The influence of dietary fat on postprandial lipaemia and factor VII coagulant activity in human subjects.

Factor VII coagulant activity (FVIIc) is a potent risk factor for heart disease. The Northwick Park Heart Study (NPHS) found that elevated levels of FVIIc are associated with increased risk of fatal IHD, particularly in men over the age of 55 years and this association was stronger than that for plasma cholesterol (Meade et al. 1986). Subsequent studies have confirmed this association (Meade et al. 1993). Factor VII is a key factor in the coagulation cascade. The coagulant glycoprotein factor VII circulates as a single-chain zymogen at a concentration of about 450 n g / d with about 4ng/ml present in normal plasma as an activated two-chain form, factor VIIa (FVIIa; Broze, 1994). The coagulation cascade can be initiated when FVIIa forms a complex with its cofactor, tissue factor (TF). The FVIIa-TF complex then cleaves factors IX and X to their active enzymes (IXa and Xa respectively), thereby inducing the conversion of prothrombin (Davie, 1995). In the presence of TF and a physiological concentration of Ca2+, factor Xa can activate the single-chain factor VII, thus accelerating the generation of prothrombin. FVIIa can also be generated in the absence of TF by enzymes involved in the contact system of coagulation, factors XIIa or IXa. The contact system can be activated in vitro when citrated plasma is incubated in the presence of a negatively-charged surface such as glass. During incubation of citrated plasma in the presence of a contact surface, the activation of factor XI1 and the sequential activation of factors XI and IX results in activation of factor VII (Thomson, 1980). There are several measurements of factor VII which need describing. Plasma FVIIc can be measured in the presence of TF and an appropriate factor VII-deficient substrate such that the test plasma’s FVIIa is rate-limiting, and related to the recorded clotting time. FVIIc and FVIIa are not synonymous. FVIIa is quantitative, whereas FVIIc is qualitative and is influenced also by the concentration of factor VII zymogen. In practice, most studies have measured FVIIc. A striking feature of FVIIc is its positive association with plasma triacylglycerol (TAG) concentration (Table 1). Treatment of hypertriacylglycerolaemia leads to a fall in FVIIc (Elkeles et al. 1980; Simpson et al. 1983; Andersen et al. 1990). This suggests that the relationship is causal. Thus, a fat-rich meal is frequently followed by transient increases in the levels of plasma TAG and WIIa without any change in the factor VII zymogen concentration (Sanders et al. 1996). However, when the diet is habitually rich in fat, an increase in the fasting level of factor VII zymogen also occurs (Miller et al. 1986, 1989).