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CLINICAL RESEARCH: CORONARY ARTERY DISEASE

High-Dose Folic Acid Acutely Improves Coronary Vasodilator Function in Patients With Coronary Artery Disease

Ahmed Tawakol, MD^_*,_*, Raymond Q. Migrino, MD, Kusai S. Aziz, MD^_*, Justyna Waitkowska, MD^_*, Gotfred Holmvang, MD^_*, Nathaniel M. Alpert, PhD, James E. Muller, MD^_*, Alan J. Fischman, MD, PhD and Henry Gewirtz, MD^_*

^_* Department of Medicine (Cardiac Unit), Massachusetts General Hospital, Boston, Massachusetts
Department of Radiology, and Nuclear Medicine, Massachusetts General Hospital, Boston, Massachusetts

Manuscript received August 20, 2004; revised manuscript received January 5, 2005, accepted February 1, 2005.

^_* Reprint requests and correspondence: Dr. Ahmed Tawakol, Cardiac Unit/Vincent Burnham 3, Massachusetts General Hospital, Boston, Massachusetts 02114 (Email: atawakol{at}partners.org).

OBJECTIVES: We investigated the acute effect of orally administered high-dose folic acid on coronary dilator function in humans.

BACKGROUND: Folic acid and its active metabolite, 5-methyltetrahydrofolate, increase endothelium-dependent vasodilation in human peripheral circulation. However, the acute effect on coronary circulation is not known.

METHODS: Fourteen patients with ischemic heart disease, age 62 ± 12 years (mean ± SD), were enrolled in a double-blind, placebo-controlled crossover trial. Basal and adenosine-stimulated myocardial blood flow (MBF) were determined by positron emission tomography, and myocardial flow reserve was calculated. Each patient was studied after ingestion of placebo and after ingestion of 30 mg folic acid. Myocardial zones were prospectively defined physiologically as "normal" versus "abnormal" on the basis of MBF response to adenosine 140 µg/kg/min (normal = MBF >1.65 ml/min/g). Abnormal and normal zones were analyzed separately in a patient-based analysis.

RESULTS: Folate was associated with a reduction in mean arterial pressure (100 ± 12 mm Hg vs. 96 ± 11 mm Hg, placebo vs. folate, p < 0.03). Despite the fall in mean arterial pressure, folic acid significantly increased the MBF dose response to adenosine (p < 0.001 using analysis of variance) in abnormal zones, whereas MBF in normal zones did not change. In abnormal segments, folic acid increased peak MBF by 49% (1.45 ± 0.59 ml/min/g vs. 2.16 ± 1.01 ml/min/g, p < 0.02). Furthermore, folate increased dilator reserve by 83% in abnormal segments (0.77 ± 0.59 vs. ml/min/g 1.41 ± 1.08 ml/min/g, placebo vs. folate, p < 0.05), whereas dilator reserve in normal segments remained unchanged (2.00 ± 0.61 ml/min/g vs. 2.12 ± 0.69 ml/min/g, placebo vs. folate, p = NS).

CONCLUSIONS: The data demonstrate that high-dose oral folate acutely lowers blood pressure and enhances coronary dilation in patients with coronary artery disease.

Abbreviations and Acronyms   Ado 140 = adenosine 140 µg/kg/min   MBF = myocardial blood flow   PET = positron emission tomography

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