Understanding the Complexity of Homocysteine Lowering With Vitamins The Potential Role of Subgroup Analyses

Stroke Prevention & Atherosclerosis Research Centre, Robarts Research Institute, University of Western Ontario, 1400 Western Rd, London, ON, Canada N6G 2V2.
JAMA The Journal of the American Medical Association (Impact Factor: 29.98). 12/2011; 306(23):2610-1. DOI: 10.1001/jama.2011.1834
Source: PubMed
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    ABSTRACT: Hyperhomocystemia has been reported to be associated with cardiovascular disease, especially stroke. The resistive index (RI) estimated by carotid ultrasound is an established variable for estimating the risk of cerebral infarction. The aim of this study was to evaluate the relationship between homocysteine concentration and carotid RI, a marker of cerebral vascular resistance in essential hypertensive patients. We measured serum total homocysteine and carotid RI in 261 patients. Multiple linear regression analysis was used to determine the association of homocysteine with carotid RI and intima media thickness (IMT). Age, sex, BMI, systolic blood pressure (SBP), homocysteine, total cholesterol, high density lipoprotein-cholesterol (HDL-C), uric acid, CRP, HbA1c, estimated glomerular filtration rate, and use of antihypertensive agents were included as independent variables. Age, sex, use of antihypertensive agents, HDL-C and homocysteine levels were shown to be significant predictors of carotid RI, but not IMT. Multiple regression analysis in men older than 65 years showed homocysteine and SBP were associated significantly with carotid RI. In elderly male patients, homocysteine was the strongest predictor of carotid RI (B = 0.0068, CI = 0.0017-0.0120, P = 0.011) in the multivariate model. In conclusion, hyperhomocysteinemia is associated with carotid RI, a surrogate marker of cerebral vascular resistance, especially in elderly men.
    Scientific Reports 07/2014; 4:5663. DOI:10.1038/srep05663 · 5.08 Impact Factor
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    ABSTRACT: Background: Clinical trials have failed to show a benefit of B vitamin therapy in reducing composite outcomes of cardiovascular death, myocardial infarction, and stroke among stroke survivors with elevated total serum homocysteine (tHcy) levels. Recent post hoc analyses have shown that numerous factors including age, baseline tHcy levels, folic acid fortification of grains, B12 status, renal function, comorbidities, and medications may modify the effect of B vitamin therapy on vascular risk in individuals with high tHcy. It remains possible that tHcy-lowering therapy may reduce cardiovascular risk in certain subgroups of stroke survivors. Post hoc subgroup analysis of the Heart Outcomes Prevention Evaluation-2 randomized controlled trial, which randomized participants with known cardiovascular disease to tHcy-lowering therapy or placebo, revealed larger treatment benefit for patients aged younger than 69 years; however, that analysis did not control for other factors. The aim of this study was to determine the effect of age on the impact of tHcy-lowering therapy for reducing vascular risk after stroke while controlling for other factors known to modify the effect of tHcy and tHcy-lowering therapy on vascular risk. Methods: In this post hoc analysis of the Vitamin Intervention for Stroke Prevention (VISP) trial, a randomized controlled trial of tHcy lowering for secondary stroke prevention, we excluded individuals who had poor renal function (glomerular filtration rate <47; the 10th percentile) or were treated with vitamin B12 injections. We assessed the effects of high-dose vitamin replacement on primary (stroke, myocardial infarction, or death) and secondary (stroke) outcomes, after stratifying by age (< vs. ≥ median age, 67 years) and adjusting for demographic and clinical factors. Results: This subgroup consisted of 2,993 individuals. Among individuals older than 67 years, high-dose vitamin therapy was associated with reduced risk of stroke, myocardial infarction or death (adjusted HR 0.76, 95% CI 0.58-0.99) and a trend towards reduced likelihood of stroke (adjusted HR 0.86, 95% CI 0.59-1.25). High-dose vitamin therapy did not impact outcomes among individuals younger than 67 years. Conclusions: In this post hoc subgroup analysis of the VISP trial, age modified the association between B vitamin therapy and recurrent vascular risk among stroke survivors with elevated serum tHcy levels. Older individuals with stroke were more likely to benefit from B vitamin therapy than younger individuals. These findings can help inform the future design of clinical trials of tHcy-lowering therapy for cardiovascular risk reduction after stroke. © 2014 S. Karger AG, Basel.
    Cerebrovascular Diseases 04/2014; 37(4):263-267. DOI:10.1159/000360153 · 3.70 Impact Factor
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    ABSTRACT: With the advent of new oral anticoagulants, the place of warfarin for stroke prevention in patients with atrial fibrillation needs re-evaluation. Warfarin is difficult to use, because of large individual differences in response and metabolism, many significant interactions with drugs and foods, and fluctuations in vitamin K absorption. It requires frequent blood testing and dose adjustments, so with good reason patients and physicians are eager for the newer agents that are easier to use. However, the purchase price of the new anticoagulants is so high that warfarin will remain in widespread use. It is important therefore for physicians to know how to use it well. Anticoagulants work much better for stroke prevention in atrial fibrillation than do antiplatelet agents; physicians need to understand the concept of red thrombus (for which anticoagulants are required) versus white thrombus-platelet aggregates-which are the target of antiplatelet agents. Stroke from atrial fibrillation increases steeply with age, and the elderly benefit disproportionately from anticoagulation. It is still necessary for physicians to know how to use warfarin, and to use it better than it has been used in the past.
    Journal of Neural Transmission 10/2012; 120(10). DOI:10.1007/s00702-012-0941-5 · 2.87 Impact Factor