Homocysteine Levels in Patients with Stroke
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CNS Drugs 2001; 15 (6) 437-443 1172-7047/01/0006-0437/$22.00/0 © Adis International Limited. All rights reserved.
Homocysteine Levels in Patients with Stroke Clinical Relevance and Therapeutic Implications Graeme J. Hankey1 and John W. Eikelboom2 1 Royal Perth Hospital, and Department of Medicine, University of Western Australia, Perth, Western Australia, Australia 2 Preventive Cardiology and Therapeutics Program, McMaster University, Hamilton, Ontario, Canada
Abstract
High plasma levels of the amino acid homocysteine have been implicated in the development of vascular diseases, including stroke. Elevated plasma levels of total homocysteine (tHcy) above 15 μmol/L are present in less than 5% of the general population, but in as many as 50% of patients with stroke (and other atherothromboembolic vascular diseases). However, it remains uncertain whether a high tHcy level is a causal risk factor for stroke and should be lowered, or is a marker of another factor associated with stroke (e.g. acute tissue damage or tissue repair after an acute vascular event) and therefore should not be lowered. Plasma levels of tHcy can be lowered effectively by folic acid, vitamin B6 and vitamin B12 supplementation, and controlled trials have shown some beneficial effects on surrogate markers of vascular function. However, these markers are not established vascular risk factors or valid predictors of ‘hard’ clinical vascular outcome events. Until it has been shown in large randomised trials [such as the ongoing Vitamins to Prevent Stroke Study (VITATOPS) and the Vitamins in Stroke Prevention (VISP) study] that multivitamin therapy reduces the rate of recurrent stroke and other serious vascular events in patients with prior stroke or transient ischaemic attack, widespread screening for, and treatment of, high tHcy levels remains experimental and cannot be recommended.
1. Stroke: A Major Public Health Problem and a Looming Epidemic Stroke is a clinical syndrome characterised by: (i) rapidly developing symptoms and signs of focal, and at times global (as may be seen in patients in coma or with subarachnoid haemorrhage) loss of
brain function; (ii) symptoms lasting >24 hours or leading to earlier death; and (iii) no apparent cause other than that of vascular origin.[1,2] Each year, stroke affects about 0.2% of the population (2000 individuals per million),[3] of whom about one-third die over the next year, one-third remain permanently disabled, and one-third make
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a reasonable recovery.[2,4] The one-third of affected individuals who die (700 per million per year) make stroke the second most common cause of death throughout the world (behind ischaemic heart disease), causing 4.4 million (9%) of a total of 50.5 million deaths each year.[5] The two-thirds of individuals who survive a stroke (1300 per million per year) add to a large pool of prevalent stroke survivors (about 1.2% of the population, or 12,000 per million), of whom at least half are disabled.[6] This makes stroke the most important single cause of severe disability in
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