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: 35.29). 12/2011; 306(23):2610-1. DOI: 10.1001/jama.2011.1834
Source: PubMed
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    • "Subsequently, numerous cross-sectional and case control studies have demonstrated a clear association between total serum homocysteine and the presence of coronary, carotid, and peripheral vascular disease23456. However, a systemic review of 12 randomized controlled trials involving 47,429 participants showed that homocysteine-lowering interventions compared with placebo did not significantly affect non-fatal or fatal myocardial infarction, stroke or death by any cause313233. Clinical benefit of homocysteine lowering therapy is very controversial topics. "
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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 · 5.58 Impact Factor
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    • "In our current meta-analysis, subgroup analyses were also performed on the basis of the factors that could affect the treatment effects [39]. These subgroups analyses suggested that the risk of stroke was significantly reduced if trials including a man/woman ratio of more than 2 or subjects received dose of folic acid less than 1 mg. "
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    ABSTRACT: B vitamins have been extensively used to reduce homocysteine levels; however, it remains uncertain whether B vitamins are associated with a reduced risk of stroke. Our aim was to evaluate the effects of B vitamins on stroke. We systematically searched PubMed, EmBase, and the Cochrane Central Register of Controlled Trials to identify studies for our analysis. Relative risk (RR) was used to measure the effect of B-vitamin supplementation on the risk of stroke. The analysis was further stratified based on factors that could affect the treatment effects. Of the 13,124 identified articles, we included 18 trials reporting data on 57,143 individuals and 2,555 stroke events. B-vitamin supplementation was not associated with a significant reduction in the risk of stroke (RR, 0.91, 95%CI: 0.82-1.01, P = 0.075; RD, -0.003, 95%CI: -0.007-0.001, P = 0.134). Subgroup analyses suggested that B-vitamin supplementation might reduce the risk of stroke if included trials had a man/woman ratio of more than 2 or subjects received dose of folic acid less than 1 mg. Furthermore, in a cumulative meta-analysis for stroke, the originally proposed nonsignificant B-vitamin effect was refuted by the evidence accumulated up to 2006. There is a small effect with borderline statistical significance based on data gathered since 2007. Our study indicates that B-vitamin supplementation is not associated with a lower risk of stroke based on relative and absolute measures of association. Subgroup analyses suggested that B-vitamin supplementation can effectively reduce the risk of stroke if included trials had a man/woman ratio of more than 2 or subjects received dose of folic acid less than 1 mg.
    PLoS ONE 11/2013; 8(11):e81577. DOI:10.1371/journal.pone.0081577 · 3.23 Impact Factor
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    ABSTRACT: With folate supplementation of the grain supply, only 1.7% of the population are deficient in folate(4), and In folate-replete subjects, the key factor determining plasma tHcy is B12(3). Since folate fortification of the grain supply in North America, we showed that serum B12 is directly related with plasma total homocysteine, and patients with lower B12 levels have significantly more carotid plaque than those with higher levels of serum B12(3). Although folate supplementation has not been shown to reduce the risk of myocardial infarction, a meta-analysis showed a significant reduction of stroke(5). In elderly patients with serum B12 in the lowest quartile, 1000 mcg per day of oral B12 is needed to achieve adequate absorption (2). The only clinical trial to use that dose of B12, the HOPE study, showed a 23% reduction of stroke with vitamin therapy (p
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