Evaluation of the relationship between flow-mediated vasodilation and some atherogenic risk markers in severe hypercholesterolemia.

Background: In recent years, there has been a shift of interest in preventive cardiology towards primary prevention in high risk patients such as the patients with severe hypercholesterolemia. There is scanty information available in the respective literature on the levels of asymmetric dimethylarginine in severe hypercholesterolemia and on the correlation of flow-mediated vasodilation with some atherogenic risk biomarkers.

Aim: To assess the relationship of flow-mediated vasodilation with lipids, apoproteins and some serum markers of endothelial activation in severe hypercholesterolemia.

Patients And Methods: The study population consisted of 58 patients with severe hypercholesterolemia (> 7.5 mmol/l) as categorised by Simon-Broome's criteria for clinical definite and probable diagnosis of familial hypercholesterolemia. All patients were asymptomatic. The study included also 50 control subjects that had no evidence of hypercholesterolemia.

Results: The analysis of the lipid profile, the atherogenic lipid indices, and the apoproteins of patients and controls supports the alternative hypothesis: there is a statistically significant difference determined by the higher values of these parameters in the patients group (P < 0.0001). The mean values of asymmetric dimethylarginine calculated at baseline in both groups differed significantly (1.64 +/- 0.04 micromol/l vs. 0.47 +/- 0.02 micromol/l for patients and controls, respectively, P < 0.001). There was also a significant difference in the mean values of flow-mediated vasodilation calculated at baseline between the two groups (4.49 +/- 0.62% vs. 8.64 +/- 0.61% for patients and controls, respectively, P < 0.001). We found a very strong negative correlation, which reached statistical significance, between the flow-mediated vasodilation and the asymmetric dimethylarginine, apoprotein B and the apoprotein B/apoprotein A-I ratio (rxy = -0.687 with apoprotein B, p < 0.0001; rxy = -0.518 with apoprotein B/apoprotein A-I ratio, p < 0.0001; and rxy = -0.895 with asymmetric dimethylarginine, p < 0.0001).

Conclusions: Univariate analysis showed that 80% of all variations in the values of flow-mediated vasodilation can be explained by variations in the values of asymmetric dimethylarginine. The significant negative correlation between the flow-mediated vasodilation and apoprotein B, the apoprotein B/apoprotein A-I ratio and the asymmetric dimethylarginine indicates that these biomarkers are more strongly associated with the endothelial dysfunction (the earliest functional abnormality of the vascular wall) than with the lipid profile components that are usually used in clinical practice.