RESUMO
Metabolic syndrome (MetS) is associated with alterations of lipoprotein structure and function that can be characterized with advanced lipoprotein testing (ADLT). The effect of the Mediterranean diet (MedDiet) and weight loss on the lipoprotein subclass profile has been scarcely studied. Within the PREDIMED-Plus randomized controlled trial, a sub-study conducted at Bellvitge Hospital recruiting center evaluated the effects of a weight loss program based on an energy-reduced MedDiet (er-MedDiet) and physical activity (PA) promotion (intervention group) compared with energy-unrestricted MedDiet recommendations (control group) on ADLT-assessed lipoprotein subclasses. 202 patients with MetS (n = 107, intervention; n = 95, control) were included. Lipid profiles were determined, and ADLT was performed at baseline, 6, and 12 months. Linear mixed models were used to assess the effects of intervention on lipoprotein profiles. Compared to the control diet, at 12 months, the er-MedDiet+PA resulted in a significant additional 4.2 kg of body weight loss, a decrease in body mass index by 1.4 kg/m2, reduction in waist circumference by 2.2 cm, decreased triglycerides, LDL-cholesterol and non-HDL-cholesterol, and increased HDL-cholesterol. In er-MedDiet+PA participants, ADLT revealed a decrease in small dense-LDL-cholesterol (sd-LDL-C), intermediate-density lipoproteins, VLDL-triglyceride, and HDL-Triglyceride, and an increase in large LDL and large VLDL particles. In conclusion, compared to an ad libitum MedDiet (control group), er-MedDiet+PA decreased plasma triglycerides and the triglyceride content in HDL and VLDL particles, decreased sd-LDL-C, and increased large LDL particles, indicating beneficial changes against cardiovascular disease.
Assuntos
Dieta Mediterrânea , Síndrome Metabólica , Humanos , LDL-Colesterol , Lipoproteínas , Triglicerídeos , Colesterol , Estilo de VidaRESUMO
Background: Genetic risk scores (GRSs) have partially improved the understanding of the etiology of moderate hypertriglyceridemia (HTG), which until recently was mainly assessed by secondary predisposing causes. The main objective of this study was to assess whether this variability is due to the interaction between clinical variables and GRS. Methods: We analyzed 276 patients with suspected polygenic HTG. An unweighted GRS was developed with the following variants: c.724C > G (ZPR1 gene), c.56C > G (APOA5 gene), c.1337T > C (GCKR gene), g.19986711A > G (LPL gene), c.107 + 1647T > C (BAZ1B gene) and g.125478730A > T (TRIB gene). Interactions between the GRS and clinical variables (body mass index (BMI), diabetes mellitus, diet, physical activity, alcohol consumption, age and gender) were evaluated. Results: The GRS was associated with triglyceride (TG) concentrations. There was a significant interaction between BMI and GRS, with the intensity of the relationship between the number of alleles and the TG concentration being greater in individuals with a higher BMI. Conclusions: GRS is associated with plasma TG concentrations and is markedly influenced by BMI. This finding could improve the stratification of patients with a high genetic risk for HTG who could benefit from more intensive healthcare interventions.
Assuntos
Hipertrigliceridemia , Índice de Massa Corporal , Predisposição Genética para Doença , Genótipo , Humanos , Hipertrigliceridemia/genética , Herança Multifatorial , Fatores de Transcrição/genética , TriglicerídeosRESUMO
Statin therapy response is highly variable. Variants of lipid metabolism genes and statin pharmacokinetic modulators could play a role, however, the impact of most of these variants remains unconfirmed. A prospective and multicenter study included 252 patients was carried out in order to assess, according to achievement of LDL-C or non-HDL-C therapeutic targets and quantitative changes in lipid profiles, the impact of CETP, ABCA1, CYP2D6, and CYP2C9 gene candidate variants on the simvastatin, atorvastatin, and rosuvastatin response. Patients carrier ABCA1 rs2230806 and CYP2D6*3 variants are less likely to achieve therapeutic lipid targets (p = 0.020, OR = 0.59 [0.37, 0.93]; p = 0.040, OR = 0.23 [0.05, 0.93], respectively). Among CETP variants, rs708272 was linked to a 10.56% smaller reduction in LDL-C with rosuvastatin (95% CI = [1.27, 19.86] %; p = 0.028). In contrast, carriers of rs5882 had a 13.33% greater reduction in LDL-C (95% CI = [25.38, 1.28]; p = 0.032). If these findings are confirmed, ABCA1, CYP2D6, and CETP genotyping could be used to help predict which statin and dosage is appropriate in order to improve personalized medicine.
Assuntos
Transportador 1 de Cassete de Ligação de ATP/genética , Proteínas de Transferência de Ésteres de Colesterol/genética , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Citocromo P-450 CYP2D6/genética , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , HDL-Colesterol/antagonistas & inibidores , LDL-Colesterol/antagonistas & inibidores , Feminino , Seguimentos , Variação Genética/genética , Humanos , Hiperlipidemias/sangue , Hiperlipidemias/tratamento farmacológico , Hiperlipidemias/genética , Lipídeos/antagonistas & inibidores , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
INTRODUCTION: The clinical impact on fertility in carriers of BRCA1 and BRCA2 mutations remains unclear. The aim of this study was to assess ovarian reserve as measured by anti-mullerian hormone levels in BRCA1 or BRCA2 mutation carriers, as well as to investigate the impact of anti-mullerian hormone levels on reproductive outcomes. METHODS: The study involved a cohort of women who tested positive for BRCA1 and BRCA2 screening or were tested for a BRCA1 or BRCA2 family mutation. Blood samples were collected for anti-mullerian hormone analysis and the reproductive outcomes were analyzed after a mean follow-up of 9 years. Participants were classified into BRCA mutation-positive versus BRCA mutation-negative. Controls were healthy relatives who tested negative for the family mutation. All patients were contacted by telephone to collect data on reproductive outcomes. Linear regression was used to predict anti-mullerian hormone levels by BRCA status adjusted for a polynomial form of age. RESULTS: Results of anti-mullerian hormone analysis and reproductive outcomes were available for 135 women (BRCA mutation-negative, n=66; BRCA1 mutation-positive, n=32; BRCA2 mutation-positive, n=37). Anti-mullerian hormone curves according to BRCA status and adjusted by age showed that BRCA2 mutation-positive patients have lower levels of anti-mullerian hormone as compared with BRCA-negative and BRCA1 mutation-positive. Among the women who tried to conceive, infertility was observed in 18.7% of BRCA mutation-negative women, in 22.2% of BRCA1 mutation-positive women, and in 30.8% of BRCA2 mutation-positive women (p=0.499). In the multivariable analysis, there were no factors independently associated with infertility. DISCUSSION: BRCA2 mutation-positive carriers showed more diminished anti-mullerian hormone levels than BRCA1 mutation-positive and BRCA mutation-negative women. However, these differences do not appear to have a negative impact on reproductive outcome. This is important to consider at the time of reproductive counseling in women with BRCA1 or BRCA2 mutations.
Assuntos
Proteína BRCA1/genética , Proteína BRCA2/genética , Mutação em Linhagem Germinativa , Reserva Ovariana/genética , Reprodução/genética , Adulto , Hormônio Antimülleriano/sangue , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Fertilidade/genética , Genes BRCA2 , HumanosRESUMO
BACKGROUND: LDL-C lowering is the main measure in cardiovascular disease prevention but a residual risk of ischemic events still remains. Alterations of lipoproteins, specially, increase in small dense LDL (sdLDL) particles are related to this risk. OBJECTIVE: To investigate the potential use of sdLDL cholesterol concentration (sdLDL-C) isolated by an easy precipitation method and to assess the impact of a set of clinical and biochemical variables determined by NMR on sdLDL concentration. METHODS: sdLDL-C and NMR lipid profile were performed in 85 men samples. Association among them was evaluated using Pearson coefficients (rxy ). A multivariate regression was performed to identify the influence of NMR variables on sdLDL-C. RESULTS: A strong association between sdLDL-C and LDLLDL-P (rxy = 0.687) and with LDL-Z (rxy = -0.603) was found. The multivariate regression explained a 56.8% in sdLDL-C variation (P = 8.77.10-12). BMI, ApoB, triglycerides, FFA, and LDL-Z showed a significant contribution. The most important ones were ApoB and LDL-Z; a 1nm increase (LDL-Z) leads to decrease 126 nmol/L in sdLDL-C. CONCLUSION: The association between sdLDL-C, LDL-Z, and LDL-P is clear. From a large number of variables, especially LDL-Z and apoB influence on sdLDL-C. Results show that the smaller the LDL size, the higher their cholesterol concentration. Therefore, sdLDL-C determination by using this easy method would be useful to risk stratification and to uncover cardiovascular residual risk.
Assuntos
LDL-Colesterol/sangue , LDL-Colesterol/química , Espectroscopia de Ressonância Magnética/métodos , Adulto , Idoso , Precipitação Química , Humanos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Tamanho da Partícula , Análise de Regressão , Reprodutibilidade dos Testes , Adulto JovemRESUMO
BACKGROUND: Patients with dyslipidemia are often treated with statins to reduce lipids and hence cardiovascular risk, but treatment response is variable, partly due to genetic factors. METHODS: We studied the influence of 6 gene variants (APOE c.526C > T (APOE2), APOE c.388T > C (APOE4), SLCO1B1 c.521T > C, CYP3A4 c.-392G > A, HMGCR c.1564-106A > G, and LPA c.3947 + 467T > C) on statin efficacy assessing 2 indicators: the percent reduction in total cholesterol (TC) and non-HDL cholesterol (non-HDL), as well as the achievement of therapeutic goals. The study was performed in a group of patients (n = 100) without previous pharmacological treatment. Multiple regression models were used to calculate the percentage of explanation in response variability added by every variant to a basal model constructed with significant nongenetic control variables. RESULTS: The most influential variant was HMGCR c.1564-106A > G (rs3846662), and carriers showed a significantly lower reduction in TC and non-HDL. This variant is related to an alternative splicing involving exon 13, which is also regulated by lipid concentrations in patients without the variant. Concerning therapeutic goals, HMGCR c.1564-106A > G hindered the achievement of TC targets on patients. CONCLUSIONS: The HMGCR c.1564-106A > G variant was associated with less statin efficacy to decrease cholesterol.
Assuntos
Colesterol/sangue , Dislipidemias/tratamento farmacológico , Dislipidemias/genética , Hidroximetilglutaril-CoA Redutases/genética , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Polimorfismo de Nucleotídeo Único/genética , Adulto , Dislipidemias/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Resultado do TratamentoRESUMO
BACKGROUND: The APOE Christchurch (APOECh) is a rare variant (c.543C>A) in codon 154. It was first described in an E2 patient with type III dyslipidemia, and thus initially called E2Ch. Its prevalence and the lipid profile of carriers remain unclear. METHODS: E2, E3, and E4 screening for the APOE gene was performed by PCR-RFLP. The rare APOECh variant was firstly found after detecting an unexpected 109 base-pair band in the high-resolution agarose gel electrophoresis leading to a genotype misinterpretation: the presence of APOECh alters the restriction-bands pattern. To confirm the Ch variant, a second PCR-RFLP method was specifically designed to detect this variant and Sanger sequencing was also performed for all positive samples. RESULTS: We identified 12 unrelated subjects for the APOECh among a cohort of 2,560 patients: nine E3/E3Ch, two E3Ch/E4, and one E2/E3Ch or E2Ch/E3. The frequency of the variant is 0.4% in our study population, which represents the highest percentage published so far. If there is a 109 bp band, it is easy to recognize the presence of the variant. However, in APOE routine genotyping, an E4Ch allele is indistinguishable from a standard E3. Therefore, E4Ch alleles might be underrepresented in the results. CONCLUSION: We recommend APOE exon 4 sequencing to unequivocally detect the common three variants E2, E3, and E4 and the rare variants as well, to find out the real role they play in atherosclerosis and to estimate its real frequency which is nowadays unclear, in part by the small number of cases identified.
Assuntos
Apolipoproteínas E/genética , Aterosclerose/genética , Polimorfismo Genético/genética , Sequência de Bases , Erros de Diagnóstico , Frequência do Gene , Técnicas de Genotipagem , Humanos , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Isoformas de Proteínas/genética , Análise de Sequência de DNARESUMO
INTRODUCTION: Most of the cost-effectiveness analyses are based on estimations to make decisions on the future implementation of a test. However, the model should be verified with real data to prove that previous estimations have been successfully fulfilled. OBJECTIVE: To study the economic impact of the systematic HLA-B*57:01 genotyping in preventing hypersensitivity reactions (HSRs) in the patient population of a tertiary-care hospital treated with abacavir (ABC) using retrospective data of 5 years of experience. METHODS: A retrospective study was carried out with two cohorts including 780 and 473 patients before and after the implementation of the systematic HLA-B*57:01 genotyping before ABC treatment. Cost-effectiveness analysis was carried out by the parameter 'cost per HSR avoided'. The clinical utility of the test was verified by evaluating the differences in HSR incidence between both cohorts. Finally, a sensitivity analysis including all variables was carried out. RESULTS: In the population studied, systematic genotyping represents an additional cost of &OV0556;306 per HSR avoided. In the sensitivity analysis, pharmacological therapy cost is the major influencing factor found in the estimation of the 'cost per HSR avoided'. In terms of clinical utility, the incidence ratio was 0.040 (95% confidence interval 0.0009-0.2399) and statistically significant differences were found between both groups (P=1.40×10). CONCLUSION: Retrospective data from 5 years of experience have confirmed the cost-effectiveness of the systematic genotyping in candidate patients for ABC therapy, and have shown that cost-effectiveness is a dynamic parameter closely linked to allele prevalence and pharmacological therapy costs.
Assuntos
Fármacos Anti-HIV/efeitos adversos , Didesoxinucleosídeos/efeitos adversos , Hipersensibilidade a Drogas/prevenção & controle , Soropositividade para HIV/tratamento farmacológico , HIV-1/imunologia , Antígenos HLA-B/genética , Adulto , Análise Custo-Benefício , Hipersensibilidade a Drogas/genética , Hipersensibilidade a Drogas/imunologia , Feminino , Genótipo , Humanos , Masculino , Farmacogenética , Estudos RetrospectivosRESUMO
The VII European Symposium of the Clinical Laboratory and In Vitro Diagnostic Industry, co-organized between the Catalan Association for Clinical Laboratory Sciences (ACCLC) and the Catalan Society of Biology, was held on May 28th-29th, 2013 in Barcelona (Catalonia, Spain) under the IFCC auspices and the IUPAC sponsorship. The subject of the present Symposium was "Molecular Genetics in the Clinical Laboratory" and began with an opening conference that was a stroll through the history of molecular genetics in the context of the clinical laboratory. The scientific program was structured in several 2-h length roundtables that dealt with the following topics: recent advances in molecular genetics for clinical microbiology, latest evidences and real applicability of pharmacogenetics in the clinical practice, quality assurance of a molecular genetics laboratory, and latest trends in prenatal genetic diagnosis. The aim of the Symposium was the discussion of the transformation that molecular genetics has generated on clinical laboratories in terms of organization, specialization, interpretation of results and fast technical and knowledge evolution. High-qualified professionals from several countries together with in-country experts formed the roundtables. Attendants participated actively in the debates, increasing the overall interest.
Assuntos
Técnicas de Laboratório Clínico , Testes Genéticos , Técnicas de Diagnóstico Molecular , Europa (Continente) , HumanosRESUMO
OBJECTIVE: SLE is associated with increased cardiovascular risk (CVR). High serum concentrations of triglyceride-rich lipoproteins and apolipoprotein B-rich particles constitute the characteristic dyslipidaemia of SLE. METHODS: A cross-sectional study was conducted to study the relationship between genetic variants involved in polygenic hypertriglyceridaemia, subclinical atherosclerosis and lipoprotein abnormalities. 73 women with SLE and 73 control women age-matched with the case group were recruited (age range 30-75 years). Serum analysis, subclinical atherosclerosis screening studies for the detection of plaque, and genetic analysis of the APOE, ZPR1, APOA5 and GCKR genes were performed. RESULTS: Triglyceride concentrations and the prevalence of hypertension, dyslipidaemia and carotid atherosclerosis were higher in women with SLE than in the control group. Multivariate logistic regression showed that CC homozygosity for the GCKR rs1260326 gene (OR=0.111, 95% CI 0.015 to 0.804, p=0.030) and an increase of 1 mmol/L in triglyceride concentrations were associated with a greater risk of carotid plaque in women with SLE (OR=7.576, 95% CI 2.415 to 23.767, p=0.001). CONCLUSIONS: GCKR CC homozygosity (rs1260326) and serum triglyceride concentrations are independently associated with subclinical carotid atherosclerosis in women with SLE. Subclinical carotid atherosclerosis is also more prevalent in these women compared with the control group. The study of GCKR rs1260326 gene variants may contribute to more precise assessment of CVR and modulation of the intensity of lipid-lowering treatment in patients with SLE.
Assuntos
Aterosclerose , Doenças das Artérias Carótidas , Dislipidemias , Hipertrigliceridemia , Lúpus Eritematoso Sistêmico , Placa Aterosclerótica , Adulto , Idoso , Aterosclerose/epidemiologia , Aterosclerose/genética , Doenças das Artérias Carótidas/complicações , Doenças das Artérias Carótidas/epidemiologia , Doenças das Artérias Carótidas/genética , Grupos Controle , Estudos Transversais , Dislipidemias/complicações , Feminino , Humanos , Hipertrigliceridemia/complicações , Hipertrigliceridemia/genética , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/epidemiologia , Lúpus Eritematoso Sistêmico/genética , Pessoa de Meia-Idade , Placa Aterosclerótica/complicações , Fatores de Risco , TriglicerídeosRESUMO
Diagnosis and treatment of triglyceride metabolism disorders: from pathophysiology to clinical practice. Hypertriglyceridaemia (HTG) affects 15%-20% of the world's population, and is frequently discovered as an incidental finding in a laboratory test. Disorders of triglyceride (TG) metabolism have a complex genetic basis. New genetic tools that allow a more precise approach to the disorders have made it possible to redefine and classify HTG into two groups: monogenic HTG (TG>10 mmol/L) and polygenic HTG (2 mmol/LAssuntos
Hipertrigliceridemia
, Jejum
, Humanos
, Hiperlipidemias
, Hipertrigliceridemia/genética
, Fenótipo
, Triglicerídeos
RESUMO
BACKGROUND: Lipid metabolism disorders, especially hypertriglyceridemia (HTG), are risk factors for non-alcoholic fatty liver disease (NAFLD). However, the association between genetic factors related to HTG and the risk of NAFLD has been scarcely studied. METHODS: A total of 185 subjects with moderate HTG were prospectively included. We investigated the association between genetic factors' (five allelic variants with polygenic hypertriglyceridemia) clinical and biochemical biomarkers with NAFLD severity. The five allelic variants' related clinical and biochemical data of HTG were studied in all the subjects. NAFLD was assessed by abdominal ultrasound and patients were divided into two groups, one with no or mild NAFLD and another with moderate/severe NAFLD. RESULTS: Patients with moderate/severe NAFLD had higher weight and waist values and a higher prevalence of insulin resistance than patients with no or mild NAFLD. Moderate/severe NAFLD was independently associated with APOA5 rs3134406 and ZPR1 rs964184 variants, and also showed a significant inverse relationship with lipoprotein(a) [Lp(a)] concentrations. CONCLUSIONS: APOA5 rs3135506 and ZPR1 rs964184 variants and lipoprotein(a) are associated with moderate/severe NAFLD. This association was independent of body weight, insulin resistance, and other factors related to NAFLD.
Assuntos
Apolipoproteína A-V/genética , Hipertrigliceridemia/genética , Proteínas de Membrana Transportadoras/genética , Hepatopatia Gordurosa não Alcoólica/genética , Índice de Gravidade de Doença , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Peso Corporal/genética , Feminino , Predisposição Genética para Doença/genética , Variação Genética/genética , Estudo de Associação Genômica Ampla , Humanos , Resistência à Insulina/genética , Lipoproteínas/sangue , Masculino , Pessoa de Meia-Idade , Herança Multifatorial , Estudos Prospectivos , Fatores de Risco , Triglicerídeos/sangue , Circunferência da Cintura/genética , Adulto JovemRESUMO
SLE is associated with increased cardiovascular risk. The objective of this study was to determine the prevalence of asymptomatic carotid atherosclerosis to analyze its relationship with dyslipidemia and related genetic factors in a population of patients with SLE. Seventy-one SLE female patients were recruited. Carotid ultrasound, laboratory profiles, and genetic analysis of the ZPR1, APOA5, and GCKR genes were performed. SLE patients were divided into two groups according to the presence or absence of carotid plaques. Patients with carotid plaque had higher plasma TG (1.5 vs. 0.9 mmol/L, p = 0.001), Non-HDL-C (3.5 vs. 3.1 mmol/L, p = 0.025), and apoB concentrations (1.0 vs. 0.9 g/L, p = 0.010) and a higher prevalence of hypertension (80 vs. 37.5%, p = 0.003) than patients without carotid plaque. The GCKR C-allele was present in 83.3% and 16.7% (p = 0.047) of patients with and without carotid plaque, respectively. The GCKR CC genotype (OR = 0.026; 95% CI: 0.001 to 0.473, p = 0.014), an increase of 1 mmol/L in TG concentrations (OR = 12.550; 95% CI: 1.703 to 92.475, p = 0.013) and to be hypertensive (OR = 9.691; 95% CI: 1.703 to 84.874, p = 0.040) were independently associated with carotid atherosclerosis. In summary, plasma TG concentrations, CGKR CC homozygosity, and hypertension are independent predictors of carotid atherosclerosis in women with SLE.
RESUMO
OBJECTIVES: Few data are available regarding follow up of patients with coronavirus disease 2019 (COVID-19) after their discharge. We aim to describe the long-term outcomes of survivors of hospitalization for COVID-19 followed up first at an outpatient facility and subsequently by telephone. METHODS: Observational prospective study conducted at a tertiary general hospital. Clinical and radiological progression was assessed and data were recorded on a standardized reporting form. Patients were divided into three groups according to Pao2/Fio2 at hospitalization: Pao2/Fio2 >300, Pao2/Fio2 300-200 and Pao2/Fio2 <200. A logistic multivariate regression model was performed to identify factors associated with persistence of symptoms. RESULTS: For facility follow up, 302 individuals were enrolled. Median follow up was 45 days after discharge; 78% (228/294) of patients had COVID-19-related symptoms (53% asthenia, 56% respiratory symptoms) and 40% (122/302) had residual pulmonary radiographic lesions. Pao2/Fio2 <200 was an independent predictor of persistent dyspnoea (OR 1.87, 95% CI 1.38-2.52, p < 0.0001). Pao2/Fio2 >300 was associated with resolution of chest radiographic lesions (OR 0.56, 95% CI 0.42-0.74, p < 0.0001). Fifty per cent of patients required specific medical follow up after the first consultation and were transferred to another physician. A total of 294 patients were contacted for telephone follow up after a median follow-up time of 7 months. Fifty per cent of patients (147/294) still presented symptoms and 49% (145/294) had psychological disorders. Asthenia was identified in 27% (78/294) and dyspnoea in 10% (28/294) of patients independently of Pao2/Fio2. CONCLUSIONS: Patients with COVID-19 require long-term follow up because of the persistence of symptoms; patients with low Pao2/Fio2 during the acute illness require special attention.
Assuntos
COVID-19/diagnóstico , Oxigênio/sangue , SARS-CoV-2/fisiologia , Idoso , Idoso de 80 Anos ou mais , COVID-19/psicologia , COVID-19/virologia , Feminino , Seguimentos , Hospitalização , Humanos , Modelos Logísticos , Pulmão/patologia , Pulmão/virologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Prospectivos , Espanha , Sobreviventes , Centros de Atenção Terciária , Tratamento Farmacológico da COVID-19RESUMO
Some lipoprotein disorders related to the residual risk of premature cardiovascular disease (PCVD) are not detected by the conventional lipid profile. In this case-control study, the predictive power of PCVD of serum sdLDL-C, measured using a lipoprotein precipitation method, and of the physicochemical properties of serum lipoproteins, analyzed by nuclear magnetic resonance (NMR) techniques, were evaluated. We studied a group of patients with a first PCVD event (n = 125) and a group of control subjects (n = 190). Conventional lipid profile, the size and number of Very Low Density Lipoproteins (VLDL), Low Density Lipoproteins (LDL), High Density Lipoproteins (HDL) particles, and the number of particles of their subclasses (large, medium, and small) were measured. Compared to controls, PCVD patients had lower concentrations of all LDL particles, and smaller and larger diameter of LDL and HDL particles, respectively. PCVD patients also showed higher concentrations of small dense LDL-cholesterol (sdLDL), and triglycerides (Tg) in LDL and HDL particles (HDL-Tg), and higher concentrations of large VLDL particles. Multivariate logistic regression showed that sdLDL-C, HDL-Tg, and large concentrations of LDL particles were the most powerful predictors of PCVD. A strong relationship was observed between increased HDL-Tg concentrations and PCVD. This study demonstrates that beyond the conventional lipid profile, PCVD patients have other atherogenic lipoprotein alterations that are detected by magnetic resonance imaging (MRI) analysis.
RESUMO
Objective: To assess the effect of omega-3 polyunsaturated fatty acids (n-3 PUFA) supplementation on bone metabolism in HIV-infected patients presenting with hypertriglyceridemia.Methods: Patients were randomized 1:1 to receive 2 g of n-3 PUFA or fenofibrate (FF). The primary endpoint was % change in bone mineral density (BMD) from baseline to month 24 in lumbar spine (LS) and femoral neck (FN). Secondary endpoints were changes in Z-score, calcitriol, calcitonin, parathyroid hormone, osteocalcin, and C-terminal telopeptide of type I collagen (CTX-I) at 12 and 24 months. Differences in continuous variables were evaluated using the t test or Mann-Whitney U-test for independent samples and differences in means of intra- and inter-subject continuous variables using a general linear model. Categorical variables were compared by the chi-squared or Fisher's exact test.Results: 30 patients were included in each arm; 23 in the n-3 PUFA arm and 22 in the FF arm completed follow-up. No significant differences between arms were observed after 24 months in either region (FN: -12.51% ± 7.89 in the n-3 PUFA arm and -8.18% ± 7.72 in the FF arm, p = .07; LS: 2.94% ± 6.63 in the n-3 PUFA arm, -3.07% ± 16.85 in the FF arm, p = .07), although the BMD reduction in the FN region after 24 months was noticeable in both arms (n-3 PUFA: -12.51% ± 7.89%, p =< .001; FF: -8.183% ± 7.72%, p =< .001). There was a significant difference in calcitriol changes between arms after 96 weeks. No differences in Z-score or bone turnover markers were observed between the two arms.Conclusions: Omega-3 fatty acid supplementation resulted in no beneficial changes in BMD or bone turnover markers. n-3 PUFA supplementation achieved similar reductions in triglyceride levels as FF.
RESUMO
BACKGROUND: Lipemia, a significant source of analytical errors in clinical laboratory settings, should be removed prior to measuring biochemical parameters. We investigated whether lipemia in serum/plasma samples can be removed using a method that is easier and more practicable than ultracentrifugation, the current reference method. METHODS: Seven hospital laboratories in Spain participated in this study. We first compared the effectiveness of ultracentrifugation (108,200×g) and high-speed centrifugation (10,000×g for 15 minutes) in removing lipemia. Second, we compared high-speed centrifugation with two liquid-liquid extraction methods-LipoClear (StatSpin, Norwood, USA), and 1,1,2-trichlorotrifluoroethane (Merck, Darmstadt, Germany). We assessed 14 biochemical parameters: serum/plasma concentrations of sodium ion, potassium ion, chloride ion, glucose, total protein, albumin, creatinine, urea, alkaline phosphatase, gamma-glutamyl transferase, alanine aminotransferase, aspartate-aminotransferase, calcium, and bilirubin. We analyzed whether the differences between lipemia removal methods exceeded the limit for clinically significant interference (LCSI). RESULTS: When ultracentrifugation and high-speed centrifugation were compared, no parameter had a difference that exceeded the LCSI. When high-speed centrifugation was compared with the two liquid-liquid extraction methods, we found differences exceeding the LCSI in protein, calcium, and aspartate aminotransferase in the comparison with 1,1,2-trichlorotrifluoroethane, and in protein, albumin, and calcium in the comparison with LipoClear. Differences in other parameters did not exceed the LCSI. CONCLUSIONS: High-speed centrifugation (10,000×g for 15 minutes) can be used instead of ultracentrifugation to remove lipemia in serum/plasma samples. LipoClear and 1,1,2-trichlorotrifluoroethane are unsuitable as they interfere with the measurement of certain parameters.
Assuntos
Hiperlipidemias/sangue , Lipídeos/isolamento & purificação , Extração Líquido-Líquido/métodos , Alanina Transaminase/sangue , Cálcio/sangue , Centrifugação , Creatinina/sangue , Humanos , Hiperlipidemias/patologia , Laboratórios HospitalaresRESUMO
INTRODUCTION: The therapeutic response to statins has a high interindividual variability with respect to reductions in plasma LDL-cholesterol (c-LDL) and increases in HDL cholesterol (c-HDL). Many studies suggest that there is a relationship between the rs20455 KIF6 gene variant (c.2155T> C, Trp719Arg) and a lower risk of cardiovascular disease in patients being treated with statins. AIM: The aim of this study was to investigate whether or not the c.2155T> C KIF6 gene variant modulates the hypercholesteremic effects of treatment with simvastatin, atorvastatin, or rosuvastatin. MATERIALS AND METHODS: This was a prospective, observational and multicenter study. Three hundred and forty-four patients who had not undergone prior lipid-lowering treatment were recruited. Simvastatin, atorvastatin or rosuvastatin were administered. Lipid profiles and multiple clinical and biochemical variables were assessed before and after treatment. RESULTS: The c.2155T> C variant of the KIF6 gene was shown to influence physiological responses to treatment with simvastatin and atorvastatin. Patients who were homozygous for the c.2155T> C variant (CC genotype, ArgArg) had a 7.0% smaller reduction of LDL cholesterol levels (p = 0.015) in response to hypolipidemic treatment compared to patients with the TT (TrpTrp) or CT (TrpArg) genotype. After pharmacological treatment with rosuvastatin, patients carrying the genetic variant had an increase in c-HDL that was 21.9% lower compared to patients who did not carry the variant (p = 0.008). CONCLUSION: Being a carrier of the c.2155T> C variant of the KIF6 gene negatively impacts patient responses to simvastatin, atorvastatin or rosuvastatin in terms of lipid lowering effect. Increasing the intensity of hypolipidemic therapy may be advisable for patients who are positive for the c.2155T> C variant.
Assuntos
Anticolesterolemiantes/uso terapêutico , Biomarcadores Farmacológicos/sangue , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipercolesterolemia/sangue , Hipercolesterolemia/tratamento farmacológico , Cinesinas/genética , Atorvastatina/uso terapêutico , LDL-Colesterol/sangue , LDL-Colesterol/efeitos dos fármacos , DNA/sangue , DNA/genética , Feminino , Humanos , Cinesinas/sangue , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Testes Farmacogenômicos , Estudos Prospectivos , Rosuvastatina Cálcica/uso terapêutico , Sinvastatina/uso terapêuticoRESUMO
BACKGROUND: High serum concentrations of small dense low-density lipoprotein cholesterol (sd-LDL-c) particles are associated with risk of cardiovascular disease (CVD). Their clinical application has been hindered as a consequence of the laborious current method used for their quantification. OBJECTIVE: Optimize a simple and fast precipitation method to isolate sd-LDL particles and establish a reference interval in a Mediterranean population. MATERIALS AND METHODS: Forty-five serum samples were collected, and sd-LDL particles were isolated using a modified heparin-Mg2+ precipitation method. sd-LDL-c concentration was calculated by subtracting high-density lipoprotein cholesterol (HDL-c) from the total cholesterol measured in the supernatant. This method was compared with the reference method (ultracentrifugation). Reference values were estimated according to the Clinical and Laboratory Standards Institute and The International Federation of Clinical Chemistry and Laboratory Medicine recommendations. sd-LDL-c concentration was measured in serums from 79 subjects with no lipid metabolism abnormalities. RESULTS: The Passing-Bablok regression equation is y = 1.52 (0.72 to 1.73) + 0.07x (-0.1 to 0.13), demonstrating no significant statistical differences between the modified precipitation method and the ultracentrifugation reference method. Similarly, no differences were detected when considering only sd-LDL-c from dyslipidemic patients, since the modifications added to the precipitation method facilitated the proper sedimentation of triglycerides and other lipoproteins. The reference interval for sd-LDL-c concentration estimated in a Mediterranean population was 0.04-0.47 mmol/L. CONCLUSION: An optimization of the heparin-Mg2+ precipitation method for sd-LDL particle isolation was performed, and reference intervals were established in a Spanish Mediterranean population. Measured values were equivalent to those obtained with the reference method, assuring its clinical application when tested in both normolipidemic and dyslipidemic subjects.