Introduction: The aim of this study was to evaluate the plasma levels of endothelial haemostatic markers - von Willebrand factor (vWF), plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (t-PA) and soluble thrombomodulin (sTM) - in asymptomatic, nonsmoking members of families with familial combined hyperlipidemia (FCH). We investigated the association between these factors and the intima-media thickness (IMT) of the common carotid artery, selected risk factors of atherosclerosis and markers of insulin resistance.
Methods: 82 members of 29 FCH families were divided into two groups: HL (probands and hyperlipidemic first-degree relatives, n=47) and NL (normolipidemic first-degree relatives, n=35). The control groups C-HL (n=20) and C-NL (n=20) consisted of sex- and age-matched healthy individuals. IMT was measured by ultrasound at a far wall of both common carotid arteries.
Results: Compared with healthy controls, hyperlipidemic subjects had significantly higher levels of vWF (146.4+/-73.2% versus 112.2+/-29.4%, p<0.05), of PAI-1 (102.4[83.0-117.0] ng/ml versus 63.5[31.8-87.3] ng/ml, p<0.01) and of t-PA (5.1[2.5-7.9] ng/ml versus 3.4[1.4-5.8] ng/ml, p<0.05). They had increased IMT, which correlated with vWF (r=0.29, p<0.05). Their normolipidemic relatives had significantly higher levels of vWF (137.2+/-42.8% versus 106.6+/-24.0%, p<0.01) and of PAI-1 (75.3[53.2-92.0] ng/ml versus 48.6[37.4-85.9] ng/ml, p<0.05). Levels of vWF, PAI-l and t-PA were independently associated with several markers of insulin resistance.
Conclusions: Asymptomatic members of FCH families have increased endothelial haemostatic factors- vWF, PAI-1, t-PA, which are associated with insulin resistance. VWF correlates with morphological vascular changes, detected by the increase of IMT, presented in only hyperlipidemic subjects.