Variability in baseline laboratory measurements of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

Multi-center epidemiological studies must ascertain that their measurements are accurate and reliable. For laboratory measurements, reliability can be assessed through investigation of reproducibility of measurements in the same individual. In this paper, we present results from the quality control analysis of the baseline laboratory measurements from the ELSA-Brasil study. The study enrolled 15,105 civil servants at 6 research centers in 3 regions of Brazil between 2008-2010, with multiple biochemical analytes being measured at a central laboratory. Quality control was ascertained through standard laboratory evaluation of intra- and inter-assay variability and test-retest analysis in a subset of randomly chosen participants. An additional sample of urine or blood was collected from these participants, and these samples were handled in the same manner as the original ones, locally and at the central laboratory. Reliability was assessed with the intraclass correlation coefficient (ICC), estimated through a random effects model. Coefficients of variation (CV) and Bland-Altman plots were additionally used to assess measurement variability. Laboratory intra and inter-assay CVs varied from 0.86% to 7.77%. From test-retest analyses, the ICCs were high for the majority of the analytes. Notably lower ICCs were observed for serum sodium (ICC=0.50; 95%CI=0.31-0.65) and serum potassium (ICC=0.73; 95%CI=0.60-0.83), due to the small biological range of these analytes. The CVs ranged from 1 to 14%. The Bland-Altman plots confirmed these results. The quality control analyses showed that the collection, processing and measurement protocols utilized in the ELSA-Brasil produced reliable biochemical measurements.

Sex-specific associations of birth weight with measures of adiposity in mid-to-late adulthood: the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

BACKGROUND/OBJECTIVES: To investigate sex-specific associations of birth weight with body mass index (BMI), waist circumference (WC) and waist-to-hip ratio (WHR) in mid-to-late adulthood. SUBJECTS/METHODS: ELSA-Brasil is a multicenter cohort study of adults aged 35-74 years affiliated with universities or research institutions of six capital cities in Brazil. After exclusions, we investigated 11 636 participants. Socio-demographic factors and birth weight were obtained by interview. All anthropometry was directly measured at baseline. We categorized birth weight as low (⩽2.5 kg); normal (2.5-4 kg) and high (⩾4 kg). We performed analysis of covariance (ANCOVA) for continuous outcomes and ordinal logistic regression for categorical adiposity outcomes. We examined interaction on the multiplicative scale by sex and by race. RESULTS: High birth weight uniformly predicted greater overall and central obesity in men and women. However, low (vs normal) birth weight, in ANCOVA models adjusted for participant age, family income, race, education, maternal education, and maternal and paternal history of diabetes, was associated with lower BMI, WC and WHR means for men, but not for women (Pinteraction=0.01, <0.0001 and <0.0001, respectively). In similarly adjusted ordinal logistic regression models, odds of obesity (odds ratio (OR)=0.65, 0.46-0.90) and of being in the high (vs low) tertile of WC (OR=0.66, 0.50-0.87) and of WHR (OR=0.79, 0.60-1.03) were lower for low (vs normal) birth weight men, but trended higher (BMI: OR=1.18, 0.92-1.51; WC: OR=1.21, 0.97-1.53; WHR: OR=1.44, 1.15-1.82) for low (vs normal) birth weight women. CONCLUSIONS: In this Brazilian sample of middle-aged and elderly adults who have lived through a rapid nutritional transition, low birth weight was associated with adult adiposity in a sex-specific manner. In men, low birth weight was associated with lower overall and central adult adiposity, while in women low birth weight was generally associated with greater central adiposity.

Neck circumference is associated with carotid intimal-media thickness but not with coronary artery calcium: Results from The ELSA-Brasil.

BACKGROUND AND AIMS: It is uncertain whether neck circumference can be a risk indicator for subclinical atherosclerosis. We aimed to investigate their relationships measured by coronary artery calcium (CAC) and common carotid intima-media thickness (cc-IMT) with neck circumference in ELSA-Brasil. METHODS AND RESULTS: In cross-sectional and sex-specific analyses of 2266 women (50.6 ± 8.4 yrs) and 1886 men (50.7 ± 9.0 yrs) with both cc-IMT and CAC, free from previous cardiovascular disease at baseline, we built logistic models using diverse cut-off points for CAC score (0 vs > 0, < 100 vs ≥ 100, < 400 vs ≥ 400 Agatston units) and cc-IMT (< 75 th percentile vs ≥ 75 th; <90th percentile vs ≥ 90 th) as dependent variables, after which adjustments for age and traditional cardiovascular risk factors were made. Mean neck circumference was 33.6 (± 2.4 cm) for women and 38.8 (± 2.6 cm) for men. In fully adjusted models including sociodemographic, cardiovascular risk factors and body-mass index and waist circumference, for each 1 standard deviation increase in neck circumference we found an odds ratio (OR, 95% CI) for IMT above the 75th percentile of (1.52, 1.16; 1.99) for women and (1.66, 1.28; 2.14) for men, and above the 90th cc-IMT percentile [1.66 (1.19; 2.32) for men but not for women [1.21 (0.80; 1.82)]. We found no association between neck circumference and CAC using different cut-off points (p > 0.05 for all). CONCLUSION: Neck circumference was significantly and independently associated with cc-IMT but not with CAC in women and men, indicating a possible effect of perivascular fat tissue on atherosclerosis.

Carboxymethyl lysine, an advanced glycation end product, and incident diabetes: a case-cohort analysis of the ARIC Study.

AIMS: To verify whether elevated fasting levels of circulating carboxymethyl lysine (CML), an advanced glycation end product, predict the development of diabetes in middle-age adults. METHODS: Using a stratified case-cohort design, we followed 543 middle-aged individuals who developed diabetes and 514 who did not over a median 9 years in the Atherosclerosis Risk in Communities Study. Weighted Cox proportional hazards analyses were used to account for the design. RESULTS: In weighted analyses, correlation between CML levels and anthropometric, inflammatory or metabolic variables was minimal (Pearson correlations usually < 0.10). CML, when modelled as a continuous variable and after adjustment for age, sex, race, centre, parental history of diabetes, BMI, waist-to-hip ratio, non-esterified fatty acids, oxidized LDL-cholesterol, GFR, smoking, an inflammation score, adiponectin, leptin, insulin and glucose levels, was associated with an increased risk of diabetes [Hazard ratio (HR) = 1.35; 95% confidence interval (CI) 1.09-1.67, for each 100 ng/ml CML increment]. Baseline glucose level and race each modified the association (P < 0.05 for interaction), which was present only among those with impaired fasting glucose (≥ 5.6 mmol/l, HR = 1.61, 95% CI 1.26-2.05) and among white participants (HR = 1.50, 95% CI 1.13-1.99). CONCLUSIONS: Elevated fasting CML, after adjustment for multiple risk factors for diabetes, predicts the development of incident diabetes, the association being present among those with impaired fasting glucose and in white participants. These prospective findings suggest that advanced glycation end products might play a role in the development of diabetes.

Variability in baseline laboratory measurements of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

Multi-center epidemiological studies must ascertain that their measurements are accurate and reliable. For laboratory measurements, reliability can be assessed through investigation of reproducibility of measurements in the same individual. In this paper, we present results from the quality control analysis of the baseline laboratory measurements from the ELSA-Brasil study. The study enrolled 15,105 civil servants at 6 research centers in 3 regions of Brazil between 2008–2010, with multiple biochemical analytes being measured at a central laboratory. Quality control was ascertained through standard laboratory evaluation of intra- and inter-assay variability and test-retest analysis in a subset of randomly chosen participants. An additional sample of urine or blood was collected from these participants, and these samples were handled in the same manner as the original ones, locally and at the central laboratory. Reliability was assessed with the intraclass correlation coefficient (ICC), estimated through a random effects model. Coefficients of variation (CV) and Bland-Altman plots were additionally used to assess measurement variability. Laboratory intra and inter-assay CVs varied from 0.86% to 7.77%. From test-retest analyses, the ICCs were high for the majority of the analytes. Notably lower ICCs were observed for serum sodium (ICC=0.50; 95%CI=0.31–0.65) and serum potassium (ICC=0.73; 95%CI=0.60–0.83), due to the small biological range of these analytes. The CVs ranged from 1 to 14%. The Bland-Altman plots confirmed these results. The quality control analyses showed that the collection, processing and measurement protocols utilized in the ELSA-Brasil produced reliable biochemical measurements.

Fasting plasma glucose to avoid a full OGTT in the diagnosis of gestational diabetes.

AIMS: To evaluate the performance of fasting plasma glucose (FPG) in determining the need for a full oral glucose tolerance test (OGTT) to diagnose gestational diabetes (GDM) by the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria. METHODS: A multicenter cohort study of 4926 pregnant women 20 years or older consecutively enrolled in prenatal care clinics of the Brazilian National Health Service from 1991 to 1995. All women underwent a single 2 h 75 g OGTT by weeks 24-28 of pregnancy and were followed to detect adverse pregnancy outcomes. RESULTS: A FPG cut-off value of 80 mg/dl indicated that only 38.7% of all women needed to undergo a complete OGTT, while detecting 96.9% of all GDM cases. When the 85 mg/dl cut-off was used, the corresponding percentages were 18.7% and 92.5%, respectively. The fraction of women labeled with GDM who had adverse pregnancy outcomes was nearly identical when using FPG strategies and universal full testing. CONCLUSIONS: Using a FPG cut-off to diagnose GDM and to determine the need for post-load OGTT measurements is a valid strategy to diagnose GDM by IADPSG criteria. This approach may improve feasibility of applying IADPSG diagnostic criteria by reducing costs and increasing convenience.

Metabolic syndrome risk for cardiovascular disease and diabetes in the ARIC study.

OBJECTIVE: The metabolic syndrome is associated with increased risk for cardiovascular disease and diabetes. Several analyses from the Atherosclerosis Risk in Communities (ARIC) study have been performed to examine the role of the metabolic syndrome and its components in predicting risk for cardiovascular disease and diabetes. DESIGN AND SUBJECTS: The large, biracial, population-based ARIC study enrolled 15792 middle-aged Americans in four communities in the United States and has followed them for the development of cardiovascular disease and diabetes. MEASUREMENTS: Outcome parameters included prevalence of the metabolic syndrome and its individual components, carotid intima-media thickness, incident coronary heart disease, incident ischemic stroke and incident diabetes. RESULTS AND CONCLUSION: Several analyses from the ARIC study have shown that the metabolic syndrome, as well as individual metabolic syndrome components, is predictive of the prevalence and incidence of coronary heart disease, ischemic stroke, carotid artery disease and diabetes.

Birth weight is not related to risk of diabetic retinopathy in type 2 diabetes: the Atherosclerosis Risk in Communities Study.

PURPOSE: Low birth weight has been suggested as a risk factor for diabetes. Whether it is related to diabetic retinopathy is unclear and is examined in this study. MATERIALS AND METHODS: We examined 609 adults with type 2 diabetes from the population-based Atherosclerosis Risk in Communities Study. Retinal photographs were graded for diabetic retinopathy. Birth weight was assessed by self-report. RESULTS: Retinopathy was present in 116 (19%) participants (113 non-proliferative and 3 proliferative). After adjusting for age, sex, race, education level, body mass index, fasting glucose, duration of diabetes, glycosylated hemoglobin A1c, family history of diabetes, serum total cholesterol, and blood pressure, there was no evidence of either a linear or non-linear relationship between birthweight and diabetic retinopathy. CONCLUSIONS: Birth weight was not associated with diabetic retinopathy.

Glutamic acid decarboxylase antibodies are indicators of the course, but not of the onset, of diabetes in middle-aged adults: the Atherosclerosis Risk in Communities Study.

To efficiently examine the association of glutamic acid decarboxylase antibody (GADA) positivity with the onset and progression of diabetes in middle-aged adults, we performed a case-cohort study representing the ~9-year experience of 10,275 Atherosclerosis Risk in Communities Study participants, initially aged 45-64 years. Antibodies to glutamic acid decarboxylase (GAD65) were measured by radioimmunoassay in 580 incident diabetes cases and 544 non-cases. The overall weighted prevalence of GADA positivity (>or=1 U/mL) was 7.3%. Baseline risk factors, with the exception of smoking and interleukin-6 (P or=2.38 U/mL) of positivity. GADA-positive and GADA-negative non-diabetic individuals had similar risk profiles for diabetes, with central obesity and elevated inflammation markers, aside from glucose, being the main predictors. Among diabetes cases at study's end, progression to insulin treatment increased monotonically as a function of baseline GADA level. Overall, being GADA positive increased risk of progression to insulin use almost 10 times (HR = 9.9; 95%CI = 3.4, 28.5). In conclusion, in initially non-diabetic middle-aged adults, GADA positivity did not increase diabetes risk, and the overall baseline profile of risk factors was similar for positive and negative individuals. Among middle-aged adults, with the possible exception of those with the highest GADA levels, autoimmune pathophysiology reflected by GADA may become clinically relevant only after diabetes onset.

Glutamic acid decarboxylase antibodies are indicators of the course, but not of the onset, of diabetes in middle-aged adults: the Atherosclerosis Risk in Communities Study

To efficiently examine the association of glutamic acid decarboxylase antibody (GADA) positivity with the onset and progression of diabetes in middle-aged adults, we performed a case-cohort study representing the ~9-year experience of 10,275 Atherosclerosis Risk in Communities Study participants, initially aged 45-64 years. Antibodies to glutamic acid decarboxylase (GAD65) were measured by radioimmunoassay in 580 incident diabetes cases and 544 non-cases. The overall weighted prevalence of GADA positivity (³1 U/mL) was 7.3 percent. Baseline risk factors, with the exception of smoking and interleukin-6 (P ú 0.02), were generally similar between GADA-positive and -negative individuals. GADA positivity did not predict incident diabetes in multiply adjusted (HR = 1.04; 95 percentCI = 0.55, 1.96) proportional hazard analyses. However, a small non-significant adjusted risk (HR = 1.29; 95 percentCI = 0.58, 2.88) was seen for those in the highest tertile (³2.38 U/mL) of positivity. GADA-positive and GADA-negative non-diabetic individuals had similar risk profiles for diabetes, with central obesity and elevated inflammation markers, aside from glucose, being the main predictors. Among diabetes cases at study's end, progression to insulin treatment increased monotonically as a function of baseline GADA level. Overall, being GADA positive increased risk of progression to insulin use almost 10 times (HR = 9.9; 95 percentCI = 3.4, 28.5). In conclusion, in initially non-diabetic middle-aged adults, GADA positivity did not increase diabetes risk, and the overall baseline profile of risk factors was similar for positive and negative individuals. Among middle-aged adults, with the possible exception of those with the highest GADA levels, autoimmune pathophysiology reflected by GADA may become clinically relevant only after diabetes onset.

Circulating oxidised low-density lipoprotein and intercellular adhesion molecule-1 and risk of type 2 diabetes mellitus: the Atherosclerosis Risk in Communities Study.

AIMS/HYPOTHESIS: To evaluate the role of oxidative stress and inflammation in the aetiology of type 2 diabetes, we examined the association of oxidised LDL (ox-LDL) and soluble intercellular adhesion molecule-1 (sICAM-1) levels with type 2 diabetes incidence over 9 years in the Atherosclerosis Risk in Communities Study. MATERIALS AND METHODS: In a large, prospective, case-cohort design, ox-LDL and sICAM-1 were measured in stored plasma samples collected at baseline in stratified samples of 581 diabetes cases and 572 non-cases selected from 10,275 middle-aged men and women without prevalent diabetes at baseline. RESULTS: Compared with non-cases, diabetes cases had significantly higher mean baseline levels of ox-LDL and sICAM-1. Elevated ox-LDL and sICAM-1 were both associated with increased risk of incident diabetes after adjustment for age, sex, race and centre, with hazard ratios for the highest vs lowest tertiles of 1.68 (95% CI 1.25-2.24) and 1.91 (95% CI 1.45-2.50), respectively. After additional adjustment for fasting glucose, waist circumference, HDL-cholesterol, triacylglycerol, hypertension and C-reactive protein, only sICAM-1 remained an independent predictor of incident diabetes (hazard ratio 1.50; 95% CI 1.02-2.23). CONCLUSIONS/INTERPRETATION: In this community-based cohort of middle-aged US adults, elevated plasma ox-LDL and sICAM-1 levels were associated with increased risk of type 2 diabetes. Measurement of ICAM-1 or ox-LDL, or other measures related to inflammation or oxidative stress, may be helpful in identifying those patient populations in which to test whether novel therapies that inhibit specific pathways related to inflammation or oxidative stress are beneficial in the prevention of diabetes in humans.

Leptin and incident type 2 diabetes: risk or protection?

AIMS/HYPOTHESIS: The aim of this study was to investigate the association of leptin levels with incident diabetes in middle-aged adults, taking into account factors purportedly related to leptin resistance. SUBJECTS AND METHODS: We conducted a case-cohort study (570 incident diabetes cases and 530 non-cases) representing the 9-year experience of 10,275 participants of the Atherosclerosis Risk in Communities Study. Plasma leptin was measured by direct sandwich ELISA. RESULTS: In proportional hazards models adjusting for age, study centre, ethnicity and sex, high leptin levels (defined by sex-specific cut-off points) predicted an increased risk of diabetes, with a hazard ratio (HR) comparing the upper with the lower quartile of 3.9 (95% CI 2.6-5.6). However, after further adjusting additionally for obesity indices, fasting insulin, inflammation score, hypertension, triglycerides and adiponectin, high leptin predicted a lower diabetes risk (HR=0.40, 95% CI 0.23-0.67). Additional inclusion of fasting glucose attenuated this protective association (HR=0.59, 95% CI 0.32-1.08, p<0.03 for linear trend across quartiles). In similar models, protective associations were generally seen across subgroups of sex, race, nutritional status and smoking, though not among those with lower inflammation scores or impaired fasting glucose (interaction p=0.03 for both). CONCLUSIONS/INTERPRETATION: High leptin levels, probably reflecting leptin resistance, predict an increased risk of diabetes. Adjusting for factors purportedly related to leptin resistance unveils a protective association, independent of adiponectin and consistent with some of leptin's described protective effects against diabetes.

Hypertensive retinopathy and incident coronary heart disease in high risk men.

BACKGROUND/AIM: Although routine ophthalmoscopy is recommended in the evaluation of people with hypertension, the prognostic significance of retinopathy is unknown. The purpose of this study is to determine if hypertensive retinopathy predicts coronary heart disease (CHD). METHODS: A prospective cohort study involving 560 hypertensive, hyperlipidaemic, middle aged men enrolled in the Lipid Research Clinic's Coronary Primary Prevention Trial. Signs of hypertensive retinopathy (generalised and focal arteriolar narrowing, arteriovenous nicking, widened arteriolar light reflex, retinal haemorrhage and exudates, microaneurysms, and disc swelling) were evaluated by direct funduscopy during a baseline examination by study physicians. Incident CHD events were ascertained from hospital records, necropsy reports, and death certificates, and reviewed by a masked panel of cardiologists. RESULTS: There were 51 definite CHD events (definite CHD deaths or myocardial infarctions) during a median follow up of 7.8 years. After adjusting for age, blood pressure, electrocardiographic manifestations of left ventricular hypertrophy, cholesterol levels and treatment, glucose and creatinine levels, and smoking status in proportional hazards analysis, the presence of hypertensive retinopathy predicted a doubling of the risk of definite CHD events (relative risk 2.1; 95% confidence interval (CI) 1.0 to 4.2 ). The presence of either generalised or focal arteriolar narrowing predicted almost a tripling of the risk (relative risk 2.9; 95% CI 1.3 to 6.2). Associations were similar for stage 1 hypertension (systolic and diastolic blood pressures of 140-159 and 90-99 mm Hg, respectively) and for other CHD end points. CONCLUSION: Hypertensive retinopathy predicts CHD in high risk men, independent of blood pressure and CHD risk factors. The data support the concept that retinal microvascular changes are markers of blood pressure damage and may be useful in risk stratification and in the tailoring of hypertension treatment decisions.

[Drug use by pregnant women in six Brazilian cities]. / Uso de medicamentos por gestantes em seis cidades brasileiras.

OBJECTIVE: To describe drugs used during pregnancy by women attending prenatal clinics of the national public health system (SUS) in Brazilian cities. METHODS: Using a structured questionnaire, 5,564 pregnant women between the week 21 to 28 who attended prenatal visits of the SUS in six Brazilian cities were interviewed. The interview questions were grouped in "guided use" to cover pain, cramps, nausea, cough, and others, and "guided medicine" to cover vitamins, iron, and fluoride. The Food and Drug Administration gestational risk classification (1991-1995) was applied. RESULTS: Of a total of 5,564 women, 4,614 (83.8%) used at least one drug during pregnancy, with a total of 9,556 drugs used. The drugs most frequently used were vitamins associated with anti-anemics (33.5%), gastrointestinal drugs (31.3%), analgesics and anti-inflammatory drugs (22.2%), anti-anemics (19.8%), and antibiotics (11.1%). Regarding gestational risk, 3,243 drugs used (34%) belonged to category A risk, 1,923 (22.6%) to category B, 3,798 (39.7%) to category C, 289 (3.0%) to category D, and 55 (0.6%) to category X. CONCLUSIONS: A large variation in drug use across the cities was observed, especially for anti-anemics and vitamins associated with anti-anemics, revealing the lack of a national consensus regarding the use of these drugs during pregnancy. There was no literature data about safety during pregnancy for 12.9% of the drugs used. This percentage, plus the 26.9% of category C drugs, shows that 40% of the drugs used during pregnancy do not belong to the approved safety categories. However, only 3% of the 9,956 drugs used were clearly contraindicated during pregnancy.

Sensitivity and specificity of anthropometrics for the prediction of diabetes in a biracial cohort.

OBJECTIVE: To evaluate the ability of body mass index, waist circumference, waist-to-hip ratio, and combinations of these variables to discriminate individuals who will develop diabetes in adulthood. RESEARCH METHODS AND PROCEDURES: Data were from 45- to 64-year-old men and women who were members of the Atherosclerosis Risk in Communities cohort. The analysis sample consisted of 12,814 African American and white participants who were free of diabetes at baseline. Body mass index, waist circumference, waist-to-hip ratio, and diabetes incidence (defined as one glucose measure > or =126 mg/dL after fasting for at least 8 hours, one nonfasting glucose measure > or =200 mg/dL, and self-report of diabetes or report of taking medication for diabetes). RESULTS: 1515 new cases of diabetes were identified over the 9-year follow-up. Areas under receiver operating characteristic curves ranged from 0.66 to 0.73 for single measures. The curves were smooth, with no indication of a threshold. Waist tended to have the highest receiver operating characteristic statistic in all groups, but differences were small. DISCUSSION: The three anthropometric indices tested were approximately equivalent in their ability to predict diabetes. Sensitivity and specificities differed among ethnic and gender groups.

Gestational diabetes mellitus diagnosed with a 2-h 75-g oral glucose tolerance test and adverse pregnancy outcomes.

OBJECTIVE: To evaluate American Diabetes Association (ADA) and World Health Organization (WHO) diagnostic criteria for gestational diabetes mellitus (GDM) against pregnancy outcomes. RESEARCH DESIGN AND METHODS: This cohort study consecutively enrolled Brazilian adult women attending general prenatal clinics. All women were requested to undertake a standardized 2-h 75-g oral glucose tolerance test (OGTT) between their estimated 24th and 28th gestational weeks and were then followed to delivery. New ADA criteria for GDM require two plasma glucose values > or = 5.3 mmol/l (fasting), > or = 10 mmol/l (1 h), and > or = 8.6 mmol/l (2 h). WHO criteria require a plasma glucose > or = 7.0 mmol/l (fasting) or > or = 7.8 mmol/l (2 h). Individuals with hyperglycemia indicative of diabetes outside of pregnancy were excluded. RESULTS: Among the 4,977 women studied, 2.4% (95% CI 2.0-2.9) presented with GDM by ADA criteria and 7.2% (6.5-7.9) by WHO criteria. After adjustment for the effects of age, obesity, and other risk factors, GDM by ADA criteria predicted an increased risk of macrosomia (RR 1.29, 95% CI 0.73-2.18), preeclampsia (2.28, 1.22-4.16), and perinatal death (3.10, 1.42-6.47). Similarly, GDM by WHO criteria predicted increased risk for macrosomia (1.45, 1.06-1.95), preeclampsia (1.94, 1.22-3.03), and perinatal death (1.59, 0.86-2.90). Of women positive by WHO criteria, 260 (73%) were negative by ADA criteria. Conversely, 22 (18%) women positive by ADA criteria were negative by WHO criteria. CONCLUSIONS: GDM based on a 2-h 75-g OGTT defined by either WHO or ADA criteria predicts adverse pregnancy outcomes.

Chronic activation of the innate immune system may underlie the metabolic syndrome.

CONTEXT: The metabolic syndrome is characterized by a clustering, in free-living populations, of cardiovascular and diabetes risk factors generally linked to insulin resistance, obesity and central obesity. Consonant with the well-established inflammatory pathogenesis of atherosclerotic disease, the metabolic syndrome is now being investigated in relation to its inflammatory nature. OBJECTIVE: We present cross-sectional findings demonstrating that markers of inflammation correlate with components of the metabolic syndrome, and prospective findings of the ARIC Study indicating that markers of inflammation and endothelial dysfunction predict the development of diabetes mellitus and weight gain in adults. We present biological evidence to suggest that chronic activation of the innate immune system may underlie the metabolic syndrome, characterizing the common soil for the causality of type 2 diabetes mellitus and cardiovascular disease. CONCLUSIONS: Better understanding of the role of the innate immune system in these diseases may lead to important advances in the prediction and management of diabetes and cardiovascular disease.

Alcohol and atherosclerosis.

Observational studies have attributed a protective effect to alcohol consumption on the development of atherosclerosis and cardiovascular morbidity and mortality. Alcohol intake in the amount of one to two drinks per day results in an estimated 20-40% reduction in cardiovascular events. An additional protective effect, according to major cohort studies, has been attributed to wine, probably due to antioxidant effects and platelet antiaggregation agents. On the other hand, the influence of different patterns of alcohol consumption and environmental factors may explain a great part of the additional effect of wine. Protection may be mediated by modulation of other risk factors, because alcohol increases HDL-C, produces a biphasic response on blood pressure, and modulates the endothelial function, while it neither increases body weight nor impairs glucose-insulin homeostasis. Alcohol may also have a direct effect on atherogenesis. Despite these favorable effects, the current evidence is not enough to justify prescribing alcohol to prevent cardiovascular disease.

Hypertensive disorders in pregnancy: frequency and associated factors in a cohort of Brazilian women.

OBJECTIVE: To evaluate the frequency of and risk factors associated with hypertensive disorders in general antenatal care in five distinct areas of Brazil. METHODS: We performed a cohort study of 4892 women enrolled in midpregnancy from 1991 to 1995. Patients were queried at enrollment about hypertension prior to pregnancy. Medical diagnoses of hypertensive disorders in pregnancy were abstracted from patient records. Hypertensive disorders in pregnancy were classified according to recommendations of the American College of Obstetrics and Gynecology (ACOG). RESULTS: Of 4892 women studied, 367 (7.5%) presented hypertensive disorders, 113 (2.3%) being preeclampsia/eclampsia and 198 (4.0%) chronic hypertension. Frequencies of superimposed preeclampsia/eclampsia and transitory hypertension were 0.5% and 0.7%, respectively. Greater brachial arm circumference was strongly associated both with preeclampsia/eclampsia and with chronic hypertension (threefold difference across extreme quartiles, p < or =0.001). In adjusted analyses, being older, black, and obese were important and statistically significant risk factors for chronic hypertension. Similarly, nulliparity was a statistically significant risk factor for preeclampsia/eclampsia, and tendencies toward increased risk were seen for older, black, and obese women in adjusted analyses. Preeclampsia/eclampsia and chronic hypertension were notably less frequent in Manaus, although regional differences were statistically significant only for chronic hypertension. CONCLUSIONS: Hypertensive disorders commonly complicate pregnancy in Brazilian women. Risk factors for these disorders appear similar to those reported in other countries. Use of an inappropriately sized cuff to measure blood pressure may result in many false-positive diagnoses in more obese women. The considerably lower frequency of hypertensive disorders found in Manaus, in the Amazon region, warrants further study.