933 resultados para LDL-cholesterol
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Collagen XVIII can generate two fragments, NC11-728 containing a frizzled motif which possibly acts in Wnt signaling and Endostatin, which is cleaved from the NC1 and is a potent inhibitor of angiogenesis. Collagen XVIII and Wnt signaling have recently been associated with adipogenic differentiation and obesity in some animal models, but not in humans. In the present report, we have shown that COL18A1 expression increases during human adipogenic differentiation. We also tested if polymorphisms in the Frizzled (c.1136C>T; Thr379Met) and Endostatin (c.4349G>A; Asp1437Asn) regions contribute towards susceptibility to obesity in patients with type 2 diabetes (113 obese, BMI =30; 232 non-obese, BMI < 30) of European ancestry. No evidence of association was observed between the allele c.4349G>A and obesity, but we observed a significantly higher frequency of homozygotes c.1136TT in obese (19.5%) than in non-obese individuals (10.9%) [P = 0.02; OR = 2.0 (95%CI: 1.07-3.73)], suggesting that the allele c.1136T is associated to obesity in a recessive model. This genotype, after controlling for cholesterol, LDL cholesterol, and triglycerides, was independently associated with obesity (P = 0.048), and increases the chance of obesity in 2.8 times. Therefore, our data suggest the involvement of collagen XVIII in human adipogenesis and susceptibility to obesity.
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OBJETIVO: Avaliar se o conteúdo de auto-anticorpos anti-LDL oxidada (anti-LDLox) no plasma de adolescentes correlaciona-se com suas medidas antropométricas e com o perfil lipídico. MÉTODOS: O estudo incluiu 150 adolescentes com idade entre 10 e 15 anos, recrutados do ambulatório de obesidade da Universidade Federal de São Paulo (SP) e de escolas públicas de Piracicaba (SP). Foram avaliadas medidas antropométricas, como índice de massa corporal, circunferência de cintura e do braço, classificando os adolescentes em eutrófico, sobrepeso e obeso. Para as análises bioquímicas, foi realizado o perfil lipídico através de métodos enzimáticos colorimétricos, e para detecção do conteúdo de auto-anticorpos anti-LDLox, utilizou-se o método de ELISA. RESULTADOS: Segundo análises das variáveis antropométricas, o grupo obeso apresentou perfil alterado em relação aos grupos eutrófico e sobrepeso (p < 0,01), indicando risco cardiovascular. Quando o perfil lipídico foi avaliado, observaram-se diferenças estatisticamente significativas para as concentrações de colesterol total (p = 0,011), HDL-colesterol (p = 0,001) e LDL-colesterol (p < 0,042) nos grupos eutrófico e obeso. Para as análises de auto-anticorpos anti-LDLox plasmática, os grupos sobrepeso (p = 0,012) e obeso (p < 0,001) apresentaram valores superiores ao grupo eutrófico. Também houve correlações entre os auto-anticorpos anti-LDLox e variáveis antropométricas. CONCLUSÃO: A presença de auto-anticorpos anti-LDLox em adolescentes e as alterações metabólicas no perfil lipídico variaram de modo proporcional com parâmetros antropométricos, o que torna o conteúdo de anti-LDLox um potencial indicador bioquímico de risco para síndrome metabólica.
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Objetivos: Examinar a prevalência da sub e supernotificação da ingestão energética em adolescentes e seus fatores associados. Métodos: Estudo transversal com 96 adolescentes na pós-puberdade (47 com peso normal e 49 obesos), com idade média de 16,6±1,3 anos. Peso e altura foram medidos e o índice de massa corporal foi calculado. A composição corporal foi avaliada através de absorciometria por raios X de dupla energia. A ingestão de alimentos foi avaliada por meio de um registro alimentar de 3 dias. Realizou-se uma avaliação bioquímica (níveis séricos de colesterol total, LDL, HDL, glicose plasmática e insulina). Os subnotificadores relataram uma ingestão energética < 1,35 x taxa metabólica basal (TMB), enquanto os supernotificadores relataram uma ingestão energética > 2,4 x TMB. Resultados: Notificação imprecisa (sub ou supernotificação) da ingestão energética foi identificada em 65,6 por cento dos adolescentes (64,6 e 1 por cento de sub e supernotificação, respectivamente). Os adolescentes obesos apresentaram 5.0 vezes mais chances de subnotificar a ingestão energética (IC95 por cento 2,0-12,7) do que os participantes com peso normal. Os subnotificadores apresentaram taxas mais altas de ingestão insuficiente de carboidratos (19,3 versus 12,1 por cento, p = 0,046) e de lipídios (11,3 versus 0 por cento, p < 0,001) do que os notificadores plausíveis. A ingestão de colesterol também foi mais baixa entre os subnotificadores (p = 0,017). Não houve diferenças significativas na composição corporal e nos parâmetros bioquímicos em relação à notificação imprecisa. Conclusões: Os resultados obtidos demonstraram alta porcentagem de notificação imprecisa da ingestão energética entre adolescentes, principalmente entre os obesos, o que sugere que os valores de consumo de nutrientes ajustado para o consumo de energia deveriam ser empregados na análise de risco da relação dieta-doença a fim de contribuir para a redução de erros associados à notificação imprecisa
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There is a considerable debate about the potential influence of fetal programming on cardiovascular diseases in adulthood. In the present prospective epidemiological cohort study, the relationship between birthweight and arterial elasticity in 472 children between 5 and 8 years of age was assessed. LAEI (large artery elasticity index), SAEI (small artery elasticity index) and BP (blood pressure) were assessed using the HDI/PulseWave CR-2000 CardioVascular Profiling System. Blood concentrations of glucose, total cholesterol and its fractions [LDL (low-density lipoprotein)-cholesterol and HDL (high-density lipoprotein)-cholesterol] and triacylglycerols (triglycerides) were determined by automated enzymatic methods. Insulin was assessed by a chemiluminescent method, insulin resistance by HOMA (homoeostasis model assessment) and CRP (C-reactive protein) by immunonephelometry. Two linear regression models were applied to investigate the relationship between the outcomes, LAEI and SAEI, and the following variables: birthweight, gestational age, glucose, LDL-cholesterol, HDL-cholesterol, triacylglycerols, insulin, CRP, HOMA, age, gender, waist circumference, per capita income, SBP (systolic BP) and DBP (diastolic BP). LAEI was positively associated with birthweight (P=0.036), waist circumference (P<0.001) and age (P<0.001), and negatively associated with CRP (P=0.024) and SBP (P<0.001). SAEI was positively associated with birthweight (P=0.04), waist circumference (P=0.001) and age (P<0.001), and negatively associated with DBP (P<0.001). Arterial elasticity was decreased in apparently healthy children who had lower birthweights, indicating an earlier atherogenetic susceptibility to cardiovascular diseases in adolescence and adult life. Possible explanations for the results include changes in angiogenesis during critical phases of intrauterine life caused by periods of fetal growth inhibition and local haemodynamic anomalies
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Chronic diseases that are typical of adulthood may originate in intra-uterine life through inadequate fetal development. The present epidemiological cohort study of 506 healthy children aged 5\20138 years evaluated the relationship between birth weight and insulin resistance in an age group that has been assessed in few similar studies. Insulin concentration was determined by chemiluminescence and insulin resistance by the homeostasis model assessment (HOMA). Blood glucose, total cholesterol and fractions (LDL cholesterol and HDL cholesterol) and TAG concentrations were determined by automated enzymatic methods. Linear regression analysis investigated the relationship between birth weight (assessed as a continuous variable and in three categories: small for gestational age, SGA; adequate for gestational age and large for gestational age) and the HOMA index, using backward stepwise selection and biological models to explain the causal pathway of the relationship. There were negativeassociations between birth weight (P < 0·001), SGA (P = 0·027) and the HOMA index, and a positive association between waist circumference (P < 0·001) and the HOMA index. Considering the significant associations between birth weight and waist circumference (P < 0·001) and waist circumference and insulin resistance (P < 0·001), we can probably suspect that lower birth weight is a common cause of higher waist circumference and insulin resistance. In summary, the results of the present study showed increased insulin resistance in apparently healthy, young children, who had lower weight at birth and higher measurements of waist circumference. There is a need to develop public health policies that adopt preventive measures to promote adequate maternal-fetal and child development and enable early diagnosis of metabolic abnormalities
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Background: Obstructive Sleep Apnea (OSA) is tightly linked to some components of Metabolic Syndrome (MetS). However, most of the evidence evaluated individual components of the MetS or patients with a diagnosis of OSA that were referred for sleep studies due to sleep complaints. Therefore, it is not clear whether OSA exacerbates the metabolic abnormalities in a representative sample of patients with MetS. Methodology/Principal Findings: We studied 152 consecutive patients (age 48 +/- 9 years, body mass index 32.3 +/- 3.4 Kg/m(2)) newly diagnosed with MetS (Adult Treatment Panel III). All participants underwent standard polysomnography irrespective of sleep complaints, and laboratory measurements (glucose, lipid profile, uric acid and C-reactive protein). The prevalence of OSA (apnea-hypopnea index >= 15 events per hour of sleep) was 60.5%. Patients with OSA exhibited significantly higher levels of blood pressure, glucose, triglycerides, cholesterol, LDL, cholesterol/HDL ratio, triglycerides/HDL ratio, uric acid and C-reactive protein than patients without OSA. OSA was independently associated with 2 MetS criteria: triglycerides: OR: 3.26 (1.47-7.21) and glucose: OR: 2.31 (1.12-4.80). OSA was also independently associated with increased cholesterol/HDL ratio: OR: 2.38 (1.08-5.24), uric acid: OR: 4.19 (1.70-10.35) and C-reactive protein: OR: 6.10 (2.64-14.11). Indices of sleep apnea severity, apnea-hypopnea index and minimum oxygen saturation, were independently associated with increased levels of triglycerides, glucose as well as cholesterol/HDL ratio, uric acid and C-reactive protein. Excessive daytime sleepiness had no effect on the metabolic and inflammatory parameters. Conclusions/Significance: Unrecognized OSA is common in consecutive patients with MetS. OSA may contribute to metabolic dysregulation and systemic inflammation in patients with MetS, regardless of symptoms of daytime sleepiness.
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Background: The effects of chronic aerobic exercise upon lipid profile has been previously demonstrated, but few studies showed this effect under resistance exercise conditions. Objective: The aim of this study was to examine the effects of different resistance exercise loads on blood lipids. Methods: Thirty healthy, untrained male volunteers were allocated randomly into four groups based at different percentages of one repetition maximum (1 RM); 50%-1 RM, 75%-1 RM, 90%-1 RM, and 110%-1 RM. The total volume (sets x reps x load) of the exercise was equalized. The lipid profile (Triglycerides [TG], HDL-cholesterol [HDL-c], LDL-cholesterol, and Total cholesterol) was determined at rest and after 1, 24, 48 and 72 h of resistance exercise. Results: The 75%-1 RM group demonstrated greater TG reduction when compared to other groups (p < 0.05). Additionally, the 110%-1 RM group presented an increased TG concentration when compared to 50% and 75% groups (p = 0.01, p = 0.01, respectively). HDL-c concentration was significantly greater after resistance exercise in 50%-1 RM and 75%-1 RM when compared to 110%-1 RM group (p = 0.004 and p = 0.03, respectively). Accordingly, the 50%-1 RM group had greater HDL-c concentration than 110%-1 RM group after 48 h (p = 0.05) and 72 h (p = 0.004), respectively. Finally, The 50% group has showed lesser LDL-c concentration than 110% group after 24 h (p = 0.007). No significant difference was found in Total Cholesterol concentrations. Conclusion: These results indicate that the acute resistance exercise may induce changes in lipid profile in a specific-intensity manner. Overall, low and moderate exercise intensities appear to be promoting more benefits on lipid profile than high intensity. Long term studies should confirm these findings.
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Aims: The relationship between variants in SLCO1B1 and SLCO2B1 genes and lipid-lowering response to atorvastatin was investigated. Material and Methods: One-hundred-thirty-six unrelated individuals with hypercholesterolemia were selected and treated with atorvastatin (10 mg/day/4 weeks). They were genotyped with a panel of ancestry informative markers for individual African component of ancestry (ACA) estimation by SNaPshot (R) and SLCO1B1 (c.388A>G, c.463C>A and c.521T>C) and SLCO2B1 (-71T>C) gene polymorphisms were identified by TaqMan (R) Real-time PCR. Results: Subjects carrying SLCO1B1 c.388GG genotype exhibited significantly high low-density lipoprotein (LDL) cholesterol reduction relative to c.388AA+c.388AG carriers (41 vs. 37%, p = 0.034). Haplotype analysis revealed that homozygous of SLCO1B1*15 (c.521C and c.388G) variant had similar response to statin relative to heterozygous and non-carriers. A multivariate logistic regression analysis confirmed that c.388GG genotype was associated with higher LDL cholesterol reduction in the study population (OR: 3.2, CI95%: 1.3-8.0, p < 0.05). Conclusion: SLCO1B1 c.388A>G polymorphism causes significant increase in atorvastatin response and may be an important marker for predicting efficacy of lipid-lowering therapy.
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Background: Thyroid receptors, TRa and TR beta, are involved in important physiological functions such as metabolism, cholesterol level and heart activities. Whereas metabolism increase and cholesterol level lowering could be achieved by TR beta isoform activation, TRa activation affects heart rates. Therefore, beta-selective thyromimetics have been developed as promising drug-candidates for treatment of obesity and elevated cholesterol level. GC-1 [ 3,5-dimethyl-4-(4'-hydroxy- 3'-isopropylbenzyl)-phenoxy acetic acid] has ability to lower LDL cholesterol with 600-to 1400-fold more potency and approximately two-to threefold more efficacy than atorvastatin (Lipitor(C)) in studies in rats, mice and monkeys. Results: To investigate GC-1 specificity, we solved crystal structures and performed molecular dynamics simulations of both isoforms complexed with GC-1. Crystal structures reveal that, in TRa Arg228 is observed in multiple conformations, an effect triggered by the differences in the interactions between GC-1 and Ser277 or the corresponding asparagine (Asn331) of TR beta. The corresponding Arg282 of TR beta is observed in only one single stable conformation, interacting effectively with the ligand. Molecular dynamics support this model: our simulations show that the multiple conformations can be observed for the Arg228 in TR alpha, in which the ligand interacts either strongly with the ligand or with the Ser277 residue. In contrast, a single stable Arg282 conformation is observed for TR beta, in which it strongly interacts with both GC-1 and the Asn331. Conclusion: Our analysis suggests that the key factors for GC-1 selectivity are the presence of an oxyacetic acid ester oxygen and the absence of the amino group relative to T(3). These results shed light into the beta-selectivity of GC-1 and may assist the development of new compounds with potential as drug candidates to the treatment of hypercholesterolemia and obesity.
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According to Brazilian National Data Survey diabetes is the fifth cause for hospitalization and is one of the ten major causes of mortality in this country. Aims to stratify the estimated cardiovascular risk (eCVR) in a population of type 2 diabetics (T2DM) according to the Framingham prediction equations as well as to determine the association between eCVR with metabolic and clinical control of the disease. Methods From 2000 to 2001 a cross-sectional multicenter study was conducted in 13 public out-patients diabetes/endocrinology clinics from 8 Brazilian cities. The 10-year risk of developing coronary heart disease (CHD) was estimated by the prediction equations described by Wilson et al (Circulation 1998). LDL equations were preferably used; when patients missed LDL data we used total cholesterol equations instead. Results Data from 1382 patients (59.0% female) were analyzed. Median and inter-quartile range (IQ) of age and duration of diabetes were 57.4 (51-65) and 8.8 (3-13) years, respectively without differences according to the gender. Forty-two percent of these patients were overweight and 35.4% were obese (the prevalence of higher BMI and obesity in this T2DM group was significantly higher in women than in men; p < 0.001). The overall estimated eCVR in T2DM patients was 21.4 (13.5-31.3). The eCVR was high (> 20%) in 738 (53.4%), intermediate in 202 (14.6%) and low in 442 (32%) patients. Men [25.1(15.4-37.3)] showed a higher eCVR than women [18.8 (12.4-27.9) p < 0.001]. The most common risk factor was high LDL-cholesterol (80.8%), most frequently found in women than in men (p = 0.01). The median of risk factors present was three (2-4) without gender differences. Overall we observed that 60 (4.3%) of our patients had none, 154(11.1%) one, 310 (22.4%) two, 385 (27.9%) three, 300 (21.7%) four, 149 (10.5%) five and six, (2%) six risk factors. A higher eCVR was noted in overweight or obese patients (p = 0.01 for both groups). No association was found between eCVR with age or a specific type of diabetes treatment. A correlation was found between eCVR and duration of diabetes (p < 0.001), BMI (p < 0.001), creatinine (p < 0.001) and triglycerides levels (p < 0.001) but it was not found with HbA1c, fasting blood glucose and postprandial glucose. A higher eCVR was observed in patients with retinopathy (p < 0.001) and a tendency in patients with microalbuminuria (p = 0.06). Conclusion: our study showed that in this group of Brazilian T2DM the eCVR was correlated with the lipid profile and it was higher in patients with microvascular chronic complications. No correlation was found with glycemic control parameters. These data could explain the failure of intensive glycemic control programs aiming to reduce cardiovascular events observed in some studies.
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Background: Progression of atherosclerosis in coronary artery disease is observed through consecutive angiograms. Prognosis of this progression in patients randomized to different treatments has not been established. This study compared progression of coronary artery disease in native coronary arteries in patients undergoing surgery, angioplasty, or medical treatment. Methods: Patients (611) with stable multivessel coronary artery disease and preserved ventricular function were randomly assigned to CABG, PCI, or medical treatment alone (MT). After 5-year follow-up, 392 patients (64%) underwent new angiography. Progression was considered a new stenosis of >= 50% in an arterial segment previously considered normal or an increased grade of previous stenosis > 20% in nontreated vessels. Results: Of the 392 patients, 136 underwent CABG, 146 PCI, and 110 MT. Baseline characteristics were similar among treatment groups, except for more smokers and statin users in the MT group, more hypertensives and lower LDL-cholesterol levels in the CABG group, and more angina in the PCI group at study entry. Analysis showed greater progression in at least one native vessel in PCI patients (84%) compared with CABG (57%) and MT (74%) patients (p < 0.001). LAD coronary territory had higher progression compared with LCX and RCA (P < 0.001). PCI treatment, hypertension, male sex, and previous MI were independent risk factors for progression. No statistical difference existed between coronary events and the development of progression. Conclusion: The angioplasty treatment conferred greater progression in native coronary arteries, especially in the left anterior descending territories and treated vessels. The progression was independently associated with hypertension, male sex, and previous myocardial infarction.
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Background: In family studies, it is important to evaluate the impact of genes and environmental factors on traits of interest. In particular, the relative influences of both genes and the environment may vary in different strata of the population of interest, such as young and old individuals, or males and females. Methods: In this paper, extensions of the variance components model are used to evaluate heterogeneity in the genetic and environmental variance components due to the effects of sex and age (the cutoff between young and old was 43 yrs). The data analyzed were from 81 Brazilian families (1,675 individuals) of the Baependi Family Heart Study. Results: The models allowing for heterogeneity of variance components by sex suggest that genetic and environmental variances are not different in males and females for diastolic blood pressure, LDL-cholesterol, and HDL-cholesterol, independent of the covariates included in the models. However, for systolic blood pressure, fasting glucose and triglycerides, the evidence for heterogeneity was dependent on the covariates in the model. For instance, in the presence of sex and age covariates, heterogeneity in the genetic variance component was suggested for fasting glucose. But, for systolic blood pressure, there was no evidence of heterogeneity in any of the two variance components. Except for the LDL-cholesterol, models allowing for heterogeneity by age provide evidence of heterogeneity in genetic variance for triglycerides and systolic and diastolic blood pressure. There was evidence of heterogeneity in environmental variance in fasting glucose and HDL-cholesterol. Conclusions: Our results suggest that heterogeneity in trait variances should not be ignored in the design and analyses of gene-finding studies involving these traits, as it may generate additional information about gene effects, and allow the investigation of more sophisticated models such as the model including sex-specific oligogenic variance components.
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Background: Ezetimibe specifically blocks the absorption of dietary and biliary cholesterol and plant sterols. Synergism of ezetimibe-statin therapy on LDL-cholesterol has been demonstrated, but data concerning the pleiotropic effects of this combination are controversial. Objective: This open-label trial evaluated whether the combination of simvastatin and ezetimibe also results in a synergistic effect that reduces the pro-inflammatory status of pre-diabetic subjects. Methods: Fifty pre-diabetic subjects were randomly assigned to one of 2 groups, one receiving ezetimibe (10 mg/day), the other, simvastatin (20 mg/d) for 12 weeks, followed by an additional 12-week period of combined therapy. Blood samples were collected at baseline, 12 and 24 weeks. RESULTS: Total cholesterol, LDL-cholesterol and apolipoprotein B levels decreased in all the periods analyzed (p < 0.01), but triglycerides declined significantly only after combined therapy. Both drugs induced reductions in C-reactive protein, reaching statistical significance after combining ezetimibe with the simvastatin therapy (baseline 0.59 +/- 0.14, simvastatin monotherapy 0.48 +/- 0.12 mg/dL and 0.35 +/- 0.12 mg/dL, p < 0.023). Such a reduction was independent of LDL-cholesterol change. However, mean levels of TNF-alpha and interleukin-6 and leukocyte count did not vary during the whole study. Conclusion: Expected synergistic lowering effects of a simvastatin and ezetimibe combination on LDL-cholesterol, apolipoprotein B and triglycerides levels were confirmed in subjects with early disturbances of glucose metabolism. We suggest an additive effect of this combination also on inflammatory status based on the reduction of C-reactive protein. Attenuation of pro-inflammatory conditions may be relevant in reducing cardiometabolic risk.
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Physical exercise protects against the development of cardiovascular disease, partly by lowering plasmatic total cholesterol, LDL-cholesterol and increased HDL-cholesterol levels. In addition, it is now established that reduction plasmatic adiponectin and increased C-reactive protein (CRP) and plasminogen activator inhibitor-1 (PAI-1) levels play a role in the maintenance of an inflammatory state and in the development of cardiovascular disease. This study aimed to examine plasma lipid profile and inflammatory markers levels in individual with sedentary lifestyle and/or highly trained athletes at rest. Methods: Fourteen male subjects (sedentary lifestyle n = 7 and highly trained athletes n = 7) were recruited. Blood samples were collected after an overnight fast (similar to 12 h). The plasmatic lipid profile (Triglycerides, HDL-cholesterol, LDL-cholesterol, total cholesterol, LDL-oxidized and total cholesterol/HDL-c ratio), glucose, adiponectin, C - reactive protein and PAI-1 levels were determined. Results: Total cholesterol, LDL-cholesterol, TG and PAI-1 levels were lower in highly trained athletes group in relation to sedentary subjects (p < 0.01). In addition, we observed a positive correlation between PAI-1 and total cholesterol (r = 0.78; p < 0.0009), PAI-1 and LDL-c (r = 0.69; p < 0.006) and PAI-1 and TG levels (r = 0.56; p < 0.03). The plasma concentration of adiponectin, CRP, glucose, HDL-cholesterol and total cholesterol/HDL-c ratio levels were not different. These results indicate that lifestyle associated with high intensity and high volume exercise induces changes favourable in the lipid profile and PAI-1 levels and may reduce risk cardiovascular diseases.
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Background: Few studies have evaluated seasonal variations of biochemical parameters routinely analyzed in clinical laboratories. Rhythmic patterns for lipids and lipoproteins have been demonstrated and have been the object of research, mainly because of their demonstrated association with coronary artery disease. This study evaluated the occurrence of biological rhythms on serum lipids and lipoproteins and the effects of sex and age on the rhythms in a Brazilian hospital outpatient population. Methods: Retrospective laboratory study was carried out to evaluate the results of total cholesterol (TC), HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C) and triglycerides (TG), from individuals registered at a university referral hospital over 8years. The studied population was composed of individuals of both sexes and all ages totaling 38,579 participants and 301,934 measurements. Statistical analyses were carried out using the SAS program and the temporal analysis used the Cosinor method. Results: TG rhythm was present only in females. All other parameters were equally rhythmic in both sexes. Regarding age, HDL-C presented rhythms in all age groups, but TC and LDL-C showed seasonality only for those > 13years, TG did not present rhythms in all age groups. Conclusion: Effects of sex and age on biological rhythms detected in TC, LDL-C and HDL-C should be considered a significant cause of pre-analytical variation in these laboratory tests. (C) 2009 Elsevier B.V. All rights reserved.