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In this article we focus on comparing measurement error correction methods for rate-of-change exposure variables in survival analysis, when longitudinal data are observed prior to the follow-up time. Motivational examples include the analysis of the association between changes in cardiovascular risk factors and subsequent onset of coronary events. We derive a measurement error model for the rate of change, estimated through subject-specific linear regression, assuming an additive measurement error model for the time-specific measurements. The rate of change is then included as a time-invariant variable in a Cox proportional hazards model, adjusting for the first time-specific measurement (baseline) and an error-free covariate. In a simulation study, we compared bias, standard deviation and mean squared error (MSE) for the regression calibration (RC) and the simulation-extrapolation (SIMEX) estimators. Our findings indicate that when the amount of measurement error is substantial, RC should be the preferred method, since it has smaller MSE for estimating the coefficients of the rate of change and of the variable measured without error. However, when the amount of measurement error is small, the choice of the method should take into account the event rate in the population and the effect size to be estimated. An application to an observational study, as well as examples of published studies where our model could have been applied, are also provided. [ABSTRACT FROM AUTHOR]

Risk prediction models have been widely applied for the prediction of long-term incidence of disease. Several parameters have been identified and estimators developed to quantify the predictive ability of models and to compare new models with traditional models. These estimators have not generally accounted for censoring in the survival data normally available for fitting the models. This paper remedies that problem. The primary parameters considered are net reclassification improvement (NRI) and integrated discrimination improvement (IDI). We have previously similarly considered a primary measure of concordance, area under the ROC curve (AUC), also called the c-statistic. We also include here consideration of population attributable risk (PAR) and ratio of predicted risk in the top quintile of risk to that in the bottom quintile. We evaluated estimators of these various parameters both with simulation studies and also as applied to a prospective study of coronary heart disease (CHD). Our simulation studies showed that in general our estimators had little bias, and less bias and smaller variances than the traditional estimators. We have applied our methods to assessing improvement in risk prediction for each traditional CHD risk factor compared to a model without that factor. These traditional risk factors are considered valuable, yet when adding any of them to a risk prediction model that has omitted the one factor, the improvement is generally small for any of the parameters. This experience should prepare us to not expect large values of the risk prediction improvement evaluation parameters for any new risk factor to be discovered. Copyright © 2010 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Aims: Although studies of the accuracy of heart failure (HF) classification scoring systems are available, few have examined their performance when restricted to self-reported items. [ABSTRACT FROM PUBLISHER]

Background: Adherence to non-specific prescription therapy may be associated with clinical outcomes beyond a given treatment effect. We assessed the association of blinded randomized pill prescription adherence with vascular outcomes after ischemic stroke. Methods: We analyzed the Vitamin Intervention for Stroke Prevention (VISP) study database. VISP was a double-blind randomized trial, designed to determine whether high doses of vitamins (vs. low doses) would reduce recurrent stroke risk in 3,680 participants over a 2-year period. We examined the independent association of adherence with a composite endpoint (stroke, myocardial infarction, death). Results: Among 3,357 (91%) subjects with complete data, women, non-White persons, current smokers, those not on statins and those without a history of coronary artery bypass surgery were significantly less likely to be optimally adherent. Over the trial, persons who adhered well to treatment were less likely to experience the combined outcome than those who adhered poorly (13.4 vs. 20.6%, p < 0.0001). After multivariable analysis using various adherence measures, there were no significant differences between ≥80% vs. <80% adherence, but compared to <65% adherence, pill adherence levels of ≥90 to <99% (HR 0.56, 95% CI = 0.34–0.91; p = 0.02) and ≥99% (HR 0.46, 95% CI = 0.29–0.73; p = 0.001) were associated with lower occurrence of the combined outcome at 18 months. Conclusions: Long-term excellent adherence to non-specific pill prescription among ischemic stroke patients is independently associated with lower vascular risk, and is likely a marker of overall healthy behavior that may be helpful in targeting stroke patients with unhealthy practices. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The authors sought to examine the relation between serum or dietary magnesium and the incidence of ischemic stroke among blacks and whites. Between 1987 and 1989, 14,221 men and women aged 45–64 years took part in the first examination of the Atherosclerosis Risk in Communities Study cohort. The incidence of stroke was ascertained from hospital records. Higher serum magnesium levels were associated with lower prevalence of hypertension and diabetes mellitus at baseline. During the 15-year follow-up, 577 ischemic strokes occurred. Serum magnesium was inversely associated with ischemic stroke incidence. The age-, sex-, and race-adjusted rate ratios of ischemic stroke for those with serum magnesium levels of ≤1.5, 1.6, 1.7, and ≥1.8 mEq/L were 1.0, 0.78 (95% confidence interval (CI): 0.62, 0.96), 0.70 (95% CI: 0.56, 0.88), and 0.75 (95% CI: 0.59, 0.95) (Ptrend = 0.005). After adjustment for hypertension and diabetes, the rate ratios were attenuated to nonsignificant levels. Dietary magnesium intake was marginally inversely associated with the incidence of ischemic stroke (Ptrend = 0.09). Low serum magnesium levels could be associated with increased risk of ischemic stroke, in part, via effects on hypertension and diabetes. [ABSTRACT FROM PUBLISHER]

Few studies have determined whether carotid artery intima-media thickness (IMT) is associated prospectively with risk of first ischemic stroke. In the Atherosclerosis Risk in Communities Study, carotid IMT, an index of generalized atherosclerosis, was defined as the mean of IMT measured by B-mode ultrasonography at six sites of the carotid arteries. The authors assessed the relation of mean IMT to stroke incidence over 6–9 years' follow-up (1987–1995) among 7,865 women and 6,349 men aged 45–64 years without prior stroke at baseline in four US communities. There were 90 incident ischemic stroke events for women and 109 for men. In sex-specific Cox proportional hazards models adjusting only for age, race, and community, the hazard rate ratios comparing extreme mean IMT values (≥1 mm) to values less than 0.6 mm were 8.5 for women (95% confidence interval: 3.5, 20.7) and 3.6 for men (95% confidence interval: 1.5, 9.2). The relation was graded, and models with cubic splines indicated significant nonlinearity, with hazards increasing more rapidly at lower IMTs than at higher IMTs. Thus, models using linear IMT values substantially underestimate the strength of the association at lower IMTs. The strength of the association was reduced by the inclusion of putative stroke risk factors, but it remained elevated at higher IMTs. Hence, mean carotid IMT is a noninvasive predictor of future ischemic stroke incidence. Am J Epidemiol 2000;151:478–87. [ABSTRACT FROM PUBLISHER]

Various studies have reported an inverse association between serum albumin level and incident coronary heart disease (CHD), though biologic mechanisms have not been established. The authors examined the association between serum albumin level and CHD in the Atherosclerosis Risk in Communities cohort, comprising 14,506 White and African-American middle-aged men and women. The mean albumin level in this population was 3.9 g/dl (standard deviation 0.3). During 5.2 years of follow-up, 470 incident CHD events occurred. The hazard ratio for incident CHD associated with a 1-standard deviation decrease in serum albumin level was 1.26 (95% confidence interval (CI): 1.15, 1.38) after adjustment for age, gender, and ethnicity and 1.18 (95% CI: 1.07, 1.30) after additional adjustment for covariates related to CHD. Hazard ratios were similar across gender and ethnic groups. However, there was statistically significant effect modification by smoking status, with hazard ratios of 1.01 (95% CI: 0.84, 1.22) among never smokers, 1.09 (95% CI: 0.92, 1.30) among former smokers, and 1.35 (95% CI: 1.17, 1.54) among current smokers. Further adjustment for factors related to renal disease, nutrition, platelet aggregation, inflammation, use of angiotensin-converting enzyme inhibitors, and hemostasis factors attenuated the albumin-CHD relation only slightly. In this study, serum albumin was inversely associated with incident CHD at the baseline examination in current smokers but not in never or former smokers. Albumin level may be a marker of susceptibility to the inflammatory response that results from smoking. Am J Epidemiol 2000;151:468–77. [ABSTRACT FROM PUBLISHER]

Pathologic findings and cross-sectional epidemiologic studies suggest that past infection with Chlamydia pneumoniae is associated with clinical and subclinical atherosclerotic disease, although evidence from prospective studies is still scarce. The association between chronic infection by C. pneumoniae and incident coronary heart disease (CHD) was investigated in a case-cohort study conducted among participants in the Atherosclerosis Risk in Communities Study who were free of CHD at the baseline examination (1986–1989). Levels of C. pneumoniae immunoglobulin G (IgG) antibodies in serum collected at baseline from 246 incident cases of CHD identified during follow-up (median, 3.3 years; maximum, 5 years) were compared with those from a stratified sample of the baseline cohort (n = 550). Among incident CHD cases, 65% had IgG antibody titers >1:64, compared with 55% of noncases (compared with negative IgG titers, the relative hazard of CHD was 1.6 (p < 0.01)). In multivariate analyses controlling for other risk factors (age, gender, smoking, serum cholesterol, hypertension, diabetes mellitus, and educational level), the above estimates were substantially reduced and became statistically nonsignificant (relative hazard = 1.2). A significantly increased CHD hazard associated with IgG antibody titers >1:64 was observed among nonsmokers, even after adjustment for other risk factors. Overall, these results do not provide strong support for the hypothesis that C. pneumoniae infection is a risk factor for clinical CHD. Studies with longer follow-up periods will be necessary to determine whether C. pneumoniae infection is involved as an etiologic factor in earlier phases of atherogenesis. Am J Epidemiol 1999;150:149–56. [ABSTRACT FROM PUBLISHER]

Objective: Although variants in the transcription factor 7-like 2 (TCF7L2) gene are consistently associated with type 2 diabetes, large population-based studies of African Americans are lacking. Moreover, few studies have investigated the effects of TCF7L2 on type 2 diabetes in the context of metabolic risk factors of type 2 diabetes.Research Design and Methods: We investigated the association between the TCF7L2 rs7903146 polymorphism and type 2 diabetes in 2,727 African American and 9,302 Caucasian participants without diabetes who were inducted into the Atherosclerosis Risk in Communities study in 1987-1989 and followed for 9 years.Results: A total of 485 and 923 cases of type 2 diabetes were identified in African Americans and Caucasians, respectively. Compared with homozygous CC individuals, heterozygous CT and homozygous TT individuals had higher cumulative incidence of type 2 diabetes over 9 years of follow-up: 11.3% (95% CI 10.2-12.4) vs. 21.1% (20.8-21.4) and 27.9% (19.3-36.5) in African Americans, respectively, and 9.7% (8.8-10.6) vs. 11.3% (10.2-12.4) and 13.6% (11.1-16.1), respectively, in Caucasians. Individuals with the risk allele had the highest hazards of diabetes if they were obese and had low HDL cholesterol, followed by individuals with any one and none of the traits.Conclusions: Our study provides the first significant evidence of association between the TCF7L2 rs7903146 polymorphism and type 2 diabetes risk in a large African American population and also demonstrates that the diabetes risk conveyed by the rs7903146 risk allele is substantially increased in the context of some metabolic risk factors for type 2 diabetes. Our study findings need to be replicated in other large, population-based studies. [ABSTRACT FROM AUTHOR]

Background: Studies indicate that diet may be related to the occurrence of brain lesions. The cross-sectional association between food intake and brain lesion volumes in late-life depression was examined in a cohort of elderly individuals with current or prior depression.Methods: Food intake was assessed in 54 elderly vascular depression subjects (vascular depression defined by presence of hyperintensities on brain MRI) using a Block 1998 food frequency questionnaire. Food and kilocalorie intake were determined. Brain lesion volumes were calculated from MRI. Subjects were aged 60 or over and were participants in a longitudinal study of major depression. All subjects received psychiatric assessment and treatment, and medical comorbidity assessments.Results: High-fat dairy and whole grains were significantly positively correlated with brain lesion volume, while other food groups were not significantly associated with lesion volume. In multivariable analyses, controlling for age, sex, hypertension, diabetes and total kilocalories, the positive association with lesion volume remained significant for both high-fat dairy and whole grains.Conclusions: High fat dairy and whole grain consumption may be associated with brain lesions in elderly subjects with depression. [ABSTRACT FROM AUTHOR]

The article examines the incidence of cardiovascular disease (CVD) events in African American subjects. Elevated or borderline risk factors explain the more than 90 percent of CVD events in African American subjects according to the Atherosclerosis Risk in Communities Study. Results suggest that primary prevention of elevated CVD risk factors might reduce CVD occurrence.

The article presents an assessment of several studies on incremental coronary risk prediction using C-reactive protein and other novel risk markers. It is still a question of whether specific novel, risk factors or blood markers like C-reactive protein can enhance existing coronary heart disease (CHD) prediction models. More information could be found in the article.

Folic acid fortification of grain products was mandated in the USA by January 1998 and in Canada by November 1998. It was hypothesized thatscreeningtotal plasma homocysteine levels adjusted for age, sex, race and country that were drawn in stroke patients for the Vitamin Intervention for Stroke Prevention trial from 1997 to 2001 would be steady when fortification was completed. Samples were grouped by years 1997/1998, 1999 and 2000/2001, and adjusted means were calculated using a general linear regression model. In 2,612 US and 1,059 Canadian patients, levels showed no consistent trend in the USA alone, while Canadian levels declined (p = 0.06 overall, 0.0003 in the oldest age group). US levels were 0.39 μmol/l (95% CI: –0.08, 0.85) lower than in Canada. Neither fasting nor time since stroke affected the results. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background Measurement of inflammatory markers has been reported to identify individuals at increased risk for ischemic stroke. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a proinflammatory enzyme secreted by macrophages. We assessed Lp-PLA2 and C-reactive protein (CRP) levels along with traditional risk factors to examine their relation to ischemic stroke. Methods A proportional hazards model was used in a prospective case-cohort study of 12 762 apparently healthy middle-aged men and women in the Atherosclerosis Risk in Communities (ARIC) study who were observed for about 6 years. Results Mean Lp-PLA2 and CRP levels adjusted for sex, race, and age were higher in the 194 stroke cases than the 766 noncases, whereas low-density lipoprotein cholesterol (LDL-C) level was not significantly different. Both Lp-PLA2 and CRP levels were associated with ischemic stroke after adjustment for age, sex, and race: hazard ratios were 2.23 for the highest vs the lowest tertile of Lp-PLA2 and 2.70 for CRP level higher than 3 vs lower than 1 mg/L. In a model that included smoking, systolic hypertension, lipid levels, and diabetes, Lp-PLA2 and CRP levels in the highest category were associated with hazard ratios of 1.91 (95% confidence interval, 1.15-3.18; P = .01) and 1.87 (95% confidence interval, 1.13-3.10; P = .02), respectively. Individuals with high levels of both CRP and Lp-PLA2 were at the highest risk after adjusting for traditional risk factors compared with individuals with low levels of both, whereas others were at intermediate risk. Conclusion Levels of Lp-PLA2 and CRP may be complementary beyond traditional risk factors in identifying middle-aged individuals at increased risk for ischemic stroke. [ABSTRACT FROM AUTHOR]

Objective: To develop and evaluate clinical rules to predict risk for diabetes in middle-aged adults.Research Design and Methods: The Atherosclerosis Risk in Communities is a cohort study conducted from 1987-1989 to 1996-1998. We studied 7,915 participants 45-64 years of age, free of diabetes at baseline, and ascertained 1,292 incident cases of diabetes by clinical diagnosis or oral glucose tolerance testing.Results: We derived risk functions to predict diabetes using logistic regression in a random half of the sample. Rules based on these risk functions were evaluated in the other half. A risk function based on waist, height, hypertension, blood pressure, family history of diabetes, ethnicity, and age was performed similarly to one based on fasting glucose (area under the receiver-operating characteristic curve [AUC] 0.71 and 0.74, respectively; P = 0.2). Risk functions composed of the clinical variables plus fasting glucose (AUC 0.78) and additionally including triglycerides and HDL cholesterol (AUC 0.80) performed better (P < 0.001). Evaluation of scores based on the metabolic syndrome as defined by the National Cholesterol Education Program or with slight variations showed AUCs of 0.75 and 0.78, respectively. Rules based on all these approaches, while identifying 20-56% of the sample as screen positive, achieved sensitivities of 40-87% and specificities of 50-86%.Conclusions: Rules derived from clinical information, alone or combined with simple laboratory measures, can characterize degrees of diabetes risk in middle-aged adults, permitting preventive actions of appropriate intensity. Rules based on the metabolic syndrome are reasonable alternatives to rules derived from risk functions. [ABSTRACT FROM AUTHOR]

Background: Numerous studies have identified risk factors and markers associated with incidence of cardiovascular disease (CVD). However, few studies have examined whether established risk factors, novel blood markers, carotid ultrasonography, or ankle-brachial index can predict recurrent CVD events. Methods and Results: We analyzed the relation of established risk factors and markers of atherosclerosis with the risk of recurrent CVD in 766 participants. Over a mean of 8.7 years of follow-up, 70 women and 243 men had a recurrent CVD event (85.3% coronary heart disease and 23.7% stroke). Adjusting for age and sex, this study found that established risk factors were associated with recurrent CVD events in the anticipated direction. Being in the highest (vs lowest) quartiles of lipoprotein (a), fibrinogen, white blood cells, and creatinine at baseline were associated with 47%, 69%, 65%, and 81%, respectively, greater risk of a CVD event, and being in the highest quartile of albumin was associated with 39% lower risk. Being in the highest (vs lowest) quartile of carotid intima-media thickness (IMT) was associated with a doubling of risk, and having carotid plaque with acoustic shadowing (vs having no plaque) was associated with 83% increased risk of a CVD event. After adjustment for established risk factors, creatinine, albumin, and carotid IMT in the highest quartile (vs lowest quartile) and carotid plaque with acoustic shadowing (vs no plaque) were independently associated with recurrent CVD events. Conclusion: Established risk factors, but only a few of novel risk factors and markers, were independent predictors of recurrent CVD events. [ABSTRACT FROM AUTHOR]

Abstract: Although ventricular repolarization abnormalities reflect arrhythmic susceptibility, few reliable tools exist to identify their presence. We investigated the repeatability of the spatial T-wave axis and QT interval from standard 12-lead electrocardiograms in 63 asymptomatic volunteers. Certified technicians used a standardized protocol to digitally record 2 electrocardiograms per participant at each of 2 visits separated by 1 to 2 weeks. Absolute paired differences within and between visits were 0.19° and 0.90° for the T-wave axis and 1.08 and 1.55 milliseconds for the QT interval, respectively. The intraclass correlation coefficients for the T-wave axis and QT interval were 0.87 and 0.86, respectively. The impact of repeated measurements on the precision of the QT-interval measurements was evaluated for a hypothetical clinical trial aimed at detecting a drug-induced QT prolongation. We conclude that the spatial T-wave axis is as repeatable a measure of ventricular repolarization as the QT interval. [Copyright &y& Elsevier]

Objective: To describe the progression of autonomic impairment among individuals with diabetes and pre-diabetic metabolic impairments.Research Design and Methods: We investigated the consequence of diabetes and pre-diabetic metabolic impairments on the 9-year change in heart rate variability (HRV) in a population-based cohort of 6,245 individuals aged 45-64 years at baseline and cross-sectional associations among 9,940 individuals.Results: Diabetic subjects had a more rapid temporal decrease in HRV conditional on baseline HRV than nondiabetic subjects. Adjusted mean annual changes (95% CI) (ms/year) in the SD of all normal-to-normal R-R intervals were -0.65 (-0.69 to -0.61) for those with normal fasting glucose vs. -0.95 (-1.09 to -0.81) for diabetic subjects, in root mean square of successive differences in normal-to-normal R-R intervals -0.35 (-0.39 to -0.30) vs. -0.66 (-0.82 to -0.51), and in R-R interval 6.70 (6.37-7.04) vs. 3.89 (2.72-5.05). While we found cross-sectional associations between decreased HRV and diabetes and nondiabetic hyperinsulinemia and a weak inverse association with fasting glucose, neither impaired fasting glucose nor nondiabetic hyperinsulimenia was associated with a measurably more rapid decline in HRV than normal.Conclusions: Cardiac autonomic impairment appears to be present at early stages of diabetic metabolic impairment, and progressive worsening of autonomic cardiac function over 9 years was observed in diabetic subjects. The degree to which pre-diabetic metabolic impairments in insulin and glucose metabolism contribute to decreases in cardiac autonomic function remains to be determined. [ABSTRACT FROM AUTHOR]

Variations in the validity of hospital discharge diagnoses can complicate the assessment of trends in incidence of acute myocardial infarction (AMI). To clarify trends in the validity of discharge codes, the authors compared event classification based on published Atherosclerosis Risk in Communities (ARIC) Study criteria with the presence or absence of an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) hospital discharge code for AMI (code 410). Between 1987 and 2000, 154,836 coronary heart disease events involving hospitalization in the four ARIC communities had ICD-9-CM codes screened for AMI. The sensitivity of ICD-9-CM code 410 for classifying AMI in men (sensitivity = 0.65, 95% confidence interval (CI): 0.63, 0.66) was statistically significantly greater than that found for women (sensitivity = 0.60, 95% CI: 0.58, 0.62) and was greater in Whites (sensitivity = 0.67, 95% CI: 0.65, 0.68) than in Blacks (sensitivity = 0.50, 95% CI: 0.47, 0.53). The ethnic difference was related to a greater frequency of hypertensive heart disease and congestive heart failure codes encompassing AMI among Blacks as compared with Whites. The authors found that although the validity of ICD-9-CM code 410 to identify AMI was generally stable from 1987 through 2000, differences between Blacks and Whites and across geographic locations support investment in validation efforts in ongoing surveillance studies. [ABSTRACT FROM AUTHOR]

The authors evaluated the relation between consumption of alcoholic beverages and incidence of coronary heart disease in White and African-American participants in the Atherosclerosis Risk in Communities Study. The average duration of follow-up was 9.8 years between 1987 and 1998. The association was analyzed by means of Cox proportional hazards regression models. The authors found a positive association between ethanol consumption and incident coronary heart disease for Black men (for a 13-g/day increment in ethanol consumption, adjusted hazard ratio (HR) = 1.13, 95% confidence interval (CI): 1.01, 1.28) and an inverse association for White men (HR = 0.88, 95% CI: 0.79, 0.99). There was an inverse association of coronary heart disease with rare drinking (HR = 0.47, 95% CI: 0.28, 0.80) and with consumption of ≥70 g of ethanol per week (HR = 0.49, 95% CI: 0.24, 0.98) in White women and with consumption of ≥210 g/week (HR = 0.56, 95% CI: 0.33, 0.95) in White men. In Black men, the association was positive for consumption of 140–<210 g/week (HR = 2.61, 95% CI: 1.11, 6.17). The contrasting findings in Whites and Black men in this cohort raise the question of whether the cardioprotective effect of alcohol is real or may be confounded by lifestyle characteristics of drinkers. [ABSTRACT FROM AUTHOR]

The authors assessed the increase in the predictivity of ischemic stroke (IS) resulting from the addition of nontraditional risk factors and markers of subclinical disease to a basic model containing only traditional risk factors (current smoking, diabetes mellitus, systolic blood pressure, antihypertensive therapy, prior coronary disease, and left ventricular hypertrophy) among 14,685 middle-aged persons in the Atherosclerosis Risk in Communities Study. Participants were recruited from four US communities in 1987–1989. Risk prediction scores for IS through 2000 were estimated from Cox models. The ability to predict which persons would develop IS was assessed by means of the area under the receiver operating characteristic curve—the probability that persons with IS had a higher risk score than those without IS. Among 22 nontraditional factors considered, the joint addition of body mass index, waist:hip ratio, high density lipoprotein cholesterol, albumin, von Willebrand factor, alcohol consumption, peripheral arterial disease, and carotid artery wall thickness modestly and statistically significantly improved prediction of future IS over a risk score that included traditional factors. Further improvement was obtained by adding age and race. For women, the area under the receiver operating characteristic curve went from 0.79 to 0.83 to 0.84; for men, it went from 0.76 to 0.78 to 0.80. These modest improvements are not enough to influence clinical and public health efforts to reduce the community burden of IS. [ABSTRACT FROM AUTHOR]

Context: In observational studies, elevated plasma total homocysteine levels have been positively associated with ischemic stroke risk. However the utility of homocysteine-lowering therapy to reduce that risk has not been confirmed by randomized trials. Objective: To determine whether high doses of folic acid, pyridoxine (vitamin B[sub 6]), and cobalamin (vitamin B[sub 12]), given to lower total homocysteine levels, reduce the risk of recurrent stroke over a 2-year period compared with low doses of these vitamins. Design: Double-blind randomized controlled trial (September 1996–May 2003). Setting and Participants: 3680 adults with nondisabling cerebral infarction at 56 university-affiliated hospitals, community hospitals, private neurology practices, and Veterans Affairs medical centers across the United States, Canada, and Scotland. Interventions: All participants received best medical and surgical care plus a daily multivitamin containing the US Food and Drug Administration's reference daily intakes of other vitamins; patients were randomly assigned to receive once-daily doses of the high-dose formulation (n = 1827), containing 25 mg of pyridoxine, 0.4 mg of cobalamin, and 2.5 mg of folic acid; or the low-dose formulation (n = 1853), containing 200 µg of pyridoxine, 6 µg of cobalamin[sub ,]and 20 µg of folic acid. Main Outcome Measures: Recurrent cerebral infarction (primary outcome); coronary heart disease (CHD) events and death (secondary outcomes). Results: Mean reduction of total homocysteine was 2 µmol/L greater in the high-dose group than in the low-dose group, but there was no treatment effect on any end point. The unadjusted risk ratio for any stroke, CHD event, or death was 1.0 (95% confidence interval [CI], 0.8-1.1), with chances of an event within 2 years of 18.0% in the high-dose group and 18.6% in the low-dose group. The risk of ischemic stroke within 2 years was 9.2% for the high-dose and 8.8% for the low-dose groups (risk ratio, 1.0; 95% CI, 0.8-1.3) (P = .80 by log-rank test of the primary hypothesis of difference in ischemic stroke between treatment groups). There was a persistent and graded association between baseline total homocysteine level and outcomes. A 3-µmol/L lower total homocysteine level was associated with a 10% lower risk of stroke (P = .05), a 26% lower risk of CHD events (P<.001), and a 16% lower risk of death (P = .001) in the low-dose group and a nonsignificantly lower risk in the high-dose group by 2% for stroke, 7% for CHD events, and 7% for death. Conclusions: In this trial, moderate reduction of total homocysteine after nondisabling cerebral infarction had no effect on vascular outcomes during the 2 years of follow-up. However, the consistent findings of an association of total homocysteine with vascular risk suggests that further exploration of the hypothesis is warranted and longer trials in different populations with elevated total homocysteine may be necessary. INSET: BOX. Inclusion and Exclusion Criteria.. [ABSTRACT FROM AUTHOR]

Objective: To determine the 10-year probability of coronary heart disease (CHD) in diabetic adults and how well basic and novel risk factors predict CHD risk.Research Design and Methods: We measured risk factors in 14054 participants (1500 with diabetes) initially free of CHD in the Atherosclerosis Risk in Communities study from 1987 to 1989 and followed them prospectively for CHD incidence through 1998. We used proportional hazards regression models and receiver operating characteristic (ROC) curves for CHD risk prediction.Results: Based on our model using basic risk factors (age, race, total and HDL cholesterol, systolic blood pressure, antihypertensives, and smoking status), approximately 61% of diabetic women and 86% of diabetic men had a predicted 10-year CHD probability >or=10%. This CHD risk-prediction model had an area under the ROC curve of 0.72 in diabetic women and 0.67 in diabetic men. Novel risk factors or subclinical disease markers individually added only modest predictivity, but the addition of multiple markers (BMI, waist-to-hip ratio, Keys dietary score, serum albumin and creatinine, factor VIII, white blood cell count, left ventricular hypertrophy determined by electrocardiogram, and carotid intima-media thickness) increased the area under the curve by approximately 10%.Conclusions: Although all diabetic adults are at high risk for CHD, their variation in CHD risk can be predicted moderately well by basic risk factors. No single novel risk marker greatly enhanced absolute CHD risk assessment, but a battery of novel markers did. Our model can provide estimates of CHD risk for the primary prevention of this disease in people with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Risk prediction functions for incident coronary heart disease (CHD) were estimated using data from the Atherosclerosis Risk in Communities (ARIC) Study, a prospective study of CHD in 15,792 persons recruited in 1987–1989 from four U.S. communities, with follow-up through 1998. Predictivity of which individuals had incident CHD was assessed by increase in area under ROC curves resulting from adding nontraditional risk factors and markers of subclinical disease to a basic model containing only traditional risk factors. We also assessed the increase in population attributable risk. The additional factors were body mass index; waist–hip ratio; sport activity index; forced expiratory volume; plasma fibrinogen, factor VIII, von Willebrand factor, and Lp(a); heart rate; Keys score; pack-years smoking; and subclinical disease marker carotid intima-media thickness. These factors substantially improved prediction of future CHD for men, less for women, and also increased attributable risks. [Copyright &y& Elsevier]

Background: As part of the Atherosclerosis Risk in Communities Study, the race-specific incidence rates and risk factor prediction for coronary heart disease (CHD) were determined for black and white persons over 7 to 10 years of follow-up, from 1987 to 1997. Methods: The sample included 14 062 men and women (2298 black women, 5686 white women, 1396 black men, and 4682 white men) aged 45 to 64 years who were free of clinical CHD at baseline. Results: Average age-adjusted incidence rates (95% confidence intervals) for CHD per 1000 person-years were as follows: black women, 5.1 (4.2-6.2); white women, 4.0 (3.5-4.6); black men, 10.6 (8.9-12.7); and white men, 12.5 (11.5-13.7). Incidence rates (95% confidence intervals) using a definition for CHD that excluded revascularization procedures were as follows: black women, 4.9 (4.6-6.0); white women, 2.9 (2.5-3.4); black men, 9.2 (7.6-11.1); and white men, 7.9 (7.0-8.8). In a multivariable analysis, hypertension was a particularly strong risk factor in black women, with hazard rate ratios (95% confidence intervals) as follows: black women, 4.8 (2.5-9.0); white women, 2.1 (1.6-2.9); black men, 2.0 (1.3-3.0); and white men, 1.6 (1.3-1.9). Diabetes mellitus was somewhat more predictive in white women than in other groups. Hazard rate ratios (95% confidence intervals) were as follows: black women, 1.8 (1.2-2.8); white women, 3.3 (2.4-4.6); black men, 1.6 (1.1-2.5); and white men, 2.0 (1.6-2.6). Low-density lipoprotein cholesterol level was similarly predictive in all race-sex groups (hazard rate ratio, 1.2-1.4 per SD increment of low-density lipoprotein cholesterol level). High-density lipoprotein cholesterol level seemed somewhat more protective in white than in black persons. Conclusions: Findings from this study, along with clinical trial evidence showing efficacy, support aggressive management of traditional risk factors in black persons, as in white persons. Understanding the intriguing racial differences in risk... [ABSTRACT FROM AUTHOR]

This study evaluated whether small shifts in cardiac autonomic balance with standing, as measured by heart rate variability (HRV), were prospectively associated with incident coronary heart disease (CHD) and mortality. Both Black and White men and women aged 45-64 years from the Atherosclerosis Risk in Communities Study (n = 9,267) were followed from 1987 to 1997 for myocardial infarction (n = 296), fatal CHD (n = 63), and non- CHD mortality (n = 533). HRV indices and mean R-R interval length (inverse of heart rate) were measured in the supine and standing positions for 2 minutes each; HRV shift was calculated as the difference between positions. After adjustment for demographic characteristics and medication use, HRV in each position was significantly inversely related to events in Cox proportional hazards models. With the exception of R-R interval length shift and myocardial infarction (hazard ratio = 1.42, 95% confidence interval: 1.02, 1.98 for the smallest vs. the largest quartile), there was no association between HRV shift and the other events. Despite clinical research suggesting that HRV shift with standing is a more sensitive measure of autonomic balance than is HRV in one position, simple measures such as heart rate change and supine and standing HRV were better predictors of events. Am J Epidemiol 2002;155:48-56. [ABSTRACT FROM AUTHOR]

Intima-media thickness of the common carotid arteries is a marker of atherosclerosis and has been shown to be associated with prevalent and incident coronary heart disease and with coronary heart disease risk factors. The authors examined the association of baseline risk factors or change in risk factors with change in intimamedia thickness over follow-up (1987-1998) in the Atherosclerosis Risk in Communities (ARIC) population-based cohort (baseline: age 45-64 years, n = 15,792). Subjects were members of households sampled in four areas of the United States. Either not adjusting for baseline intima-media thickness or doing so with correction for its measurement error resulted in statistically significant associations of change in intima-media thickness with baseline diabetes, current smoking, high density lipoprotein cholesterol, pulse pressure, white blood cell count, and fibrinogen. The associations were of a similar order of magnitude as anticipated from the authors' cross-sectional findings. Statistically significant associations were found between change in intima-media thickness and change in low density lipoprotein cholesterol and triglycerides and with onset of diabetes and hypertension. In summary, established risk factors for coronary heart disease are associated with the rate of change of subclinical atherosclerosis. Am J Epidemiol 2002;155:38-47. [ABSTRACT FROM AUTHOR]

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 (≥7,000 cells/mm3) 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/mm3). 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. [ABSTRACT FROM PUBLISHER]

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. [ABSTRACT FROM PUBLISHER]

Examines the association of traditional and nontraditional risk factors with incidence of coronary heart disease in adults with diabetes. Identification of levels of albumin, fibrinogen and von Willebrand factor, factor VIII activity and leukocyte count as predictors of coronary heart disease among persons with diabetes; Inflammatory reaction or microvascular injury related to atherosclerosis.

Presents information on a study that tested the hypothesis that diabetes, body fat distribution, and (in non-diabetic subjects) fasting insulin levels are positively associated with ischemic stroke incidence in the general population. Research design and methods; Results; Conclusions.