Aronia melanocarpa Fruit Juice Modulates ACE2 Immunoexpression and Diminishes Age-Related Remodeling of Coronary Arteries in Rats.

The aim of the study is to evaluate the effect of Aronia melanocarpa fruit juice (AMJ) supplementation on age-related coronary arteries remodeled in aged rat hearts. Male Wistar rats (n = 24) were divided into three groups: (1) young controls (CY), aged 2 months, without AMJ supplementation; (2) old controls (CO), aged 27 months, without AMJ supplementation; and (3) the AMJ group (A), which used 27-month old animals, supplemented orally with AMJ for 105 days. AMJ supplementation did not influence the wall-to-diameter parameter (Kernohan index) of the coronary arteries of test animals. Aged rats supplemented with AMJ showed a significant decrease in the amount of collagen fibers in their coronary tunica media, as compared with the old controls. The intensity of the immunoreaction for alpha smooth muscle actin (αSMA) in the coronary tunica media was significantly lower in the supplemented group than in the old controls. The intensity of the angiotensin-converting enzyme 2 (ACE2) immunoreaction in the coronary tunica media of the supplemented group was significantly higher than the one observed in the old controls. These results indicate the positive effects of AMJ supplementation on the age-dependent remodeling of coronary arteries and support for the preventive potential of antioxidant-rich functional food supplementation in age-related diseases.

Case Report: Difficulties in the Treatment of a 12-Year-Old Patient With Homozygous Familial Hypercholesterolemia, Compound Heterozygous Form - 5 Years Follow-Up.

The literature review we conducted reveals the limited use of proprotein convertase subtilisin/kexin type 9-inhibitors (PCSK9i) in children with familial hypercholesterolemia (FH). In 2015, a 10-year-old boy presented with round, xanthochromic lesions on his right knee and elbow. The values of total and LDL-cholesterol (LDL-C)-18 and 15 mmol/l, respectively-along with normal triglycerides and HDL-cholesterol (HDL-C) confirmed the lesions were xanthomas. The data suggested a homozygous form of FH. The level of lipoprotein (a) was high: 270 mg/dl. Initial treatment, based on European recommendations, included Atorvastatin 20 mg and Ezetimibe 10 mg and led to a decrease in LDL-C by 46% for 5 months; however, the patient developed severe statin intolerance. Atorvastatin was replaced with Rosuvastatin 10 mg, but the symptoms persisted. Success was achieved by switching to an intermittent regimen: Rosuvastatin 10 mg three times a week with a daily intake of Ezetimibe 10 mg. However, the results were far from the desired LDL target. LDL-apheresis was advisable, but unfortunately, it is not performed in Bulgaria. In May 2017, a genetic analysis [two pathological mutations within the LDLR gene: c.1519A>G; p.(Lys507Glu) and c.2403_2406del; p.(Leu802Alafs*126)] confirmed the initial diagnosis: the patient had homozygous FH with compound heterozygosity indeed. Having turned 12 in September 2017, the patient was eligible for treatment with a PCSK9i: Evolocumab 140 mg. The mean reduction of LDL-C with the triple combination reached a reduction of 52.17% for the whole 2-year period. The LDL target was reached in January 2020. The triple therapy significantly reduced Apolipoprotein B by 29.16%. No statistically significant difference was found in Lp (a) levels (p > 0.05) Our clinical case demonstrates that the triple lipid-lowering combination in a patient with compound heterozygous FH is a good therapeutic option for reaching the LDL-target.

Black Chokeberry (Aronia melanocarpa) Functional Beverages Increase HDL-Cholesterol Levels in Aging Rats.

Plant-based foods rich in phenolic phytochemicals are among the promising strategies to counteract age-related changes in lipid profile. Aronia melanocarpa (AM) fruits are a rich source of phenolic compounds possessing lipid-modulating effects. The present study investigated the effect of 3-month supplementation of AM-based functional beverages on the lipid profile of healthy aging rats. Male Wistar rats (n = 40) were separated into five groups: (YC) young controls (2-month-old); (AC) adult controls (13-month-old); (A) adult animals supplemented with pure AM extract; (A + P) adult animals supplemented with pectin-enriched (1%) AM extract; (A + H) adult animals supplemented with AM extract enriched with a herbal mixture. Total cholesterol (TC), triglycerides (TG), HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C) and atherogenic indices were investigated at the end of the study. Adult controls demonstrated age-related dyslipidemia resulting in decreased HDL-C, and increased TG and TC/HDL index. The supplemented groups showed a significant increase in HDL-C levels: A + P (1.49 mmol/L) and A + H (1.61 mmol/L), respectively, vs. AC (1.09 mmol/L), p < 0.05. The TC/HDL-C and LDL-C/HDL-C indices were decreased in the A + P and A + H groups in comparison to the AC group (p < 0.05). These results indicate that supplementation with polyphenol-rich AM beverages can successfully alter HDL-C levels and this effect is further potentiated by pectin and herbs.

Desaturation during Physical Exercise in COPD Patients - a Stable-over-time Phenomenon.

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.

Aronia melanocarpa (Michx.) Elliot fruit juice reveals neuroprotective effect and improves cognitive and locomotor functions of aged rats.

The aim of the study was to investigate the effect of polyphenol-rich Aronia melanocarpa (Michx.) Elliot juice (AMJ) on learning ability and memory, and brain morphology of aged rats. A model of healthy male Wistar rats (24 months of age) divided in 2 groups was used: AMJ group supplemented orally with AMJ (10 mL/kg for 105 days) and old control (CO) group without supplementation. Activity cage test showed that AMJ supplemented rats increased the number of vertical movements compared with old controls (p < 0.05). In active avoidance test, supplemented rats increased the number of avoidances on 3rd, 4th and 5th days of learning session, compared with the respective day of old controls (p < 0.05). AMJ supplementation did not affect the mean neuronal number in the dentate gyrus but significantly increased the density of nerve fibers in the perforant path of the hippocampus (p < 0.05). AMJ supplementation increased acetylcholinesterase activity in hippocampus, which is a marker of improved functional activity of the cholinergic neurons. These results indicate that AMJ induced ameliorating changes in the ability of old rats to learn tasks and improved their locomotor functions. AMJ showed a neuroprotective effect by increasing the density of nerve fibers in the hippocampal perforant pathway.

Antiatherogenic and Cardioprotective Effects of Black Chokeberry (Aronia melanocarpa) Juice in Aging Rats.

Age-related diseases are a social problem of global significance and their prevention by natural products is a research area of particular interest. The present study is an approach to counteract the risk factors for atherosclerosis arising in the aging process by supplementation of chokeberry juice. It employed a model of healthy adult rats monitored for a number of somatometric, serum lipidogram, and histopathological parameters, related to risk factors and their response to supplementation with antioxidant-rich chokeberry juice. The results were used to calculate different atherogenic and cardioprotective indices, and all results were compared to those of young healthy rats. Chokeberry juice proved an extremely rich source of polyphenols resulting in very high antioxidant activity. Treatment with Aronia juice significantly lowered the proatherogenic low-density lipoprotein fraction of the animals studied and led to a 16.5% decrease in their total cholesterol. Atherogenic indices in Aronia-supplemented animals clearly showed lower atherogenic risk and cardioprotective indices indicated protection of the cardiovascular system. Besides that, chokeberry juice retarded the age-related changes in the aortic wall and can be recommended as a prophylactic tool for healthy aging.

The effect of simvastatin on asymmetric dimethylarginine and flow-mediated vasodilation after optimizing the LDL level: a randomized, placebo-controlled study.

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.

Effect of moderate and high dose simvastatin on adhesion molecules in severe hypercholesterolemia after targeting the LDL-cholesterol--a randomised, placebo-controlled study.

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.

Serum levels of siCAM-1, sVCAM-1, sE-selectin, sP-selectin in healthy Bulgarian people.

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.

Plasma asymmetric dimethylarginine levels in healthy people.

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.

Increased intima-media thickness in carriers of the ldl-receptor defective gene versus noncarriers with newly detected asymptomatic severe hypercholesterolemia.

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.

Effect of moderate and high-dose simvastatin on asymmetric dimethylarginine-homocysteine metabolic pathways in patients with newly detected severe hypercholesterolemia.

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.

Asymmetric dimethylarginine--a determinant of the effect of the high dose Simvastatin.

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.

Non-invasive vessel examinations in carriers of LDL-receptor defective gene versus non-carriers with newly detected asymptomatic severe hypercholesterolemia.

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.

Prevalence and type of dyslipidaemia in a population at risk for cardiovascular death in Bulgaria.

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.

Cardiovascular risk factors in type 2 diabetic patients in Bulgaria.

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.

Intima-media thickness and flow-mediated vasodilation in asymptomatic subjects with newly detected severe hypercholesterolemia.

BACKGROUND: The aim was to establish the predictors of early functional and structural vascular alterations (using intima-media thickness (IMT)) and flow-mediated vasodilation (%FMD) as well as to investigate the interrelationship between IMT and %FMD in asymptomatic, never-treated, severe hypercholesterolemia (HH). METHODS: One hundred and twenty patients with asymptomatic, severe, untreated HH and 100 controls were included. ELISA was used for asymmetric dimethylarginine (ADMA) and cellular adhesion molecules, and fluid chromatography for total homocysteine (tHcy). Hewlett Packard SONOS 5500 with a 7.5 MHz transducer and MedicaSoft IMT software were used for evaluation of %FMD and IMT of common carotid artery (CCA). RESULTS: Patients and controls differ with respect to all tested biomarkers (P < 0.05), except for P-selectin and E-selectin (P < 0.05). %FMD was lower in patients (P < 0.001). The IMT of the CCA was higher in patients (P < 0.001). Inverse correlations were found between %FMD and IMT mean and age, ADMA, Apo-B, Apo-B/Apo-A(1), and tHcy. ADMA was established as the most important factor related to %FMD. Age and Apo-B were established as the most important factors related to IMT mean. An inverse correlation was established between %FMD and IMT mean (r(xy)= 0.546; P < 0.001)). If cases with IMT mean > or =1 were excluded, the correlation weakened. In patients with IMT mean > or =1 mm, the correlation did not change. CONCLUSION: In conclusion, asymptomatic, untreated patients with severe hypercholesterolemia are at high risk of having increased IMT of the CCA, especially if there is endothelial dysfunction, verified by %FMD of the brachial artery.

Pulse pressure is a strong predictor of cardiovascular risk: Data of the risk factors in impaired glucose tolerance for atherosclerosis and diabetes and the Sofia Metabolic Syndrome studies.

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.

Role of some biomarkers of atherogenic risk in the screening for molecular defects in the low density lipoprotein receptor in severe hypercholesterolemia.

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.

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.