RESUMO
BACKGROUND: In postmenopausal women (PMW), an adverse lipoprotein pattern and high risk of coronary artery disease has been described. Studies of the mechanisms promoting the higher atherogenic risk observed in healthy PMW are relevant. We evaluated the interactions among several circulating factors involved in the endothelial injury and inflammation in relation to LDL characteristics, beyond LDL cholesterol. METHODS: Lipoprotein profile, including apolipoproteins A-I and B, small dense LDL, hepatic lipase, cholesterol transfer protein (CETP), LDL composition and oxidability were assessed in PMW (n=30) in comparison to premenopausal (PreMW, n=28). The following emerging factors were measured: homocysteine, phospholipase A2, ferritin, hs-CRP and fibronectin from extracellular vascular matrix. Insulin-resistance was evaluated by waist circumference, HOMA and TG/HDL cholesterol ratios. RESULTS: The risk index apo B/apo A-I was significantly increased in PMW (p<0.0001), PMW showed higher proportion of small dense LDL which correlated with the increase in hepatic lipase activity (p<0.005) and with insulin-resistance markers (p<0.05), but not with CETP. Phospholipase A2 (p<0.05), homocysteine (p<0.005), hs-CRP (p<0.005), fibronectin (p<0.05) and ferritin (p<0.0001) were increased in PMW. LDL oxidability positively correlated with waist (p<0.02), homocysteine (p<0.05), fibronectin (p<0.05), hs-CRP (p<0.04), phospholipase A2 (p<0.05), and small dense LDL (p<0.01). After adjusting by menopausal condition, age and waist, LDL oxidability remained associated with waist (beta: 0.35, p=0.047), homocysteine (beta: 0,36 p<0,038), fibronectin (beta: 0,41 p=0.05), and small dense LDL (beta: 0.36, p=0.027). CONCLUSIONS: Evaluation of classic and non-traditional circulating risk factors in hypoestrogenism reflected endothelial and subendothelial inflammation and subclinical atherogenic processes.
Assuntos
Endotélio Vascular/patologia , Fibronectinas/sangue , Lipoproteínas LDL/sangue , Pós-Menopausa/sangue , Adulto , Antropometria , Biomarcadores , Feminino , Humanos , Resistência à Insulina , Lipase/sangue , Lipase Lipoproteica/sangue , Fígado/enzimologia , Pessoa de Meia-Idade , Oxirredução , Valores de Referência , Relação Cintura-QuadrilRESUMO
OBJECTIVES: Small dense low-density lipoproteins (LDLs) should be considered a major risk factor for cardiovascular disease, but there is still no recommended method for measuring them or expressing clinical values. We measured the dense LDL portion relatively simply by isolating it using density ultracentrifugation and then giving it a relative, quantitative value. DESIGN AND METHODS: Dense LDLs (d=1.048-1.063 g/mL) were isolated from human plasma at the same time as total LDL (d=1.021-1.063 g/mL) by means of sequential ultracentrifugation, and the former was assessed as a percentage of the latter. A receiver operator characteristic (ROC) curve was used to compare the different LDL components as markers of dense LDLs. The proposed method was compared with non-denaturing gradient gel electrophoresis (NDGGE). In order to obtain clinical data, the dense LDL portion was measured in diabetic and postmenopausal subjects and healthy controls. RESULTS: The ROC curve showed that cholesterol level was a more accurate marker of dense LDLs. The within-run precision (CV) was 2.28%, and the between-run CV was 5.1%. Analytical recovery was 80.2+/-1.6%. The correlation between the proposed method and NDGGE was r=0.90, p<0.001. The dense LDL percentage significantly correlated with serum triglyceride (r=0.57, p<0.001) and high-density lipoprotein cholesterol levels (r=-0.33, p<0.01), but not with the LDL-cholesterol/apolipoprotein B ratio. The diabetic patients and postmenopausal women had higher dense LDL values than the healthy controls. CONCLUSIONS: The results obtained using this procedure are in line with those obtained using NDGGE, which is the conventional assay system for measuring LDL size. Determining the small dense LDL portion by means of its cholesterol content may be a better approach to characterising the risk of cardiovascular disease, even in the presence of relatively normal LDL-cholesterol levels.
Assuntos
Apolipoproteínas B/sangue , Centrifugação com Gradiente de Concentração/métodos , LDL-Colesterol/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/sangue , Colesterol/sangue , HDL-Colesterol/sangue , Diabetes Mellitus Tipo 2/sangue , Eletroforese em Gel de Poliacrilamida , Feminino , Humanos , Pessoa de Meia-Idade , Pós-Menopausa/sangue , Curva ROC , Fatores de Risco , Sensibilidade e Especificidade , Triglicerídeos/sangueRESUMO
The behavior of lipoproteins during the menopausal transition and their relationship with sex hormones and body fat distribution is still unclear. Our aim was to evaluate atherogenic IDL, LDL, Lp(a) and antiatherogenic HDL lipoproteins in four groups of women: premenopausal (n = 20), menopausal transition women with menstrual bleeding (n = 31), menopausal transition women with 3 to 6 months amenorrhea (n = 36), and postmenopausal women (n = 30). We also measured their FSH, LH and estradiol levels along with BMI and waist circumference. Menopausal transition and postmenopausal women showed higher values of waist circumference (p < 0.0032), LDL-cholesterol (p < 0.002), IDL-cholesterol (p < 0.002) and apoprotein B (p < 0.0001) than premenopausal women. Total-cholesterol (p < 0.0001), triglycerides (p < 0.004), IDL-cholesterol and Lp(a) were higher in menopausal transition women with amenorrhea and in postmenopausal women in comparison with premenopausal women. After adjustment according to age and waist circumference, multiple regression analysis showed the increase in total-cholesterol and LDL-cholesterol to be linearly associated to menopausal status and estradiol concentration, whereas Lp(a) was only related to menopausal status. Age was found to be an independent variable in relation to apoprotein B concentration changes. The effect of menopausal status on TG levels did not remain in the model when age, waist and BMI were included (beta = 0.05, p = 0.356). HDL-cholesterol levels were the same in all the groups. Menopause, age and the increase in abdominal fat distribution were three independent and significant factors impairing lipoprotein profiles from the beginning of the menopausal transition.