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Endothelial haemostatic markers in members of families with familial combined hyperlipidemia
Authors:Karásek David  Vaverková Helena  Halenka Milan  Slavík Ludek  Novotný Dalibor
Institution:a 3rd Department of Internal Medicine, University Hospital, I. P. Pavlova 6, Olomouc 77520, Czech Republic
b Department of Hematooncology, University Hospital, Olomouc, Czech Republic
c Department of Biochemistry, University Hospital, Olomouc, Czech Republic
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 (102.483.0-117.0] ng/ml versus 63.531.8-87.3] ng/ml, p < 0.01) and of t-PA (5.12.5-7.9] ng/ml versus 3.41.4-5.8] 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 (75.353.2-92.0] ng/ml versus 48.637.4-85.9] 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.
Keywords:ACE  angiotensin converting enzyme  AI  atherogenic index  ANOVA  analysis of variance  apoB  apolipoprotein B  apoE2  apolipoprotein E2  BMI  body mass index  CCA  common carotid artery  CHD  coronary heart disease  DBP  diastolic blood pressure  ELISA  enzyme-linked immunosorbent assay  FCH  familial combined hyperlipidemia  FMD  flow mediated dilatation  HDL  high density lipoprotein  HDL-C  HDL cholesterol  HL  hyperlipidemic members of FCH families  HOMA  homeostasis model assessment  hs-CRP  high sensitivity C reactive protein  IMT  intima-media thickness  IRMA  immunoradiometric assay  LDL  low density lipoprotein  LDL-C  LDL-cholesterol  MONICA study  monitoring of trends and determinants in cardiovascular diseases study  NL  normolipidemic members of FCH families  non-HDL-C  non-HDL cholesterol  PAI-1  plasminogen activator inhibitor-1  RIA  radioimmune assay  SBP  systolic blood pressure  s-TM  soluble thrombomodulin  TC  total cholesterol  TG  triglycerides  t-PA  tissue plasminogen activator  vWF  von Willebrand factor  
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