Vitamin Intervention For Stroke Prevention trial: an efficacy analysis.

Background And Purpose: The Vitamin Intervention for Stroke Prevention trial (VISP) intention-to-treat analysis did not show efficacy of combined vitamin therapy for recurrent vascular events in patients with nondisabling stroke. Reasons for lack of efficacy may have included folate fortification of grain products, inclusion of the recommended daily intake for B12 in the low-dose arm, treatment with parenteral B12 in patients with low B12 levels in both study arms, a dose of B12 too low for patients with malabsorption, supplementation with nonstudy vitamins, and failure of patients with significant renal impairment to respond to vitamin therapy. We conducted an efficacy analysis limited to patients most likely to benefit from the treatment, based on hypotheses arising from evidence developed since VISP was initiated.

Estimation of time-dependent area under the ROC curve for long-term risk prediction.

Sensitivity, specificity, and area under the ROC curve (AUC) are often used to measure the ability of survival models to predict future risk. Estimation of these parameters is complicated by the fact that these parameters are time-dependent and by the fact that censoring affects their estimation just as it affects estimation of survival curves or coefficients of survival regression models. The authors present several estimators that overcome these complications.

Elevated levels of interleukin-18 predict the development of type 2 diabetes: results from the MONICA/KORA Augsburg Study, 1984-2002.

We investigated prospectively the association between serum levels of interleukin (IL)-18 and the risk of type 2 diabetes in a case-cohort study conducted in middle-aged men and women who represented 7,936 participants of the three MONItoring of trends and determinants in CArdiovascular disease (MONICA)/Cooperative Research in the Region of Augsburg (KORA) surveys. Levels of IL-18 were measured in stored samples of 527 case subjects with incident type 2 diabetes and 1,698 noncase subjects. Elevated levels of IL-18 were associated with a significantly increased risk of type 2 diabetes after adjustment for age, sex, survey, BMI, systolic blood pressure, ratio of total cholesterol to HDL cholesterol, physical activity, alcohol intake, smoking status, and parental history of diabetes.

Trends in prehospital delay time and use of emergency medical services for acute myocardial infarction: experience in 4 US communities from 1987-2000.

Background: Prolonged delay in seeking care for acute myocardial infarction (AMI) is associated with decreased use of time-dependent treatments and increased mortality and morbidity.

Methods: Time from symptom onset to arrival at hospital and emergency medical service use were abstracted from medical records of 18,928 patients hospitalized for AMI and captured in the community surveillance component of the ARIC study from 1987 to 2000. A cut point of 4 hours was used to assess clinically relevant delay time recommendations for treatment with current therapies.

Identifying individuals at high risk for diabetes: The Atherosclerosis Risk in Communities study.

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.

Risk factors for cardiovascular event recurrence in the Atherosclerosis Risk in Communities (ARIC) study.

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.

Short-term repeatability of electrocardiographic spatial T-wave axis and QT interval.

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.

Diabetes, glucose, insulin, and heart rate variability: the Atherosclerosis Risk in Communities (ARIC) study.

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.

Prediction of coronary events in a low incidence population. Assessing accuracy of the CUORE Cohort Study prediction equation.

Background: The aims of this paper are to derive a 10-year coronary risk predictive equation for adult Italian men, and to assess its accuracy in comparison with the Framingham Heart Study (FHS) and PROCAM study equations.

Methods: The CUORE study is a prospective fixed-cohort study. Eleven cohorts, from the north and the centre-south of Italy, had been investigated at baseline between 1982 and 1996, adopting MONICA methods to measure risk factors.

The association of spatial T wave axis deviation with incident coronary events. The ARIC cohort.

Background: Although current evidence suggests that the spatial T wave axis captures important information about ventricular repolarization abnormalities, there are only a few and discordant epidemiologic studies addressing the ability of the spatial T wave axis to predict coronary heart disease (CHD) occurrence.

Methods: This prospective study analyzed data from 12,256 middle-aged African American and white men and women, from the Atherosclerosis Risk in Communities Study (ARIC). Following a standardized protocol, resting standard 12-lead, 10-second electrocardiograms were digitized and analyzed with the Marquette GE program.

Trends in the sensitivity, positive predictive value, false-positive rate, and comparability ratio of hospital discharge diagnosis codes for acute myocardial infarction in four US communities, 1987-2000.

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.

Association between alcoholic beverage consumption and incidence of coronary heart disease in whites and blacks: the Atherosclerosis Risk in Communities Study.

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 relation between birth weight and intima-media thickness in middle-aged adults.

Background: Birth weight has been found to be inversely associated with the risk of coronary heart disease and stroke, although the mechanisms for this association remain unclear. Here, we investigate the relation between reported birth weight and atherosclerosis in middle age.

Methods: We included the 9817 participants (age 44-65) in the Atherosclerosis Risk in Communities (ARIC) study who were neither a twin nor born prematurely.

Repeatability of heart rate variability measures.

Due to the sparse data on the repeatability of short and ultra-short term heart rate variability (HRV) measures, we measured the repeatability of common HRV measures derived from 10-second, 2-minute, and 6-minute recordings in 63 healthy men and women, aged 45-64, in Chapel Hill, North Carolina. Three 10-second and 2 six-minute heart rate recordings were obtained during each of 2 visits, separated by 1 to 2 weeks. We partitioned the measurement error into components and computed intraclass correlation coefficients using nested, random effects models.

Prediction of ischemic stroke risk in the Atherosclerosis Risk in Communities Study.

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.

Synergism between smoking and vital exhaustion in the risk of ischemic stroke: evidence from the ARIC study.

Purpose: To examine the synergism between vital exhaustion and cigarette smoking in producing ischemic stroke. Vital exhaustion (VE), a state characterized by unusual fatigue, irritability, and feelings of demoralization, is measured by the Maastricht questionnaire (MQ), a 21-item inventory of symptoms.

Methods: The Atherosclerosis Risk in Communities (ARIC) Study is an ongoing cohort study, initiated in 1987.

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.

Lowering homocysteine in patients with ischemic stroke to prevent recurrent stroke, myocardial infarction, and death: the Vitamin Intervention for Stroke Prevention (VISP) randomized controlled trial.

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 B6), and cobalamin (vitamin B12), given to lower total homocysteine levels, reduce the risk of recurrent stroke over a 2-year period compared with low doses of these vitamins.

Association between symptoms reported in a population questionnaire and future ischemic stroke: the ARIC study.

The association between computer diagnosis derived from a symptom questionnaire and onset of first hospitalized ischemic stroke during follow-up for up to 11 years has been assessed for 11,804 participants in the Atherosclerosis Risk in Communities Study who had no baseline history of stroke. Of these participants, 578 reported prior positive transient ischemic attack/stroke symptoms, and 265 strokes occurred during the years 1987-1998. Adjusted for age, locale, sex, and race, persons with self-reported baseline symptoms had 2.

Risk factors for progression to incident hyperinsulinemia: the Atherosclerosis Risk in Communities Study, 1987-1998.

Hyperinsulinemia is a marker of insulin resistance, a correlate of the metabolic syndrome, and an established precursor of type 2 diabetes. This US study investigated the role of risk factors associated with hyperinsulinemia in cross-sectional studies in progression to incident hyperinsulinemia. Nondiabetic participants from the Atherosclerosis Risk in Communities Study (n = 9,020) were followed from 1987 to 1998 for the development of hyperinsulinemia (fasting serum insulin > or = 90th percentile, 19.

Inflammation markers predict increased weight gain in smoking quitters.

Objective: Undesirable weight gain often follows smoking cessation. We investigated whether weight gain after smoking cessation is greater in those with higher levels of inflammatory markers.

Research Methods And Procedures: We studied weight gain and risk of a large gain (> or = 90th percentile) over 3 years in a cohort study of 11,687 U.

Hypertension, blood pressure, and heart rate variability: the Atherosclerosis Risk in Communities (ARIC) study.

Dysregulation of the autonomic nervous system has been implicated in the development of hypertension. Heart rate variability is a noninvasive tool to quantitatively estimate cardiac autonomic activity and has been used to document decreased cardiac autonomic activity in hypertension. The ability of decreased heart rate variability to predict incident hypertension has not been well studied, and there are no studies of whether hypertension leads to changes in heart rate variability.

Prediction of coronary heart disease in middle-aged adults with diabetes.

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.

Coronary heart disease risk prediction in the Atherosclerosis Risk in Communities (ARIC) study.

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.

B vitamin status and inflammatory markers.

Limited evidence has suggested that low levels of circulating pyridoxal-5'-phosphate (PLP) may be associated with elevation of the inflammatory marker, C-reactive protein (CRP). We sought to determine whether the reported association of CRP with PLP was specific versus generalizable to other inflammation or hemostasis markers. Among 519 healthy middle aged adults in the Atherosclerosis Risk in Communities (ARIC) Study, we analyzed the cross-sectional relation of homocysteine, plasma and dietary B vitamin levels with multiple markers implicated in inflammation, endothelial dysfunction, or thrombogenesis: CRP, fibrinogen, white blood cell count, intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, factor VIII, and von Willebrand factor.