RESUMO
This case reports on an 8-year-old boy with homozygous familial hypercholesterolemia with large tuberous xanthomas over his hands, elbows, buttocks, knees, and feet. Lomitapide 40 mg daily (steadily increased) was added to his classical lipid-lowering therapy. A 50% reduction in the thickness, hardness, size, and color intensity of xanthomas was reported after 2 years of treatment. (Level of Difficulty: Intermediate.).
RESUMO
The limited distribution of lipoprotein (a) (Lp(a)) to humans, Old World primates and to the European hedgehog, has raised considerable interest and speculation regarding its possible physiological role. Lp(a) has variable circulating concentrations (<0.1 - >100 mg/ml) which are highly genetically determined in humans. These characteristics gave rise to several theories concerning the origins and evolution of Lp(a). Lp(a) has a protective role after injury since Lp(a) particles bind to macrophages and platelets membrane receptors, leading to fibrin activation and injury healing. On the other hand, Lp(a) seems to be implicated in the formation of atheromatic plaques but also in cerebrovascular events and stenosis of the aortic valve. The main genetic factor determining plasma Lp(a) levels is the Lp(a) gene (LPA). Most Caucasian people have normal plasma Lp(a) concentrations, but there is important distribution variation according to race. Women seem to have increased Lp(a) levels compared with men, while diabetes mellitus type 2 favours lower plasma Lp(a) levels. Nutrition, hormones and several drugs may also influence circulating Lp(a) levels.
Assuntos
Lipoproteínas , Animais , Humanos , Lipoproteínas/sangue , Lipoproteínas/genéticaRESUMO
The aim of this study was to evaluate the influence of gender differences on triglyceride (TG) response after a fatty meal in clinically defined heterozygous (h) patients with familial hypercholesterolemia (FH). Nineteen hFH men were age-matched with an equal number of premenopausal women. Plasma TG was measured before and 2, 4, 6, and 8 hr after a standardized fat load. The men with hFH had a greater body mass index (BMI) than hFH women. An abnormal postprandial response was observed in 63% and 16% of hFH men and women, respectively. The mean TG-area under the curve value was higher in hFH men compared to hFH women. Both gender (p = 0.032) and BMI (p = 0.006) equally affected postprandial TG response, but fasting TG levels (p <0.001) were the main determinant. In summary, hFH men have higher BMI, fasting TG level, and postprandial TG level, compared to age-matched premenopausal hFH women, which may partially explain the earlier onset of coronary heart disease in hFH men.
Assuntos
Heterozigoto , Hipercolesterolemia/fisiopatologia , Hiperlipidemias/diagnóstico , Período Pós-Prandial , Triglicerídeos/sangue , Adulto , Feminino , Predisposição Genética para Doença , Humanos , Hipercolesterolemia/diagnóstico , Hipercolesterolemia/genética , Hiperlipidemias/sangue , Hiperlipidemias/genética , Masculino , Pessoa de Meia-Idade , Caracteres SexuaisRESUMO
BACKGROUND: In patients with left ventricular (LV) dysfunction the mitral leaflet coaptation point (CPMA) is displaced towards the LV apex. The aim of our study was to estimate the value of CPMA measurement as a simple index regarding the acute effects of cardiac resynchronization therapy (CRT), which is coming to be an established method of treatment for congestive heart failure (CHF). METHODS: We studied 20 patients with CHF (NYHA III-IV) and LV ejection fraction (LVEF) 22 +/- 4%. All patients received CRT and an echocardiogram was performed within 24-48 hours. The echocardiographic indices LV end-diastolic diameter (LVEDD) and end-systolic diameter (LVESD), LVEF, mitral annulus diameter (MAD), and the degree of intraventricular desynchronization, were measured at CRT off and CRT on. The CPMA, the distance between the coaptation point of the mitral leaflets and the mitral annulus, was measured from the apical 4-chamber view in end-systole at both CRT on and CRT off. RESULTS: CRT improved both the contractility and dimensional indices in CHF patients. CPMA decreased from 11.3 +/- 2 mm at CRT off to 9.1 +/- 1.8 mm after CRT on (p < 0.001) and MAD from 38.9 +/- 3.9 mm at CRT off to 37.5 +/- 3.7 mm at CRT on (p < 0.002). LVEF improved from 24.5 +/- 5.7% at CRT off to 29.5 +/- 5.1% at CRT on (p < 0.001). There was an improvement in LV synchronization from 88 +/- 7 ms at CRT off to 48 +/- 3 ms at CRT on (p < .001). CPMA was correlated with MAD (r = 0.52, p < 0.05 and r = 0.59, p < 0.05 at CRT off and CRT on, respectively). Moreover, the absolute change in CPMA was correlated with LVESD (r = 0.68) and LVEDD (r = 0.65), both p < 0.05, with the time difference of the basal segments of the septal and lateral wall at CRT on (r = 0.68, p < 0.01), and inversely correlated with LVEF (r = -0.55, p < 0.05). CONCLUSION: In patients with severe LV systolic dysfunction and dilatation CRT was associated with an improvement in both CPMA and MAD.
Assuntos
Estimulação Cardíaca Artificial , Insuficiência Cardíaca/terapia , Insuficiência da Valva Mitral/prevenção & controle , Marca-Passo Artificial , Volume Sistólico , Disfunção Ventricular Esquerda/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Ecocardiografia , Feminino , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência da Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/fisiopatologia , Contração Miocárdica , Variações Dependentes do Observador , Resultado do Tratamento , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/fisiopatologiaRESUMO
A 13-year-old Greek boy with severe dyslipidemia, large tuberous xanthomas over the knees and elbows, Achilles' tendon xanthomas, and a bilateral corneal arcus was referred to the Lipid Clinic. He had a supravalvular aortic stenosis, 50% to 60% stenosis of both carotid arteries, and normal coronary arteries. Familial hypercholesterolemia was clinically diagnosed. A V408M null low-density lipoprotein receptor (LDLR) mutation was identified in homozygosity. He responded to lipid-lowering drugs by decreasing total cholesterol by 32%, low-density lipoprotein cholesterol by 33%, and triglyceride levels by 30%. Additional treatment with low-density lipoprotein-apheresis further decreased total cholesterol by 52%, low-density lipoprotein cholesterol by 55%, and triglycerides by 43%. Low-density lipoprotein cholesterol levels between apheresis sessions showed a declining pattern. A significant regression of tuberous xanthomas was noted. A suitable combination of lipid-lowering drugs is effective even in this case of homozygosity for a null LDLR mutation. Furthermore, the coadministration of statins, cholestyramine, and ezetimibe during low-density lipoprotein-apheresis tends to counterbalance the postapheresis relapse in low-density lipoprotein cholesterol levels.
Assuntos
Hipercolesterolemia/tratamento farmacológico , Hipolipemiantes/uso terapêutico , Mutação , Receptores de LDL/genética , Adolescente , Anticolesterolemiantes/uso terapêutico , Azetidinas/uso terapêutico , Remoção de Componentes Sanguíneos , Colesterol/sangue , LDL-Colesterol/sangue , Resina de Colestiramina/uso terapêutico , Ezetimiba , Homozigoto , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipercolesterolemia/genética , Masculino , Triglicerídeos/sangueRESUMO
Studies in several populations have indicated that genetic variation at the apolipoprotein E (apoE) structural locus influences the risk of coronary artery disease (CAD) and myocardial infarction (MI). This study aimed at investigating whether apoE polymorphism has an allelic and/or genotypic impact on the risk of MI in Greek patients with CAD. We compared apoE gene polymorphism in a group of patients with angiographically confirmed CAD but not MI [CAD/MI (-)-group, n = 143] and a group of age and sex-matched CAD patients who had experienced a non-fatal Ml [CAD/MI (+)-group, n = 124]. The patients were also compared with a group of healthy younger individuals (n = 240) with no family history of CAD. The apoE genotype distribution differed significantly between the two groups of CAD patients (p = 0.02). The epsilon2 allele was 5.3-fold less frequent in the CAD/ MI (+)-group compared with the CAD/MI (-)-group (1.2% vs. 6.3%, p = 0.01). The frequency of the epsilon2 allele in healthy subjects was 8.1%, which is 6.8-fold higher than in CAD/MI (+)-patients (p = 0.001) and twice as high compared with all CAD patients (p = 0.02). No differences in epsilon4 allele frequencies were observed between CAD/MI (+)- and CAD/MI (-)-patients (10.9% vs. 9.8%), or between patients with CAD and healthy subjects (10.3% vs. 10.2%). In summary, the epsilon4 allele was not found to be associated with an increased risk for CAD or MI. In contrast, a negative association of the epsilon2 allele with Ml was observed among Greek patients with CAD.