Genetic and phenotypic architecture of metabolic syndrome-associated components in dyslipidemic and normolipidemic subjects: the GEMS Study.

Atherogenic dyslipidemia, manifest by low HDL-cholesterol and high TG levels, is an important component of ATP-III defined metabolic syndrome. Here, we dissected the phenotypic and genetic architecture of these traits by assessing their relationships with other metabolically relevant measures, including plasma adipo-cytokines, highly sensitive C-reactive protein (hsCRP) and LDL particle size, in a large family data set (n=2800) and in an independent set of dyslipidemic cases (n=716) and normolipidemic controls (n=1073). We explored the relationships among these phenotypes using variable clustering and then estimated their genetic heritabilities and cross-trait correlations. In families, four clusters explained 61% of the total variance, with one adiposity-related cluster (including hsCRP), one BP-related cluster, and two lipid-related clusters (HDL-C, TG, adiponectin and LDL particle size; apoB and non-HDL-C). A similar structure was observed in dyslipidemic cases and normolipidemic controls. The genetic correlations in the families largely paralleled the phenotype clustering results, suggesting that common genes having pleiotropic effects contributed to the correlations observed. In summary, our analyses support a model of metabolic syndrome with two major components, body fat and lipids, each with two subcomponents, and quantifies their degree of overlap with each other and with metabolic-syndrome related measures (adipokines, LDL particle size and hsCRP).

FGF21 signalling pathway and metabolic traits - genetic association analysis.

Fibroblast growth factor 21 (FGF21) is a novel master regulator of metabolic profile. The biological actions of FGF21 are elicited upon its klotho beta (KLB)-facilitated binding to FGF receptor 1 (FGFR1), FGFR2 and FGFR3. We hypothesised that common polymorphisms in the FGF21 signalling pathway may be associated with metabolic risk. At the screening stage, we examined associations between 63 common single-nucleotide polymorphisms (SNPs) in five genes of this pathway (FGF21, KLB, FGFR1, FGFR2, FGFR3) and four metabolic phenotypes (LDL cholesterol - LDL-C, HDL-cholesterol - HDL-C, triglycerides and body mass index) in 629 individuals from Silesian Hypertension Study (SHS). Replication analyses were performed in 5478 unrelated individuals of the Swiss CoLaus cohort (imputed genotypes) and in 3030 directly genotyped individuals of the German Myocardial Infarction Family Study (GerMIFS). Of 54 SNPs that met quality control criteria after genotyping in SHS, 4 (rs4733946 and rs7012413 in FGFR1; rs2071616 in FGFR2 and rs7670903 in KLB) showed suggestive association with LDL-C (P=0.0006, P=0.0013, P=0.0055, P=0.011, respectively) and 1 (rs2608819 in KLB) was associated with body mass index (P=0.011); all with false discovery rate q<0.5. Of these, only one FGFR2 polymorphism (rs2071616) showed replicated association with LDL-C in both CoLaus (P=0.009) and men from GerMIFS (P=0.017). The direction of allelic effect of rs2071616 upon LDL-C was consistent in all examined populations. These data show that common genetic variations in FGFR2 may be associated with LDL-C in subjects of white European ancestry.

Common variants associated with plasma triglycerides and risk for coronary artery disease.

Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 × 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.

(Des)controle de parâmetros clínicos e antropométricos em indivíduos com doença arterial coronária

Estudo de corte transversal que avaliou parâmetros clínicos e antropométricos em 100 indivíduos com doença arterial coronária, atendidos em um ambulatório de cardiologia preventiva em um hospital público, em Salvador/BA. Na coleta de dados empregou-se entrevista, avaliação clínica e laboratorial. Os resultados foram analisados em médias e percentuais. Predominou homens, faixa etária <60 anos, raça/cor negra casado(a)s, baixa escolaridade e renda, indivíduos sem ocupação e com diagnóstico de infarto do miocárdio. A maioria relatou hipertensão arterial, dislipidemia, sedentarismo, abandono do tabagismo e da bebida alcoólica. Todas as mulheres e 82% dos homens tinham circunferência abdominal aumentada, 19% glicemia casual >200 mg/dl, 36% sobrepeso, 28% obesidade, 65% algum estágio de hipertensão arterial, 65% HDL-C baixo e 43% estava com colesterol total alto. Em indivíduos de alto risco cardiovascular e condições socioeconômicas deficitárias constatou-se o descontrole de vários fatores de risco cardiovascular, demandando práticas de cuidar efetivas para o controle da doença.

Risco cardiovascular em profissionais de saúde de serviços de atendimento pré-hospitalar

Avaliar os fatores de risco cardiovascular, com ênfase na hipertensão, e estratificá-los de acordo com o Escore de Risco de Framingham (ERF). Estudo com 154 profissionais que atuavam em aten-dimento pré-hospitalar na cidade de São Paulo e rodovia Br-116. Foi considerado significante o valor de p<0,05. A prevalência de hipertensão foi de 33%, sendo que 20,1% eram tabagistas, 47% ingeriam bebidas alcoólicas, 64% eram sedentários, 66% apresentaram obesidade/sobrepeso e 70% cintura abdominal alterada, glicemia>110mg/dL- 11%, colesterol total>200mg/dL- 36%, LDL-c>130mg/dL- 33%, HDL-c<60mg/dL- 89%, triglicérides>150mg/dL- 30% e proteína C reativa>0,5mg/dL- 16%. O ERF foi médio em 10,3% e alto em 1,3%. Na análise de regressão logística verificou-se que a hipertensão associou-se com as variáveis: HDL-c (odds ratio: 0,257) e ERF (odds ratio: 23,159). Houve forte associação entre ERF e hipertensão. Os dados chamam a atenção, por se tratar principalmente de profissionais da área da saúde relativamente jovens.

Impact of antiretroviral therapy (ART), immunosuppression and viraemia on lipid levels: the D:A:D study

Purpose of the study: To investigate the impact of ART, HIV viremia and immunosuppression on triglyceride (TG), total cholesterol (TC) and high density lipoprotein cholesterol (HDL-C) levels. Methods: We considered the cross-sectional associations between TG, TC and HDL-C (mmol/l; first available measurement on/after enrolment in the D:A:D study) and use of ART, HIV viral load (VL; copies/ml), and CD4 count (cells/mm3) measured at the same time. TG was log10 transformed to ensure normality. Analyses were performed using linear regression and adjusted for other factors known to impact lipid levels (table footnote). ART and VL status were combined (off ART&VL _100,000, off ART&VL B100,000, on ART&VL B500, on ART&VL _500), current and nadir CD4 count were categorised as B200, 200_349, 350_499 and _500. Summary of results: 44,322/49,734 participants in the D:A:D Study (89.1%) contributed a TG measurement (median; IQR 1.52; 1.00_ 2.45), 45,169 (90.8%) a TC measurement (4.80; 4.00_5.70) and 38,604 (77.6%) a HDL-C measurement (1.12; 0.90_1.40). Most participants were male (74%), of white ethnicity (51%), without AIDS (78%), were not receiving lipid-lowering drugs (4%) and were ART experienced (61%) with 47% previously exposed to PIs, 61% previously exposed to NRTIs and 29% previously exposed to NNRTIs. The median (IQR) age, current CD4 count and CD4 nadir were 38 (36_45) years, 400 (242_590) cells/ml and 240 (100_410) cells/ml respectively. Compared to those on ART with a suppressed VL, all lipids were lower for those off ART (Table); non-suppressive ART was also associated with lower TC and HDL-C levels (no impact on TG). A low current CD4 count was associated with lower lipid levels, whereas a low nadir CD4 count was associated with higher TC and TG levels. Prior AIDS diagnosis was associated with higher TG and TC, but lower HDL-C levels. Conclusion: Although specific drug classes were not considered, lipid levels are considerably higher in those on a suppressive ART regimen. The higher TC/TG and lower HDL-C levels seen among those with low nadir CD4 count and with a prior AIDS diagnosis suggests severe immunosuppression may be associated with dyslipidaemia over the long-term.

Prescription d'un traitement hypolipémiant lors d'un syndrome coronarien aigu en fonction du profil lipidique

Introduction: Les données épidémiologiques montrent que seuls25-30% des patients avec syndrome coronarien aigu (SCA) atteignentles valeurs cibles de LDL-cholestérol (LDL-C). Les recommandationsexistantes précisent le choix et le dosage des statines à utiliser enfonction du LDL-C cible souhaité. Le but de cette étude observationnelleétait de connaître les pratiques actuelles au CHUV avant d'introduireune étude d'intervention.Méthode: Pour être inclus, les patients devaient être admis au CHUVpour un SCA avec troponine positive (>= 0.1 microg/l) entre le23.11.2008 et le 29.05.2010. Un bilan lipidique complet (CT, HDL-C,LDL-C, TG) a été dosé à leur admission et un nouveau contrôle desparamètres lipidiques a été effectué à 3 mois. Les hypolipémiantsutilisés durant cette période ont été analysés pour chaque patient.Résultats: 141 patients, 101 hommes (âge moyen 63 ± 13 ans) et 40femmes (âge moyen 73 ± 13 ans) admis aux urgences pour un SCAavec troponine positive ont été inclus. La valeur moyenne du LDL-C àl'admission était de 3,4 ± 1,1 mmol/l (hommes 3,5 ± 1,1; femmes 3,3 ±1,1) et de 2,4 ± 0,8 mmol/l (hommes 2,4 ± 0,8; femmes 2,2 ± 0,7) aucontrôle de 3 mois. Parmi ces 141 patients, 52 (37%) étaient déjàtraités par une statine (36 hommes et 16 femmes). Leur valeur deLDL-C à l'admission était de 2,8 ± 0,9 mmol/l et de 2,5 ± 0,6 mmol/l aucontrôle de 3 mois. 7 patients (13%) ont eu une augmentation dudosage de leur statine, 14 patients (27%) ont eu un changement destatine et 31 patients (60%) n'ont eu aucune modification de leurtraitement. 89 patients n'avaient pas de statine (65 hommes et 24femmes) à leur admission mais ont quitté l'hôpital sous une statine.Leur valeur de LDL-C à l'entrée s'élevait à 3,8 ± 1 mmol/l et à 2,3 ± 0,8mmol/l au contrôle de 3 mois.Conclusion: Chez les patients hospitalisés pour un SCA mais sanstraitement par statine préalable, les résultats montrent une bonneadéquation (peut-être liée au hasard au vu d'une prescriptionstandardisée) entre le traitement prescrit et l'obtention d'un LDL-C ciblesouhaitable à 3 mois. Chez les patients déjà sous traitement de statine,les résultats montrent une faible baisse du LDL-C à 3 mois malgré leurrisque cardio-vasculaire plus élevé. Une prise en charge individualiséesemble d'autant plus nécessaire que le risque est élevé.

Serum insulin and inflammatory markers in overweight individuals with and without dyslipidemia.

CONTEXT: The worldwide epidemic of overweight and obesity is setting the scene for a new wave of premature cardiovascular disease. OBJECTIVE: The objective of this study was to define relationships between dyslipidemia and other metabolic abnormalities in overweight subjects. DESIGN: This study included comparison of overweight subjects with and without dyslipidemia. SETTING: The setting was an institutional practice. PATIENTS: Dyslipidemic subjects (n = 715) had plasma triglyceride greater than or equal to the 75th percentile in combination with high-density lipoprotein cholesterol (HDL-C) less than or equal to the 25th percentile. Unrelated, normolipidemic controls (n = 1073) had HDL-C higher than the median and triglyceride lower than the median. It was a requirement for the control subjects to have a body mass index (BMI) greater than 25 kg/m(2). MAIN OUTCOME MEASURES: The main outcome measures included BMI, inflammatory markers, adipokines, blood pressure, and fasting plasma glucose and insulin. RESULTS: The mean BMI in the subjects and controls was 28.7 and 28.2 kg/m(2), respectively. Subjects had higher levels of plasma high-sensitivity C-reactive protein (3.0 vs. 2.0 mg/liter; P < 0.001), lower levels of adiponectin (4.7 vs. 6.6 mg/liter; P < 0.001), and, after adjustment for age, BMI, gender, smoking, statin, and beta-blocker use, higher systolic (P = 0.001) and diastolic (P = 0.05) blood pressures. Fasting plasma glucose, insulin, and homeostasis model of assessment-insulin resistance were all significantly higher in subjects than controls (P < 0.0001). CONCLUSIONS: Identification of people solely on the basis of an elevated plasma triglyceride and a low HDL-C uncovers an overweight group of people who have a generalized metabolic disorder. In contrast, overweight people with normal plasma lipids have normal glucose and insulin metabolism, low levels of inflammatory markers, and normal blood pressure. Such people may thus be at relatively low risk of developing diabetes and cardiovascular disease despite being overweight.

Genetic variants influencing circulating lipid levels and risk of coronary artery disease.

OBJECTIVE: Genetic studies might provide new insights into the biological mechanisms underlying lipid metabolism and risk of CAD. We therefore conducted a genome-wide association study to identify novel genetic determinants of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides. METHODS AND RESULTS: We combined genome-wide association data from 8 studies, comprising up to 17 723 participants with information on circulating lipid concentrations. We did independent replication studies in up to 37 774 participants from 8 populations and also in a population of Indian Asian descent. We also assessed the association between single-nucleotide polymorphisms (SNPs) at lipid loci and risk of CAD in up to 9 633 cases and 38 684 controls. We identified 4 novel genetic loci that showed reproducible associations with lipids (probability values, 1.6×10(-8) to 3.1×10(-10)). These include a potentially functional SNP in the SLC39A8 gene for HDL-C, an SNP near the MYLIP/GMPR and PPP1R3B genes for LDL-C, and at the AFF1 gene for triglycerides. SNPs showing strong statistical association with 1 or more lipid traits at the CELSR2, APOB, APOE-C1-C4-C2 cluster, LPL, ZNF259-APOA5-A4-C3-A1 cluster and TRIB1 loci were also associated with CAD risk (probability values, 1.1×10(-3) to 1.2×10(-9)). CONCLUSIONS: We have identified 4 novel loci associated with circulating lipids. We also show that in addition to those that are largely associated with LDL-C, genetic loci mainly associated with circulating triglycerides and HDL-C are also associated with risk of CAD. These findings potentially provide new insights into the biological mechanisms underlying lipid metabolism and CAD risk.

PPAR-β/δ activation promotes phospholipid transfer protein expression.

The peroxisome proliferator-activated receptor (PPAR)-β/δ has emerged as a promising therapeutic target for treating dyslipidemia, including beneficial effects on HDL cholesterol (HDL-C). In the current study, we determined the effects of the PPAR-β/δ agonist GW0742 on HDL composition and the expression of liver HDL-related genes in mice and cultured human cells. The experiments were carried out in C57BL/6 wild-type, LDL receptor (LDLR)-deficient mice and PPAR-β/δ-deficient mice treated with GW0742 (10mg/kg/day) or a vehicle solution for 14 days. GW0742 upregulated liver phospholipid transfer protein (Pltp) gene expression and increased serum PLTP activity in mice. When given to wild-type mice, GW0742 significantly increased serum HDL-C and HDL phospholipids; GW0742 also raised serum potential to generate preβ-HDL formation. The GW0742-mediated effects on liver Pltp expression and serum enzyme activity were completely abolished in PPAR-β/δ-deficient mice. GW0742 also stimulated PLTP mRNA expression in mouse J774 macrophages, differentiated human THP-1 macrophages and human hepatoma Huh7. Collectively, our findings demonstrate a common transcriptional upregulation by GW0742-activated PPAR-β/δ of Pltp expression in cultured cells and in mouse liver resulting in enhanced serum PLTP activity. Our results also indicate that PPAR-β/δ activation may modulate PLTP-mediated preβ-HDL formation and macrophage cholesterol efflux.

A short screener is valid for assessing mediterranean diet adherence among older spanish men and women

Ensuring the accuracy of dietary assessment instruments is paramount for interpreting diet-disease relationships. The present study assessed the relative and construct validity of the 14-point Mediterranean Diet Adherence Screener (MEDAS) used in the Prevencio´n con Dieta Mediterra´nea (PREDIMED) study, a primary prevention nutrition-intervention trial. A validated FFQ and the MEDAS were administered to 7146 participants of the PREDIMED study. The MEDASderived PREDIMED score correlated significantly with the corresponding FFQ PREDIMED score (r = 0.52; intraclass correlation coefficient = 0.51) and in the anticipated directions with the dietary intakes reported on the FFQ. Using Bland Altman"s analysis, the average MEDAS Mediterranean diet score estimate was 105% of the FFQ PREDIMED score estimate. Limits of agreement ranged between 57 and 153%. Multiple linear regression analyses revealed that a higher PREDIMED score related directly (P , 0.001) to HDL-cholesterol (HDL-C) and inversely (P , 0.038) to BMI, waist circumference, TG, the TG:HDL-C ratio, fasting glucose, and the cholesterol:HDL-C ratio. The 10-y estimated coronary artery disease risk decreased as the PREDIMED score increased (P , 0.001). The MEDAS is a valid instrument for rapid estimation of adherence to the Mediterranean diet and may be useful in clinical practice.

A short screener is valid for assessing mediterranean diet adherence among older spanish men and women

Ensuring the accuracy of dietary assessment instruments is paramount for interpreting diet-disease relationships. The present study assessed the relative and construct validity of the 14-point Mediterranean Diet Adherence Screener (MEDAS) used in the Prevencio´n con Dieta Mediterra´nea (PREDIMED) study, a primary prevention nutrition-intervention trial. A validated FFQ and the MEDAS were administered to 7146 participants of the PREDIMED study. The MEDASderived PREDIMED score correlated significantly with the corresponding FFQ PREDIMED score (r = 0.52; intraclass correlation coefficient = 0.51) and in the anticipated directions with the dietary intakes reported on the FFQ. Using Bland Altman"s analysis, the average MEDAS Mediterranean diet score estimate was 105% of the FFQ PREDIMED score estimate. Limits of agreement ranged between 57 and 153%. Multiple linear regression analyses revealed that a higher PREDIMED score related directly (P , 0.001) to HDL-cholesterol (HDL-C) and inversely (P , 0.038) to BMI, waist circumference, TG, the TG:HDL-C ratio, fasting glucose, and the cholesterol:HDL-C ratio. The 10-y estimated coronary artery disease risk decreased as the PREDIMED score increased (P , 0.001). The MEDAS is a valid instrument for rapid estimation of adherence to the Mediterranean diet and may be useful in clinical practice.

Impact of Roux-en-Y gastric bypass on lipid and inflammatory profiles

Objective: To evaluate the behavior of acute phase proteins and lipid profile in patients undergoing Roux-en-Y gastric bypass. Methods : We conducted a prospective study, consisting of three moments: M1 - preoperative (24 hours before surgery); M2 - 30 days after surgery; and M3 - 180 days after surgery. We carried measured height and BMI, as well as determined the concentrations of acute phase proteins (C-reactive protein (CRP), albumin and Alpha-1-acid glycoprotein) and total cholesterol, LDL-c, HDL-c and triacylglycerol. Results : participants comprised 25 individuals, with a mean age of 39.28 ± 8.07, 72% female. At all times of the study there was statistically significant difference as for weight loss and BMI. We found a significant decrease in CRP concentrations between the moments M1 and M3 (p = 0.041) and between M2 and M3 (p = 0.018). There was decrease in Alpha-1-GA concentrations between M1 and M2 (p = 0.023) and between M1 and M3 (p = 0.028). The albumin values increased, but did not differ between times. Total cholesterol and triacylglycerol decreased significantly ay all times. LDL-c concentrations decreased and differed between M1 and M2 (p = 0.001) and between M1 and M3 (p = 0.001). HDL-c values increased, however only differing between M1 and M2 (p = 0.050). Conclusion : Roux-en-Y gastric bypass promoted a decrease in plasma concentrations of CRP and Alpha-1-acid glycoprotein, improving lipid and inflammatory profiles.

Efeitos do implante subdérmico de acetato de nomegestrol sobre o metabolismo de carboidratos, lipoproteínas séricas e função hepática

Objetivos: avaliar variações de peso corporal, pressão arterial, glicemia em jejum, HbA1C, insulina, colesterol total, HDL-C, LDL-C, triglicérides, TGO, TGP, GGT e bilirrubina em mulheres usuárias de um implante único, subdérmico, de Silástico, contendo 55 mg (±10%) de acetato de nomegestrol, durante dois anos. Métodos: dezoito voluntárias saudáveis e em idade reprodutiva, que desejavam fazer uso de anticoncepcionais e não apresentavam contra-indicações para o uso de contracepção hormonal, participaram deste estudo. Todas as mulheres foram avaliadas antes do início do tratamento e a seguir, acompanhadas por um período de dois anos. Ao final do primeiro ano, as cápsulas foram retiradas e novas cápsulas foram inseridas. Resultados: o peso corporal aumentou de 54,9 ± 1,5 kg na admissão para 55,3 ± 2,0 kg no 12º mês de uso (p<0,05), e para 56,0 ± 2,7 kg no 24º mês de uso. Registrou-se discreto aumento da pressão arterial, tanto sistólica quanto diastólica, no mês 12 (p<0,01). No mês 24, a pressão arterial não era significativamente diferente dos valores de admissão. Todos os valores estiveram dentro dos limites da normalidade. Insulina, HbA1C, LDL-C e GGT permaneceram inalterados durante os vinte e quatro meses de uso do implante. Diminuição significativa do colesterol total (p<0,05) foi observada no 3º mês e de HDL-C (p<0,01) no 6º mês. Observou-se aumento significativo de triglicérides (p<0,05) apenas no 12º mês. Todas as alterações de lipoproteínas foram inconsistentes, e os valores estiveram dentro dos limites da normalidade. Aumentos significativos dos níveis de glicemia em jejum (p<0,05 e p<0,01) foram observados respectivamente no 3º e no 6º mês. Diminuições significativas da TGO (p<0,05, p<0,01 e p<0,05) foram observadas respectivamente no 6º, 18º e 24º mês e da TGP (p<0,05) no 18º mês. Somente se observou aumento significativo de bilirrubina (p<0,05) no 3º mês de uso do implante. Todas estas variações permaneceram dentro dos limites da normalidade. Conclusões: esses resultados demonstraram que, dentro dos limites da normalidade, as variações de glicemia em jejum não se correlacionam às alterações dos níveis de insulina. As alterações discretas em lipoproteínas séricas, TGO, TGP e bilirrubina foram transitórias. Não foram observados efeitos clínicos em lipoproteínas, metabolismo de carboidratos, níveis de insulina e função hepática entre as usuárias por dois anos.

Aspectos clínicos e metabólicos de mulheres na pós-menopausa tratadas com tibolona

Objetivos: analisar a repercussão da tibolona sobre os sintomas do climatério e sobre algumas variáveis clínicas e metabólicas. Métodos: foram avaliadas 34 pacientes na pós-menopausa que foram submetidas ao tratamento com tibolona na dose de 2,5 mg/dia por 48 semanas. Foram analisados os seguintes parâmetros: peso, pressão arterial e perfis lipídico e lipoprotéico, representados pelos níveis de colesterol total, HDL-c, LDL-c, VLDL-c e triglicerídeos. Resultados: melhora relevante da sintomatologia do climatério foi demonstrada por decréscimo significativo do índice menopausal de Kupperman (p<0.001) e da freqüência média das ondas de calor (p<0.001). Estes efeitos foram observados já no primeiro mês de tratamento, mantendo-se até o final do estudo. Houve decréscimo significante nos níveis de colesterol total, triglicerídeos e VLDL-c (p<0.001). Os níveis de LDL-c apresentaram discreta redução (não-significante). Os níveis de HDL-c mostraram decréscimo significante na 24ª semana de tratamento, mas retornaram aos níveis basais na 48ª semana. Não foram observadas modificações significantes no peso e pressão arterial. Os efeitos colaterais relatados incluíram sangramento vaginal, náusea e edema, todos temporários e de intensidade leve. Conclusão: a tibolona representa uma opção para o tratamento dos sintomas climatéricos em mulheres na pós-menopausa, sem alterações relevantes no perfil lipídico e lipoprotéico.