Gender differences of disturbed hemostasis related to fasting insulin level in healthy very elderly Japanese aged ≥75 years

We investigated the relationship between fasting insulin level and various hemostatic factors, including fibrinolytic factors (active plasminogen activator inhibitor-1 (PAI-1), tissue type plasminogen activator (tPA)-PAI-1 complex, plasmin-α₂-plasmin inhibitor (PIC), and D-dimer), coagulation factors (activated factor VII, factor VII coagulant activity and antigen, factor VIII, factor X, and fibrinogen), coagulation inhibitors (antithrombin III, heparin cofactor II, and protein C), and an acute phase marker (sialic acid) in 102 healthy individuals aged ≥ 75 years (46 men and 56 women). Active PAI-1 levels had a significant negative correlation with PIC levels (r = -0.342, P = 0.0006), indicating that PAI-1 influences in vivo fibrinolytic activity in the very elderly. Gender differences were found in the relationship between insulin and hemostatic abnormalities, with the insulin level being positively correlated with coagulation factors in men (factor VIII activity: r = 0.422, P < 0.01; factor VII activity: r = 0.386, P < 0.01) and with hypofibrinolysis in women (active PAI-1: r = 0.549, P < 0.0001). Insulin levels were positively correlated with the levels of factor VII antigen and factor VII activity in men (P < 0.01), but there was no correlation with activated factor VII levels. The fasting insulin level was also correlated with the levels of heparin cofactor II and sialic acid in men (P < 0.05). However, other hemostatic factors were not related to the insulin level in either sex. Multiple linear regression analysis disclosed that insulin showed an independent positive correlation with factor VIII activity in men (P < 0.001) and with active PAI-1 in women (P < 0.0001). These relationships would seem likely to increase the risk of cardiovascular disease, but they were found in healthy very elderly subjects without cardiovascular disease. Thus, these relationships may develop as part of the normal aging process and abnormal hemostasis should be recognized as one of the characteristics of the insulin resistance syndrome.