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Published on: July 21, 2012
Microvascular Function and Endothelial Progenitor Cells in Patients with Severe Hypercholesterolemia and the Familial
Andrea De Lorenzo1, Annie S B Moreira, Fabiana B Muccillo
1Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Insights
Patients with definite familial hypercholesterolemia (DFH) show impaired microvascular function compared to probable/possible FH (PFH). This suggests more severe vascular disease in DFH patients, despite similar endothelial progenitor cell (EPC) counts.
Area of Science:
- Cardiovascular Research
- Vascular Biology
- Lipid Metabolism
Background:
- Familial hypercholesterolemia (FH) presents a spectrum of atherosclerotic disease severity.
- Understanding the pathophysiology of vascular disease in different FH phenotypes is crucial.
Purpose of the Study:
- To compare endothelial progenitor cells (EPCs) and microvascular function in severe hypercholesterolemia patients with definite FH (DFH) versus probable/possible FH (PFH).
- To elucidate the differential impact of FH phenotypes on vascular health.
Main Methods:
- Severe hypercholesterolemia patients (LDL-C >190 mg/dL) classified as DFH or PFH.
- EPCs quantified via flow cytometry (CD45-, CD45low, CD34+, CD133+, CD309+).
- Cutaneous microvascular reactivity assessed using laser speckle contrast imaging with acetylcholine (ACh) or sodium nitroprusside iontophoresis.
Main Results:
- DFH patients exhibited higher LDL-C levels than PFH patients.
- No significant difference in median EPC counts was observed between DFH and PFH groups.
- Endothelial-dependent, ACh-induced vasodilation was significantly reduced in DFH patients.
Conclusions:
- Patients with DFH demonstrate impaired microvascular endothelial-dependent vasodilation compared to PFH patients.
- This finding indicates a more advanced stage of vascular disease in the DFH phenotype.
- Microvascular function is a key differentiator in FH severity.
Objective:
To evaluate endothelial progenitor cells (EPCs) and systemic microvascular function in patients with severe hypercholesterolemia, comparing patients with the definite familial hypercholesterolemia (FH) phenotype (DFH) or probable/possible FH phenotype (PFH). There is a large spectrum of atherosclerotic disease between these two clinical phenotypes of FH, and to acquire further knowledge of the pathophysiology of vascular disease in both is desirable.
Methods:
Subjects with severe hypercholesterolemia, defined as low-density lipoprotein cholesterol (LDL-C) >190 mg/dL, were classified as DFH or PFH and underwent measurement of the number of EPCs by flow cytometry and evaluation of cutaneous microvascular reactivity using a laser speckle contrast-imaging system with iontophoresis of acethylcholine (ACh) or sodium nitroprusside. EPCs were defined as CD45- or CD45low, CD34+CD133+CD309+ cells. Categorical variables were compared using Fisher test and continuous variables with Student t test or Mann-Whitney test, and a value of p < 0.05 was considered statistically significant.
Results:
Patients with DFH had higher LDL-C than those with PFH. There was no difference in the median number of EPCs between patients with DFH or PFH, but there was a significant reduction of endothelial-dependent, ACh-induced vasodilatation in the former.
Conclusion:
Patients with DFH have impaired microvascular endothelial-dependent vasodilatation compared to those with PFH, indicating more severe vascular disease in the former.
