Search

Introduction: Exercise-induced desaturation is a common finding in patients with moderate and severe COPD. It is an important marker in the course of disease that has a prognostic value for mortality risk., Aim: To monitor over time COPD patients with and without desaturation during 6-minute walking test (6MWT) and to assess the stability of that phenomenon., Materials and Methods: A 6MWT was administered to 70 patients with COPD which ranged in severity from stage 2A to stage 4D (GOLD 2011); the patients had a mean age of 64.5±10.1, mean pack-years - 38.8±21, FEV1% = 46.4%±15.7%, FVC% = 73.7%±1.3%, MRC = 2.31±0.84, CAT = 20.8±6.6. Oxygen saturation was monitored during the test; indications for desaturation were a decrease of SpO2 by ≥4% and a fall in SpO2 to ≤88% for at least 3 min. The patients were followed-up for mean 40.9±22.3 months and tests were repeated., Results: Patients were divided into two groups based on the decrease in SpO2: Group A included patients with desaturation (n=35) and Group B - patients with no desaturation (n=35). In 66 of the patients the desaturation profile was stable over time. Only two patients, who did not desaturated at baseline, experienced desaturation in the follow-up 6MWT and another two patients, who desaturated at baseline, did not have it later in the follow-up., Conclusion: Desaturation is a phenomenon that is persistent over time. Based on the results, it could be concluded that exercise-induced desaturation is a major marker of a particular COPD phenotype.

Background: The risk of excessive bleeding often prompts physicians to interrupt the antiplatelet agents as acetylsalicilyc acid and clopidogrel before dental extractions which puts patients at risk of adverse thrombotic events., Aim: To assess the bleeding risk during dental extractions in patients with continued antiplatelet therapy., Materials and Methods: The study included 130 patients (64 men and 66 women) aged between 18 and 99 years old. Sixty-eight of the patients received 100 mg acetilsalicilic acid (ASA); these were divided into two groups: 34 patients continued taking ASA and 34 patients stopped it 72 hours before extraction. Sixty-two of the patients were treated with 75 mg clopidogrel; these were also divided into two groups: 31 continued taking clopidogrel and 31 patients stopped it 72 hours before extractions. Extraction was performed under local anaesthesia as no more than 3 teeth per visit were extracted. Local haemostasis with gelatine sponge and/or suturing was used to control bleeding., Results: Mild bleeding was observed most frequently in the first 30 minutes, successfully managed by local haemostasis. Only 1 patient in the control and 1 in the experimental group receiving ASA reported mild bleeding in the first 24 hours, controlled by compression with gauze. No major haemorrhage requiring emergency or more than local haemostasis occurred. No statistically significant difference in bleeding between two groups was found., Conclusion: Single and multiple dental extractions in patients receiving acetylsalicylic acid or clopidogrel can be safely performed without discontinuation of the therapy with provided appropriate local haemostasis.

Research of statin influence on asymmetric dimethylarginine (ADMA) and flow-mediated vasodilatation (FMD) reveals controversial results. The aim of this study was to investigate the effects of moderate (40mg) and high (80mg) simvastatin doses on the levels of ADMA, total homocysteine (tHcy) and %FMD in patients with newly diagnosed severe hypercholesterolemia, after optimizing the LDL level. The study included 650 patients with severe hypercholesterolemia (total cholesterol≥7.5mmol/l; LDL≥4.9mmol/l). The treatment groups were administered 80mg simvastatin over a period of one month. The results indicated a reduction in ADMA and tHcy levels and an increase in %FMD in the treatment groups, compared with the control groups (receiving placebo or 40mg simvastatin). There was a statistically significant correlation between the %FMD changes and the baseline levels of Apo-B, ADMA and tHcy, as well as between the %ADMA changes and %LDL, % apolipoprotein-B and %tHcy-changes in patients on 80mg Simvastatin. A statistical linear regression analysis (in the treatment group) indicated that the baseline ADMA level is the most important statistically significant predictor related to %FMD-changes. A linear regression analysis additionally documented that % apolipoprotein-B-changes is a predictor of %ADMA-changes. In conclusion, in cases with optimized LDL-target levels (patients on 80mg Simvastatin), the baseline level of ADMA appears to be a major modulator of %FMD-changes., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The assumption that statin therapy can decrease asymmetric dimethylarginine through lowering low-density lipoprotein cholesterol levels seems logical and yet arises some controversy. The aim of the present study is to compare the effects of moderate (40 mg) to high (80 mg) simvastatin doses on asymmetric dimethylarginine and total homocysteine levels in patients with newly detected severe hypercholesterolemia (after target LDL-C levels, ≤2.6 mmol/L, are reached). The study included 120 adult patients with newly detected severe hypercholesterolemia (total cholesterol ≥7.5 mmol/L and low-density lipoprotein cholesterol ≥4.9 mmol/L). Asymmetric dimethylarginine levels were determined by enzyme-linked immunosorbent assay, total homocysteine-by a high-performance liquid chromatographic method. There was a statistically significant decrease in total cholesterol, triglycerides, low-density lipoprotein cholesterol, and apolipoprotein-B levels as well as in the apolipoprotein-B/apolipoprotein-A1 index after a 1-month therapy with 40 mg simvastatin (P <0.001). Asymmetric dimethylarginine and total homocysteine levels were also decreased but the difference did not reach statistical significance (P= 0.571; P= 0.569). A dose-dependent effect was established, comparing the influence of moderate (40 mg) to high (80 mg) simvastatin doses on the tested atherogenic biomarkers (lipid profile, apolipoprotein-A1, and apolipoprotein-B). Asymmetric dimethylarginine and total homocysteine levels were lowered significantly with 80 mg simvastatin (P <0.001; P= 0.038). In conclusion, optimizing the target values of low-density lipoprotein cholesterol, a moderate dose (40 mg) of simvastatin has no effect on asymmetric dimethylarginine and total homocysteine in contrast to a high dose (80 mg) after target LDL-C levels are reached (≤2.6 mmol/L) in patients with newly detected severe hypercholesterolemia., (© 2010 Blackwell Publishing Ltd.)

Background: Endothelial dysfunction is increasingly recognized as an important early feature of vascular disease. As the damage to endothelium is a key underlying factor in the development and progression of atherosclerotic processes, markers of endothelial abnormalities have been sought. Increased expression of cell adhesion molecules (CAMs) on the vascular endothelium has been postulated to play a significant role in atherogenesis. Both in vitro and in vivo studies have suggested that different risk factors of atherosclerosis may increase expression of CAMs. The elevated level of soluble forms of CAMs in circulation is associated with a higher risk to future cardiovascular events in subjects predisposed to atherosclerosis, Objective: To determine the reference range for serum concentration of soluble cell adhesion molecules - slCAM-1, sVCAM-1, sE-selectin, sP-selectin., Material and Methods: We studied 110 healthy people of Bulgarian nationality aged 18-65. The selection criteria for the reference group were made in accordance with the requirements of the International Federation of Clinical Chemistry (IFCC). Serum concentrations of CAMs were analysed by means of ELISA assay., Results: The results are presented as central 95% interval and 0.90 confidence interval of the reference range. Reference ranges were determined for sICAM-1 (128.9 - 347.48 ng/ml), sVCAM-1 (170.42 - 478.36 ng/ml), sE-selectin (9.15 - 65.19 ng/ml) and sP-selectin (101.86 - 209.7 ng/ml). As we found no sex-related differences in the CAMs concentrations (p > 0.05) there needed to be no separate reference intervals for men and women. The single-factor dispersion analysis we used in analysing the effect of age found no age-related dependence (p > 0.05, F = 1.038) for the serum CAM concentrations in the 18-65 age range, which means that it is not necessary to establish reference intervals for smaller age ranges in this age group., Conclusion: The reference ranges for slCAM-1, sVCAM-1, sE-selectin, sP-selectin computed in accordance with the results distribution can be used as baseline criteria in clinical laboratory studies.

Introduction: The effect of statins on the levels of cell adhesion molecules (CAM) is discussed in the literature as one of the pleiotropic effects of the drugs. This effect is one of the ways that could be used to control the initial stage of atherogenesis. The research in this field is inadequate and controversial. Prevention guidelines recommend that target levels of LDL cholesterol in high-risk patients should be less than 2.6 mmol/l. If the primary target is LDL-cholesterol, it is doubtful if patients can have any significant changes in the levels of the cell adhesion molecules (CAM)., Aim: Study the effect of simvastatin administered in a moderate dose of 40 mg and in a high dose of 80 mg on endothelium activation in the context of the plasma levels of soluble cellular adhesion molecules (sICAM-1, sVCAM-1, sE-selectin, sP-selectin) in recently diagnosed untreated severe hypercholesterolemia after reaching target levels for the LDL-cholesterol below 2.6 mmol/1., Patients and Methods: One hundred patients (aged > 16 years) were included in the study. Hypercholesterolemia was defined as fasting total serum cholesterol level greater than 7.5 mmol/l and LDL-cholesterol > 4.9 mmol/l. The study was carried out in three phases, the main goal being titration of simvastatin dose from 40 to 80 mg with the purpose of achieving the target LDL level of < 2.6 mmol/l in a randomised placebo-controlled study., Results: There was a statistically significant reduction of sVCAM-1 following the 80-mg simvastatin therapy for one month after reaching target levels of LDL-cholesterol < 2.6 mmol/l in hypercholesterolemic patients in comparison with the moderate dose (40 mg) of simvastatin for one month (p < 0.001). The results of the study demonstrated that simvastatin in a dose of 80 mg exerted an effect on the levels of some CAM, and particularly on VCAM-1 in contrast to the same drug used in a dose of 40 mg., Conclusion: As different statins most likely have a distinctly specific effect on different adhesion molecules, this study seeks to establish a suitable panel of such adhesion molecules that may be used in monitoring statin therapy.

Background: The data on the examination of early vascular alterations in carriers of molecular defects of the low-density lipoprotein-receptor (LDL-R) in comparison to noncarriers with severe hypercholesterolemia are controversial., Aims: To examine the difference between patients with severe hypercholesterolemia, who are carriers and noncarriers of LDL-R defective gene, with respect to their functional (flow-mediated vasodilation) and structural (intima-media thickness of carotid artery) characteristics of arterial wall. A total of 250 hypercholesterolemic patients were enrolled. Biochemistry parameters were examined by routine methods. The molecular biological analysis included-R3500Q-mutation in the Apolipoprotein-B (Apo-B) gene, LDL-R gene mutation and polymorphism (and the promoter region), as large rearrangements. Determination of flow-mediated vasodilation and intima-media thickness of common carotid artery was performed with Hewlett Packard Sonos 5500, using automated computer software MedicaSoft. IMT.lab., Results: There was no significant difference between the groups with respect to total cholesterol, LDL, HDL, Apo-B, Apolipoprotein A(1) (Apo-A(1) ), asymmetric dimethylarginine (ADMA), homocysteine, and cellular adhesion molecules. The Apo-B/Apo A(1) index differed significantly (t = 11.23, P < 0.001) between the two groups and this difference was found even after adjustment for age and gender. There was no significant difference with respect to the endothelial dependent and independent vasodilatation between the examined groups (P > 0.05). We were founded a significantly higher carotid IMT in the carriers versus noncarriers. This significant difference was confirmed after adjustment for age and gender. Statistically significant correlations we were founded between IMT mean and age (log) (r(xy) = 0.45; P < 0.01), cholesterol × years score (log) (r(xy) = 0.53; P < 0.01), Apo-B/A(1) (log) (r(xy) = 0.66; P < 0.001) in the group of the carriers. Backward selection process selected Apo-B/A(1) as the most important statistically significant factor related to IMT mean of common carotid artery (F = 105.22; P = 0.001; R(2) = 0.72)., Conclusion: Our data demonstrate that carriers of the LDL-R defective gene have a higher carotid IMT and Apo B/Apo A(1) index than noncarriers, whereas no difference between the groups was found with respect to the level of lipid parameters, ADMA, total homocysteine, cell adhesion molecules and %FMD. Apo-B/A(1) is a predictor of IMT mean in the group of the carriers of the LDL-receptor gene., (© 2011, Wiley Periodicals, Inc.)

Unlabelled: Asymmetric dimethylarginine (ADMA) is an endogenous competitive inhibitor of the endothelial nitric oxide synthase (eNOs). ADMA is believed to be implicated in angiogenesis because it regulates the nitric oxide biosynthesis; any pathological abnormalities in ADMA play a crucial role in the pathogenesis and progression of atherosclerosis. The AIM of the present study was to determine the reference range for plasma concentration of ADMA in a sample of Bulgarian population., Patients and Methods: To establish the reference interval of ADMA plasma levels and study the impact of sex and age we recruited 150 healthy subjects of Bulgarian nationality aged between 18 and 65 years. The selection criteria for the reference group were made to comply with the generally approved recommendations of the International Federation of Clinical Chemistry (IFCC). Plasma concentrations of ADMA were determined using ELISA assay (DLD, Diagnostics, Hamburg, Germany)., Results: The reference ranges for ADMA, given as 95% of the measured values, were from 0.22 to 0.69 micromol/1. We found no sex-related differences in ADMA concentration (P > 0.05), which obviates the need for separate reference intervals for men and women. Single-factor dispersion analysis found no age dependency ofADMA (P > 0.05, F = 1.038) in the studied reference group in the age range 18-65 which makes unnecessary establishment of reference intervals for lower age ranges in this age group., Conclusion: The reference values for ADMA plasma concentrations calculated according to the type of distribution of results can be used as baseline criteria in clinical laboratory studies and for clinical purposes.

Unlabelled: The results of the research of early vascular alterations in LDL-R carriers in comparison with those in non-carriers with severe hypercholesterolemia are controversial., Aim: To investigate the difference between severe hypercholesterolemia patients that carry LDL-R defective gene and those that do not have it, in their functional (flow-mediated vasodilation) and structural (intima-media thickness of carotid artery and ankle-brachial index) characteristics of arterial wall., Patients and Methods: The study included 120 hypercholesterolemic patients. Biochemistry parameters were studied by routine methods. The flow-mediated vasodilation (%FMD), ankle-brachial index (ABI) and intima-media thickness (IMT) of common carotid artery were determined using Hewlett Packard Sonos 5 500; MedicaSoft. IMT.lab was the software programme used in the study., Results: There was no significant difference between the groups with respect to total cholesterol, LDL, HDL, Apo-B, Apo-A1, cellular adhesion molecules (sICAM-1, sVCAM-1, sP- and sE-selectine). The Apo-B/Apo A1 index differed significantly (t = 11.23, p < 0.001) between the two groups; there was difference even after adjustment for age. There was no significant difference in the endothelial dependent and independent vasodilatation between the examined groups (p > 0.05). We found a significantly greater carotid IMT and lower ABI in the carriers than the respective parameters in the non-carriers. This significant difference was confirmed after adjustment for age., Conclusion: Our data show that LDL-R carriers have a higher carotid IMT and lower ABI than non-carriers, whereas no difference between the groups was found with respect to the level of lipid parameters and %FMD.

Objective: Research of statins influence on flow induced vasodilatation reveals controversial results., Design and Methods: We analyze whether asymmetric dimethylarginine (ADMA) levels influence the effect of 80mg/day simvastatin on flow-mediated vasodilation (%FMD). A total of 200 hypercholesterolemic patients were enrolled. Biochemistry parameters were examined by routine methods. Determination of %FMD was performed with software MedicaSoft. Patients were assigned into two groups according to the ADMA level., Results: Simvastatin, 80mg/day for 1month, resulted in changes in routine lipid profile and apolipoproteins, but there was not reduction of ADMA and homocysteine. In the group with ADMA<1.03micromol/L a significant increase of %FMD was observed, whereas no such was found in the group with ADMA>or=1.03micromol/L. %FMD-change correlated significant with baseline level of Apo-capital VE, Cyrillic and capital A, CyrillicDMA., Conclusion: Asymmetric dimethylarginine level was found to determine the effect of high-dose simvastatin on %FMD., (Copyright 2010 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Background: The idea that statin therapy decreases asymmetric dimethylarginine through lowering low-density lipoprotein cholesterol levels seems logic. However, controversy exists in the literature concerning this issue. This study compares the effect of moderate (40 mg) to high (80 mg) simvastatin doses on asymmetric dimethylarginine levels in patients with newly detected severe hypercholesterolemia (after targeted LDL levels of < or = 2.6 mmol/L are reached)., Methods: The study included 120 adult patients with newly detected severe hypercholesterolemia (total cholesterol > or = 7.5 mmol/L and low-density lipoprotein cholesterol > or = 4.9 mmol/L). Asymmetric dimethylarginine levels were determined by enzyme-linked immunosorbent assay, total homocystein by the high performance liquid chromatography method., Results: A statistically significant decrease exists in total cholesterol, triglycerides, low-density lipoprotein cholesterol and apolipoprotein-B levels as well as apolipoprotein-B/apolipoprotein-A1 index following one month of 40 mg simvastatin therapy (P < 0.001). Asymmetric dimethylarginine and total homocystein levels were also decreased but the difference was not significant (p = 0.571; p = 0.569). A dose-dependent effect was established comparing the influence of moderate (40 mg) to high (80 mg) simvastatin doses on the tested atherogenic biomarkers (lipid profile, apolipoprotein-A1, apolipoprotein-B). Asymmetric dimethylarginine and total homocystein levels showed a statistically significant decrease with 80 mg simvastatin (p < 0.001; p = 0.038). In the group of 40 patients, who had reached LDL-cholesterol target levels on 80 mg simvastatin, a reduction in ADMA levels demonstrated a statistically significant correlation with the reduction of LDL-cholesterol (r(xy) = 0.355; p < 0.01) and of Apo-B (r(xy) = 0.508; p < 0.001). The backward selection process selected percent ApoB-change as the most important statistically significant factor related to percent ADMA-change (F = 21.127; p = 0.001; R2 = 0.265)., Conclusions: Optimizing the target values of low-density lipoprotein cholesterol to the moderate dose (40 mg) of simvastatin has no effect on asymmetric dimethylarginine and total homocysteine in contrast to high dose (80 mg) after targeted LDL of < or = 2.6 mmol/L levels are reached in patients with newly detected severe hypercholesterolemia.

Unlabelled: Type 2 diabetes mellitus is associated with an excessively high morbidity and mortality from cardiovascular disease. Macrovascular disease with its complications is the leading cause of death in Bulgaria., Aim of This Study: To examine cardiovascular risk factors in patients with type 2 diabetes., Material and Methods: The study included 556 patients with type 2 diabetes and 575 healthy subjects. All participants filled a questionnaire on medical history, lifestyle and family history and standardised measurements were taken of some of their anthropometric parameters and blood pressure. Venous blood was drawn after an overnight fast for the examination of glucose, lipids, C-reactive protein and other cardiovascular risk factors., Results: Seventy-eight percent of the diabetic subjects had a history of coronary heart disease. The diabetics had significantly higher body mass index (27.1 +/- 4.4 kg/m2 vs. 25.0 +/- 3.8 kg/m2; mean +/- SD), waist circumference (101 +/- 10.2 vs. 87 +/- 8), systolic (131 +/- 12 mm Hg vs. 123 +/- 11) and diastolic blood pressure (85 +/- 9 mm Hg vs. 78 +/- 7), blood glucose (8.4 +/- 2.3 mmol/l vs. 5.4 +/- 0.7), total cholesterol (5.8 +/- 0.78 mmol/l vs. 4.9 +/- 1.0), triglycerides (2.18 +/- 1.02 mmol/l vs. 0.98 +/- 0.60) and C-reactive protein (5.2 +/- 3.9 vs. 3.7 +/- 3.1 mg/l) as well as significantly lower levels of HDL-cholesterol (0.96 +/- 0.28 mmol/l vs. 1.45 +/- 0.47) vs. controls., Conclusions: Our study demonstrates that patients with type 2 diabetes in Bulgaria have significantly increased levels of cardiovascular risk factors, which could explain the excessive cardiovascular mortality of these patients.

Unlabelled: Hypercholesterolaemia, hypertriglyceridaemia and low high-density lipoprotein (HDL) cholesterol are established risk factors of macrovascular disease, which leads to stroke and myocardial infarction and is the leading cause of death in Bulgaria. The AIM of our study was to examine the prevalence and type of hyper/dyslipidaemia in patients with myocardial infarction, hypertension and type 2 diabetes mellitus in Bulgaria., Material and Methods: A total of 1230 subjects were examined who had positive own and family history of acute myocardial infarction (AMI) (n=365), hypertension (n=250), type 2 diabetes mellitus (n=250), or neither of the diseases, healthy controls (n=365). All participants filled a questionnaire on medical history, current medication, lifestyle and family history. They underwent standardised measurements of anthropometric parameters and blood pressure. Venous blood was drawn after an overnight fast to test for atherosclerosis risk factors such as lipids, glucose, etc., Results: Although younger than the controls the patients with history of AMI, hypertension and type 2 diabetes had a significantly higher body mass index and waist circumference, as well as significantly higher blood pressure. Seventy percent of the AMI patients received lipid lowering treatment. Total cholesterol level was higher in all patients groups than that in controls, the difference being statistically significant for the AMI patients. Triglycerides were significantly higher in the AMI and the diabetic group in comparison with the controls. HDL cholesterol was lower in all patients groups than that in the controls, the difference being significant between the controls and patients with history ofAMI and diabetes. Hypercholesterolemia was observed in 69.6% of the AMI patients, 51% of the hypertensive patients, 56% of the diabetics and 36% of the controls; triglycerides level above 1.7 mmol/l was found in 85% of the AMI subjects, 28% of the hypertensive patients, 36% of the diabetic patients and 14% of the controls; and low HDL cholesterol--in 61% of the AMI patients, 21% of the hypertensive patients, 28% of the diabetics and 16% of the controls., Conclusions: Our study demonstrates that hypercholesterolemia, hypertriglyceridemia and low HDL cholesterol are very common in patients with history of myocardial infarction, hypertension and type 2 diabetes in Bulgaria and that treatment of the main cardiovascular risk factors seems to be insufficient in these patients.

Unlabelled: The aim of the present study was to examine the relationship between pulse pressure (PP), cardiovascular risk factors and intima-media thickness (IMT) in a population at risk for type 2 diabetes and atherosclerosis in Saxony, and to assess the association between PP and history of myocardial infarction in the general population of Bulgaria., Material and Methods: The Risk factors in IGT for Atherosclerosis and Diabetes (RIAD) study included 1139 subjects, aged 40-70 years, with a family history of type 2 diabetes, obesity and/or hyper/dyslipoproteinemia. The SMS study included 1018 subjects (> 14 years of age) from the general population of Bulgaria., Results: In RIAD study, PP was significantly correlated with age, plasma glucose, body mass index, microalbuminuria, triglycerides, waist-to-hip ratio, plasminogen activator inhibitor, total cholesterol, free fatty acids, leucocytes count and HDL-cholesterol (inversely). PP was also significantly correlated with carotid IMT. In multivariate analysis PP was an independent determinant of IMT. In the Sofia Metabolic Syndrome (SMS) study PP was significantly correlated with age, body mass index, waist circumference and fasting glucose and was an independent significant determinant of history of myocardial infarction., Conclusions: PP was an important cardiovascular risk factor both in a risk population for type 2 diabetes and atherosclerosis in Saxony and in the general population of Bulgaria.

We determined melatonin reference limits in blood serum of 129 healthy volunteers, aged 21 to 70 years, using enzyme-linked immunosorbent assay (IBL ELISA kit, Hamburg, Germany). At 3:00 AM, in almost full dark, the reference limits were found to be 18.3-134 pg/ml in males, 19.0-197 pg/ml in females and 18.5-180 pg/ml in the whole group. At 8:00 AM, they were statistically lower (5.63-61.8, 3.30-93.2 and 3.83-80.4 pg/ml respectively) possibly due to the light.

Background: Familial hypercholesterolemia is difficult to diagnose because of different expressions of the defective gene in low density lipoprotein (LDL) receptor mutation carriers and the presence of elevated LDL levels in noncarriers., Aim: To study specific biomarkers of atherogenic risk in carriers and noncarriers of low density lipoprotein receptor (LDLR) defective gene and utilize them to screen in molecular biological analysis for defects in the LDL receptor (spot mutation and polymorphism) in severe hypercholesterolemia., Patients and Methods: We investigated 120 patients after screening using the Simon-Broome criteria. According to whether there were molecular defects or not, the patients were assigned to two groups--carriers (22 patients, 18.33%) and non-carriers (98 patients, 81.67%). Total cholesterol, triglycerides, HDL cholesterol, apolipoproteins Apo-B and Al were determined using routine methods. LDL-cholesterol was determined by direct methods. ELISA was used in determining the soluble cell adhesion molecules (sICAM-1, sVCAM-1), P-selectine and E-selectine, and high-performance liquid chromatography--total homocysteine., Results: There were no significant differences in gender and anthropometric parameters (P > 0.05) between carriers and non-carriers, but the groups differed significantly in age (P < 0.001). No significant differences were found between the groups in the routine lip profile, the atherogenic lipid index, apolipoproteins B and A1, ADMA, total homocysteine, and the soluble cell adhesion molecules (P > 0.05). We found a statistically significant difference only for the Apo-B/Apo-A1 index in values non standardized by age, which was confirmed after standardization., Conclusions: Examining all 18 exons of LDLR gene in patients with severe HC we found that 18.33% of them were carriers of mutations and polymorphisms. There was no correlation between the presence of a molecular defect and the routine lipid profile, ADMA, total homocysteine and the soluble cell adhesion molecules; the presence of a molecular defect however, correlated with the Apo-B/Apo-A1 index.

Evidence has been accrued recently that chronic high levels of asymmetric dimethylarginine (ADMA) can be directly beneficial to the treatment of atherosclerotic vascular disorders thus making the substance a promising new therapeutic target. A therapeutic target can be theoretically each stage in the process of generation and elimination of asymmetric dimethylarginine. The methylation of L-arginine residues is a universal biological process involving hundreds of proteins but still with unknown effects. Interference with these mechanisms can generate ambiguous and speculative discussions. Supplementation with L-arginine seems to be the most natural way to reverse the detrimental effect of ADMA on the endothelium. The enzymatic activity of endogenous nitric oxide synthase is regulated by the ratio between the concentrations of L-arginine (the natural substrate) and that of ADMA (the endogenous inhibitor): in the presence of normal L-arginine levels, any elevation ofADMA levels may cause relative L-arginine deficiency thus attenuating the activity of the endogenous nitric oxide synthase. Target replacement therapy with L-arginine to increase the L-arginine plasma levels results in the normalisation of the L-arginine/ADMA ratio in the presence of higher levels of the latter. There is still some controversy about the effects of the most frequently used drugs on asymmetric dimethylarginine. Most of the relevant studies show that statins do not affect the ADMA levels. On the other hand, patients with high levels of ADMA are resistant to statin therapy--to improve the endothelium-dependent vasodilation they need a combined therapy with L-arginine. The angiotensin-converting enzyme inhibitors and the angiotensin receptor blockers are the most extensively studied substances, the studies predominantly centring on confirming their ADMA reducing effect. Until the specific ADMA-reducing therapy becomes readily available, it is the therapies of modification of the risk factors causing the increase of ADMA or the depletion of L-arginine, and the L-arginine replacement therapy that are the most realistic therapeutic solutions for patients with high plasma levels of ADMA because the synthesis of nitric oxide correlates with the L-arginine/ADMA ratio. A study was conducted in the Surgery of Preventive Cardiology with the Clinic of Cardiology in Plovdiv which included 40 patients with pronounced hypercholesterolemia (HC)--it was found that a one-month therapy with 40 mg simvastatin did not change statistically significantly ADMA plasma levels in spite of the optimal lipid regulation.

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.

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.

Endothelial dysfunction is a systemic disorder with a key role in the pathogenesis of atherosclerosis and its complications. Current evidence suggests that endothelial status is not determined solely by the individual risk factor burden but is rather regarded as an integrated index of all atherogenic and atheroprotective factors present in an individual, including known as well as yet-unknown variables and genetic predisposition. Endothelial dysfunction reflects a vascular phenotype prone to atherogenesis and may therefore serve as a marker of the inherent atherosclerotic risk in an individual. Recent advances in the understanding of pathophysiology of early atherosclerosis have opened up new opportunities for development of methods for assessment of the earliest changes in the vessel wall. During the last decade some noninvasive techniques have been introduced in clinical practice among which the ultrasound assessment of flow-mediated vasodilation of the brachial artery is the most widely used. These stimuli induce the endothelium to release nitric oxide which causes vasodilation that can be visualized and measured as an index of the vasomotor activity. This technique is attractive because it is non-invasive, accessible and reproducible in everyday clinical practice.