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Background: Familial hypercholesterolaemia (FH) is a genetic disorder causing accelerated atherosclerosis and premature cardiovascular disease (CVD). This retrospective observational study examined the clinical characteristics and management of FH subjects in Bulgaria over a 12-month period.

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.

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: 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: 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.

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.

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.