Patients who take levodopa for Parkinson’s disease and develop elevated levels of homocysteine may be at increased risk for heart disease, according to an article in the January issue of Archives of Neurology. Researchers had hypothesized for some time that levodopa, which can cause an increase in homocysteine level, may ultimately put patients at higher risk for vascular disease.

In the current study, an American research team measured plasma homocysteine levels in 235 patients with Parkinson’s disease. Of the total, 201 had been treated with levodopa, whereas 34 had not used the drug. Before testing, each patient was asked questions to determine whether there was any evidence of coronary artery disease, such as prior myocardial infarction or reperfusion procedure.

Plasma homocysteine level was significantly higher in patients treated with levodopa than in patients who had never been treated with the drug (16.1 micromol/L compared with 12.2 micromol/L). Patients with a homocysteine level in the highest quartile were 75 percent more likely to have coronary artery disease than patients with lower homocysteine levels.

"We did find that there is a statistically modest increased risk of heart disease in Parkinson's patients with elevated homocysteine," said senior study author Ramon Diaz-Arrastia, M.D. He added that the findings indicate that physicians should monitor patients treated with levodopa for evidence of elevated homocysteine level, especially if other risk factors for cardiovascular disease are present.

"This medicine is necessary for parkinsonism," Diaz-Arrastia said. "It is very effective therapy, but physicians may need to pay attention to their patients' homocysteine levels."

The authors also noted that the retrospective nature of the study showed a correlation between levodopa usage, elevated homocysteine levels, and prevalence of heart disease, but it wasn’t possible to determine whether levodopa directly caused vascular disease.

Low levels of vitamin B12 and folic acid are a common cause of elevated homocysteine levels. The investigators compared blood levels of folate, cobalamin, and methylmalonic acid for both groups of patients and found no difference in levels between patients treated with levodopa and those who had not used the drug.

"Homocysteine has gotten a lot of attention over the last 10 years or so as a risk factor for heart disease and has gotten even more attention lately as a risk factor for Alzheimer's disease," Diaz-Arrastia said. He noted that about one third of patients with Parkinson’s develop dementia and said the study raises the question of whether levodopa-induced vascular disease may increase that risk.