Endothelial haemostatic markers in members of families with familial combined hyperlipidemia.
BACKGROUND
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.
Karásek
David
D
3rd Department of Internal Medicine, University Hospital, I. P. Pavlova 6, Olomouc 77520, Czech Republic. david.karasek@fnol.cz
Vaverková
Helena
H
Halenka
Milan
M
Slavík
Ludek
L
Novotný
Dalibor
D
D000328:Adult; D050197:Atherosclerosis / Q000097:blood / Q000209:etiology / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood; D004730:Endothelium, Vascular / Q000503:physiopathology; D005260:Female; D006487:Hemostasis; D006801:Humans; D006950:Hyperlipidemia, Familial Combined / Q000097:blood* / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D012307:Risk Factors; D018180:Thrombomodulin / Q000097:blood; D010959:Tissue Plasminogen Activator / Q000097:blood; D017539:Tunica Intima / Q000473:pathology; D055815:Young Adult; D014841:von Willebrand Factor / Q000378:metabolism
D015415:Biomarkers; D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; D018180:Thrombomodulin; D014841:von Willebrand Factor; D010959:Tissue Plasminogen Activator