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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:2783.)
© 2007 American Heart Association, Inc.

Thrombosis

Heritability of Clot Formation, Morphology, and Lysis

The EuroCLOT Study

Angela M. Carter; Charlotte M. Cymbalista; Tim D. Spector; Peter J. Grant on behalf of the EuroCLOT Investigators

From the Academic Unit of Molecular Vascular Medicine (A.M.C., C.M.C., P.J.G.), The LIGHT Laboratories, University of Leeds, UK; and Twin Research & Genetic Epidemiology Unit (T.D.S.), King’s College London, London, UK.

Correspondence to Prof Peter J. Grant, Academic Unit of Molecular Vascular Medicine, The LIGHT Laboratories, University of Leeds. Leeds LS2 9JT, UK. E-mail P.J.Grant{at}leeds.ac.uk

Objective— The relative balance between clot formation and fibrinolysis is considered to reflect thrombotic potential following vascular injury. The aims of the present study were to (1) to determine the contribution of genetic and environmental factors to variance in measures of clot structure/function in the Leeds Family Study, and (2) to determine the relationship between measures of clot structure/function and cardiovascular risk.

Methods and Results— Using high throughput turbidimetric assays, heritabilities of measures of clot formation, clot structure, and clot lysis were 0.30. Fibrinogen contributed to variance in all measures and plasminogen activator inhibitor-1 to variance in lysis variables. Subjects at increased cardiovascular risk due to the presence of the metabolic syndrome (MetS) had increased clot density (MaxAbs_C: 0.358 [0.340, 0.375]au) and prolonged lysis times (Lys_T: 510 [6569, 7939]s) compared with those without MetS (MaxAbs_C: 0.319 [0.310, 0.328]au, P=0.003; Lys_T: 7221 [4884, 5328]s, P<0.001). Furthermore, measures of clot structure/function increased progressively with increasing number of MetS components.

Conclusions— This study indicates that genetic factors contribute modestly to variance in clot structure/function and that clot structure/function is related to presence of the MetS and number of MetS components. Identification of the genetic and environmental factors influencing clot structure/function may further our understanding of the underlying factors predisposing to cardiovascular disease.

Heritabilities of turbidimetric measures of structure/function were 0.30 in the Leeds Family Study. Clot structure/function was related to presence of the metabolic syndrome and number of metabolic syndrome components. Identification of the genetic and environmental factors influencing clot structure/function may further our understanding of factors predisposing to cardiovascular disease.

Key Words: heritability • coagulation • fibrinolysis • metabolic syndrome • cardiovascular disease