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.

Association between angiographic coronary stenosis morphology and acute coronary syndrome manifestation in patients with ischemic heart disease.

AIM: Patients with acute coronary syndrome (ACS) often show complex morphology of coronary stenosis at angiography. In the present study we evaluated the association between different clinical forms of manifestation of acute coronary syndrome and the angiographic morphological patterns of coronary stenosis. PATIENTS AND METHODS: A total of 112 patients with angiographically verified single vessel coronary artery disease were divided into two groups: a control group of 44 patients with simple coronary stenosis at angiography and a study group of 66 patients with complex coronary stenosis. Angiographic analysis was performed using a modified Ambrose classification. The two groups were compared according to the manifestation and distribution of the acute coronary syndrome based on Braunwald classification. RESULTS: There were no statistically significant differences between the mean values of stenosis severity in the group with simple stenosis (79.8% +/- 10.7%) and the group with complex stenosis (82.7% +/- 8.2%) (P > 0.05). The incidence of current acute coronary syndrome - unstable angina or myocardial infarction - was higher in the group with complex stenosis (30.00% +/- 8.37% vs. 52.00% +/- 7.07%, P < 0.05). Patients with previous ACS were prevailing in the group with simple stenosis (70.00% +/- 8.37% vs. 48.00% +/- 7.07%, P < 0.05). CONCLUSION: Complex coronary stenosis is associated with higher prevalence of acute coronary syndrome in acute clinical stage while simple coronary stenosis is associated with higher prevalence of previous acute coronary syndrome. A possible metamorphosis of coronary stenoses is taken into consideration.

Endothelium-independent coronary vasodilatation in patients with single vessel ischemic heart disease and its relationship with coronary artery morphology.

AIM: Investigation of the endothelium-independent coronary vasoreactivity in a single stenosed coronary artery and its correlation with the type of coronary morphology. PATIENTS AND METHODS: Ninety patients with single vessel coronary artery disease were allocated into two groups: a control group of 34 patients with simple coronary stenosis and an experimental group of 56 patients with complex coronary stenosis (modified Ambrose classification). The reference lumen diameter in the proximal, medial and distal segments of a stenosed coronary artery was assessed at baseline and after the intracoronary administration of glyceryl trinitrate in selective coronarography. RESULTS: After administration of the drug the lumen was dilated in 71.48% of the segments while there was no dilation in the remaining 28.52%. The dilated segments were 82.74% in the complex stenosis group versus 52.94% in the control group (P < 0.001). The mean change of the reference lumen diameter in the complex stenosis patients was 0.52 +/- 0.59 mm versus 0.24 +/- 0.46 mm in the simple stenosis group (P < 0.001). The change in the segments with dilated lumen was 0.39 +/- 0.36 of the baseline value in the complex stenosis group versus 0.24 +/- 0.23 in the control group (P < 0.001). CONCLUSIONS: The coronary arteries with single stenosis react to intracoronary glyceryl trinitrate primarily with endothelium-independent vasodilatation. In complex stenosis coronary arteries there are more dilated segments and greater increase of the baseline reference lumen diameter.

Assessment of respiratory compensation phase during graded exercise in patients with chronic heart failure.

BACKGROUND: The VE-VO2 relationship during graded exercise has an inflection point beyond the ventilatory anaerobic threshold (VAT) termed the respiratory compensation point (RCP). Metabolic variables analyzed at the level of VAT and RCP may contribute to the better understanding of such limiting symptoms in chronic heart failure (CHF) patients as dyspnea and early fatigue. The AIM of the present study was to analyze the RCP during symptom limited ramp exercise testing in CHF patients. PATIENTS AND METHODS: Forty six CHF patients (II and III NYHA functional class; age = 51 +/- 9 years, LVEF% = 35% +/- 6%; mean +/- SD) and 20 matched controls performed graded cardiopulmonary exercise test on a cycle ergometer. RESULTS: The duration and productivity of RCP (delta(x) = peak(x) - VAT(x)) in patients were significantly (p < 0.001) reduced compared to healthy subjects: delta duration = 3.0 +/- 1.2 vs 4.3 +/- 1.5 min, delta watts = 24.3 +/- 11.5 vs. 39.4 +/- 11.5, delta VO2/kg (ml.kg-1 x min-1) = 3.8 +/- 1.3 vs 8.8 +/- 2.3. An important characteristic of this phase was the higher subjective cost of physical effort assessed by Borg scale and Watts/Borg ratio (Borg peak = 9.9 +/- 0.4 vs. 6.0 +/- 1.2; p < 0.001, Watts/Borg peak = 9.2 +/- 2.3 vs 23.9 +/- 6.4, p < 0.001). The relative hyperventilation of patients on the basis of the watt exercise can be seen in the values of derivative index V (ml x min-1 x watt-1) 478 +/- 59 vs 568 +/- 118; (p < 0.001) in controls and patients, respectively. CONCLUSIONS: The impaired efficiency of oxygen delivery systems in patients with CHF is what causes the appearance of early limiting symptoms. Duration and productivity of respiratory compensation phase in CHF patients are considerably reduced compared to controls.