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.

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.

Improving long-term prediction of first cardiovascular event: the contribution of family history of coronary heart disease and social status.

OBJECTIVE: The aim of this study is to assess whether family history of coronary heart disease (CHD) and education as proxy of social status improve long-term cardiovascular disease risk prediction in a low-incidence European population. METHODS: The 20-year risk of first coronary or ischemic stroke events was estimated using sex-specific Cox models in 3956 participants of three population-based surveys in northern Italy, aged 35-69 years and free of cardiovascular disease at enrollment. The additional contribution of education and positive family history of CHD was defined as change in discrimination and Net Reclassification Improvement (NRI) over the model including 7 traditional risk factors. RESULTS: Kaplan-Meier 20-year risk was 16.8% in men (254 events) and 6.4% in women (102 events). Low education (hazard ratio=1.35, 95%CI 0.98-1.85) and family history of CHD (1.55; 1.19-2.03) were associated with the endpoint in men, but not in women. In men, the addition of education and family history significantly improved discrimination by 1%; NRI was 6% (95%CI: 0.2%-15.2%), raising to 20% (0.5%-44%) in those at intermediate risk. NRI in women at intermediate risk was 7%. CONCLUSION: In low-incidence populations, family history of CHD and education, easily assessed in clinical practice, should be included in long-term cardiovascular disease risk scores, at least in men.

Ankle brachial index combined with Framingham Risk Score to predict cardiovascular events and mortality: a meta-analysis.

CONTEXT: Prediction models to identify healthy individuals at high risk of cardiovascular disease have limited accuracy. A low ankle brachial index (ABI) is an indicator of atherosclerosis and has the potential to improve prediction. OBJECTIVE: To determine if the ABI provides information on the risk of cardiovascular events and mortality independently of the Framingham risk score (FRS) and can improve risk prediction. DATA SOURCES: Relevant studies were identified. A search of MEDLINE (1950 to February 2008) and EMBASE (1980 to February 2008) was conducted using common text words for the term ankle brachial index combined with text words and Medical Subject Headings to capture prospective cohort designs. Review of reference lists and conference proceedings, and correspondence with experts was conducted to identify additional published and unpublished studies. STUDY SELECTION: Studies were included if participants were derived from a general population, ABI was measured at baseline, and individuals were followed up to detect total and cardiovascular mortality. DATA EXTRACTION: Prespecified data on individuals in each selected study were extracted into a combined data set and an individual participant data meta-analysis was conducted on individuals who had no previous history of coronary heart disease. RESULTS: Sixteen population cohort studies fulfilling the inclusion criteria were included. During 480,325 person-years of follow-up of 24,955 men and 23,339 women, the risk of death by ABI had a reverse J-shaped distribution with a normal (low risk) ABI of 1.11 to 1.40. The 10-year cardiovascular mortality in men with a low ABI (< or = 0.90) was 18.7% (95% confidence interval [CI], 13.3%-24.1%) and with normal ABI (1.11-1.40) was 4.4% (95% CI, 3.2%-5.7%) (hazard ratio [HR], 4.2; 95% CI, 3.3-5.4). Corresponding mortalities in women were 12.6% (95% CI, 6.2%-19.0%) and 4.1% (95% CI, 2.2%-6.1%) (HR, 3.5; 95% CI, 2.4-5.1). The HRs remained elevated after adjusting for FRS (2.9 [95% CI, 2.3-3.7] for men vs 3.0 [95% CI, 2.0-4.4] for women). A low ABI (< or = 0.90) was associated with approximately twice the 10-year total mortality, cardiovascular mortality, and major coronary event rate compared with the overall rate in each FRS category. Inclusion of the ABI in cardiovascular risk stratification using the FRS would result in reclassification of the risk category and modification of treatment recommendations in approximately 19% of men and 36% of women. CONCLUSION: Measurement of the ABI may improve the accuracy of cardiovascular risk prediction beyond the FRS.

Time trends of myocardial infarction 28-day case-fatality in the 1990s: is there a contribution from different changes among socioeconomic classes?

BACKGROUND/OBJECTIVE: Almost two-thirds of the coronary death rate decrease in the northern Italian Brianza MONICA male population, between 1993-4 and 1997-8, are attributable to a reduction in 28-day myocardial infarction (MI) case-fatality. The present paper investigates the factors associated with MI case-fatality decrease and in particular the role of socio-occupational classes (SOCs). METHODS: Standardised information on acute coronary care and intervention before and during the hospitalisation was collected for all coronary events (n = 1817) registered in 1993-4 and in 1997-8 among 35-64-year-old male residents in Brianza. Deaths within 28 days after MI were carefully investigated. Five SOCs were defined adopting the Erikson-Goldthorpe-Portocarero method. Differences in 28-day MI case-fatality and in acute phase intervention and treatment over time and among SOCs in each period were assessed. RESULTS: 28-day MI case-fatality reduction (27.2%) can be mainly attributed to a decreased proportion of MI events that were fatal before reaching the hospital. In the lower SOCs significant changes in MI case-fatality were detected between 1993-4 and 1997-8. Differences in acute phase intervention and treatment between the periods were observed. SOC differences both in prevalence of out-of-hospital cardiac arrest and in the pre-hospital qualified intervention score were detected in the first period only. CONCLUSIONS: In the study population MI case-fatality reduction can be mainly attributed to a more effective and prompt management before hospitalisation and to an improvement in acute treatment during hospitalisation. This enhancement is made available to the whole population overtaking social differences.

The Emerging Risk Factors Collaboration: analysis of individual data on lipid, inflammatory and other markers in over 1.1 million participants in 104 prospective studies of cardiovascular diseases.

Many long-term prospective studies have reported on associations of cardiovascular diseases with circulating lipid markers and/or inflammatory markers. Studies have not, however, generally been designed to provide reliable estimates under different circumstances and to correct for within-person variability. The Emerging Risk Factors Collaboration has established a central database on over 1.1 million participants from 104 prospective population-based studies, in which subsets have information on lipid and inflammatory markers, other characteristics, as well as major cardiovascular morbidity and cause-specific mortality. Information on repeat measurements on relevant characteristics has been collected in approximately 340,000 participants to enable estimation of and correction for within-person variability. Re-analysis of individual data will yield up to approximately 69,000 incident fatal or nonfatal first ever major cardiovascular outcomes recorded during about 11.7 million person years at risk. The primary analyses will involve age-specific regression models in people without known baseline cardiovascular disease in relation to fatal or nonfatal first ever coronary heart disease outcomes. This initiative will characterize more precisely and in greater detail than has previously been possible the shape and strength of the age- and sex-specific associations of several lipid and inflammatory markers with incident coronary heart disease outcomes (and, secondarily, with other incident cardiovascular outcomes) under a wide range of circumstances. It will, therefore, help to determine to what extent such associations are independent from possible confounding factors and to what extent such markers (separately and in combination) provide incremental predictive value.

Statin treatment and adherence to national cholesterol guidelines after ischemic stroke.

BACKGROUND: National cholesterol guidelines have defined high vascular risk individuals as those who could potentially benefit most from statin therapy. The authors aimed to determine the rate of statin use, its predictors, and the achievement of national guideline target lipid goals among ischemic stroke survivors. METHODS: The authors abstracted data from the Vitamin Intervention for Stroke Prevention (VISP) study database from the United States and Canada to incorporate into algorithms for initiating statin therapy according to the National Cholesterol Education Program (NCEP) guidelines for high-risk individuals. The authors applied these algorithms to all study subjects. Univariate as well as multivariate associations for target lipid levels and statin implementation were then evaluated utilizing pertinent demographic, clinical, and laboratory data. RESULTS: Of 2,894 subjects in the analysis dataset, 38% were women; 71% were recruited in the United States and 29% in Canada. Of 769 high-risk subjects, 262 (34%) had a low-density lipoprotein (LDL) level > or =130 mg/dL and 124 of these (47%) were not on statin. Among those high-risk persons on statin treatment, only 42% had an LDL < or =100 mg/dL. Subjects in the overall cohort were more likely to be on a statin if they were treated in the United States or had a history of hypertension or coronary artery disease. CONCLUSIONS: Approximately one out of three guideline-eligible high vascular risk ischemic stroke patients in this study had low-density lipoprotein cholesterol concentrations above qualifying levels for pharmacologic therapy, but half of these patients were not taking a statin, and of those receiving statin treatment, less than half were within recommended lipid goals.

Is diabetes an independent risk factor for mortality after myocardial infarction? The ARIC (Atherosclerosis Risk in Communities) Surveillance Study.

We investigated the age-, gender- and race-specific 1-year case fatality rates of diabetic and non-diabetic individuals with a myocardial infarction. Data were obtained from the Atherosclerosis Risk in Communities (ARIC) Surveillance Study, which monitors both hospitalized myocardial infarction and coronary heart disease (CHD) deaths in residents aged 35-74 years in four communities in the USA. The study population comprised 3242 hospitalized myocardial infarctions (HMIs) in diabetic subjects and 9826 HMIs in non-diabetic individuals between 1987 and 1997. Age-adjusted and gender- and race-specific odds ratios (OR) for 1-year case fatality comparing diabetic to non-diabetic patients were 2.0 (95% CI, 1.6-2.4) for white men and 1.4 (95% CI, 1.1-1.8) for white women. Further adjustment for severity of HMI, history of previous MI, stroke and hypertension, and therapy variables showed significantly higher case fatality in white diabetic men than in non-diabetic white men (OR=1.5; 95% CI, 1.2-1.9), but no significant association in the other race-gender groups. The age-adjusted odds of out of hospital death was significantly higher among white diabetic men (OR=1.7; 95% CI, 1.2-2.3), white women (OR=2.3; 95% CI, 1.4-3.8), and African-American women (OR=2.9; 95% CI, 1.5-5.9) as compared to their non-diabetic counterparts. In conclusion, diabetes is an independent factor for mortality within one year following a myocardial infarction among white men, and following out-of hospital coronary death in white men and women and in African-American women. It is possible that these differences could be explained, at least in part, by a less than optimal medical management of the high cardiovascular risk profile of these patients after hospital discharge.

Associations of weight loss and changes in fat distribution with the remission of hypertension in a bi-ethnic cohort: the Atherosclerosis Risk in Communities Study.

BACKGROUND: To examine associations of weight loss and changes in fat distribution with changes in blood pressure and the remission of hypertension in a community-based sample. METHODS: Participants were 3245 white and African-American men and women, 45-64 years of age, who participated in the Atherosclerosis Risk in Communities Study over an average of 9 years. Mixed models analyses were used to examine the associations of weight loss and changes in fat distribution with changes in blood pressure. Proportional hazard models with time-dependent covariates were used to examine the associations of weight loss and changes in fat distribution with the remission of hypertension. RESULTS: Weight loss was associated with a decrease in systolic blood pressure and diastolic blood pressure and with an increased rate of remission of hypertension. Hazard ratios of the remission of hypertension associated with 1-kg increment in annual weight loss were 2.04 (95% confidence interval [CI]: 1.62-2.59), 1.38 (95% CI: 1.14-1.67), 1.84 (95% CI: 1.47-2.29), and 1.53 (95% CI: 1.14-2.05) for white women, African-American women, white men, and African-American men, respectively. Changes in fat distribution were associated with the remission of hypertension in younger (45-54 years) participants. CONCLUSIONS: Weight loss was associated with a decrease in blood pressure and with remission of hypertension in white and African-American men and women.

Associations between weight gain and incident hypertension in a bi-ethnic cohort: the Atherosclerosis Risk in Communities Study.

OBJECTIVE: To examine associations between weight gain and changes in blood pressure and the incidence of hypertension in four ethnicity-gender groups. DESIGN: Longitudinal closed cohort studied over an average of 6 y. SUBJECTS: Total of 9309 white and African-American men and women 45-64 y of age who participated in the Atherosclerosis Risk in Communities (ARIC) Study. METHODS: Weight and blood pressure were measured at baseline and after an average of 3 and 6 y of follow-up. Proportional hazard models with weight gain as a time-dependent variable were used to examine the association between weight gain and changes in blood pressure and hypertension. Multivariate models were used with baseline SBP, DBP, age, BMI, height, WHR, smoking, physical activity, education, caloric intake, fat intake and study center as covariates. RESULTS: Weight gain was associated with increases in SBP and DBP in all groups. Hazard ratios for hypertension associated with 1 kg annual weight gain were 1.36 (95% CI, 1.29, 1.45) in white women, 1.12 (95% CI, 1.03, 1.21) in African-American women, 1.35 (95% CI, 1.27, 1.43) in white men and 1.43 (95% CI, 1.27,1.61) in African-American men. CONCLUSION: Weight gain was associated with increased blood pressure and increased incidence of hypertension. The association was weaker among African-American women compared to other ethnicity-gender groups.

White blood cell count and incidence of coronary heart disease and ischemic stroke and mortality from cardiovascular disease in African-American and White men and women: atherosclerosis risk in communities study.

The authors examined the association between white blood cell (WBC) count and incidence of coronary heart disease and ischemic stroke and mortality from cardiovascular disease in 13,555 African-American and White men and women from the Atherosclerosis Risk in Communities (ARIC) Study. Blood was drawn at the ARIC baseline examination, beginning in 1987-1989. During an average of 8 years of follow-up (through December 1996), there were 488 incident coronary heart disease events, 220 incident strokes, and 258 deaths from cardiovascular disease. After adjustment for age, sex, ARIC field center, and multiple risk factors, there was a direct association between WBC count and incidence of coronary heart disease (p < 0.001 for trend) and stroke (p for trend < 0.001) and mortality from cardiovascular disease (p for trend < 0.001) in African Americans. The African Americans in the highest quartile of WBC count (> or =7,000 cells/mm(3)) had 1.9 times the risk of incident coronary heart disease (95% confidence interval (CI): 1.19, 3.09), 1.9 times the risk of incident ischemic stroke (95% CI: 1.03, 3.34), and 2.3 times the risk of cardiovascular disease mortality (95% CI: 1.38, 3.72) as their counterparts in the lowest quartile of WBC count (<4,800 cells/mm(3)). These associations were similar in Whites and in never smokers. An elevated WBC count is directly associated with increased incidence of coronary heart disease and ischemic stroke and mortality from cardiovascular disease in African-American and White men and women.

Acoustic shadowing on B-mode ultrasound of the carotid artery predicts ischemic stroke: the Atherosclerosis Risk in Communities (ARIC) study.

BACKGROUND AND PURPOSE: We examined the relationship of carotid artery lesions (CALs), with and without acoustic shadowing (AS), to incident ischemic stroke events in the Atherosclerosis Risk in Communities study cohort. METHODS: The study population consisted of 13 123 men and women aged 45 to 64 years, and free of stroke, examined during 1986-1989. Over an average follow-up time of 8.0 years, 226 incident ischemic stroke cases (thromboembolic brain infarctions) were identified and classified by a standardized protocol. Three levels of exposure were defined on the basis of the presence of B-mode ultrasound-detected CALs and AS in a 3-cm segment of the carotid arteries centered at the bifurcation. RESULTS: The hazard ratio for ischemic stroke adjusted for age, ethnicity, and study site for women with a CAL without AS, compared with those without a CAL, was 1.92 (95% CI, 1.23, 3.01), and the hazard ratio comparing those with a CAL with AS with those without a CAL was 4.01 (95% CI, 2.28, 7.06). The corresponding hazard ratios for men were 1.99 (95% CI, 1.36, 2.91) and 2.23 (95% CI, 1.32, 3.79). Although adjustment for diabetes, hypertension medication, systolic blood pressure, left ventricular hypertrophy score, fibrinogen, von Willebrand factor antigen, and smoking status attenuated these associations somewhat, when compared with no evidence of CALs, CALs with AS remained statistically significant predictors of ischemic stroke in women, while CALs without AS were predictive of ischemic stroke in men. CONCLUSIONS: B-mode ultrasound-detected CALs and AS serve as markers of atherosclerosis and thus are predictive of ischemic stroke.

Alcohol consumption with age: a cross-sectional and longitudinal study of the Atherosclerosis Risk in Communities (ARIC) study, 1987-1995.

Previous cross-sectional and longitudinal studies assessing the association between age and drinking are inconsistent. Evaluating 15,425 Black and White men and women from four communities, this study sought to determine whether there was a consistent relation between age and drinking in cross-sectional and longitudinal analyses and to determine change in drinking status and level of consumption (occasional, light to moderate, and heavier drinkers) at follow-up. Cross-sectional analyses of drinking were performed for Atherosclerosis Risk in Communities examinations 1 (1987-1989) and 3 (1993-1995). The changes in drinking status and level were determined for the 12,565 persons with information at both examinations. Prevalence of drinking was generally inversely associated with age in the cross-sectional analyses for all ethnic/gender groups, and drinking prevalence decreased over the 6 years of follow-up for all except Black women. Only among Black drinkers was younger age associated with a higher level of alcohol consumption in both cross-sectional and prospective analyses. Thus, whether drinking prevalence declines, the amount consumed by drinkers is decreased, or whether both factors contribute to the decrease appears to vary with ethnicity and gender. The change in drinking level was substantial with more than 40% of baseline drinkers reporting drinking cessation or a different level of consumption at follow-up.

Alcohol consumption and the incidence of hypertension: The Atherosclerosis Risk in Communities Study.

A close relationship between alcohol consumption and hypertension has been established, but it is unclear whether there is a threshold level for this association. In addition, it has infrequently been studied in longitudinal studies and in black people. In a cohort study, 8334 of the Atherosclerosis Risk in Communities (ARIC) Study participants, aged 45 to 64 years at baseline, who were free of hypertension and coronary heart disease had their blood pressures ascertained after 6 years of follow-up. Alcohol consumption was assessed by dietary interview. The type of alcoholic beverage predominantly consumed was defined by the source of the largest amount of ethanol consumed. Incident hypertension was defined as a systolic blood pressure >/=140 mm Hg or diastolic blood pressure >/=90 mm Hg or use of antihypertensive medication. There was an increased risk of hypertension in those who consumed large amounts of ethanol (>/=210 g per week) compared with those who did not consume alcohol over the 6 years of follow-up. The adjusted odds ratios (95% confidence interval) were 1.2 (0.85 to 1.67) for white men, 2.02 (1.08 to 3.79) for white women, and 2.31 (1.11 to 4.86) for black men. Only 4 black women reported drinking >210 g ethanol per week. At low to moderate levels of alcohol consumption (1 to 209 g per week), the adjusted odds ratios (95% confidence interval) were 0.88 (0.71 to 1.08) in white men, 0.89 (0.73 to 1.09) in white women, 1.71 (1.11 to 2.64) in black men, and 0.88 (0.59 to 1.33) in black women. Systolic and diastolic blood pressures were higher in black men who consumed low to moderate amounts of alcohol compared with the nonconsumers but not in the 3 other race-gender strata. Models with polynomial terms of alcohol exposure suggested a nonlinear association in white and black men. Higher levels of consumption of all types of alcoholic beverages were associated with a higher risk of hypertension for all race-gender strata. The consumption of alcohol in amounts >/=210 g per week is an independent risk factor for hypertension in free-living North American populations. The consumption of low to moderate amounts of alcohol also appears to be associated with a higher risk of hypertension in black men.

Association of hemostatic variables with MRI-detected cerebral abnormalities: the atherosclerosis risk in communities study.

OBJECTIVES: Population-based and clinical prospective studies have shown independent associations of several hemostatic factors with ischemic heart disease and stroke. MRI-detected cerebral infarcts and white matter lesions are often detected in elderly individuals without clinical disease. It has been hypothesized that these types of lesions are often the consequence of cerebral ischemic damage and may be the precursors of clinical stroke. METHODS: This study examined the relation between a range of hemostatic factors measured at baseline in middle-aged participants who were free of diagnosed cardiovascular disease in the Atherosclerosis Risk in Communities Study and MRI-detected cerebral abnormalities at a 6-year follow-up examination. RESULTS: Plasma fibrinogen and perhaps von Willebrand factor were associated positively, and protein C was associated negatively, with cerebral infarctions. Adjusted for other risk factors, the odds ratio for cerebral infarction was 1.21 (95% confidence interval, CI = 1.02-1.44) per standard deviation increment for fibrinogen, 1.15 (95% CI = 0.97-1.37) per standard deviation increment for von Willebrand factor, and 0.77 (95% CI = 0.62-0.95) per standard deviation increment for protein C. No hemostatic factor, however, was associated with white matter disease. CONCLUSIONS: This study has only a follow-up MRI, and it is likely that some MRI lesions were present at baseline. Nevertheless, increased levels of fibrinogen and von Willebrand factor and reduced levels of protein C appear to be associated with cerebral infarction identified by MRI.

Acoustic shadowing on B-mode ultrasound of the carotid artery predicts CHD.

The relationship between carotid artery lesions (CALs), with and without acoustic shadowing (AS) as an index of arterial mineralization, and incident coronary heart disease (CHD) was examined in the Atherosclerosis Risk in Communities study cohort. Among 12,375 individuals, ages 45-64 years, free of CHD at baseline, 399 CHD events occurred between 1987-1995. In a 3-cm segment centered at the carotid bifurcation, CALs with and without AS were identified by B-mode ultrasound (US). After adjustment for the major CHD risk factors, the CHD hazard ratio (HR) for women with CAL without AS compared to women without CAL was 1.78 (95% CI: 1.22, 2.60) and the HR comparing women with CAL with AS to women with CAL without AS was 1.73 (95% CI: 1.07, 2.80). Corresponding HRs for men were 1.59 (95% CI: 1.22, 2.07) and 1.04 (95% CI: 0.72, 1.51). CALs predicted CHD events; this association was stronger for mineralized CALs in women, but not men.

Vitamin Intervention for Stroke Prevention (VISP) trial: rationale and design.

Elevated plasma levels of homocyst(e)ine [H(e)] are surprisingly common and strongly associated with endothelial dysfunction and a marked increase in vascular risk. Treatment with a combination of folic acid, pyridoxine (vitamin B6) and cobalamin (vitamin B12) reduces plasma H(e) levels in most cases, restores endothelial function, and regresses carotid plaque, but there is no evidence that such treatment will reduce clinical events. The Vitamin Intervention for Stroke Prevention (VISP) study is a double-masked, randomized, multicenter clinical trial designed to determine if, in addition to best medical/surgical management, high-dose folic acid, vitamin B6, and vitamin B12 supplements will reduce recurrent stroke compared to lower doses of these vitamins. Patients at least 35 years old with a nondisabling ischemic stroke within 120 days, and screening plasma H(e) > the 25th percentile of benchmark population data are eligible. Secondary endpoints are myocardial infarction or fatal coronary heart disease. This paper describes the design and rationale of the study.

Metabolic and lifestyle determinants of postprandial lipemia differ from those of fasting triglycerides: The Atherosclerosis Risk In Communities (ARIC) study.

Despite the reported association of lipoprotein responses to a fatty meal with atherosclerosis, little is known about the determinants of these responses. Plasma triglyceride, retinyl palmitate, and apolipoprotein B-48 responses to a standardized fatty meal containing a vitamin A marker were measured in 602 Atherosclerosis Risk in Communities (ARIC) study participants. To focus on postprandial responses specifically, which have been reported to be related to atherosclerosis independently of fasting triglycerides, analyses for determinants of postprandial responses were adjusted for fasting triglycerides. Major determinants of fasting triglycerides, namely, diabetes, obesity, other factors related to insulin resistance, and male sex, were not independently associated with postprandial responses. Fasting triglycerides were the strongest predictor of postprandial lipids, but independent of triglycerides, the predictors of postprandial responses were smoking, diet, creatinine, and alcohol. Smokers had substantially increased retinyl palmitate and apolipoprotein B-48 responses, indicators of chylomicrons and their remnants. Persons who consume more calories or omega3 fatty acids had reduced chylomicron responses. Triglyceride responses were associated positively with serum creatinine levels and negatively with moderate alcohol consumption. Thus, determinants of fasting and postprandial lipids differ. The independent atherogenic influence of postprandial lipids may relate more to smoking and diet than to obesity and insulin resistance.

Coronary heart disease trends in four United States communities. The Atherosclerosis Risk in Communities (ARIC) study 1987-1996.

OBJECTIVE: The objective of this paper is to report trends in mortality due to coronary heart disease (CHD), rates of first and recurrent hospitalized myocardial infarction, and survival after myocardial infarction in the Atherosclerosis Risk in Communities (ARIC) Study from 1987 through 1996. METHOD: The ARIC study used retrospective community surveillance to monitor admissions to acute care hospitals and deaths due to CHD (both in- and out-of-hospital) among all residents 35-74 years of age. The surveillance areas included over 360 000 men and women in four communities: Forsyth County, North Carolina; the city of Jackson, Mississippi; eight northern suburbs of Minneapolis, Minnesota; and Washington County, Maryland. RESULTS: The annual age-adjusted mortality rate of CHD fell 3.2% (95% CI: 2.0, 4.3) among men and 3.8% (95% CI: 1.9, 5.6) among women. The greater part of the decline took place between 1987 and 1991. Significant declines were observed for both in-hospital and out-of-hospital CHD death. Significant improvements in case-fatality were also observed. Recurrent hospitalized myocardial infarction event rate fell an average of 1.9% per year among men (95% CI: 0.7, 3.1) and 2.1% (95% CI: 0.3, 3.9) among women. Average annual per cent change in incident hospitalized myocardial infarction was not statistically significant, except in blacks where there was evidence of an increase over time. CONCLUSION: Factors associated with the occurrence of recurrent hospitalized myocardial infarction, as well as those creating a better chance of survival after an event (including reductions in sudden death), were likely the prominent components in the recent decline in CHD mortality in ARIC communities.