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Clin Lab ; 64(7): 1105-1112, 2018 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30146832


BACKGROUND: The use of point-of-care testing (POCT) in different clinical applications is justified by the fact that the time to release the result is shortened, allowing the physician to define the diagnosis and most appropriate therapy in a shorter time. However, the negative aspects must also be highlighted and studied so that we can move forward with the use of these devices. These negative aspects include greater analytical imprecision compared to laboratory automation, the variability between different equipment from different manufacturers, the risk of inappropriate use, a low level of global regulation, higher costs compared with laboratory testing and cost ineffectiveness in terms of health care. Methods and. RESULTS: This review presents some clinical applications of POCT in different scenarios, such as for diabetes mellitus, infectious diseases, pediatrics, and chronic kidney disease, among others. CONCLUSIONS: We hope to see a global consensus on an acceptable quality standard for performing POCT that is adaptable, practical, and cost effective in primary care settings, ensuring patient safety, and minimizing the risk of harm.

Clin Lab ; 64(1): 1-9, 2018 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-29479878


Point-of-Care Testing (POCT) has been highlighted in the health care sector in recent decades. On the other hand, due to its low demand, POCT is at a disadvantage compared to conventional equipment, since its cost is inversely proportional to the volume of use. In addition, for the implementation of POCT to succeed, it is essential to rely on the work of a multidisciplinary team. The awareness of health professionals of the importance of each step is perhaps the critical success factor. The trend towards the continuous advancement of the use of POCT and the great potential of its contributions reinforce the need to implement quality management tools, including performance indicators, to ensure their results. This review presents some advantages and disadvantages concerning POCT and the real need to use it. A worldwide call for the availability of easy-to-use health technologies that are increasingly closer to the final user is one of the main reasons for this focus.

Arq Bras Cardiol ; 109(2 Supl 1): 1-76, 2017 Jul.
Artigo em Português | MEDLINE | ID: mdl-28813069
Faludi, André Arpad; Izar, Maria Cristina de Oliveira; Saraiva, José Francisco Kerr; Chacra, Ana Paula Marte; Bianco, Henrique Tria; Afiune Neto, Abrahão; Bertolami, Adriana; Pereira, Alexandre C.; Lottenberg, Ana Maria; Sposito, Andrei C.; Chagas, Antonio Carlos Palandri; Casella Filho, Antonio; Simão, Antônio Felipe; Alencar Filho, Aristóteles Comte de; Caramelli, Bruno; Magalhães, Carlos Costa; Negrão, Carlos Eduardo; Ferreira, Carlos Eduardo dos Santos; Scherr, Carlos; Feio, Claudine Maria Alves; Kovacs, Cristiane; Araújo, Daniel Branco de; Magnoni, Daniel; Calderaro, Daniela; Gualandro, Danielle Menosi; Mello Junior, Edgard Pessoa de; Alexandre, Elizabeth Regina Giunco; Sato, Emília Inoue; Moriguchi, Emilio Hideyuki; Rached, Fabiana Hanna; Santos, Fábio César dos; Cesena, Fernando Henpin Yue; Fonseca, Francisco Antonio Helfenstein; Fonseca, Henrique Andrade Rodrigues da; Xavier, Hermes Toros; Mota, Isabela Cardoso Pimentel; Giuliano, Isabela de Carlos Back; Issa, Jaqueline Scholz; Diament, Jayme; Pesquero, João Bosco; Santos, José Ernesto dos; Faria Neto, José Rocha; Melo Filho, José Xavier de; Kato, Juliana Tieko; Torres, Kerginaldo Paulo; Bertolami, Marcelo Chiara; Assad, Marcelo Heitor Vieira; Miname, Márcio Hiroshi; Scartezini, Marileia; Forti, Neusa Assumpta; Coelho, Otávio Rizzi; Maranhão, Raul Cavalcante; Santos Filho, Raul Dias dos; Alves, Renato Jorge; Cassani, Roberta Lara; Betti, Roberto Tadeu Barcellos; Carvalho, Tales de; Martinez, Tânia Leme da Rocha; Giraldez, Viviane Zorzanelli Rocha; Salgado Filho, Wilson.
Arq. bras. cardiol ; 109(2,supl.1): 1-76, ago. 2017. tab, graf
Artigo em Português | LILACS-Express | ID: biblio-887919
J. bras. patol. med. lab ; 52(6): 387-390, Nov.-Dec. 2016. tab, graf
Artigo em Inglês | LILACS-Express | ID: biblio-841210


ABSTRACT Introduction: Elevated plasma levels of lipids are considered the main modifiable risk factor for the cardiovascular disease. The Point-of-care testing (POCT) method provides quick results and allows anticipating diagnosis and treatment. Objective: To compare the lipid profile results obtained from both POCT and the traditional clinical laboratory. Methods: Fasting blood samples were collected from 111 patients who sought, for any reason, the private medical offices participating on this study. Capillary whole blood samples were analyzed in CardioChek® PA (CCPA) equipment, and the serum samples were analyzed in clinical laboratories (LAB) that have internal and external quality control, with certification. The mean values of each variable of the lipid profile obtained by CCPA and LAB were calculated. Linear regression was used to determine the existence of correlation between the two methods. Results: We observed a positive correlation between the values obtained by CCPA and LAB for all variables of the lipid profile. Our data, extracted from the routine use of CCPA in private medical offices, supports a substantial contribution of the POCT methodology in the detection of the main cardiovascular risk factors. Conclusion: The POCT CardioChek® PA Analyzer is an easy-to-operate tool, with adequate analytical performance and a good correlation with the results of the conventional laboratory method, therefore, considered a reliable method.

RESUMO Introdução: Níveis plasmáticos elevados de lipídios são considerados como principal fator de risco modificável para a doença cardiovascular. A metodologia Point-of-care testing (POCT) fornece resultados rápidos e permite antecipar o diagnóstico e o tratamento. Objetivo: Comparar os resultados do perfil lipídico obtidos pelo POCT e pelo laboratório convencional. Métodos: Foram coletadas amostras em jejum de 111 pacientes que procuraram, por qualquer motivo, os consultórios médicos privados participantes desta pesquisa. As amostras de sangue total da punção capilar foram analisadas no equipamento CardioChek® PA (CCPA) e as de sangue da punção venosa, coletadas e analisadas em laboratórios clínicos (LAB) que apresentam controle de qualidade interno e externo, com certificação. Os valores médios de cada variável do perfil lipídico obtidos pelo CCPA e pelo LAB foram calculados. Regressão linear foi utilizada para determinar a existência de correlação entre os dois métodos. Resultados: Observamos correlação positiva entre os valores obtidos pelo CCPA e pelo LAB para todas as variáveis do perfil lipídico. Nossos dados, extraídos do uso rotineiro do CCPA em consultórios médicos privados, suporta substancial contribuição da metodologia POCT na detecção dos principais fatores de risco cardiovascular. Conclusão: O analisador POCT CCPA configura-se como uma ferramenta de fácil operação, com performance analítica adequada e excelente correlação com os resultados do método laboratorial convencional, portanto confiáveis.

Clin Chim Acta ; 446: 263-6, 2015 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-25952166


BACKGROUND: We evaluated the clinical correlation between the CardioChek PA analyzer and a clinical laboratory reference method to use for screening program purposes. METHODS: Fasting blood samples were collected on 516 patients (age 20-85 y). One venous sample was collected using a serum tube for the evaluation on a COBAS reference analyzer. A second venous sample was collected in a lithium heparin tube and was evaluated on the CardioChek PA analyzer (CCPA venous). A fingerstick sample (CCPA fingerstick) was evaluated only on the CardioChek PA analyzer. Linear regression analyses were performed for each measured analyte, total cholesterol, HDL-cholesterol and triglycerides. RESULTS: The correlation between the CCPA fingerstick and CCPA venous was extremely high for HDL-C and triglycerides, and good for total cholesterol. Our results demonstrated a good clinical agreement for total cholesterol, HDL-C and triglycerides between 97.7% and 94.6% in the comparison of the CCPA to the reference analyzer. CONCLUSIONS: We identified the pre-analytic phase as an important step to guarantee the quality of results and indicate that the CardioChek PA is a reliable lipid point-of-care testing system that can be used for the application of clinical screening anywhere.

Automação Laboratorial/normas , Doenças Cardiovasculares/sangue , HDL-Colesterol/sangue , Testes Imediatos/normas , Triglicerídeos/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/diagnóstico , Jejum/sangue , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto
Pharm Pract (Granada) ; 12(2): 378, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25035713


OBJECTIVE: to evaluate the relation between patient adherence and therapeutic effectiveness of hypolipidemic agents in clinical practice. METHODS: A retrospective cohort study of 417 patients using hypolipidemic drugs (simvastatin, atorvastatin) between 2003 and 2010 was performed. The population studied consists of patients assisted by the Public Health Service in the far-west region of the State of Santa Catarina, Brazil. The Medication Possession Ratio obtained from pharmacy refill data was used to measure patient adherence. Therapeutic effectiveness was evaluated based on the difference obtained in the serum levels of total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides, before and after taking the drug, in an average time of 8.3 months. RESULTS: Following the treatment with hypolipidemic agents, it has been observed a reduction of 14.3% for total cholesterol, 19.6% for LDL-cholesterol, and 14.4% for triglycerides. HDL-cholesterol increased by an 8.0% average. The major changes in lipid profile were promoted by atorvastatin 20 mg daily. The medication adherence rate decreased over the monitoring period. Adherence rates below 60% were associated with therapeutic failure, while rates equal to 80% or higher were associated with the best response to the lipid-lowering drugs. CONCLUSION: Adherence to hypolipidemic agents is higher at the beginning of the treatment, but it decreases over time, affecting the achievement of therapeutic goals.

Rev. bras. anal. clin ; 46(1-4): 8-13, 2014. tab, graf
Artigo em Português | LILACS | ID: lil-775371


A principal causa de morte na população mundial continua sendo as doenças cardiovasculares, frequentemente, associadas às dislipidemias . Diagnosticar e tratar indivíduos com alterações lipídicas nem sempre é simples, mas o controle das dislipidemias, em particular a redução nas concentrações do colesterol LDL (lipoproteina de baixa densidade) , tem se mostrado eficaz na diminuição de eventos cardiovasculares e morte. Frente a um panorama epidêmico, um comitê de especialistas publicou, em outubro de 2013, a V Diretriz Brasileira de Dislipidemias e Prevenção de Aterosclerose. O documento traz algumas modificações em relação às edições anteriores, mostrando a importância da estratificação do risco individual e do alcance da meta terapêutica. Sob o ponto de vista laboratorial, uma nova abordagem em relação aos valores de referência do perfil lipídico foi inserida e, a partir destes novos direcionamentos, especial atenção deve ser sada para valores de colesterol total (CT)>310 mg/dL (para adultos) ou CT > 230 mg/dL }entre os 2 e os 19 anos], os quais podem indicar a presença de hipercolesterolemia familiar.

Pré-Escolar , Criança , Adolescente , Adulto Jovem , Aterosclerose/prevenção & controle , Dislipidemias
Biochem Med (Zagreb) ; 21(2): 152-9, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22135855


INTRODUCTION: Tourniquet due venous stasis can alter both concentration and/or activity of several blood analytes, but is rarely regarded as an issue of laboratory variability. To overcome the problem transillumination devices (TD) have been proposed for a stasis-free phlebotomy. In this paper the use of a TD in place of tourniquet during blood collection has been evaluated. MATERIALS AND METHODS: Blood was collected from 250 volunteers divided in five homogenous groups of tourniquet times (G1: 30 sec, G2: 60 sec, G3: 90 sec, G4:120 sec, G5: 180 sec) and compared to blood obtained using TD. All samples were analyzed for glucose (GLU), total protein (TP), albumin (ALB), triglycerides (TRIG), potassium (K), sodium (NA), phosphate (PHOS), calcium (CA), alkaline phosphatase (ALKP) and magnesium (MG). RESULTS: In respect of TD, G1 did not show statistically significant increases in all clinical chemistry tests; G2 showed increases for GLU, TP, ALB, TRIG, K, CA, MG and ALKP. G3 and G4, showed no significant increase only for PHOS. G5 showed significant increases in all the tests evaluated. Moreover, clinically significant variations were observed for TP, ALB, K and CA in G2 to G5; for NA in G3 to G5; for MG in G4 and G5; for GLU, TRIG, ALKP only in G5. CONCLUSIONS: These results support the application of TD in blood collection for routine clinical chemistry laboratory tests, suggesting its use should be more diffused.

Análise Química do Sangue , Hemostasia , Flebotomia/métodos , Transiluminação , Análise Química do Sangue/instrumentação , Análise Química do Sangue/métodos , Análise Química do Sangue/estatística & dados numéricos , Feminino , Humanos , Masculino , Fatores de Tempo , Torniquetes/efeitos adversos , Transiluminação/instrumentação , Transiluminação/métodos
Clin Biochem ; 44(12): 1028-9, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21683694


BACKGROUND: Safety transport boxes are increasingly used to ship laboratory specimens but there is little information on their capacity to maintain suitable transportation temperatures. MATERIALS AND METHODS: Inner temperature was assessed using a commercially available transport box during an 8-h transportation period in the heat. RESULTS: Temperature stability was unsatisfactory during approximately 64% of the transportation time (i.e., from 125 to 450 min). CONCLUSIONS: Transport boxes might be unsuitable for shipping specimens over long periods.

Coleta de Amostras Sanguíneas/instrumentação , Transportes , Humanos , Fatores de Tempo
Arq Bras Endocrinol Metabol ; 54(1): 60-7, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20414550


OBJECTIVE: To investigate the relationship between butyrylcholinesterase (BChE) activities (total and band specific) and diabetes mellitus. SUBJECTS AND METHODS: BChE activities (BChEA, AC(4/5), AC(OF) and RC(5)) were analyzed in 101 type 1 (DM1) and in 145 type 2 (DM2) diabetic patients, in relation to phenotype, weight and incidence of metabolic syndrome (MS) in these patients. The C(4/5) and C(5) complex were separated from other molecular forms (C(OF)) using an acid agar gel. RESULTS: The BChE activity (BChEA) and the absolute activities of C(4/5) (AC(4/5)) and C(OF) (AC(OF)) showed a high positive correlation coefficient to weight in the CHE2 C5- group, while the relative activity of C5 complex (RC5) showed a negative correlation to weight. CONCLUSIONS: The present study suggests that the positive correlation of the BChE activities to diabetes mellitus and to insulin resistance may depend on the CHE2 locus variability. High values of BChE activities were associated with insulin resistance only in CHE2 C5- diabetic patients, while in CHE2 C5+ diabetic patients, the presence of C(5) complex, especially in a relatively high proportion, leads to less fat storage and better protection against metabolic syndrome.

Butirilcolinesterase/sangue , Colinesterases/genética , Diabetes Mellitus Tipo 1/enzimologia , Diabetes Mellitus Tipo 2/enzimologia , Adulto , Índice de Massa Corporal , Peso Corporal/fisiologia , Butirilcolinesterase/genética , Estudos de Casos e Controles , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 2/sangue , Feminino , Humanos , Resistência à Insulina/fisiologia , Masculino , Síndrome Metabólica/sangue , Pessoa de Meia-Idade , Fenótipo , Análise de Regressão
Arq. bras. endocrinol. metab ; 54(1): 60-67, fev. 2010. ilus, tab
Artigo em Inglês | LILACS | ID: lil-544034


OBJECTIVE:To investigate the relationship between butyrylcholinesterase (BChE) activities (total and band specific) and diabetes mellitus. SUBJECTS AND METHODS: BChE activities (BChEA, AC 4/5, AC OF and RC5) were analyzed in 101 type 1 (DM1) and in 145 type 2 (DM2) diabetic patients, in relation to phenotype, weight and incidence of metabolic syndrome (MS) in these patients. The C4/5 and C5 complex were separated from other molecular forms (C OF) using an acid agar gel. RESULTS: The BChE activity (BChEA) and the absolute activities of C4/5 (AC4/5) and C OF (AC OF) showed a high positive correlation coefficient to weight in the CHE2 C5- group, while the relative activity of C5 complex (RC5) showed a negative correlation to weight. CONCLUSIONS: The present study suggests that the positive correlation of the BChE activities to diabetes mellitus and to insulin resistance may depend on the CHE2 locus variability. High values of BChE activities were associated with insulin resistance only in CHE2 C5- diabetic patients, while in CHE2 C5+ diabetic patients, the presence of C5 complex, especially in a relatively high proportion, leads to less fat storage and better protection against metabolic syndrome.

OBJETIVO: Investigar a associação entre as atividades (total e banda específica) da butirilcolinesterase (BChE) e diabetes melito. SUJEITOS E MÉTODOS: As atividades da BChE (BChEA, AC4/5, AC OF e RC5) foram analisadas em 101 pacientes diabéticos do tipo 1 (DM1) e 145 do tipo 2 (DM2) em relação aos fenótipos, ao peso e à incidência da síndrome metabólica. Os complexos C4/5 e C5 foram separados das outras formas moleculares (C OF), usando gel de ágar ácido. RESULTADOS: A atividade da BChE (BChEA) e as atividades absolutas de C4/5 (AC4/5) e de C OF (AC OF) mostraram altos coeficientes de correlações positivos com peso no grupo de CHE2 C5-, enquanto a atividade relativa do complexo C5 (RC5) mostrou correlação negativa com o peso. CONCLUSÕES: O presente estudo sugere que as correlações positivas das atividades da BChE com diabetes melito e com a resistência à insulina podem depender da variabilidade do loco CHE2. Altos valores nas atividades da BChE estão associados com a resistência à insulina somente nos pacientes diabéticos CHE2 C5-, enquanto nos pacientes diabéticos CHE2 C5+ a presença do complexo C5, especialmente em alta proporção relativa, leva a um menor estoque de gordura e à maior proteção contra a síndrome metabólica.

Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Butirilcolinesterase/sangue , Colinesterases/genética , Diabetes Mellitus Tipo 1/enzimologia , /enzimologia , Índice de Massa Corporal , Peso Corporal/fisiologia , Butirilcolinesterase/genética , Estudos de Casos e Controles , Diabetes Mellitus Tipo 1/sangue , /sangue , Resistência à Insulina/fisiologia , Síndrome Metabólica/sangue , Fenótipo , Análise de Regressão
J. bras. patol. med. lab ; 45(6): 441-447, dez. 2009. ilus, tab
Artigo em Português | LILACS | ID: lil-552200


INTRODUÇÃO: A fase pré-analítica é a responsável por mais de dois terços de todos os erros atribuídos ao laboratório e contempla poucos procedimentos rotineiros para a detecção de não conformidades. Nesta fase, os procedimentos envolvendo a flebotomia, críticos para a obtenção do espécime diagnóstico, são pouco estudados no que diz respeito às principais fontes de erro, bem como aos procedimentos relacionados com o processo de controle da qualidade. OBJETIVOS: Propor uma ferramenta para averiguação de falhas na fase pré-analítica e estabelecer indicadores da qualidade, com ênfase nos procedimentos de coleta do espécime diagnóstico sanguíneo, visando monitorar potenciais fontes de erro nesta etapa. MATERIAIS E MÉTODOS: Foram observados os procedimentos de flebotomia empregados em 10 laboratórios clínicos da cidade de São Paulo, todos com programa de qualidade estabelecido. Os erros que apresentaram frequência superior a 80 por cento foram selecionados para elaboração de uma lista de verificação, com a finalidade de avaliar o desempenho de flebotomistas. Normas e recomendações estabelecidas por instituições nacionais e internacionais, como Agência Nacional de Vigilância Sanitária (ANVISA), Sociedade Brasileira de Patologia Clínica/Medicina Laboratorial (SBPC/ML) e Clinical and Laboratory Standards Institute (CLSI), serviram de referência para a elaboração da lista de verificação. RESULTADOS: A lista de verificação proposta aborda cinco pontos do processo de flebotomia: tempo de aplicação do torniquete, número de flebotomistas que solicitam ao paciente execução da constrição do músculo do antebraço previamente à coleta, fricção do músculo do antebraço no processo de antissepsia, sequência correta ou não de utilização dos tubos de coleta e avaliação da homogeneização adequada ou não do espécime diagnóstico coletado. CONCLUSÃO: A avaliação do processo de flebotomia é parte essencial no planejamento da qualidade no laboratório. A lista de verificação...

BACKGROUND: The preanalytical phase is responsible for more than two thirds of all errors attributed to the clinical laboratory and it has only a few routine procedures for the detection of nonconformity. In this phase, the procedures involving phlebotomy, critical to the obtainment of diagnostic blood specimen, are poorly studied with regard to major sources of errors and procedures related to quality control process. OBJECTIVES: The aim of this work is to propose a tool for finding failures in the preanalytical phase and to establish quality indicators, with emphasis on procedures for the collection of diagnostic blood specimens, in order to monitor potential sources of error in this phase. MATERIALS AND METHODS: We evaluated phlebotomy procedures employed in ten clinical laboratories in São Paulo city, Brazil. All of them with established quality program. The errors that had a frequency higher than 80 percent were selected to be part of a checklist aiming to evaluate the performance of phlebotomists. Standards and recommendations established by national and international institutions, such as ANVISA, SBPC/ML and CLSI, served as reference to elaborate the checklist. RESULTS: The proposed checklist covers five points of phlebotomy procedures: tourniquet application time, number of phlebotomists that ask patients to clench forearm muscle prior to collection, friction of the forearm muscle in antisepsis process, correct or incorrect sequence of blood collecting tubes and evaluation of accurate or inaccurate homogenization of collected blood specimens. CONCLUSIONS: Phlebotomy evaluation is an essential part of the quality planning in clinical laboratories. The proposed checklist allows error detection in the preanalytical phase, establishment of quality indicators and implementation of corrective and preventive actions with cost effectiveness and improvement in process efficiency.

Humanos , Coleta de Amostras Sanguíneas/métodos , Flebotomia/métodos , Controle de Qualidade , Indicadores de Qualidade em Assistência à Saúde , Técnicas de Laboratório Clínico
Arq Bras Cardiol ; 93(2): 128-34, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19838489


BACKGROUND: Epidemiological studies have established an association between dyslipidemias and atherosclerosis. Nutritional therapy is a key point in the prevention strategy for individuals who present with risk factors for atherosclerotic disease. OBJECTIVES: To investigate the effects of green tea (Camellia sinensis) in patients with dyslipidemias. METHODS: The study included 33 patients aged between 21 and 71 years who had a low-fat diet (25-35% of total calories and 200 mg of cholesterol per day). They were randomized for two sequential treatments: 250-mg capsules of green tea dry extract or placebo for a total period of 16 weeks; each patient received green tea (Camellia sinensis) for eight weeks and placebo for another eight weeks. RESULTS: Baseline lipid values (mg/dL) were: HDL-cholesterol 60.7 +/- 7.3; total cholesterol 255 +/- 30.9; LDL-cholesterol 158.8 +/- 29.0; triglycerides 169.0 +/- 61.3 and Apo-B 120.2 +/- 18.9. Mean lipid variations induced by the use of green tea (Camellia sinensis) showed a 3.9% reduction (p = 0.006) in total cholesterol concentrations and a 4.5% reduction (p = 0.026) in LDL-cholesterol. The intake of green tea did not significantly influence HDL-cholesterol, triglyceride, and Apo-B levels. Non-significant results were found in the assessment of blood lipids (total cholesterol and LDL-cholesterol) with the use of placebo. CONCLUSION: A beneficial effect of green tea (Camellia sinensis) was demonstrated, with a significant reduction of total cholesterol and LDL-cholesterol levels in eight weeks, in the patients studied.

Camellia sinensis , Dislipidemias/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Chá , Adulto , Idoso , Dieta com Restrição de Gorduras , Dislipidemias/metabolismo , Métodos Epidemiológicos , Feminino , Humanos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Adulto Jovem
Clin Chem ; 55(12): 2153-61, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19797716


BACKGROUND: We measured plasma PCSK9 concentrations in healthy men with a PCSK9 (proprotein convertase subtilisin/kexin type 9) loss-of-function variant (p.R46L), in statin-treated patients with a clinical diagnosis of familial hypercholesterolemia (FH) and carrying a PCSK9 gain-of-function mutation (p.D374Y), and in statin-treated patients with FH due to different genetic causes. METHODS: PCSK9 was measured with a previously described ELISA. RESULTS: In 81 healthy middle-aged Caucasian men, the PCSK9 concentration was significantly associated with the concentrations of total cholesterol (r = 0.42; P < 0.0001), LDL cholesterol (r = 0.34; P = 0.01), and triglycerides (r = 0.25; P = 0.02). In p.R46L carriers, mean (SD) concentrations of PCSK9 were 15% lower than in RR individuals [65.5 microg/L (21.6 microg/L) vs 77.5 microg/L (18.2 microg/L); P = 0.03]. In patients with the p.D374Y variant (n = 7), the mean PCSK9 concentration was significantly lower than in the combined group of patients with an LDLR (low density lipoprotein receptor) mutation (n = 25), an APOB [apolipoprotein B (including Ag(x) antigen)] variant encoding p.R3527Q (n = 6), or no detectable mutation (n = 14) [96.4 microg/L (42.5 microg/L) vs 151.6 microg/L (69.6 microg/L); P = 0.02]. Two of the 14 patients with no mutation had PCSK9 concentrations below the mean for p.D374Y carriers; sequencing of the PCSK9 gene and promoter revealed no mutations. Among 409 FH patients, we identified 6 carriers of the promoter variant -287G>A (1.5%), a frequency similar to that (1.0%) previously reported for 2772 healthy men in the UK. In neither group was the -287G>A variant associated with differences in lipid traits. CONCLUSIONS: The loss-of-function p.R46L variant is associated with the expected lower concentrations of circulating PCSK9; the gain-of-function p.D374Y mutation is also associated with lower concentrations, presumably because of the higher affinity of this variant for the LDL receptor and its more rapid clearance. In treated FH patients, a low plasma PCSK9 concentration does not appear to be a useful screening tool for identifying novel PCSK9 mutations.

Hiperlipoproteinemia Tipo II/genética , Serina Endopeptidases/genética , Apolipoproteínas B/genética , Heterozigoto , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Mutação , Pró-Proteína Convertase 9 , Pró-Proteína Convertases , Receptores de LDL/genética , Valores de Referência , Serina Endopeptidases/sangue