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Elevated plasma homocysteine levels in patients treated with levodopa: association with vascular disease.
Arch Neurol. 2003 Jan; 60(1):59-64.AN

Abstract

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+Show Affiliations

Yarmen Center for Parkinson's Disease, Department of Neurology, Beth Israel Medical Center, New York, NY, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

12533089

Citation

Rogers, John D., et al. "Elevated Plasma Homocysteine Levels in Patients Treated With Levodopa: Association With Vascular Disease." Archives of Neurology, vol. 60, no. 1, 2003, pp. 59-64.
Rogers JD, Sanchez-Saffon A, Frol AB, et al. Elevated plasma homocysteine levels in patients treated with levodopa: association with vascular disease. Arch Neurol. 2003;60(1):59-64.
Rogers, J. D., Sanchez-Saffon, A., Frol, A. B., & Diaz-Arrastia, R. (2003). Elevated plasma homocysteine levels in patients treated with levodopa: association with vascular disease. Archives of Neurology, 60(1), 59-64.
Rogers JD, et al. Elevated Plasma Homocysteine Levels in Patients Treated With Levodopa: Association With Vascular Disease. Arch Neurol. 2003;60(1):59-64. PubMed PMID: 12533089.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Elevated plasma homocysteine levels in patients treated with levodopa: association with vascular disease. AU - Rogers,John D, AU - Sanchez-Saffon,Anna, AU - Frol,Alan B, AU - Diaz-Arrastia,Ramon, PY - 2003/1/21/pubmed PY - 2003/2/6/medline PY - 2003/1/21/entrez SP - 59 EP - 64 JF - Archives of neurology JO - Arch Neurol VL - 60 IS - 1 N2 - 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. SN - 0003-9942 UR - https://www.unboundmedicine.com/medline/citation/12533089/Elevated_plasma_homocysteine_levels_in_patients_treated_with_levodopa:_association_with_vascular_disease_ L2 - https://jamanetwork.com/journals/jamaneurology/fullarticle/vol/60/pg/59 DB - PRIME DP - Unbound Medicine ER -