Association Between Increased Homocysteine Levels and Impaired Fibrinolytic Potential: Potential Mechanism for Cardiovascular Risk
Geoffrey H. Tofler
1
Royal North Shore Hospital, Australia
,
Ralph B. D’Agostino
2
Boston University Department of Mathematics
,
Paul F. Jacques
3
USDA Human Nutrition Research Center on Aging at Tufts University
,
Andrew G. Bostom
3
USDA Human Nutrition Research Center on Aging at Tufts University
,
Peter W. F. Wilson
4
National Heart, Lung and Blood Institute’s Framingham Heart Study
,
Izabela Lipinska
5
Beth Israel Deaconess Medical Center
,
Murray A. Mittleman
5
Beth Israel Deaconess Medical Center
,
Jacob Selhub
3
USDA Human Nutrition Research Center on Aging at Tufts University
› InstitutsangabenThis work was supported by a Grant-in-Aid from the American Heart Association (92011960) and the National Institutes of Health (RO1-HL-48157)
Elevated homocysteine levels increase cardiovascular risk although the mechanism is not well understood. Since thrombosis plays an important role in plaque development and acute coronary syndromes, hyperhomocysteinemia may increase risk by increasing the thrombotic potential.
Methods and Results
Hemostatic risk factors were measured in 3216 individuals (1451 men and 1765 women) free of cardiovascular disease who participated in cycle 5 of the Framingham Offspring Study. An increase in homocysteine level was associated with a rise in plasminogen activator inhibitor (PAI-1), tissue plasminogen activator (TPA) antigen, von Willebrand factor and fibrinogen level. After regression analyses adjusting for covariates, there remained significant associations between homocysteine and PAI-1 and TPA antigen.
Conclusion
Increasing homocysteine levels are associated with impaired fibrinolytic potential, as indicated by increased PAI-1 and TPA antigen levels. These data suggest that folic acid and other homocysteine lowering therapies may decrease cardiac events through a reduction in thrombotic tendency.
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