Document Detail


Elevated plasma homocysteine levels in patients treated with levodopa: association with vascular disease.
MedLine Citation:
PMID:  12533089     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Hyperhomocysteinemia is a risk factor for vascular disease and potentially for dementia and depression. The most common cause of elevated homocysteine levels is deficiency of folate or vitamin B(12). However, patients with Parkinson disease (PD) may have elevated homocysteine levels resulting from methylation of levodopa and dopamine by catechol O-methyltransferase, an enzyme that uses S-adenosylmethionine as a methyl donor and yields S-adenosylhomocysteine. Since S-adenosylhomocysteine is rapidly converted to homocysteine, levodopa therapy may put patients at increased risk for vascular disease by raising homocysteine levels. OBJECTIVES: To determine whether elevations in plasma homocysteine levels caused by levodopa use are associated with increased prevalence of coronary artery disease (CAD), and to determine what role folate and vitamin B(12) have in levodopa-induced hyperhomocysteinemia. DESIGN/METHODS: Subjects included 235 patients with PD followed up in a movement disorders clinic. Of these, 201 had been treated with levodopa, and 34 had not. Blood samples were collected for the measurement of homocysteine, folate, cobalamin, and methylmalonic acid levels. A history of CAD (prior myocardial infarctions, coronary artery bypass grafting, or coronary angioplasty procedures) was prospectively elicited. We analyzed parametric data by means of 1-way analysis of variance or the t test, and categorical data by means of the Fisher exact test or chi(2) test. RESULTS: Mean +/- SD plasma homocysteine levels were significantly higher in patients treated with levodopa (16.1 +/- 6.2 micro mol/L), compared with levodopa-naïve patients (12.2 +/- 4.2 micro mol/L; P<.001). We found no difference in the plasma concentration of folate, cobalamin, or methylmalonic acid between the 2 groups. Patients whose homocysteine levels were in the higher quartile (>or=17.7 micro mol/L) had increased prevalence of CAD (relative risk, 1.75; 95% confidence interval, 1.08-2.70;P=.04). CONCLUSIONS: Levodopa therapy, rather than PD, is a cause of hyperhomocysteinemia in patients with PD. Deficiency of folate or vitamin B(12) levels does not explain the elevated homocysteine levels in these patients. To our knowledge, this is the first report that levodopa-related hyperhomocysteinemia is associated with increased risk for CAD. These findings have implications for the treatment of PD in patients at risk for vascular disease, and potentially for those at risk for dementia and depression.
Authors:
John D Rogers; Anna Sanchez-Saffon; Alan B Frol; Ramon Diaz-Arrastia
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Archives of neurology     Volume:  60     ISSN:  0003-9942     ISO Abbreviation:  Arch. Neurol.     Publication Date:  2003 Jan 
Date Detail:
Created Date:  2003-01-20     Completed Date:  2003-02-05     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0372436     Medline TA:  Arch Neurol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  59-64     Citation Subset:  AIM; IM    
Affiliation:
Yarmen Center for Parkinson's Disease, Department of Neurology, Beth Israel Medical Center, New York, NY, USA.
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MeSH Terms
Descriptor/Qualifier:
Aged
Aged, 80 and over
Antiparkinson Agents / adverse effects*
Coronary Artery Disease / blood,  epidemiology
Female
Folic Acid / blood
Homocysteine / blood*
Humans
Hyperhomocysteinemia / chemically induced*
Levodopa / adverse effects*
Male
Middle Aged
Parkinson Disease / drug therapy*
Risk Factors
Vitamin B 12 / blood
Grant Support
ID/Acronym/Agency:
R01 AG17861/AG/NIA NIH HHS; R03 MH64889/MH/NIMH NIH HHS
Chemical
Reg. No./Substance:
0/Antiparkinson Agents; 0/Levodopa; 454-28-4/Homocysteine; 59-30-3/Folic Acid; 68-19-9/Vitamin B 12

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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