treatment typically involves multiple pharmacologic agents, as well as mechanical filtration using weekly or biweekly LDL apheresis. Despite combination lipid-lowering therapy, LDL-C levels and cardiovascular morbidity and mortality remain unacceptably high in HoFH patients. The European Commission and the US Food and Drug Administration approved the use of lomitapide, a novel medication designed to address this significant unmet need. Lomitapide is an orally administered inhibitor of microsomal triglyceride transfer protein that is indicated as an adjunct to a low-fat diet and other lipid-lowering treatments, including LDL apheresis where available for the reduction of LDL-C, total cholesterol, apolipoprotein B, and non-high-density lipoprotein cholesterol in adult patients with HoFH. The risks of transaminase elevations, hepatic steatosis, and gastrointestinal side effects, and the potential for drug interactions, require vigilant examination of the clinical and laboratory data and patient counseling prior to initiation of lomitapide, as well as regular monitoring during follow-up care. This article highlights important practical considerations for the use of lomitapide in the context of the evaluation and management of a HoFH patient case.
Asunto(s)
Anticolesterolemiantes/uso terapéutico , Bencimidazoles/uso terapéutico , Proteínas Portadoras/antagonistas & inhibidores , LDL-Colesterol/sangre , Homocigoto , Hiperlipoproteinemia Tipo II/tratamiento farmacológico , Anticolesterolemiantes/efectos adversos , Bencimidazoles/efectos adversos , Biomarcadores/sangre , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/prevención & control , Proteínas Portadoras/metabolismo , Interacciones Farmacológicas , Predisposición Genética a la Enfermedad , Humanos , Hiperlipoproteinemia Tipo II/sangre , Hiperlipoproteinemia Tipo II/complicaciones , Hiperlipoproteinemia Tipo II/genética , Masculino , Persona de Mediana Edad , Fenotipo , Factores de Riesgo , Resultado del TratamientoRESUMEN
Epidemiological studies indicate that high midlife plasma cholesterol levels increases the risk of Alzheimer's disease. Moreover, middle-aged familial hypercholesterolemia (FH) subjects show a particularly high incidence of mild cognitive impairments (MCI). These evidence points to hypercholesterolemia as one of the modifiable risk factors focused on prevention/treatment of cognitive deterioration. The present study draws a comparison between pharmacological (lipid-lowering drug probucol) and non-pharmacological (voluntary running wheel, RW) approaches for the management of hypercholesterolemia and cognitive impairments associated with the low-density lipoprotein receptor-deficient (LDLr(-/-)) mice, a well-established rodent model of FH. We also investigated whether exposure to environmental enrichment (EE), a feasible option to increase physical activity in young mice cohort, from birth to adolescence (PN45) yields long-term behavioral changes in adult LDLr(-/-) mice (PN90). We observed that both probucol and RW significantly decreased total and non-HDL plasma cholesterol levels in LDLr(-/-) mice. Notably, only physical exercise mitigated the spatial memory deficits of LDLr(-/-) mice. In addition, we showed that exposure to EE from birth until the adolescence did not mitigate the spatial memory deficits of adult LDLr(-/-) mice in the object location task, although it induced persistent anxyolitic-like effects in the open field arena. Collectively, our results emphasize the advantages physical exercise, in comparison to lipid-lowering drugs, for the management of cognitive deficits associated with FH.