© 2000 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Homocysteine and Lipoprotein(a) Interact to Increase CAD Risk in Young Men and Women
From the Department of Cardiology, Section of Preventive Cardiology and Rehabilitation (J.M.F., K.R., G.L.P., D.L.S.), the Department of Biostatistics and Epidemiology (J.A.M.), and the Department of Cell Biology (D.W.J.), The Cleveland Clinic Foundation, Cleveland, Ohio.
Correspondence to Dennis L. Sprecher, MD, The Cleveland Clinic Foundation, Department of Cardiology, M24, 9500 Euclid Ave, Cleveland, OH 44195. E-mail sprechd{at}.ccf.org
Abstract—A biochemical link
between homocysteine (tHcy) and lipoprotein(a) [Lp(a)] related to
fibrin binding has been proposed. This hypothesis has not been
specifically examined in human subjects. We sought to determine in a
clinical setting whether these risk factors would interact to increase
coronary artery disease (CAD) risk. We performed a
cross-sectional analysis of 750 men and 403 women referred to a
preventive cardiology clinic at the Cleveland Clinic
Foundation, in whom baseline tHcy and Lp(a) data were available.
Logistic regression after adjusting for standard
cardiovascular risk factors was used to estimate the
relative risk of CAD in patients with an Lp(a) 
30 mg/dL and a tHcy
17 µmol/L. Neither isolated high tHcy (odds ratio [OR]=1.06,
P=0.89) nor isolated high Lp(a) (OR=1.15,
P=0.60) appeared to be associated with CAD in women.
However, strong evidence of an association was seen when both risk
factors were present (OR=4.83, P=0.003). Moreover,
this increased risk showed evidence of an interactive effect beyond
that attributable to either additive or multiplicative effects of tHcy
and Lp(a) (P=0.03). In contrast, both elevated tHcy
(OR=1.93, P=0.05) and elevated Lp(a) (OR=1.87,
P=0.01) showed evidence of being independent risk
factors for CAD in men. The presence of both risk factors in men did
not appear to confer additional risk (OR=2.00, P=0.09),
even though ORs as high as 12.4 were observed within specific age
intervals. Consistent with prior studies, tHcy and Lp(a) are
risk factors, either independently or in concert, for CAD in this
clinical population. More significantly, we found evidence that when
both risk factors were present in women, the associated risk was
greater than what would be expected if the 2 risks were simply acting
independently. The absence of such an interactive effect in men may be
due to the confounding effects of age manifested as "survivor
bias." These clinical findings provide insights into the potential
roles of both tHcy and Lp(a) in the pathogenesis of
atherosclerosis.
Key Words: lipoprotein(a) • homocysteine • coronary artery disease • risk factors
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