Abstract

Objectives:
The aim of the study was to assess quality of life (QoL) in patients with peripheral arterial disease (PAD) after aortobifemoral bypass.
Methods:
QoL assessments were completed by 78 patients, 61 (78.2 %) men and 17 (21.8 %) women. QoL was measured, using Medical Outcome Survey Short Form 36 (SF-36), before surgery and 1 year later.
Results:
QoL significantly improved after revascularization in about two-third of patients with PAD. Improvement was present in all the SF-36 subscales with the exception of the score for mental health which significantly decreased after operation. Mean SF-36 scores, which were for almost all subscales significantly decreased in patients with PAD in comparison with reference populations, after operation reached or exceeded values of the populations with which they were compared.
Conclusions:
In the present study 1 year after revascularization QoL in patients with PAD was significantly improved in comparison with QoL before operation. Long-term follow-up is needed in order to assess duration of this beneficial effect of bypass surgery.

Abstract

Background:
The aim of this study was to compare demographic, clinical and biochemical characteristics, including inflammatory markers, according to the nutritional status of patients with verified atherosclerotic disease.
Methods:
This cross-sectional study involved 1045 consecutive patients with verified carotid disease or peripheral arterial disease (PAD). Anthropometric parameters and data on cardiovascular risk factors and therapy for hypertension and hyperlipidemia were collected for all participants.
Results:
Carotid disease was positively and PAD was negatively associated with body mass index (BMI). Negative association between obesity and PAD was significant only in former smokers, not in current smokers or in patients who never smoked. Overweight and general obesity were significantly related to metabolic syndrome (p < 0.001), lower values of high - density lipoprotein cholesterol (p < 0.001), increased triglycerides (p < 0.001), hyperglycemia (p < 0.001), self-reported diabetes (p < 0.001), hypertension (p < 0.001), high serum uric acid (p < 0.001), increased high sensitivity C-reactive protein (p = 0.020) and former smoking (p = 0.005) after adjustment for age, gender and type of disease. Antihypertensive therapy seems to be less effective in patients who are overweight and obese.
Conclusions:
In conclusion, ovhttps://pubmed.ncbi.nlm.nih.gov/33033455/erweight and general obesity were significantly related to several cardiovascular risk factors.
Keywords:
atherosclerosis; carotid disease; obesity; peripheral arterial disease; risk factors.

Abstract
We evaluated health-related quality of life (HRQoL) among patients with peripheral arterial disease (PAD) and compared the results with those of the general population. We also evaluated the possible association between some demographic and clinical characteristics of patients with PAD and HRQoL. A cross-sectional study involved 102 consecutive patients with verified PAD referred to the Dedinje Vascular Surgery Clinic in Belgrade. The HRQoL was measured using Medical Outcome Survey Short Form 36 (SF-36). Patients with PAD had significantly lower mean SF-36 scores for physical functioning, role-physical, bodily pain, social functioning, role-emotional, and mental health in comparison with the general population. The HRQoL was significantly more impaired in patients with severe PAD. Patients with PAD had a reduced HRQoL compared with the general population. The impact of PAD on HRQoL was independent of other factors related to both the disease and the HRQoL.
Keywords:
cross-sectional study; peripheral arterial disease; quality of life.

Abstract
We investigated whether patients with peripheral arterial disease (PAD) with various serum levels of high-sensitivity C-reactive protein (hsCRP) differ in the frequency of atherosclerotic risk factors. Among 388 patients, hsCRP levels were (1) low, <1 mg/L, in 41 (10.6%) participants; (2) medium, from 1 to 3 mg/L, in 152 (39.2%) participants, and (3) high, >3 mg/L, in 195 (50.2%) individuals. According to multivariate logistic regression analysis, in comparison with patients with hsCRP level ≤3.0 mg/L, those with higher hsCRP levels had more frequently a severe form of PAD (gangrene, P ranged from .045 to <.001; ankle-brachial index ≤.40, P = .059) and had more frequently some of atherosclerotic risk factors (metabolic syndrome, P = .007; hypertension, P = .013; abdominal obesity, P = .007; high levels of uric acid, P = .022; high level of fibrinogen, P < .001; and depression, P = .015).

Abstract

Introduction:
Peripheral arterial disease (PAD) is a severe atherosclerotic condition. The relationship between various risk factors and severity of PAD, measured by Ankle Brachial Index (ABI), has been the subject of a relatively small number of studies.
Objective:
The aim of the present study was to investigate whether there was any relationship between severity of PAD, expressed as ABI, and anthropometric, clinical and biochemical characteristics of patients, including inflammatory markers.
Methods:
The cross-sectional study, involving 388 consecutive patients with verified PAD, was performed at the Dedinje Vascular Surgery Clinic in Belgrade. The diagnosis of PAD was defined by Doppler sonography as ABI < 0.9, and by symptoms. Data on cardiovascular risk factors, anthropometric parameters, clinical and biochemical characteristics were collected for all participants. In the analysis, chi2 test, t-test and multivariate logistic regressions were used.
Results:
According to the results of multivariate analysis (the model of which included age, percentage of body fat, average value of uric acid, high sensitivity C-reactive protein--hsCRP > or = 3 mg/L, fibrinogen > or = 4 g/L, Baecke index of physical activity at work and Baecke index of leisure-time physical activity), the patients with more severe form of peripheral arterial disease (ABI < or = 0.40) had more frequently increased high sensitivity C-reactive protein (p = 0.002), lower Baecke index of physical activity at work (p = 0.050) and lower Baecke index of leisure-time physical activity (p = 0.024). Average value of body fat was significantly higher in the patients with a less severe form of disease (p = 0.006).
Conclusion:
According to the results obtained, the increased values of hsCRP and physical inactivity are associated with a more severe form of PAD (ABI < or = 0.40).

Abstract
The aim of the study was to estimate the prevalence of metabolic syndrome among 388 patients with peripheral arterial disease, to determine the relationship between the number of metabolic syndrome components (metabolic syndrome score) and the degree of established and some of the emerging vascular risk factors, and to estimate whether there was any relationship of metabolic syndrome score and other vascular risk factors with the severity of peripheral arterial disease clinical manifestations. Metabolic syndrome was present in 59.8% of the patients with peripheral arterial disease. All metabolic syndrome components were significantly related to metabolic syndrome score. The same was true for the body weight, body mass index, percentage of body fat, total cholesterol/high-density lipoprotein cholesterol ratio, uric acid, and percentage of patients with high-sensitivity C-reactive protein. The metabolic syndrome score was also significantly, but inversely, related to high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and smoking. The degree of peripheral arterial disease clinical manifestations was not related to metabolic syndrome score, but gangrene was significantly positively associated with increased fasting glucose, high-sensitivity C-reactive protein, and lower education.

Abstract

Background:
The aim of this article is to review our experience in surgical treatment of carotid atherosclerosis using eversion carotid endarterectomy (eCEA) in 9,897 patients performed in the last 20 years, with particular attention to diagnostic approach, surgical technique, medical therapy, and final outcome.
Methods:
From January 1991 to December 2010, 9,897 primary eCEAs were performed for high-grade carotid stenosis. Patients treated for restenosis after previous carotid surgery were excluded from the analysis. Follow-up included routine clinical evaluation and noninvasive surveillance, with duplex scanning, 1 and 6 months after surgery, and annually afterward.
Results:
The majority of the patients were symptomatic (stroke, 42.8%; transient ischemic attack, 55.1% [focal cerebral and retinal ischemia]), whereas only 2.1% of the patients were asymptomatic. For the final diagnosis, duplex scanning was performed in 83.4% of patients and angiography in only 16.3% (P < 0.001). Average carotid artery clamping time was 11.9 ± 3.2 minutes, and the majority of the patients were operated under general anesthesia (99.4%). Intraoperative shunting and local anesthesia were rarely performed; 0.6% of the patients were operated under local anesthesia, and in 0.5% of the patients, intraluminal shunt was used. Neurological and total morbidity showed a steady decline over time, with rate of neurological morbidity of 1.1% and total morbidity of 3.9% at the end of 2010. Neurological mortality and total mortality also showed a steady decline over time, with rate of neurological mortality of 0.3% and total mortality of 0.8% at the end of 2010. There was a low rate of both, nonsignificant restenosis (<50%), which was verified in 2.1% of the patients, and significant restenosis (>50%), which was observed in 4.3% of the patients.
Conclusion:
Our data show that eCEA is a reliable surgical technique for the treatment of atherosclerotic carotid disease, with low morbidity and mortality. The specificity of our experience is the significant number of patients with preoperative stroke, but despite this fact, results are comparable with previously published series. It also highlights the importance of comprehensive surgical training in reducing complications.

Abstract

Introduction:
Age-related changes of dental pulp tissue and atherosclerosis of carotid arteries as its feeding arteries could influence the functionality of pulpal circulation. The objective of our study was to evaluate the effect of aging (physiological process) and carotid bifurcation atherosclerosis (pathologic process) on the pulpal microcirculatory system using multifractal analysis of the laser Doppler flowmetry signal.
Methods:
Three groups of 10 subjects were enrolled in the study: the young group (healthy subjects, 20-25 years), the middle-aged group (healthy subjects, 50-60 years), and the clinical group (subjects with carotid bifurcation atherosclerosis, 50-60 years). Pulpal blood flow (PBF) signals recorded by laser Doppler flowmetry were assessed by multifractal analysis that estimates Hölder exponents of the signal. PBF levels, the average mean values, and the range of Hölder exponents were obtained.
Results:
PBF levels were significantly higher in the young group compared with the middle-aged and clinical groups, and the difference between the middle-aged and clinical groups was not statistically significant. The range of the Hölder exponents was narrower in the middle-aged and clinical groups than in the young group and narrower in the clinical group than in the middle-aged group. The average mean value of Hölder exponents was significantly higher in the young group than in the middle-aged and clinical groups, whereas there was no significant difference between the middle-aged and clinical groups.
Conclusions:
Our study investigating the multifractality of the PBF signal showed that the aging process and carotid atherosclerosis could affect the complex structure of PBF oscillations and contribute to a better understanding of pulpal hemodynamics.
Keywords:
Aging; atherosclerosis; dental pulp; laser Doppler flowmetry; multifractal analysis.

Abstract

Introduction:
Age-related changes of dental pulp tissue and atherosclerosis of carotid arteries as its feeding arteries could influence the functionality of pulpal circulation. The objective of our study was to evaluate the effect of aging (physiological process) and carotid bifurcation atherosclerosis (pathologic process) on the pulpal microcirculatory system using multifractal analysis of the laser Doppler flowmetry signal.
Methods:
Three groups of 10 subjects were enrolled in the study: the young group (healthy subjects, 20-25 years), the middle-aged group (healthy subjects, 50-60 years), and the clinical group (subjects with carotid bifurcation atherosclerosis, 50-60 years). Pulpal blood flow (PBF) signals recorded by laser Doppler flowmetry were assessed by multifractal analysis that estimates Hölder exponents of the signal. PBF levels, the average mean values, and the range of Hölder exponents were obtained.
Results:
PBF levels were significantly higher in the young group compared with the middle-aged and clinical groups, and the difference between the middle-aged and clinical groups was not statistically significant. The range of the Hölder exponents was narrower in the middle-aged and clinical groups than in the young group and narrower in the clinical group than in the middle-aged group. The average mean value of Hölder exponents was significantly higher in the young group than in the middle-aged and clinical groups, whereas there was no significant difference between the middle-aged and clinical groups.
Conclusions:
Our study investigating the multifractality of the PBF signal showed that the aging process and carotid atherosclerosis could affect the complex structure of PBF oscillations and contribute to a better understanding of pulpal hemodynamics.
Keywords:
Aging; atherosclerosis; dental pulp; laser Doppler flowmetry; multifractal analysis.

Abstract
Atherosclerosis is known as an inflammatory disease in which a recruitment of leukocytes to the endothelium wall represents a preliminary step of the initiation and the development of disease. The P-selectin glycoprotein ligand (PSGL-1) seems to be the major molecule mediating leukocyte-endothelium interactions and leukocyte rolling on stimulated endothelium. There are limited number of studies reporting on association of Met62Ile SNP in PSGL-1 gene and the risk for atherosclerosis. The aim of this study was to analyze possible association of this polymorphism with an advanced carotid atherosclerosis and biochemical markers of inflammation and haemostasis. The 275 patients consecutively admitted for carotid endarterectomy with stenosis >70% and 256 controls of the same ethnic origin were included in the study. The Met62Ile genotypes were determined by PCR RFLP. The Ile/Ile homozygotes had significantly higher CRP compared to the other genotypes in patients. Female patients had Ile allele dose-dependent association with the carotid plaque presence (Met/Met vs. Met/Ile vs. Ile/Ile; OR 1, OR 2.02, CI 1.0-4.08, OR 4.08, CI 1.0-16.81, respectively, p = 0.04). Our results suggest the impact of PSGL-1 Met62Ile polymorphism on inflammation in advanced atherosclerosis. We observed the sex-differential association of Met62Ile with advanced carotid atherosclerosis. Studies in larger and different populations should validate and further examine the suggested role of genetic variations in PSGL-1 with atherosclerosis and thrombosis.

Abstract
Atherosclerosis is a life-long illness that begins with risk factors, which in turn contribute to the development of subclinical disease, followed by the establishment of overt cardiovascular disease (CVD). Thrombotic-occlusive complications of atherosclerosis are among the most widespread and costly health problems. Oxidized low-density lipoprotein (OxLDL) plays an important role in atherogenesis by promoting an inflammatory environment and lipid deposition in the arterial wall. As cardiovascular events occur in individuals without common risk factors, there is a need for additional tools that may help in CVD risk assessment and management. The use of biomarkers has improved diagnostic, therapeutic and prognostic outcome in cardiovascular medicine. This review elaborates on the value of circulating OxLDL as a biomarker of CVD. Three enzyme-linked immunosorbent assays (4E6, DLH3 and E06) using murine monoclonal antibodies for determination of OxLDL blood levels have been developed. However, none of these assays are currently approved for routine clinical practice. We identified studies investigating OxLDL in CVD (measured by 4E6, DLH3 or E06 assay) by searching the PubMed database. Circulating OxLDL was found to be associated with all stages of atherosclerosis, from early atherogenesis to hypertension, coronary and peripheral arterial disease, acute coronary syndromes and ischemic cerebral infarction. The results of studies investigating the usefulness of OxLDL for CVD prediction were also summarized. Furthermore, OxLDL was found to be associated with pathologic conditions linked to CVD, including diabetes mellitus, obesity and metabolic syndrome (MetS). In addition, we have addressed the mechanisms by which OxLDL promotes atherogenesis, and the effects of antiatherogenic treatments on circulating OxLDL. Finally, we highlight the evidence suggesting that lipoprotein (a) [Lp(a)] is the preferential carrier of oxidized phospholipids (OxPL) in human plasma. A strong association between OxPL/apoB level (representing the content of OxPL on apolipoprotein B-100 particles, measured by E06 assay) and Lp(a) has been determined.
Keywords:
Atherogenesis; biomarker; cardiovascular risk assessment; lipoprotein (a); oxidized lipoproteins; statins.

Abstract
Atherosclerosis is a life-long illness that begins with risk factors, which in turn contribute to the development of subclinical disease, followed by the establishment of overt cardiovascular disease (CVD). Thrombotic-occlusive complications of atherosclerosis are among the most widespread and costly health problems. Oxidized low-density lipoprotein (OxLDL) plays an important role in atherogenesis by promoting an inflammatory environment and lipid deposition in the arterial wall. As cardiovascular events occur in individuals without common risk factors, there is a need for additional tools that may help in CVD risk assessment and management. The use of biomarkers has improved diagnostic, therapeutic and prognostic outcome in cardiovascular medicine. This review elaborates on the value of circulating OxLDL as a biomarker of CVD. Three enzyme-linked immunosorbent assays (4E6, DLH3 and E06) using murine monoclonal antibodies for determination of OxLDL blood levels have been developed. However, none of these assays are currently approved for routine clinical practice. We identified studies investigating OxLDL in CVD (measured by 4E6, DLH3 or E06 assay) by searching the PubMed database. Circulating OxLDL was found to be associated with all stages of atherosclerosis, from early atherogenesis to hypertension, coronary and peripheral arterial disease, acute coronary syndromes and ischemic cerebral infarction. The results of studies investigating the usefulness of OxLDL for CVD prediction were also summarized. Furthermore, OxLDL was found to be associated with pathologic conditions linked to CVD, including diabetes mellitus, obesity and metabolic syndrome (MetS). In addition, we have addressed the mechanisms by which OxLDL promotes atherogenesis, and the effects of antiatherogenic treatments on circulating OxLDL. Finally, we highlight the evidence suggesting that lipoprotein (a) [Lp(a)] is the preferential carrier of oxidized phospholipids (OxPL) in human plasma. A strong association between OxPL/apoB level (representing the content of OxPL on apolipoprotein B-100 particles, measured by E06 assay) and Lp(a) has been determined.
Keywords:
Atherogenesis; biomarker; cardiovascular risk assessment; lipoprotein (a); oxidized lipoproteins; statins.

Abstract
The role of hepatitis C virus (HCV) infection in the development of vascular disease is controversial. Insulin resistance (IR) is a recognized risk factor for cardiovascular disease (CVD) and is associated with chronic hepatitis C (CHC) infection. Thus, IR may promote atherosclerosis and vascular disease in CHC patients. HCV-associated IR may also cause hepatic steatosis and resistance to antiviral treatment. In addition, HCV may impose direct, proatherogenetic action in the vascular wall. This review will elaborate the impact of IR on interferon-α based therapy of HCV infection and the role of insulin-sensitizing agents on the response to antiviral treatment and prevention of IR complications, including vascular disease.

Abstract

Introduction:
Arterial occlusive disease is a systemic phenomenon frequently coexisting in more than one arterial system. Often in one arterial bed disease is manifested with symptoms, in another is asymptomatic. There are only several reports indicating the prevalence of carotid stenosis in patients with peripheral vascular disease. Asymptomatic carotid stenosis is defined as the presence of internal carotid/carotid bifurcation stenotic or occlusive lesions in patients with no signs or symptoms of cerebrovascular disease. Lesions are important causative factors in unheralded stroke. Two factors are particularly important: severity of stenosis and morphologic characteristics of the stenotic plaque. The recent largest completed clinical trial concerning asymptomatic carotid artery stenosis (completed 1995) ACAS (Asymptomatic Carotid Artery Study) established the benefit of surgical treatment vs. best medical treatment. The reduction in relative risk of stroke was 55% in favor of surgery. Population screening for carotid stenosis is inefficient and expensive. The current interest is focused on the efficacy of screening population at risk.
Aim of the study:
The aim of the study was to establish prevalence of asymptomatic carotid artery stenosis in patients with symptomatic lower extremities atherosclerosis. Furthermore, possibility for limiting screening to subgroups of patients concerning risk factors, carotid bruit and severity of lower extremities atherosclerosis, was examined.

Abstract

Introduction:
Cardiovascular diseases, especially heart disease and stroke are the cause of more than a half of the total number of deaths in Serbia.
Objectives:
The aim of the present study was to determine sex differences of atherosclerotic risk factors in patients with symptomatic carotid disease.
Methods:
The cross-sectional study, involving 657 consecutive patients with verified carotid atherosclerotic disease, was performed in Belgrade, Serbia. Sex differences of anthropometric parameters and atherosclerotic risk factors were analyzed by means of the univariate logistic regression.
Results:
In comparison with men, lower education and physical inactivity were significantly more frequent in women, and the frequency of metabolic syndrome (MetS), lower high-density cholesterol, abdominal obesity, body mass index > or = 30.0 kg/m2, hypercholesterolemia and depression were also significantly higher in women. Smoking and high serum uric acid level were significantly more frequent in men than in women. Women had significantly higher number of MetS components per person, but there were no significant sex differences in the number of other risk factors. Out of all observed risk factors, including MetS components, physical inactivity and hypertension were most frequent in both sexes followed by ever smoking and low education in men and low education and dyslipidemia in women.
Conclusion:
There were significant sex differences in the distribution of some atherosclerotic risk factors, but not in their number per person. Only the number of MetS components was significantly higher in women.

Abstract

Introduction:
Obesity, particularly visceral obesity, is considered one of major risk factors for cardiovascular events.
Objectives:
The aim of the present study was to investigate relationship between abdominal obesity and other cardiovascular risk factors.
Methods:
The cross-sectional study involved 657 consecutive patients with verified carotid atherosclerosis. Carotid atherosclerosis was estimated by high resolution B-mode ultrasonography. Abdominal obesity was defined as waist circumference > 102 cm in men and > 88 cm in women.
Results:
Abdominal obesity was present in 324 (49.3%) participants. Multivariate analyses showed that abdominal obesity was significantly positively associated with female sex, increased Baecke's Work Index of physical activity at work, years of school completed < 12, metabolic syndrome, increased triglycerides, hyperglycemia and high serum uric acid. Smoking, alcohol consumption, physical inactivity, hypertension, increased total cholesterol, increased HDL and LDL cholesterols, increased high sensitive C-reactive protein, increased fibrinogen, anti-lipid therapy and anti-diabetic therapy were not significantly related to abdominal obesity.
Conclusion:
Abdominal obesity among patients with symptomatic carotid disease is significantly related to other cardiovascular risk factors, especially metabolic syndrome, metabolic syndrome components and high level of serum uric acid.

Abstract

Objectives:
To evaluate health-related quality of life (HRQoL) in patients with symptomatic carotid disease (amaurosis fugax, transient ischaemic attack, stroke); to compare it with that of the general population; to explore whether HRQoL depends on the severity of the disease and to investigate the possible association between some demographic and clinical characteristics of patients and HRQoL.
Methods:
This cross-sectional study involved 175 patients with symptomatic carotid atherosclerotic disease who were referred for endarterectomy between January 2011 and December 2011. HRQoL was measured using Medical Outcome Survey Short Form 36 (SF-36).
Results:
In comparison to both referent populations, patients with carotid disease had significantly lower mean SF-36 scores for role-physical (41.6 vs. 61.5 and 67.8), social functioning (65.4 vs. 73.8 and 80.0), role-emotional (48.2 vs. 68.6 and 80.5) and mental health (51.5 vs. 61.9 and 66.0). The SF-36 scores were significantly lower in female patients with carotid disease than in men (for role-physical 32.3 vs. 46.5; for bodily pain 57.0 vs. 73.0; for general health 55.6 vs. 61.5; for vitality 55.4 vs. 60.1; for social functioning 57.1 vs. 69.8 and for role-emotional 37.2 vs. 54.1). Significantly lower SF-36 scores were also found in patient with comorbidity (for physical functioning 68.1 vs. 77.7; for role-physical 35.1 vs. 52.3; for bodily pain 62.6 vs. 75.4; for general health 56.8 vs. 63.8; for social functioning 61.9 vs. 71.0, for role-emotional 41.6 vs. 59.1and for mental health 52.5 vs 49.8). In a multivariable analysis, education, occupation, body mass index, metabolic syndrome and severity of the disease had a weak influence on patients' HRQoL, while age, marital status, smoking, alcohol consumption, physical activity and the degree of carotid stenosis had no effect on patients' HRQoL. The SF-36 scores did not substantially change after adjustment for confounding variables.
Conclusions:
Patients with symptomatic carotid disease had poorer HRQoL, especially its mental components, than the general population. The severity of the disease was significantly associated only with the SF-36 role-physical subscale. HRQoL in patients with symptomatic carotid disease was poorer in women than in men, and was not affected by age and other demographic and clinical characteristics of patients.

Abstract

Background:
To measure by Doppler sonography the blood flow volume (BFV) of the ipsilateral and contralateral extracranial internal carotid arteries (ICAs) and both vertebral arteries (VAs) before and after a carotid endarterectomy (CEA) of the ICA. We correlated the result with the degree of stenosis of the ICA.
Method:
One hundred seven patients who had a CEA were divided into 2 groups. Group I consisted of subjects with stenosis of ipsilateral ICA of >or=70% to near occlusion and Group II included subjects with near occlusion. The Doppler sonographic examinations were performed 1 day before the CEA, 7 days after the CEA, and 1 month after the CEA. The peak systolic velocity, end-diastolic velocity, time-averaged maximum blood flow velocity, resistance index of the ipsilateral ICA, and the BFV of both ICAs and both VAs were calculated.
Result:
There was a significant increase in the peak systolic velocity, maximum blood flow velocity, and the BFV of the ipsilateral ICA after the CEA. The BFV of the contralateral ICA and both VAs were not significantly altered after the CEA in both groups.
Conclusion:
The main CEA hemodynamic effect was an increase in the BFV of the ipsilateral ICA regardless of the degree of stenosis.

Abstract

Background:
Cardiovascular disease remains the major cause of mortality in the Western World.
Aims:
We aimed to assess the prevalence of polyvascular disease in patients with carotid artery disease and peripheral artery disease (PAD), and to determine the risk profile of patients with polyvascular disease.
Methods:
The study included 1045 consecutive patients presenting to our department with carotid disease or PAD. Demographic characteristics, anthropometric parameters, and data on cardiovascular risk factors were collected in all patients. On the basis of medical history, patients were classified into those who had only symptomatic carotid disease or symptomatic PAD and those who had symptomatic polyvascular disease.
Results:
Carotid disease alone was reported in 366 participants (35%), PAD alone, in 199 (19%), and polyvascular disease, in 480 (46%). Compared with carotid disease, PAD was more often a component of polyvascular disease (P = 0.002) and was combined with a higher number of other atherosclerotic diseases (P = 0.02). Compared with patients with symptomatic atherosclerotic disease in only 1 territory, patients with various types of polyvascular disease more often had hypertension (P from 0.03 to <0.001), dyslipidemia (P <0.001), high sensitivity C reactive protein levels of 3 mg/l or higher (P = 0.005), and more often were current smokers (P <0.001) or former smokers (P from 0.03 to 0.001).
Conclusions:
We showed a high prevalence of symptomatic polyvascular disease in patients with carotid disease or PAD. The risk profile was worse in patients with polyvascular disease than in those with a disease in a single vascular territory.

Abstract
Metabolic syndrome (MetS) is a leading public health and clinical challenge worldwide. MetS represents a group of interrelated risk factors that predict cardiovascular diseases (CVD) and diabetes mellitus (DM). Its prevalence ranges between 10 and 84%, depending on the geographic region, urban or rural environment, individual demographic characteristics of the population studied (sex, age, racial and ethnic origin), as well as the criteria used to define MetS. Persons with MetS have higher mortality rate when compared with people without MetS, primarily caused by progressive atherosclerosis, accelerated by pro-inflammatory and pro-coagulation components of MetS. Considering the high prevalence of metabolic disorders (glucose metabolism disorder, hypertension, dyslipidaemia, obesity etc.), preventive healthcare should focus on changing lifestyle in order to reduce obesity and increase physical activity. This narrative review considers the available evidence from clinical and experimental studies dealing with MetS, and current treatment options for patients with insulin resistance and MetS.

Abstract

Objective:
The aim of this study was to determine the distribution of major risk factors among patients with atherosclerotic disease aged ≤50 years.
Subjects and methods:
The study population comprised 944 patients aged ≤50 years with clinically significant manifestations of atherosclerotic disease compared with 350 consecutive (control) older patients (age >50 years).
Results:
The most significant risk factors for atherosclerotic disease of the supra-aortic branches were: smoking (87.5%, p < 0.001), family history of atherosclerosis (52.3%, p < 0.001), diabetes mellitus (28.5%) and being male (56.9%) (p < 0.05 for both). In patients with coronary artery disease, there was considerable disparity in the prevalence of smoking (85.4%), hyperlipoproteinemia (67.4%), and family history of atherosclerosis (68%) (p < 0.001). For peripheral artery disease, the most significant risk factors were smoking (97%, p < 0.001), hyperlipidemia (p < 0.01), and family history of atherosclerotic disease (p < 0.01). When compared to controls, patients with premature atherosclerosis smoked more frequently, had hyperlipidemia, had a family history of atherosclerosis, and were more frequently of male sex.
Conclusion:
Premature atherosclerosis was most frequently associated with smoking, hyperlipidemia, family history of atherosclerotic disease, and male sex.

Abstract

Background:
Gentiana lutea (GL), commonly known as yellow gentian, bitter root, and bitterwort, belongs to family Gentianaceae. GL belongs to genus Gentiana, which is a rich natural source of iridoids, secoiridoids, xantones, flavonoids, triterpenoids, and carbohydrates. Medicinal plants from Gentiana species have anti-oxidant, anti-inflammatory, anti-mitogenic, anti-proliferative, and lipidlowering effects, as well as a cardioprotective, hypotensive, vasodilator and anti-platelet activities.

Objective:
We reviewed the recent literature related to the effects of Gentiana species, and their active components on vascular diseases.
cMethods:
Data used for this review were obtained by searching the electronic database [PUBMED/ MEDLINE 1973 - February 2020]. The primary data search terms of interest were: Gentiana lutea, Gentienacea family, phytochemistry, vascular diseases, treatment of vascular diseases, antioxidant, anti-inflammatory, anti-atherogenic.
Conclusion:
Gentiana species and their constituents affect many different factors related to vascular disease development and progression. Therefore, Gentiana-based therapeutics represent potentially useful drugs for the management of vascular diseases.
Keywords:
Gentiana lutea; Gentienacea family; anti-atherogenic.; anti-inflammatory; antioxidant; phytochemistry; treatment of vascular diseases; vascular diseases.

Abstract
Hypothyroidism is a common endocrine disorder that predominantly occurs in females. It is associated with an increased risk of cardiovascular diseases (CVD), but the molecular mechanism is not known. Disturbance in lipid metabolism, the regulation of oxidative stress, and inflammation characterize the progression of subclinical hypothyroidism. The initiation and progression of endothelial dysfunction also exhibit these changes, which is the initial step in developing CVD. Animal and human studies highlight the critical role of nitric oxide (NO) as a reliable biomarker for cardiovascular risk in subclinical and clinical hypothyroidism. In this review, we summarize the recent literature findings associated with NO production by the thyroid hormones in both physiological and pathophysiological conditions. We also discuss the levothyroxine treatment effect on serum NO levels in hypothyroid patients.
Keywords:
Cardiovascular diseases; Endothelial dysfunction; Hypothyroidism; Levothyroxine; Nitric oxide.

Abstract

Objective:
The aim of this study was to evaluate the results of endovascular therapy on the treatment of different types of iliac occlusions.
Materials and methods:
A bi-center prospective, non-randomized study was conducted on 100 patients (mean age 59.14 ± 8.53; 64 men) who underwent endovascular treatment of iliac occlusive disease between January 2013 and November 2017. We evaluated baseline data, procedure, and follow-up results for the entire group, and according to Trans-Atlantic Inter-Society Consensus (TASC II) classification. The majority of patients (60%) were treated for severe claudication; 56 (56%) patients had TASC B occlusions, 28 patients TASC C, and 16 patients TASC D.
Results:
The mean length of the occluded segments was 61.41 ± 35.15 mm. Procedural complications developed in 6 patients (6%). Mean ankle-brachial pressure index increased from 0.40 ± 0.12 preoperatively to 0.82 ± 0.16 postoperatively. The mean follow-up was 33.18 ± 15.03 months. After 1 and 5 years, the primary patency rates were 98% and 75.1%, and the secondary patency rate was 97% respectively. Regarding occlusion complexity there were no statistical significant differences in primary patency rates (TASC B vs. C vs. D: p = 0.19). There were no statistically significant differences in primary patency rates between patients in different clinical stages, as well as between the type of stents, and location of the occlusion.
Conclusion:
In our study, endovascular treatment for iliac artery occlusions proved to be a safe and efficient approach with excellent primary and secondary patency rates regardless of the complexity of occlusions defined by TASC II classification. This study is aligned with the notion that in well selected patients, endovascular therapy can be the treatment of choice even in complex iliac lesions if performed by experienced endovascular interventionists in high volume centers.

Abstract
More people die from cardiovascular diseases (CVD) than from any other cause. Cardiovascular complications are thought to arise from enhanced levels of free radicals causing impaired "redox homeostasis," which represents the interplay between oxidative stress (OS) and reductive stress (RS). In this review, we compile several experimental research findings that show sustained shifts towards OS will alter the homeostatic redox mechanism to cause cardiovascular complications, as well as findings that show a prolonged antioxidant state or RS can similarly lead to such cardiovascular complications. This experimental evidence is specifically focused on the role of glutathione, the most abundant antioxidant in the heart, in a redox homeostatic mechanism that has been shifted towards OS or RS. This may lead to impairment of cellular signaling mechanisms and elevated pools of proteotoxicity associated with cardiac dysfunction.

Abstract
The rising pandemic of obesity in modern society should direct attention to a more comprehensive approach to abdominal aortic aneurysm (AAA) treatment in the affected population. Although overweight patients are considered prone to increased surgical risk, studies on the subject did not confirm or specify the risks well enough. Associated comorbidities inevitably lead to a selection bias leaning towards endovascular abdominal aortic repair (EVAR), as a less invasive treatment option, which makes it hard to single out obesity as an independent risk factor. The increased technical difficulty often results in prolonged procedure times and increased blood loss. Several smaller studies and two analyses of national registries, including 7935 patients, highlighted the advantages of EVAR over open repair (OR) of abdominal aortic aneurysm, especially in morbidly obese population (relative risk reduction up to 47%). On the other hand, two other studies with 1374 patients combined, concluded that EVAR might not have an advantage over OR in obese patients (P = 0.52). Obesity is an established risk factor for wound infection after both EVAR and OR, which is associated with longer length of stay, subsequent major operations, and a higher rate of graft failure. Percutaneous EVAR technique could present a promising solution to reducing this complication. EVAR seems like a more feasible treatment option than OR for obese patients with AAA, due to lower overall morbidity and mortality rates, as well as reduced wound-related complication rates. However, there is a clear lack of high-quality evidence on the subject, thus future prospective trials are needed to confirm this advantage.
Keywords:
EVAR; Obesity; abdominal aortic aneurysm; complications; risk; wound.

Abstract

Objective:
The objective of this study was to report the 1-year follow-up study results of the new Horizon stent graft (Endospan, Herzliya, Israel) from two different prospective consecutive trials. The Horizon abdominal aortic aneurysm stent graft system is a 14F profile system requiring only a single access site. It consists of three modules, introduced separately: base limb (iliac to iliac limb); distal aortic limb; and proximal aortic limb with a bare suprarenal crown and active fixation.
Methods:
Data from the first in man (FIM) clinical study with 10 patients enrolled and the pivotal study with 30 patients were analyzed. Outcomes measured were freedom from major adverse events (MAEs) including all-cause mortality, myocardial infarction, renal failure, respiratory failure, paraplegia, stroke, bowel ischemia, and procedural blood loss ≥1000 mL. Performance end points included successful delivery and deployment of the device, freedom from aneurysm growth ≥5 mm, type I or type III endoleak, stent graft occlusion, conversion to open surgery, rupture, and stent graft migration.
Results:
In the FIM study, one conversion to open surgery with >1000 mL of blood loss was registered perioperatively. In the pivotal study, no perioperative MAE was registered. Overall, at 1-year follow-up, two deaths and one aneurysm growth unrelated to endoleak were registered.
Conclusions:
The results of both the FIM and pivotal studies demonstrated that 39 of 40 procedures were successful for delivery and deployment of the Horizon stent graft. No MAE was registered during the follow-up. The primary safety and performance end points were met in both studies.
Trial registration:
ClinicalTrials.gov NCT02087501.

Abstract
Coronary artery disease (CAD) and myocardial infarction (MI) are recognized as leading causes of mortality in developed countries. Although typically associated with behavioral risk factors, such as smoking, sedentary lifestyle, and poor dietary habits, such vascular phenotypes have also long been recognized as being related to genetic background. We review the currently available data concerning genetic markers for CAD in English and non-English articles with English abstracts published between 2003 and 2018. As genetic testing is increasingly available, it may be possible to identify adequate genetic markers representing the risk profile and to use them in a clinical setting.
Keywords:
GWAS analysis; coronary artery disease; familial hypercholesterolemia; genetic markers.

Abstract

Background:
The aim of this study was to assess the knowledge and attitude of medical students in relation to cardiovascular disease (CVD) risk factors as well as to assess the impact of medical education on their knowledge and recognition of the importance of implementation of preventive measures.
Methods:
This cross-sectional study included 514 students in the second year of studying at the Faculty of Medicine in Belgrade, Serbia (younger students response rate 79.57%) and 511 students in the last year of education (older students response rate 90.21%). For data collection, an anonymous self-administered questionnaire was used, which included two types of questions about CVD risk factors and questions about the student's attitude.
Results:
Older students knew significantly more about CVD risk factors than students who were at the beginning of their medical studies; however, more than half of the older students did not know the correct answers about CVD risk factors. The only exceptions were questions about "bad" and "good" cholesterol, metabolic syndrome (MSy) and lipid lowering therapy in high risk subjects. Physical inactivity, obesity, type 2 diabetes, smoking and hypertension were not ranked highly enough as important CVD risk factors. Compared groups of students did not significantly differ in attitude scores. The majority of them recognized CVD as the leading cause of death, had normal weight and knew their own blood pressure.
Conclusion:
Knowledge of medical students from Belgrade about CVD risk factors should be improved.
Keywords:
Cardiovascular disease; Medical students; Metabolic syndrome; Risk factors.

Abstract

Background:
Vascular age (VA) represents chronological age adjusted for an individual's atherosclerotic burden. Keeping in mind the fact that facial vascularization could influence the success of esthetic interventions, we aimed to investigate the predictive value of VA in development of side effects following facial lipofilling.
Methods:
In the period from October 1, 2014, to October 1, 2015, 106 consecutive subjects who underwent a facial lipofilling were included in the study. The VA was calculated using two approaches: Systematic Coronary Risk Evaluation (SCORE) project equations and means of vascular parameters assessed by color duplex sonographic examinations. The data regarding facial lipofilling-related complications (pain, edema and/or hematoma) have been collected during the regular checkups over 2 weeks after intervention.
Results:
The average chronological age of the participants was 50.9 ± 9.4 years. Estimation of VA using vascular sonographic parameters revealed the value of 45.4 ± 29.1 years, whereas the assessment of VA using SCORE equations showed that the mean age was 53.7 ± 12.7 (p = 0.006). The total frequency of these complications was as follows: 6.6% for hematoma, 15.1% for edema (13.2% mild edema and 1.9% severe edema) and 20.8% for local facial pain (17.0% mild pain and 3.8% severe pain). The multivariate logistic regression models showed that VA had statistically significant (p < 0.01) independent prognostic value for facial lipofilling-related appearance of hematoma and pain.
Conclusions:
The results of our study revealed that advanced VA has an independent predictive role in the appearance of complications following facial plastic surgery.
Level of evidence iii:
This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
Keywords:
Lipofilling; Side effects; Vascular age.

Abstract
Apoptosis may contribute to a significant proportion of neuron death following acute brain ischemia (ABI), but the underlying mechanisms are still not fully understood. Brain ischemia may lead to stroke, which is one of the main causes of long-term morbidity and mortality in both developed and developing countries. Therefore, stroke prevention and treatment is clinically important. There are two important separate areas of the brain during ABI: the ischemic core and the ischemic penumbra. The ischemic core of the brain experiences a sudden reduction of blood flow, just minutes after ischemic attack with irreversible injury and subsequent cell death. On the other hand, apoptosis within the ischemic penumbra may occur after several hours or days, while necrosis starts in the first hours after the onset of ABI in the ischemic core. ABI is characterized by key molecular events that initiate apoptosis in many cells, such as overproduction of free radicals, Ca2+ overload and excitotoxicity. These changes in cellular homeostasis may trigger either necrosis or apoptosis, which often depends on cell type, cell age, and location in the brain. Apoptosis results in DNA fragmentation, degradation of cytoskeletal and nuclear proteins, cross-linking of proteins, formation of apoptotic bodies, expression of ligands for phagocytic cell receptors and finally uptake by phagocytic cells. This review focuses on recent findings based on animal and human studies regarding the apoptotic mechanisms of neuronal death following ABI and the development of potential neuroprotective agents that reduce morbidity. The effects of statins on stroke prevention and treatment as well as on apoptotic mediators are also considered.
Keywords:
Apoptosis; acute brain ischemia; caspase; death receptor; statins; stroke.

Abstract

Background:
Overexpression of inducible nitric oxide synthase (iNOS) is a key link between high-fat (HF) diet induced obesity and cardiovascular disease. Oestradiol has cardioprotective effects that may be mediated through reduction of iNOS activity/expression.
Methods:
In the present study, female Wistar rats were fed a standard diet or a HF diet (42% fat) for 10 weeks. iNOS gene and protein expressions were measured in heart tissue. HF-fed rats exhibited a significant increase in cardiac iNOS mRNA by 695% (p<.05), iNOS protein level by 248% (p<0.01), without changes in nitrate/nitrite levels. Expression of CD36 protein in plasma membranes was increased by 37% (p<0.05), while the concentration of free fatty acids (FFA) was reduced by 25% (p<0.01) in HF-fed rats. Expression of the p50 subunit of nuclear factor-kB (NFkB-p50) in heart was increased by 77% (p<0.01) in HF-fed rats. Expression of protein kinase B (Akt) and extracellular signalregulated kinases 1/2 (ERK1/2) were unchanged between the groups. There was a significant increase in the ratio of phospho-Akt/total Akt but not for phospho-ERK1/2/total ERK1/2 in HF-fed rats. Estrogen receptor-α levels (by 50%; p<0.05) and serum oestradiol concentrations (by 35%; p<0.05) were shown to be significantly reduced in HF-fed rats.
Results and conclusion:
Our results revealed that a HF diet led to increased iNOS expression, most likely via a mechanism involving Akt and NFκB-p50 proteins. Decreased levels of oestradiol and ERα protein in the HF-fed group, in combination with increased iNOS levels are consistent with the hypothesis that oestradiol has a cardioprotective effect through its ability to regulate iNOS expression.
Keywords:
Cardioprotection; cardiovascular disease; inducible nitric oxide synthase; insulin resistance; obesity; oestradiol.

Abstract

Introduction:
Infection of synthetic graft in the groin is a rare but devastating complication. When it occurs, several possibilities of treatment are available. Extra-anatomic reconstruction and in-situ implantation of new, infection resistant grafts are associated with high mortality and morbidity. Therefore, more conservative approach is needed in some cases. Negative-pressure wound therapy is one of the options in treating such patients.
Objective:
The aim of this study was to assess the outcome for deep groin vascular graft infection treated with negative-pressure wound therapy.
Methods:
Seventeen patients (19 wounds), treated for Szilagyi grade III groin infections between October 2011 and June 2014, were enrolled into this observational study.
Results:
Majority of the wounds (11/19) were healed by secondary intention, and the rest of the wounds (8/19) were healed by primary intention after initial negative-pressure wound therapy and graft substitution with silver-coated prostheses or autologous artery/vein implantation. No early mortality was observed. Minor bleeding was observed in one patient. Reinfection was noted in three wounds. Only one graft occlusion was noted. Late mortality was observed in three patients.
Conclusion:
Negative-pressure wound therapy seems to be safe for groin vascular graft infections and comfortable for both patient and surgeon. However, the rate of persistent infection is high. This technique, in our opinion, can be used as a “bridge” from initial wound debridement to definitive wound management, when good local conditions are achieved for graft substitution, either with new synthetic graft with antimicrobial properties or autologous artery/vein. In selected cases of deep groin infections it can be used as the only therapeutic approach in wound treatment.

Abstract

Introduction:
Necrotizing fasciitis is a rare, progressive bacterial infection of superficial fascia followed by secondary subcutaneous tissue necrosis. We pressented a patient with massive fulminant lifethreatening necrotising fasciitis after bellow-knee femoro-popliteal vein bypass grafting successfully treated by antibiotics, surgical debridement and final skin reconstruction using the Tierch method.
Case report:
A 61-year-old patient was admitted to the Vascular Surgery Clinic for below-knee femoro-popliteal bypass grafting. He complained of intermittent claudication in the left leg after 50 m, ankle brachial indexes were 0.45 on the left and 1.0 on the right side. Femoropopliteal below-knee bypass grafting was done using the autologous great saphenous vein. In the very next day, initial signs of skin infection appeared including local inflammation, erythema, swelling and cellulitis restricted to saphenectomy site. These changes had rapidly spread in the following days on the deep tissue of the whole upper and lower leg, including the groin and with clinical signs of life-threatening systemic infection. Immediate surgical debridement was done followed by extensive wound packing and wide spectrum antibiotics administration for the next 33 days when final skin reconstruction by the Tierch method was performed. Interesting point is that this entire time wound swab was sterile.
Conclusion:
In the presented case immediate surgical debridement, wide spectrum antibiotics administration and consistent wound packing gave satisfactory results in this life-threatening systemic infection. Wound swab is not always a reliable indicator of the infection while clinical findings and surgeons' experience are of great significance in rapid reaction to this rare surgical complication.

Abstract
The pathogenesis of acute brain ischemia (ABI) is highly complex and involves multiple mechanisms including free radical generation. Imbalance between the cellular production of free radicals and the ability of cells to defend against them is referred to as oxidative stress. Oxidative stress is one of the mechanisms contributing to neuronal damage, potentially induced through the ABI. Through interactions with a large number of molecules, reactive oxygen species may irreversibly destroy or alter the function of the cellular lipids, proteins, and nucleic acids and initiate cell signaling pathways after cerebral ischemia. Future investigations should focus on the understanding of oxidative stress mechanisms and neuroprotection in order to discover new treatment targets.
Keywords:
acute brain ischemia; free radicals; oxidative stress; stroke.

Abstract
Acute brain ischemia caused by transient ischemic attack initiates a complex sequence of events in the central nervous system and hypothalamic-pituitary-adrenal (HPA) axis which may ultimately culminate in neuronal and cell damage. The brain is highly susceptible to ischemia and in response to stress shows changes in morphology and chemistry that are largely reversible. These responses are known to modify the function of the HPA axis, but their mechanisms are not yet clear. Duration and size of the HPA axis activation are regulated by corticotropin-releasing hormone, vasopressin (AVP), and glucocorticoids, including cortisol. Numerous studies suggest that activation of these hormones following brain ischemia can result in neurohormonal dysfunction that can exacerbate long-term prognosis following stroke. These studies represent evidence that changes in the HPA axis play an important role in brain ischemia.
Keywords:
acute brain ischemia; hypothalamic–pituitary–adrenal axis; stroke; transient ischemic attack.

Abstract

Background:
The purpose of this study was to evaluate the initial and long-term results of endovascular treatment (EVT) in patients with symptomatic high-grade extracranial vertebral artery (VA) origin stenosis.
Methods:
From February 2001 to March 2013, 73 consecutive patients (33 men with a mean age of 61.7 ± 8.8 years) underwent EVT for symptomatic high-grade VA stenosis. Preoperative evaluation included Duplex ultrasonography and arteriography. After successful treatment, all patients were followed up at 1, 3, 6, and 12 months after the procedure and every 6 months thereafter.
Results:
Successful EVT of the VA stenosis was achieved in 68 patients (93.2%). All procedures were performed without use of cerebral protection. The early complication rate was 5.5%, which included one periprocedural transient ischemic attack, two hematomas at the puncture site, and one allergic reaction to the contrast agent. No in-hospital deaths occurred. During follow-up (mean, 44.3 ± 31.2 months; range, 2-144 months), the primary patency rates at 1, 3, 5, and 7 years were 98.4%, 87.3%, 87.3%, and 87.3%, respectively. Ultrasound Doppler controls during follow-up detected seven VA restenoses (10.3%). Univariate analysis failed to identify any variable predictive of long-term patency of successfully treated VA stenosis.
Conclusions:
EVT of symptomatic VA origin stenosis is a safe and effective procedure associated with low risk and good long-term results, even without use of cerebral protection devices.

Abstract
We present the case of a patient with extremely rare associated congenital anomalies: thoracic aorta coarctation and left ectopic kidney with pelvic presentation. A 45-year-old male patient was admitted to our institution for multidetector computed tomography (MDCT) angiography. On admission, he complained of intermittent claudication after 10 meters of walking, frequent chest pain, and hypertension crisis. Femoral pulse was absent in the left leg. At 14 years of age, he underwent insertion of a 10-mm Dacron tubular graft at the descending aorta level for isthmic coarctation. MDCT arteriography revealed significant stenosis (>90%) at the proximal anastomosis site of a previous graft in the form of a floating thrombus (pseudocoarctation‒re-coarctation) as well as an ectopic pelvic left kidney with the left renal and accessory renal artery arising from the left common iliac artery. One year ago we attempted percutaneous angioplasty of the aforementioned in-graft stenosis. At the time, the procedure was partly successful and the patient had been doing well, but all of the aforementioned symptoms reappeared and CT angiography showed no signs of improvement. Therefore, ascending-to-descending aortic bypass was done with an 18-mm Dacron tubular graft with preserved postoperative renal function and palpable peripheral pulses. MDCT angiography showed normal postoperative findings and the patient was doing well. In the case presented, MDCT angiography played a significant role in this rare aortic anomaly detection with incidental discovery of a rare developmental kidney complication.

Abstract
The structure of protein-protein interaction (PPI) networks has already been successfully used as a source of new biological information. Even though cardiovascular diseases (CVDs) are a major global cause of death, many CVD genes still await discovery. We explore ways to utilize the structure of the human PPI network to find important genes for CVDs that should be targeted by drugs. The hope is to use the properties of such important genes to predict new ones, which would in turn improve a choice of therapy. We propose a methodology that examines the PPI network wiring around genes involved in CVDs. We use the methodology to identify a subset of CVD-related genes that are statistically significantly enriched in drug targets and "driver genes." We seek such genes, since driver genes have been proposed to drive onset and progression of a disease. Our identified subset of CVD genes has a large overlap with the Core Diseasome, which has been postulated to be the key to disease formation and hence should be the primary object of therapeutic intervention. This indicates that our methodology identifies "key" genes responsible for CVDs. Thus, we use it to predict new CVD genes and we validate over 70% of our predictions in the literature. Finally, we show that our predicted genes are functionally similar to currently known CVD drug targets, which confirms a potential utility of our methodology towards improving therapy for CVDs.

Abstract

Background/aim:
Endovascular treatment of thoracic aortic diseases is an adequate alternative to open surgery. This method was firstly performed in Serbia in 2004, while routine usage started in 2007. Aim of this study was to analyse initial experience in endovacular treatment of thoracic aortic diseses of three main vascular hospitals in Belgrade - Clinic for Vascular and Endovascular Surgery of the Clinical Center of Serbia, Clinic for Vascular Surgery of the Military Medical Academy, and Clinic for Vascular Surgery of the Institute for Cardiovascular Diseases "Dedinje".
Methods:
Between March 2004. and November 2010. 41 patients were treated in these three hospitals due to different diseases of the thoracic aorta. A total of 21 patients had degenerative atherosclerotic aneurysm, 6 patients had penetrating aortic ulcer, 6 had posttraumatic aneurysm, 4 patients had ruptured thoracic aortic aneurysm, 1 had false anastomotic aneurysm after open repair, and 3 patients had dissected thoracic aneurysm of the thoracoabdominal aorta. In 15 cases the endovascular procedure was performed as a part of the hybrid procedure, after carotid-subclavian bypass in 4 patients and subclavian artery transposition in 1 patient due to the short aneurysmatic neck; in 2 patients iliac conduit was used due to hypoplastic or stenotic iliac artery; in 5 patients previous reconstruction of abdominal aorta was performed; in 1 patient complete debranching of the aortic arch, and in 2 patients visceral abdominal debranching were performed.
Results:
The intrahospital mortality rate (30 days) was 7.26% (3 patients with ruptured thoracic aneurysms died). Endoleak type II in the first control exam was revealed in 3 patients (7.26%). The patients were followed up in a period of 1-72 months, on average 29 months. The most devastating complication during a followup period was aortoesofageal fistula in 1 patient a year after the treatment of posttraumatic aneurysm. Conversion was performed with explantation of stent-graft and open aortic in situ recontruction, followed by esophagectomy and the creation of cervical and gastrical stoma.
Conclusion:
Having in mind initial results of the 3 main vascular clinics in Belgrade, Serbia, economical situation in our country, as well as the published international results, endovascular treatment of thoracic aortic diseases is indicated in hemodinamicaly unstable patients with acute traumatic aneurysm, or in stabile patients older than 65, as well as in case of chronic diseases of the thoracic aorta in patients with significant comorbid conditions or in patients older than 65 years. Endovascular procedures on the thoracic aorta could be performed, hower, only in high-volume centers with experience in routine open surgery of thoracic aorta.

Abstract

Background:
To study the initial and long-term results of endovascular treatment in patients aged <50 years with trans-Atlantic inter-society consensus-II type B unilateral iliac lesions and chronic limb ischemia.
Methods:
From January 2000 to February 2010, 60 consecutive endovascular interventions were performed on 23 women and 37 men aged ≤50 years. After successful treatment, all patients were followed up at 1, 3, 6, and 12 months after the procedure and every 6 months thereafter.
Results:
Successful percutaneous revascularization of the iliac artery was achieved in 56 patients (93.3%). The early vascular-related complication rate was 6.7%. The primary patency rates at 1, 3, and 5 years were 88%, 59%, and 49%, respectively. Cox univariate analysis revealed that an age range of 45 to 50 years (hazard ratio [HR]: 0.290; 95% confidence interval [CI]: 0.152-0.553; P = 0.0001), lower preprocedural ankle-brachial index (HR: 2.438; 95% CI: 1.04-5.715; P = 0.047), lesion length >5 cm (HR: 0.838; 95% CI: 0.746-0.943; P = 0.003), and diabetes (HR: 2.005; 95% CI: 1.010-3.980; P = 0.047) had significant influence on decreasing primary patency.
Conclusions:
Endovascular treatment of TASC-II type B iliac lesions in patients aged <50 years is a safe procedure with low procedural risk. Primary patency rates at 1, 3, and 5 years were 88%, 59%, and 49%, respectively.

Abstract

Introduction:
Telangiectasias represent an esthetic problem. Sclerotherapy, laser and radiowave coagulation are established methods of treatment. The aim of the treatment is a cosmetic improvement in the leg appearance.
Aim:
To define which method provides best results in lower extremity telangiectasias treatment and also to determine which method is most comfortable for the patient.
Materials and methods:
Thirty female volunteers, ages 30-66 years (mean 49 years), were included in the research, with telangiectasias in the thigh measuring 0,1 to 2 mm in diameter, and skin phototype according to Fitzpatrick I-IV. Three rectangular areas 3 × 5 cm, were marked on the thigh, with nearly same pattern and appearance of telangiectasias in each field. In each rectangle, only one session of sclerotherapy, laser, and radiowave coagulation were performed, respectively. It is completely documented with the digital camera prior to the therapy and 3 months after the treatment. At the end of the study, three blinded experts graded leg telangiectasias for clearance using obtained digital images. Patients were also required to describe the sense of pain during each procedure as minimal, mild, or strong. Chi-square test was used for statistical data processing.
Results:
After 3 months period, there was a high statistical significant difference among methods of treatment (χ(2) = 45.492, p < 0.01). The most efficient was sclerotherapy. Also there was a high statistical significant difference (χ(2) test = 30.549, p < 0.01) among levels of pain experienced by patients in the study. Minimal sense of pain was associated with sclerotherapy.
Conclusion:
Our study revealed that the most efficient method in terms of telangiectasias clearance is sclerotherapy. It also showed that most comfortable method for the patient is sclerotherapy, since it produces minimal pain during the procedure. It can be concluded that sclerotherapy is a successful method in treating lower extremity telangiectasias leaving both, patient and physician content.

Abstract

Background:
We and others have shown previously that left ventricular (LV) contractile reserve assessed quantitatively by high-dose dobutamine stress-echocardiography (DSE) has prognostic implications in patients with dilated cardiomyopathy.
Purpose:
To assess the feasibility of semi-quantitative assessment of LV contractile reserve by differently skilled operators in patients with dilated cardiomyopathy.
Methods:
High-dose DSE was performed in 63 consecutive patients, mean age 50 ± 10 years and ejection fraction (EF) 19 ± 8%. LVEF was calculated 1) using Simpson's biplane formula, and 2) semi-quantitatively (5% increments) by novice and experienced echocardiographers, and by a DSE expert. Patients were considered to have preserved LV contractile reserve if LVEF dobutamine-induced change was ≥5%.
Results:
Twenty-seven (45.8%) patients died during the 5-year follow-up. The feasibility of the assessment was 89%, 94%, and 98% for novice and experienced readers and DSE expert, respectively. Kaplan-Meier analysis showed that LV contractile reserve assessed semi-quantitatively by DSE expert and experienced reader achieved the best prognostic separation (log rank 19.63 and 18.99, respectively, p < 0.001 for both), followed by quantitative assessment (log rank 9.76, p = 0.0018) and assessment by novice reader (log rank 8.76, p = 0.012). Areas under the curves were similar for quantitative and semi-quantitative assessment of LV contractile reserve.
Conclusions:
Our data indicate that semi-quantitative assessment of LV contractile reserve is feasible by differently skilled operators.

Abstract

Purpose:
To study the initial and long-term results of angioplasty and primary stenting for the treatment of chronic total occlusion (CTO) of the subclavian artery (SA).
Materials and methods:
From January 1999 to February 2010, 56 patients (25 men with a mean age of 58 ± 8 years) underwent endovascular treatment for CTO of the SA. Duplex scans and arteriograms confirmed occlusion in all cases. Indications for recanalization were subclavian steal syndrome in 33 patients (58.1%), arm claudication in 13 patients (23.2%), and coronary ischemia in 7 patients (12.5%) who had a history of previous coronary artery bypass grafting that included left internal thoracic artery graft. Three patients (5.4%) were treated before the scheduled coronary artery bypass surgery, which included left internal thoracic artery graft. After successful recanalization, all arteries were stented, and all of the patients were followed-up at 1, 3, 6, and 12 months after surgery and annually thereafter.
Results:
Successful recanalization of the SA was achieved in 46 patients (82.1%), and the complication rate was 7.1%. During follow-up (mean 40 ± 26 months; range 2 to 125), the primary patency rates after 1 and 3 years were 97.9% and 82.7%, respectively. At the end of follow-up, 76% of the arteries showed no evidence of restenosis. Univariate analysis failed to identify any variable predictive of long-term patency of successfully recanalized SA.
Conclusion:
Percutaneous transluminal angioplasty with stenting of the complete total occlusion of the SA is a safe and effective procedure associated with low risks and good long-term results.

Abstract

Introduction:
A right-sided aortic arch is a rare congenital defect of the aorta with incidence of 0.05% to 0.1% reported in published series. Usually it is associated with congenital heart anomalies and esophageal and tracheal compression symptoms. We present a case of a right-sided aortic arch of anomalous left subclavian artery origin, accidentally revealed during multislice CT (MSCT) supraaortic branches angiography.
Case outline:
A 53-year-old female patient was examined at the Outpatients' Unit of the Vascular Surgery University Clinic for vertigo, occasional dizziness and difficulty with swallowing. Physical examination revealed a murmur of the left supraclavicular space, with 15 mmHg lower rate of arterial tension on the left arm. Ultrasound of carotid arteries revealed 60% stenosis of the left subclavian artery and bilateral internal carotid artery elongation. MSCT angiography revealed a right-sided aortic arch with aberrant separation of the left subclavian artery that was narrowed 50%, while internal carotid arteries were marginally elongated. There was no need for surgical treatment or percutaneous interventions, so that conservative treatment was indicated.
Conclusion:
A right-sided aortic arch is a very rare anomaly of the location and branching of the aorta. Multislice CT angiography is of great importance in the diagnostics of this rare disease.

Abstract
Unlike high-grade stenosis, dissections of craniocervical arteries are a rare cause of cerebrovascular infarction. If the internal carotid artery (ICA) dissection is verified by duplex scanning or computed tomography angiography (CTA), the therapies of choice are antiplatelet and anticoagulation drugs, and surgical treatment is rarely performed. However, despite distinct clinical and radiological manifestation, carotid dissections are still under-recognized. In this study, we demonstrate the case of a 66-year-old man with dissection of ICA verified by duplex scanning and computed tomography angiography. The cause of missed diagnosis was an ascending pharyngeal artery originating from the ICA that runs parallel to it. Other than being a rare variation, this case may be interesting as a cause of misdiagnosis.

Abstract
Nitric oxide synthases (NOS) are the enzymes responsible for nitric oxide (NO) generation. NO is a reactive oxygen species as well as a reactive nitrogen species. It is a free radical which mediates several biological effects. It is clear that the generation and actions of NO under physiological and pathophysiological conditions are regulated and extend to almost every cell type and function within the circulation. In mammals 3 distinct isoforms of NOS have been identified: neuronal NOS (nNOS), inducible NOS (iNOS) and endothelial NOS (eNOS). The important isoform in the regulation of insulin resistance (IR) is iNOS. Understanding the molecular mechanisms regulating the iNOS pathway in normal and hyperglycemic conditions would help to explain some of vascular abnormalities observed in type 2 diabetes mellitus (T2DM). Previous studies have reported increased myocardial iNOS activity and expression in heart failure (HF). This review considers the recent animal studies which focus on the understanding of regulation of iNOS activity/expression and the role of iNOS agonists as potential therapeutic agents in treatment of IR, T2DM and HF.
Keywords:
Inducible nitric oxide synthase; diabetes; heart failure.; insulin resistance.

Abstract

Introduction:
Congenital coarctation of the thoracic aorta at the ligamentum arteriosum or the aortic arch is well recognized. But a much less common variety (0.5-2.0%) of aortic coarctation is located in the distal thoracic aorta or abdominal aorta or both and is often called "middle aortic syndrome" or "mid-aortic dysplastic syndrome". This represents serious pathological condition and indicates multidisciplinary therapy approach.
Outline of cases:
From 1996 to 2007, at the Vascular Surgery Clinic of the Institute for Cardiovascular Diseases "Dedinje", Belgrade, three patients were treated due to abdominal aorta coarctation, two females aged 55 and 50 and a 4-year-old child. The patients were treated surgically (by-pass with a prosthetic graft and patch angioplasty) and endovascular- percutaneous transluminal angioplasty (PTA) with and without a stent. The follow-up period was 3-70 months. In the 50-year-old patient, angiography showed severe narrowing of the suprarenal segment of the abdominal aorta. Thoraco-abdominal bypass with a 16 mm dacronic tubular graft was performed. In the 4-year-old patient angiography also showed a suprarenal aorta narrowing. In the first act patch angioplasty was performed and after PTA of the visceral arteries was done on several occasions. In the 55-year-old patient, after diagnostic angiography, infrarenal aorta coarctation was registered. PTA was performed with stent placement. All patients were asymptomatic on control check-ups.
Conclusion:
Abdominal coarctation is a pathological disease which is seldom found in vascular surgery. Angiography is of major importance for setting the diagnosis and for the control of the results of surgical and nonsurgical treatment. The combination of surgical and endovascular treatment in our patients showed very good results in the studied period.

Abstract

Introduction:
Though surgical approach is common in arteriovenous (AV) fistula treatment, endovascular procedures such as stent-graft placement has become more popular in recent years. We aim to present a case of thrombosed femoral artery stent-graft which was placed one year earlier due to multiple AV fistulas following gunshot wounds.
Case outline:
A 43-year-old patient was admitted to the Institute for Cardiovascular Diseases "Dedinje", Belgrade, Serbia, for arteriography. Five years before, he had suffered from six gunshot wounds in his right leg and one year before, in the health centre in Vienna, stent-graft had been placed in the right superficial femoral artery due to multiple AV fistulas. Because of artery dilation proximal to AV fistula location, a large dimensional stent-graft had to be placed (24 mm). After admission, arteriography and Multislice CT (MSCT) angiography revealed thrombotic masses in the stent-graft with intraluminal stenosis of 50%. Extirpation of thrombosed stent-graft was performed followed by Dacron tubular graft 10 mm interposition. On the fifth postoperative day, the patient was discharged from the clinic, and after 3 months, the right leg vascularisation was well preserved.
Conclusion:
Large dimensional stent-graft placement in patients with mutiple AV fistulas and blood vessel dilation proximal to AV site of communication carries an increased risk of thrombotic events due to turbulent blood flow and parietal thrombosis occurrence. Though stent-graft placement can be a very useful solution in acute AV fistula treatment, the very same thrombosis should be thought of when surgical management is the only treatment choice.

Abstract
The American otolaryngologist Eagle was the first to describe styloid syndrome in 1937. Stylohyoid complex is composed of styloid process, stylohyoid ligament and a lesser horn of the hyoid bone. Embriologicaly, these anatomical structures originate from Reichert's cartilage of the second brachial arch. In the general population, the frequency of the elongated styloid process is estimated to be 4%, of which only 4% show clinical manifestations suggesting that the incidence of styloid syndrome is 0.16% (about 16,000 persons in Serbia). The styloid process deviation causes external or internal carotid impingement and pains which radiate along the arterial trunk. Classical stylohyoid syndrome is found after tonsillectomy and is characterised by pharyngeal, cervical, facial pain and headache. Stylo-carotid syndrome is the consequence of the pericarotid sympathetic fibres irritation and compression on the carotid artery. Clinical manifestations are found most frequently after head turning and neck compression. The diagnostic golden standard for styloid syndrome is 3D CT reconstruction. Sagital CT angiography has a leading role in the radiological diagnosis of the stylo-carotid syndrome. Differential diagnosis requires the differentiation of the styloid syndrome from numerous cranio-facio-cervical painful syndromes. If conservative treatment (analgesics, anticonvulsants, antidepressants, and local infiltration with steroids or anaesthetic agents) has no effect, surgical treatment is applied. Styloid syndrome is underrepresented in neurological literature. The syndrome is considered important, because it is clinically similar to many other painful cranio-facial syndromes; it is difficult to be recognized, and the patient should be treated adequately.
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Abstract

Introduction:
The sciatic artery represents the earliest embryological blood supplyto the lower extremity. It regresses after the 3rd month of embryologic development. The proximal part of the sciatic artery eventually persists as the inferior gluteal artery. Rarely, however, it persists into adulthood when it is frequently associated with numerous possible complications (aneurysm formation, embolism, nerve compression, rupture, thrombosis).
Case outline:
In March 1996, a 48-year-old male was admitted for angiography of the blood vessels of the right inferior extremity, before an elective orthopaedic procedure. Arteriography of the right leg was done in a usual manner through the right common femoral artery in order to get an angiogram of the popliteal trifurcation and crural arteries. However, on the first field we noticed a hypoplastic superficial femoral artery, as well as a huge persistent sciatic artery (PSA) originating from the internal iliac artery running distally and overlapping the deep femoral artery. There were no aneurysm and stenotic changes of PSA.
Conclusion:
If clinical condition is stable, follow-ups at 12 months intervals should be done by means of ultrasound. The therapeutic decisions also depend on complete or incomplete PSA.

Abstract

Introduction:
The American otolaryngologist Eagle was the first to describe styloid syndrome in 1937 and the syndrome was named after him (Eagle's syndrome). The original description of two separate syndromes is connected with his name: classical syndrome, which almost constantly occurs after tonsillectomy and carotid artery syndrome, which occurs without tonsillectomy and also in cases when stylohyoid complex compresses the carotid segments and perivascular sympathetic fibers. In the following years, two more syndromes were defined: stylohyoid and pseudostylohyoid, which according to their manifestations, correspond to the genuine classical form.
Case outline:
A 40-year-old male is presented, with a history of 3-year duration of pains in the upper part of the left side of the neck, in the left eye and its surroundings. Pain occurrences were not regular. Throbbing pains were most often provoked by sudden head movements and neck compression. He was healthy until the onset of these problems. The findings of all examinations were normal. The applied prophylactic therapy, typical for cluster headache, was without any effect. On 64-MSCT (multislice computed tomography), the neck arteries did not show any intraluminal pathology. The styloid processes were of normal length. On the left side, the styloid process tip pressed the internal carotid artery disturbing its longitudinal axis.
Conclusion:
In our presentation, the defined lengths of the styloid processes were normal. The medial angulation of the left styloid process was more expressed reaching 63.5 degrees (the right side angulation was normal). Persistent and throbbing pain in the region of the left eye with backward projection suggested compression on the internal carotid artery. Pains were most frequently provoked by head turning and neck compression. 64-MSCT diagnostics enabled us to determine the characteristics of styloid processes and their relation to the internal carotid artery. Improvement was achieved by administration of antiepileptic (gabapentin) and antidepressant (amitriptyline) drugs.

Abstract

Introduction:
Transplantation is the method of choice in the treatment of terminal liver diseases with acute and structural damage of liver tissue and congenital liver diseases.
Objective:
The aim of our study was to determine specificity and significance of vascular anastomosis in liver transplantation by postoperative evaluation of vascular anastomosis function.
Method:
The study included 16 patients with 16 liver transplantations and one re-do liver transplantation. In all patients, preoperative angiography and postoperative duplex sonographic and angiographic evaluation of vascular anastomosis were performed.
Results:
Preoperative angiographic evaluation did not reveal anomalies in liver blood vessels of transplant candidates. In one patient, we identified and angiographically confirmed stenosis on anastomosis of the hepatic artery on the 7th postoperative day. In another patient, we had artificial thrombosis of the hepatic artery branch due to the liver biopsy.
Conclusion:
The successful performance of vascular anastomosis in liver transplantation is significant for adequate liver graft perfusion, good postoperative graft function and overall outcome of the liver transplantation.