From the Departments of Cardiology (K.R.) and Biostatistics and
Epidemiology (K.A.), The Cleveland Clinic Foundation, Cleveland, Ohio;
Department of Clinical Biology, Division of Pharmacology (H.R., P.U.),
University of Bergen, Norway; Department of Medicine (L.B.), County Hospital,
Kalmar, Sweden; Department of Endocrinology (G.B.), Katholieke Universiteit,
Nijmegen, Netherlands; Facolta di Medicina e Chirurgia (P.R.), Universita
degli Studi di Napoli, Federico II, Naples, Italy; Servico de Medicina
(R.P.-R.), Hospital de S. Francisco Xavier Lisbon, Portugal; Department of
Cardiology, Adelaide Hospital, Trinity College, Dublin and the Department of
Epidemiology, Royal College of Surgeons in Ireland (R.M., I.G.); Department of
Public Health Medicine and Epidemiology (L.D.), University College Dublin,
Ireland; and Department of Epidemiology (J.W.), Erasmus University Medical
School, Rotterdam, Netherlands.
Correspondence to Killian Robinson, MD, Desk F15, Department of Cardiology, The Cleveland Clinic Foundation, 9500 Euclid Ave, Cleveland, OH 44195. E-mail robinsk{at}ccsmtp.ccf.org
Background—A high plasma
homocysteine concentration is a risk factor for
atherosclerosis, and circulating concentrations of
homocysteine are related to levels of folate and vitamin
B6. This study was performed to explore the
interrelationships between homocysteine, B vitamins, and vascular
diseases and to evaluate the role of these vitamins as risk factors
for atherosclerosis.
Methods—In a multicenter case-control study in Europe, 750
patients with documented vascular disease and 800 control subjects
frequency-matched for age and sex were compared. Plasma levels of total
homocysteine (before and after methionine loading) were determined, as
were those of red cell folate, vitamin B12, and vitamin
B6.
Results—In a conditional logistic regression model, homocysteine
concentrations greater than the 80th percentile for control subjects
either fasting (12.1 µmol/L) or after a methionine load
(38.0 µmol/L) were associated with an elevated risk of vascular
disease independent of all traditional risk factors. In addition,
concentrations of red cell folate below the lowest 10th percentile
(<513 nmol/L) and concentrations of vitamin B6 below the
lowest 20th percentile (<23.3 nmol/L) for control subjects were also
associated with increased risk. This risk was independent of
conventional risk factors and for folate was explained in part by
increased homocysteine levels. In contrast, the relationship between
vitamin B6 and atherosclerosis was
independent of homocysteine levels both before and after methionine
loading.
Conclusions—Lower levels of folate and vitamin B6
confer an increased risk of atherosclerosis. Clinical
trials are now required to evaluate the effect of treatment with these
vitamins in the primary and secondary prevention of vascular diseases.
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports
Low Circulating Folate and Vitamin B6 Concentrations
Risk Factors for Stroke, Peripheral Vascular Disease, and Coronary Artery Disease
Key Words: atherosclerosis • cerebrovascular disorders • coronary disease • peripheral vascular disease • risk factors
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