Endothelial haemostatic markers in members of families with familial combined hyperlipidemia

Abstract

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.