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(Circulation. 1997;95:825-830.)
© 1997 American Heart Association, Inc.

Articles

Hypobetalipoproteinemia Is Associated With Low Levels of Hemostatic Risk Factors in the Framingham Offspring Population

Francine K. Welty, MD, PhD; Murray A. Mittleman, MD, DrPH; Peter W.F. Wilson, MD; Patrice A. Sutherland, BS; Travis H. Matheney, MLA; Izabella Lipinska, PhD; James E. Muller, MD; Daniel Levy, MD; Geoffrey H. Tofler, MD

the Cardiovascular Division (F.K.W., M.A.M., P.A.S., T.H.M., I.L., J.E.M., G.H.T.), Institute for the Prevention of Cardiovascular Disease, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Mass; and Framingham Heart Study (P.W.F.W., D.L.), Framingham, Mass.

Correspondence to Dr Francine K. Welty, One Autumn St, 5th Floor, Boston, MA 02215. E-mail fwelty@nedhmail.nedh.harvard.edu.

Background Given the importance of thrombosis in causation of acute coronary syndromes, it is possible that the beneficial effect of low lipid levels on the risk of coronary events is achieved by lowering thrombotic potential of the blood. Hypobetalipoproteinemia is characterized by plasma concentrations of apolipoprotein B and LDL cholesterol that are one third of those observed in the general population. The aim of this study was to utilize subjects with hypobetalipoproteinemia to examine the relation between thrombotic potential and low levels of LDL cholesterol.

Methods and Results Hemostatic risk factors were measured in 1878 individuals (1003 women and 875 men) participating in cycle 5 of the Framingham Offspring Study. The subjects were divided into five groups on the basis of LDL cholesterol level. Subjects with hypobetalipoproteinemia (LDL cholesterol <70 mg/dL) had the lowest levels of fibrinogen, plasminogen activator inhibitor–1 antigen, and tissue plasminogen activator antigen. As LDL cholesterol increased, there was a significant increase in the levels of the hemostatic risk factors, with the exception of von Willebrand factor antigen. Adjustment with multivariate regression analyses for the covariates age, sex, body mass index, diabetes mellitus, smoking, alcohol intake, triglyceride level, and use of antihypertensive medication did not materially alter the results.

Conclusions Decreasing levels of LDL cholesterol are associated with decreasing levels of hemostatic risk factors. Subjects with hypobetalipoproteinemia have the lowest levels of hemostatic risk factors and may be protected against thrombotic complications of atherosclerotic cardiovascular disease because of reduced thrombotic potential. One mechanism by which lipid-lowering therapy may decrease clinical cardiac events is through a reduction in thrombotic tendency.

Key Words: cholesterol • fibrinogen • lipids • plasminogen activator inhibitor • von Willebrand factor

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