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In Reply: Drs Chellappa and Ramaraj raise the interesting hypothesis that elevated homocysteine concentrations may contribute to the excess risk of cardiovascular events associated with depressive symptoms. We measured red blood cell folic acid levels in 1012 participants in the Heart and Soul Study and found that the 198 patients with depressive symptoms (Patient Health Questionnaire score 10) had lower mean folic acid levels than the 814 patients without depressive symptoms (578 vs 615 ng/mL [to convert to nmol/L, multiply by 2.266]; t test P = .02). This finding is consistent with the hypothesis that lower folic acid levels (and higher homocysteine concentrations) may be partly responsible for an increased risk of cardiovascular events associated with depressive symptoms.

However, adjusting for folic acid levels did not change the strength of association between depressive symptoms and cardiovascular events (heart failure, myocardial infarction, stroke, transient ischemic attack, or death). During a mean (SD) . . . [Full Text of this Article]

Mary A. Whooley, MD
mary.whooley@ucsf.edu
VA Medical Center
San Francisco, California

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