Neurological Research A Journal of Progress in Neurosurgery, Neurology and Neurosciences
ISSN: 0161-6412 (Print) 1743-1328 (Online) Journal homepage: http://www.tandfonline.com/loi/yner20
Hyperhomocysteinemia as a risk factor for stroke Lars Brattström & Arne Lindgren To cite this article: Lars Brattström & Arne Lindgren (1992) Hyperhomocysteinemia as a risk factor for stroke, Neurological Research, 14:2, 81-84, DOI: 10.1080/01616412.1992.11740017 To link to this article: http://dx.doi.org/10.1080/01616412.1992.11740017
Published online: 23 Jul 2016.
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Citing articles: 10 View citing articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=yner20 Download by: [Australian Catholic University]
Date: 18 August 2017, At: 01:18
Hyperhomocys teinemia as a risk factor for stroke Lars Brattstrom and Arne Lindgren Neurological Section, Department of Medicine, County Hospital, Kalmar, and Department of Neurology, University Hospital, Lund, Sweden
Downloaded by [Australian Catholic University] at 01:18 18 August 2017
Keywords :Hyperhomocysteinemia; risk factor; stroke
INTRODUCTION Inherited severe hyperhomocysteinemia (also known as homocystinuria) frequently leads to stroke in children and youngsters 1 - 3 . Accordingly, the hypothesis has been put forward that even mild hyperhomocysteinemia may predispose for stroke 4 .1ndeed, the results of several recent controlled studies have uniformly shown cerebrovascular disease in adults to be frequently associated with abnormally high plasma homocystei ne concentrations 4 - 11 . It has also been shown that increased homocysteine concentrations easil¥ can be normalized with innocuous vitamins 8· 12 - 1 . These findings strongly suggest that hyperhomocysteinemia is a treatable risk factor for stroke in the general population. Here, this interesting issue is briefly reviewed.
early onset arteriosclerosis, and life-threatenin? thromboembolisms frequently leading to stroke1 •2 •1 . In cystathionine ,B-synthase deficiency, more than 50% of patients will suffer a vascular event bef ore the age of 30 years, stroke being much more frequent than myocardial infarction 2 . High doses of vitamin B6, folic acid and I or betaine are effective homocysteinelowering agents in cystathionine ,B-syntase deficiency, whereas patients with remethylation defects mostly respond to therapy with vitamin B1 2 , folic acid, and / or betaine1 •19 . Such therapy seems to be effective in preventing vascular disease2 . Because of this, and the results obtained in experimental studies both in vitro and in vivo, homocysteine or its derivatives are generally considered to cause vascular injury, arteriosclerosis and thromboembolism 1•17 .
HOMOCYSTEINE METABOUSM In man, about 15 to 20 mmol of homocysteine is formed daily, by demethylation of the amino acid methionine (Figure 1 )16, the homocysteine being rar,idly catabolized or again remethylated to methionine 7 . Cystathioni ne ,B-synthase, a vitamin B6 -dependent enzyme, catalyses the first catabolic step (Figure 1, reaction 1 ). In most tissues, a vitamin B12- and folate-dependent reaction accounts for the remethylation (reaction 2). In the liver, homocysteine is also remethylated from betaine. Excess homocysteine is rapidly exported to the extracellular fluids, and the plasma homocysteine concentration is considered to be a sensitive marker of homocysteine metabolism 17 . In plasma, most homocysteine forms disulphides (Figure 1). Normally, the total plasma homocysteine concentration is 5-15 ,umol / 1, and is slightly higher in men than in women 17-18_
IS MILD HYPERHOMOCYSTEINEMIA A RISK FACTOR FOR STROKE? However, an important question is: in the general population does mild impairment of homocysteine metabolism predispose for stroke? On average, heterozygotes for cystathionine ,B-synthase deficiency manifest 30% of normal enzyme activity, respond to oral methionine loading with higher post-load plasma
METHIONINE HOMOCYSTEINE· SH METHIONINE
~,f
''"'
HOMOCYSTEINE
STROKE AS A CONSEQUENCE OF INHERITED SEVERE HYPERHOMOCYSTEINEMIA Inherited deficiency either of cystathione ,B-syntase (blocking homocysteine catabolism ) or of certain enzymes involved in folate and vitamin B1 2 metabolism (impairing the remethylation of homocysteine to methionine) results in severe hyperhomocysteinem ia,
Correspondence to: Dr Lars Brattstr6m, MD, Neurological Section, Department of Medicine, County Hospital, S-391 85 Kalmar, Sweden. Accepted for publication December 1991.
© 1992 Forefront Publishing Croup 0161-6412/92/ 020081 -04
eDt
CYSTATHIONINE
~
•
FREE
HOMOCYSTEINE · SS ·CYSTEINE
25%
HOMOCYSTEINE · SS • HOMOCYSTEINE
--#-
ISSN: 0161-6412 (Print) 1743-1328 (Online) Journal homepage: http://www.tandfonline.com/loi/yner20
Hyperhomocysteinemia as a risk factor for stroke Lars Brattström & Arne Lindgren To cite this article: Lars Brattström & Arne Lindgren (1992) Hyperhomocysteinemia as a risk factor for stroke, Neurological Research, 14:2, 81-84, DOI: 10.1080/01616412.1992.11740017 To link to this article: http://dx.doi.org/10.1080/01616412.1992.11740017
Published online: 23 Jul 2016.
Submit your article to this journal
View related articles
Citing articles: 10 View citing articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=yner20 Download by: [Australian Catholic University]
Date: 18 August 2017, At: 01:18
Hyperhomocys teinemia as a risk factor for stroke Lars Brattstrom and Arne Lindgren Neurological Section, Department of Medicine, County Hospital, Kalmar, and Department of Neurology, University Hospital, Lund, Sweden
Downloaded by [Australian Catholic University] at 01:18 18 August 2017
Keywords :Hyperhomocysteinemia; risk factor; stroke
INTRODUCTION Inherited severe hyperhomocysteinemia (also known as homocystinuria) frequently leads to stroke in children and youngsters 1 - 3 . Accordingly, the hypothesis has been put forward that even mild hyperhomocysteinemia may predispose for stroke 4 .1ndeed, the results of several recent controlled studies have uniformly shown cerebrovascular disease in adults to be frequently associated with abnormally high plasma homocystei ne concentrations 4 - 11 . It has also been shown that increased homocysteine concentrations easil¥ can be normalized with innocuous vitamins 8· 12 - 1 . These findings strongly suggest that hyperhomocysteinemia is a treatable risk factor for stroke in the general population. Here, this interesting issue is briefly reviewed.
early onset arteriosclerosis, and life-threatenin? thromboembolisms frequently leading to stroke1 •2 •1 . In cystathionine ,B-synthase deficiency, more than 50% of patients will suffer a vascular event bef ore the age of 30 years, stroke being much more frequent than myocardial infarction 2 . High doses of vitamin B6, folic acid and I or betaine are effective homocysteinelowering agents in cystathionine ,B-syntase deficiency, whereas patients with remethylation defects mostly respond to therapy with vitamin B1 2 , folic acid, and / or betaine1 •19 . Such therapy seems to be effective in preventing vascular disease2 . Because of this, and the results obtained in experimental studies both in vitro and in vivo, homocysteine or its derivatives are generally considered to cause vascular injury, arteriosclerosis and thromboembolism 1•17 .
HOMOCYSTEINE METABOUSM In man, about 15 to 20 mmol of homocysteine is formed daily, by demethylation of the amino acid methionine (Figure 1 )16, the homocysteine being rar,idly catabolized or again remethylated to methionine 7 . Cystathioni ne ,B-synthase, a vitamin B6 -dependent enzyme, catalyses the first catabolic step (Figure 1, reaction 1 ). In most tissues, a vitamin B12- and folate-dependent reaction accounts for the remethylation (reaction 2). In the liver, homocysteine is also remethylated from betaine. Excess homocysteine is rapidly exported to the extracellular fluids, and the plasma homocysteine concentration is considered to be a sensitive marker of homocysteine metabolism 17 . In plasma, most homocysteine forms disulphides (Figure 1). Normally, the total plasma homocysteine concentration is 5-15 ,umol / 1, and is slightly higher in men than in women 17-18_
IS MILD HYPERHOMOCYSTEINEMIA A RISK FACTOR FOR STROKE? However, an important question is: in the general population does mild impairment of homocysteine metabolism predispose for stroke? On average, heterozygotes for cystathionine ,B-synthase deficiency manifest 30% of normal enzyme activity, respond to oral methionine loading with higher post-load plasma
METHIONINE HOMOCYSTEINE· SH METHIONINE
~,f
''"'
HOMOCYSTEINE
STROKE AS A CONSEQUENCE OF INHERITED SEVERE HYPERHOMOCYSTEINEMIA Inherited deficiency either of cystathione ,B-syntase (blocking homocysteine catabolism ) or of certain enzymes involved in folate and vitamin B1 2 metabolism (impairing the remethylation of homocysteine to methionine) results in severe hyperhomocysteinem ia,
Correspondence to: Dr Lars Brattstr6m, MD, Neurological Section, Department of Medicine, County Hospital, S-391 85 Kalmar, Sweden. Accepted for publication December 1991.
© 1992 Forefront Publishing Croup 0161-6412/92/ 020081 -04
eDt
CYSTATHIONINE
~
•
FREE
HOMOCYSTEINE · SS ·CYSTEINE
25%
HOMOCYSTEINE · SS • HOMOCYSTEINE
--#-
