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: 30.39). 12/2011; 306(23):2610-1. DOI: 10.1001/jama.2011.1834
Source: PubMed
  • Source
    [Show abstract] [Hide abstract]
    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
  • [Show abstract] [Hide abstract]
    ABSTRACT: The homocysteine theory of arteriosclerosis was discovered by study of arteriosclerotic plaques occurring in homocystinuria, a disease caused by deficiencies of cystathionine synthase, methionine synthase or methylenetetrahydrofolate reductase. According to the homocysteine theory, metabolic and nutritional abnormalities leading to elevation of plasma homocysteine cause atherosclerosis in the general population without these rare enzymatic abnormalities. Through studies of metabolism of homocysteine thiolactone, the anhydride of homocysteine, in cell cultures from homocystinuric children, the pathway for synthesis of sulfate was found to be dependent upon thioretinamide, the amide formed from retinoic acid and homocysteine thiolactone. Two molecules of thioretinamide form the complex thioretinaco with cobalamin, and oxidative phosphorylation is catalyzed by reduction of oxygen, which is bound to thioretinaco ozonide, by electrons from electron transport particles. Atherogenesis is attributed to formation of aggregates of homocysteinylated lipoproteins with microorganisms, which obstruct the vasa vasorum during formation of arterial vulnerable plaques.
    Expert Review of Clinical Pharmacology 02/2015; 8(2):1-9. DOI:10.1586/17512433.2015.1010516
  • Source
    [Show abstract] [Hide abstract]
    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