RESUMO
OBJECTIVE: Plant sterol (PS) supplementation has been widely used alone or combined with lipid-lowering therapies (LLTs) to reduce low-density lipoprotein (LDL) cholesterol. The effects of PS added to high-intensity LLT are less reported, especially regarding the effects on cholesterol synthesis and absorption. METHODS: A prospective, randomized, open-label study, with parallel arms and blinded end points was designed to evaluate the effects of addition of PS to LLT on LDL cholesterol, markers of cholesterol synthesis, and absorption. Eighty-six patients of both genders were submitted to a 4-wk run-in period with atorvastatin 10 mg (baseline). Following, subjects received atorvastatin 40 mg, ezetimibe 10 mg, or combination of both drugs for another 4-wk period (phase I). In phase II, capsules containing 2.0 g of PSs were added to previous assigned treatments for 4 wk. Lipids, apolipoproteins, plasma campesterol, ß-sitosterol, and desmosterol levels were assayed at all time points. Within and between-group analyses were performed. RESULTS: Compared with baseline, atorvastatin 40 mg reduced total and LDL cholesterol (3% and 22%, respectively, P < .05), increased ß-sitosterol, campesterol/cholesterol, and ß-sitosterol/cholesterol ratios (39%, 47%, and 32%, respectively, P < .05); ezetimibe 10 mg reduced campesterol and campesterol/cholesterol ratio (67% and 70%, respectively, P < .05), and the combined therapy decreased total and LDL cholesterol (22% and 38%, respectively, P < .05), campesterol, ß-sitosterol, and campesterol/cholesterol ratio (54%, 40%, and 27%, P < .05). Addition of PS further reduced total and LDL cholesterol by â¼ 7.7 and 6.5%, respectively, in the atorvastatin therapy group and 5.0 and 4.0% in the combined therapy group (P < .05, for all), with no further effects in absorption or synthesis markers. CONCLUSIONS: PS added to LLT can further improve lipid profile, without additional effects on intestinal sterol absorption or synthesis.
Assuntos
Anticolesterolemiantes/administração & dosagem , Suplementos Nutricionais , Hipercolesterolemia/tratamento farmacológico , Fitosteróis/administração & dosagem , Idoso , Apolipoproteínas/sangue , Atorvastatina/administração & dosagem , Colesterol/análogos & derivados , Colesterol/sangue , LDL-Colesterol/sangue , Sinergismo Farmacológico , Ezetimiba/administração & dosagem , Ezetimiba/efeitos adversos , Feminino , Humanos , Hipercolesterolemia/sangue , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Fitosteróis/efeitos adversos , Fitosteróis/sangue , Sitosteroides/sangueAssuntos
Combinação Ezetimiba e Simvastatina , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Metabolismo dos Lipídeos/efeitos dos fármacos , Fitosteróis , Sinvastatina , Anticolesterolemiantes/administração & dosagem , Anticolesterolemiantes/efeitos adversos , Monitoramento de Medicamentos , Combinação Ezetimiba e Simvastatina/administração & dosagem , Combinação Ezetimiba e Simvastatina/efeitos adversos , Feminino , Humanos , Hiperlipoproteinemia Tipo II/sangue , Masculino , Pessoa de Meia-Idade , Fitosteróis/administração & dosagem , Fitosteróis/efeitos adversos , Sinvastatina/administração & dosagem , Sinvastatina/efeitos adversos , Resultado do TratamentoRESUMO
Familial hypercholesterolemia (FH) is a common inherited disorder that results in premature atherosclerosis. Diagnosis of FH is suspected on the basis of clinical criteria, but confirmation requires genetic testing. In the era of statins, early diagnosis and initiation of treatment can modify disease progression and outcomes. Therefore, cascade screening with a combination of lipid concentration measurements and DNA testing should be used to identify relatives of index cases with a clinical diagnosis of FH. Autosomal dominant FH is related to mutations in the low-density lipoprotein receptor (LDLR), apolipoprotein B-100 (APOB), or proprotein convertase subtilisin/kexin type 9 (PCSK9) genes. Genetic screening of the LDLR gene is challenging to achieve at a feasible cost, especially in people who do not have a founder effect. Nucleotide sequencing of all exons and flanking splicing regions in combination with multiplex ligation probe amplification to detect large insertions or deletions is considered the gold-standard approach to screen for LDLR mutations. Alternatively, the cDNA can be sequenced; however, this procedure is not suitable for use in large populations, because of the need of RNA extraction. Multiplex analysis can be appropriate for population with founder effects or a low number of different mutations. Finally, there are many techniques for a mutation scanning approach, which have some benefits over sequencing, and also with the potential for detecting known and novel mutations. Familial defective Apo B is amenable to genetic diagnosis by screening for a few mutations. Recently, gain-of-function mutations in PCSK9 gene have been demonstrated to cause FH phenotype. Strategies for population screening, cost-effectiveness of genetic screening, ethical aspects, and insurance policies are discussed and need implementation worldwide.