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. The criteria for this subgroup were defined before any data analysis. Methods - For this analysis, we excluded patients with low and very high B12 levels at baseline (\u3c250 and \u3e637 pmol/L, representing the 25th and 95th percentiles), to exclude those likely to have B12 malabsorption or to be taking B12 supplements outside the study and patients with significant renal impairment (glomerular filtration rate \u3c46.18; the 10th percentile). Results - This subgroup represents 2155 patients (37% female), with a mean age of 66±10.7 years. For the combined end point of ischemic stroke, coronary disease, or death, there was a 21% reduction in the risk of events in the high-dose group compared with the low-dose group (unadjusted P=0.049; adjusted for age, sex, blood pressure, smoking, and B12 level P=0.056). In Kaplan-Meier survival analysis comparing 4 groups, patients with a baseline B12 level at the median or higher randomized to high-dose vitamin had the best overall outcome, and those with B12 less than the median assigned to low-dose vitamin had the worst (P=0.02 for combined stroke, death, and coronary events; P=0.03 for stroke and coronary events). Conclusions - In the era of folate fortification, B12 plays a key role in vitamin therapy for total homocysteine. Higher doses of B12, and other treatments to lower total homocysteine may be needed for some patients. © 2005 American Heart Association, Inc

Absolute and Attributable Risks of Heart Failure Incidence in Relation to Optimal Risk Factors

Epidemiologic studies have shown that a large proportion of coronary heart disease and stroke events are explained by borderline or elevated risk factors, and that adults with optimal risk factors greatly avoid these events. The degree to which this applies to heart failure incidence is not well documented

Effect of Correcting for Long-Term Variation in Major Coronary Heart Disease Risk Factors: Relative Hazard Estimation and Risk Prediction in the Atherosclerosis Risk in Communities Study

To examine the effect of correcting coronary heart disease (CHD) risk factors for long-term within-person variation on CHD risk

Assessment of pre- and post-methionine load homocysteine for prediction of recurrent stroke and coronary artery disease in the Vitamin Intervention for Stroke Prevention Trial

Methionine (Met) loading increases total plasma homocysteine (tHcy) and assesses homocysteine metabolism. We tested the hypothesis that pre- or post-Met tHcy will predict recurrent stroke or coronary artery disease (CAD) in a subgroup analysis of the Vitamin Intervention for Stroke Prevention (VISP) trial. VISP subjects with non-disabling stroke underwent measurement of tHcy at baseline (fasting pre- and post-Met load) and were randomized to high/low-dose B-vitamin therapy for prevention of recurrent stroke or CAD. In the sample cohort of 2,124 subjects, mean ± SD tHcy levels in µmol/L were: pre-Met 13.2 ± 4.3, post-Met 30.4 ± 9.76, and pre/post-Met Δ 17.1 ± 8.3. The hazard ratio (HR) for recurrent stroke was 1.16 (p=0.026) for 1 SD higher pre-Met tHcy and 1.15 (p=0.054) for 1 SD higher post-Met tHcy. For CAD, the HR for 1 SD higher pre-Met tHcy was 1.27 (p=0.001) and was 1.00 (p=0.99) for post-Met tHcy. In survival analyses using pre- or post-Met as covariates, the coefficient of pre/post-Met Δ was not significant for stroke and was only marginally significant for CAD (p<0.08), but was negative. We conclude that fasting, pre-Met tHcy is as effective as post-Met tHcy or pre/post-Met Δ in predicting the risk for stroke and CAD

Influence of single nucleotide polymorphisms in factor VIII and von Willebrand factor genes on plasma factor VIII activity: the ARIC Study

Factor VIII (FVIII) functions as a cofactor for factor IXa in the contact coagulation pathway and circulates in a protective complex with von Willebrand factor (VWF). Plasma FVIII activity is strongly influenced by environmental and genetic factors through VWF-dependent and independent mechanisms. Single nucleotide polymorphisms (SNPs) of the coding and promoter sequence in the FVIII gene have been extensively studied for effects on FVIII synthesis, secretion, and activity, but impacts of non–disease-causing intronic SNPs remain largely unknown. We analyzed FVIII SNPs and FVIII activity in 10 434 healthy Americans of European (EA) or African (AA) descent in the Atherosclerosis Risk in Communities (ARIC) study. Among covariates, age, race, diabetes, and ABO contributed 2.2%, 3.5%, 4%, and 10.7% to FVIII intersubject variation, respectively. Four intronic FVIII SNPs associated with FVIII activity and 8 with FVIII-VWF ratio in a sex- and race-dependent manner. The FVIII haplotypes AT and GCTTTT also associated with FVIII activity. Seven VWF SNPs were associated with FVIII activity in EA subjects, but no FVIII SNPs were associated with VWF Ag. These data demonstrate that intronic SNPs could directly or indirectly influence intersubject variation of FVIII activity. Further investigation may reveal novel mechanisms of regulating FVIII expression and activity

Military Combat and Risk of Coronary Heart Disease and Ischemic Stroke in Aging Men: The Atherosclerosis Risk in Communities (ARIC) Study

To assess the long-term association of military combat stress with coronary heart disease (CHD) and ischemic stroke (IS)

Military combat and burden of subclinical atherosclerosis in middle aged men: The ARIC Study

Studies of the cardiovascular consequences of combat stress are few and inconclusive

Hyperglycemia and arterial stiffness: The Atherosclerosis Risk in the Communities study

Hyperglycemia has been associated with an increased risk of cardiovascular morbidity and mortality. Although numerous studies have demonstrated that hyperglycemia is associated with the atherosis component of atherosclerosis, limited studies have addressed the independent role of hyperglycemia in the pathophysiology of sclerotic vascular disease. We hypothesized that hyperglycemia, as assessed by hemoglobin A1c (HbA1c), would be independently associated two common indices of arterial stiffness (pressure-strain elastic modulus (Ep) and Young’s elastic modulus (YEM))

A Clinical Risk Score for Atrial Fibrillation in a Biracial Prospective Cohort (from the Atherosclerosis Risk In Communities [ARIC] Study)

A risk score for AF has been developed by the Framingham Heart Study; however the applicability of this risk score, derived from whites, to predict new-onset AF in non-whites is uncertain. Therefore, we developed a 10-year risk score for new-onset AF using risk factors commonly measured in clinical practice using 14,546 individuals from the Atherosclerosis Risk in Communities study, a prospective community-based cohort of blacks and whites in the United States. During 10 years of follow-up, 515 incident AF events occurred. The following variables were included in the AF risk score: age, race, height, smoking status, systolic blood pressure, hypertension medication usage, precordial murmur, left ventricular hypertrophy, left atrial enlargement, diabetes, coronary heart disease, and heart failure. The area under the receiver-operating characteristics curve (AUC) of a Cox regression model including the previous variables was 0.78, suggesting moderately good discrimination. The point-based score developed from coefficients in the Cox model had an AUC of 0.76. This clinical risk score for AF in the ARIC cohort compared favorably with the Framingham Heart Study’s AF (AUC=0.68), CHD (AUC=0.63), and hard CHD (AUC=0.59) risk scores and the ARIC CHD risk score (AUC=0.58). In conclusion, we have developed a risk score for AF and have shown that the different pathophysiologies of AF and CHD limit the usefulness of a CHD risk score at identifying individuals at higher risk of AF

Association of Multiple Anthropometrics of Overweight and Obesity With Incident Heart Failure: The Atherosclerosis Risk in Communities Study

The association of central adiposity with incident heart failure (HF) has yet to be studied in a large population-based study