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Published on: October 12, 2017
Endothelial function in familial combined hyperlipidaemia
E Ter Avest1, S Holewijn, L J H van Tits
1Radboud University, Nijmegen Medical Centre, Nijmegen, The Netherlands.
Insights
Familial combined hyperlipidaemia (FCH) patients do not show impaired endothelial function compared to relatives. Intima-media thickness predicts vascular changes only when plaques are present, questioning flow-mediated dilation
Area of Science:
- Cardiovascular Medicine
- Lipidology
- Vascular Biology
Background:
- Familial combined hyperlipidaemia (FCH) is linked to dyslipidaemia, obesity, insulin resistance, increased intima-media thickness (IMT), and cardiovascular disease risk.
- Early functional vascular changes, such as endothelial dysfunction, are investigated in FCH.
- The relationship between endothelial function, cardiovascular risk factors, and IMT in FCH is explored.
Purpose of the Study:
- To assess endothelial function in patients with FCH compared to unaffected relatives.
- To determine if endothelial function in FCH is related to cardiovascular risk factors or IMT.
- To investigate the predictive value of IMT for endothelial function in FCH.
Main Methods:
- 98 FCH patients and 230 relatives underwent fasting blood draws after drug discontinuation.
- Intima-media thickness (IMT) was measured using B-mode ultrasound.
- Endothelial function was assessed via flow-mediated dilation (FMD) and plasma adhesion molecule concentrations (sVCAM, sICAM, sE-selectin).
Main Results:
- No significant differences in FMD or adhesion molecule levels were observed between FCH patients and relatives.
- Individual cardiovascular risk factors and IMT were not independent predictors of endothelial function in FCH patients.
- Subgroup analysis showed IMT predicted FMD in subjects with carotid artery plaques, but not in those without.
Conclusions:
- FCH patients exhibit normal endothelial function compared to unaffected relatives.
- Intima-media thickness (IMT) predicts flow-mediated dilation (FMD) only in the presence of advanced atherosclerotic changes (plaques).
- The utility of FMD for cardiovascular risk stratification in high-risk populations is questioned.
Background:
Familial combined hyperlipidaemia (FCH) is characterized by dyslipidaemia, visceral obesity and insulin resistance, and is associated with an increased intima-media thickness (IMT) and an increased risk for cardiovascular disease. In the present study, we investigated whether FCH is associated with early functional vascular wall changes, as represented by endothelial dysfunction, and we determined whether endothelial function in FCH is related to any of the cardiovascular risk factors associated with the FCH phenotype, or to the (increased) IMT.
Design:
In 98 patients with FCH [mean age 51 (48-54) years, 43% male] and 230 unaffected relatives [mean age 44 (42-46) years, 48% male], venous blood was drawn in the fasting state after discontinuation of lipid lowering drugs for at least 4 weeks (if used). IMT was measured by B-mode ultrasound and endothelial function was assessed by determination of flow mediated dilation (FMD) and by measurement of plasma concentrations of various soluble adhesion molecules, including soluble vascular cell adhesion molecule (sVCAM), soluble intercellular adhesion molecule (sICAM) and soluble E-selectin.
Results:
There were no significant differences between FCH patients and their non-affected relatives in FMD [2.9 (2.3-3.6%) vs. 2.8 (2.5-3.2%)] or in the plasma concentrations of the various adhesion molecules. None of the individual clinical and biochemical cardiovascular risk factors was an independent predictor of endothelial function in patients with FCH, nor was IMT. However, subgroup analysis revealed that IMT was an independent and powerful predictor of FMD in subjects with carotid artery plaques (St. beta = 4.11, P < 0.004), whereas IMT was no significant predictor in subjects without plaques.
Conclusions:
FCH patients have no impaired endothelial function when compared to their unaffected relatives. IMT is an important predictor of FMD when advanced morphological wall changes are present. Our results question the value of FMD measurements for cardiovascular risk stratification in populations with an anticipated high cardiovascular risk.
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