Aggeliki Papapanagiotou

Ankle-brachial index as a predictor of the extent of coronary atherosclerosis and cardiovascular events in patients with coronary artery disease

Resting ankle-brachial pressure index (ABI) is a noninvasive method to assess the patency of the lower extremity arterial system. This study aimed to examine the relation between ABI and the extent of coronary atherosclerosis, the extracoronary atherosclerosis lesions, and the prognosis of patients referred for elective coronary angiography. One hundred sixty-five consecutive patients underwent coronary angiography, ultrasound imaging for intima-media thickness measurement of carotid and femoral arteries and ABI evaluation; subjects were followed up for 14.5 +/- 2.4 months. With regard to vascular risk factors, only smoking (p = 0.025) and diabetes (p = 0.01) were related to ABI in the multiple regression analysis. ABI was independently and inversely related to carotid bifurcation (p = 0.0002) and common femoral artery intima-media thickness (p = 0.018). ABI was related to the extent of coronary artery disease as measured by number of coronary arteries diseased (analysis of variance, p = 0.04) and Gensini angiographic score (p = 0.01). In the follow-up study ABI < 0.90 was a univariate predictor of cardiovascular events (cardiac death, nonfatal myocardial infarction, unstable angina) and revascularization procedures. The estimated cumulative rate free of cardiovascular events was 90% for ABI > 0.90 and 73% for ABI < 0.90 (p = 0.02). In logistic regression analysis, ABI < 0.90 was an independent predictor for cardiovascular events after adjustment for age, low-density lipoprotein cholesterol, carotid and femoral intima-media thickness, and Gensini score. Further adjustment for the confounding effect of insulin weakened the relation between ABI and cardiovascular events (p = 0.1). In conclusion, ABI is a simple index related to the extent of atherosclerosis in coronary and noncoronary arterial beds, reflecting generalized atherosclerosis. ABI could be useful in assessing the risk for cardiovascular events in patients with coronary artery disease.

Atherosclerotic changes of extracoronary arteries are associated with the extent of coronary atherosclerosis.

The aim of the present study was to examine the association between carotid and femoral artery intima media thickness (IMT) and the extent and severity of coronary artery disease (CAD) as well as the effects of traditional vascular risk factors on the atherosclerotic changes in the carotid and femoral arteries. Two hundred twenty-four patients who underwent coronary angiography for suspected CAD were evaluated by B-mode ultrasound imaging of the common carotid, internal carotid, carotid bifurcation, and femoral artery for measurement of IMT; traditional vascular risk factors were also evaluated in these patients. CAD extent was evaluated by the number of diseased vessels and by Gensini score. Age, male gender, and diabetes were common risk factors for higher CAD extent and higher carotid and femoral IMT. Insulin levels were correlated with femoral IMT and CAD extent, whereas blood lipids were correlated predominantly with carotid IMT. IMT from carotid and femoral arteries increased significantly with an increase in CAD extent. Using multiple stepwise regression analysis, the following parameters were found to be independent predictors of CAD extent: male gender (p<0.0001), common femoral artery IMT (p = 0.0028), common carotid artery IMT (p = 0.015), age (p = 0.02), diabetes mellitus (p = 0.035), and carotid artery bulb IMT (p = 0.04). Common femoral IMT was the only independent parameter for predicting Gensini score (p<0.0001). In conclusion, there are territorial differences in the various arterial beds regarding their response to risk factors. Femoral artery and carotid bulb are independent predictors of CAD extent and the inclusion of these measurements would add information to that provided by the common carotid artery.

Genetic variations of the endothelial nitric oxide synthase gene are related to increased levels of C-reactive protein and macrophage-colony stimulating-factor in patients with coronary artery disease

It was the objective of this study to investigate the relation between nitric oxide synthase (NOS3) gene polymorphisms, vascular inflammation, endothelial function, and atherosclerosis. We examined the effects of a variable nucleotide tandem repeats (VNTR) in intron 4, G894T in exon 7 and T-786C at the promoter region of NOS3 on i) C-reactive protein (CRP) and macrophage-colony stimulating-factor (MCSF), and ii) augmentation index (AI) measured by pulse-wave analysis , flow-mediated dilation (FMD) of the brachial artery, intima-media thickness (IMT) of the carotid and femoral artery using ultrasonography and ankle-brachial index (ABI) in 122 patients with chronic coronary artery disease (CAD) who underwent coronary angiography. MCSF and CRP were increased in patients withT-786C (77/122) or VNTR (40/122) allele compared to those without (F = 10.8, p = 0.002 and F = 3.8, p = 0.04 for T-786C and F = 3.65, p = 0.04 and F = 3.2 p = 0.049 forVNTR), even after adjustment for traditional risk factors and medication. Patients with combination of VNTR and T-786C (31/122) had higher MCSF or CRP than patients with one or none of these alleles (p < 0.05). Among patients with T-786C, those with MCSF>262 pg/ml or CRP>3.2 mg/l (n = 33/77) had a higher femoral and carotid IMT and number of plaques in the peripheral arteries than those with lower values of these inflammatory indices (p < 0.05). Patients with MCSF >262 pg/ml had also lower FMD and higher Gensini score than those with lower MCSF (p < 0.05). The intron 4-VNTR and T-786C mutation of NOS3 gene enhance the inflammatory process in patients with chronic CAD.

Clinical significance of plasma HDL subfractions (HDL2, HDL3) in patients with peripheral arterial disease (PAD) in the Greek population

OBJECTIVE In this study the major high density lipoprotein (HDL) subfractions (HDL2, HDL3) were examined, in angiographically selected patients with peripheral arterial disease (PAD). RESULTS Patients with PAD have significantly high triglyceride levels. HDL2 and HDL3 levels were found significantly reduced in patients with PAD. Also, the ratio HDL2-C/HDL3-C was significantly reduced in patients with PAD. CONCLUSIONS The aim of the present study is to provide additional support to the hypothesis that the determination of HDL subfractions could be useful to elucidate possible mechanism(s) for a better assessment of the risk profile for PAD.

The value of plasma neurotensin and cytokine measurement for the detection of bowel ischaemia in clinically doubtful cases: A prospective study

The aim of this prospective study was to examine whether serum neurotensin, interleukin (IL)-6, and IL-8 are early predictor of bowel ischaemia especially in clinically equivocal cases. To this end, 56 patients were assigned to the following groups according to their disease: bowel ischaemia (group 1: n = 14), small bowel obstruction (group 2: n = 12), acute inflammation (group 3: n = 6), perforation (group 4: n = 8), and colorectal adenocarcinoma (group 5: n = 16). Fifteen healthy controls were assigned to group 6. Blood samples were obtained at enrollment, all measurements were done blindly, and all patients underwent surgery. Pretreatment doubtful diagnosis comprised of ileus, mild abdominal pain, and indeterminate imaging. Blood urea nitrogen, lactic acidosis, diagnostic workup, and IL-6 were predictors of diagnosis in univariate analysis. In multivariate analysis, IL-6 (P < 0.001) and diagnostic workup (P < 0.01) were independent predictors of the definite diagnosis. Neurotensin and IL-8 did not differentiate among groups. Considering clinically doubtful cases, IL-6 perfectly differentiates mesenteric ischaemia (of infarction/embolic/occlusive aetiology) from the rest of the indeterminate pathologies. The optimum cut-off point for IL-6 was 27.66 pg/mL. The value of serum IL-6 (27.66 pg/mL) had sensitivity = 1 and specificity = 1. In conclusion, plasma IL-6 measurement on admission might be an additional diagnostic tool that can predict bowel ischaemia in doubtful clinical situations.

Comparative analysis of oestrogen and raloxifene effects on the phospholipid composition of high density lipoproteins in healthy postmenopausal women

The beneficial effect of selective oestrogen receptor modulators such as raloxifene in cardiovascular disease may be mediated partly by favourable changes in the phospholipid composition of high density lipoprotein (HDL) subclasses. In Group A (oestrogen alone) HDL2 phosphatidylcholine increased (P < 0.001), while there was a decrease in HDL2 phosphatidylinositol (P < 0.05) and HDL2 phosphatidylethanolamine (P < 0.05) compared to controls (baseline). In the same group, HDL3 phosphatidylcholine increased (P < 0.001) and HDL3 phosphatidylethanolamine decreased (P < 0.01). In Group B (raloxifene) HDL2 phosphatidylcholine increased (P < 0.001) as well as HDL2 diphosphatidylglycerol (P < 0.01) while there were decreases in HDL2 sphingomyelin (P < 0.01) and HDL2 phosphatidylethanolamine (P < 0.05). In the same group, an increase in HDL3 phosphatidylcholine (P < 0.001) and a reduction in HDL3 phosphatidylinositol (P < 0.05) were observed as well as a decrease in HDL3 phosphatidylethanolamine (P < 0.01) and HDL3 diphosphatidylglycerol (P < 0.05). The significance of these results is discussed.

Effects of hormone replacement therapy on the phospholipid composition of high density lipoproteins in postmenopausal women.

The beneficial effect of hormone replacement therapy (HRT) in reducing the risk of cardiovascular disease may be partly mediated by favourable changes in the phospholipid composition of high density lipoprotein (HDL) subclasses. In group A(oestrogen alone) HDL phosphatidylcholine increased (P<0.01), while 2 there was a decrease in HDL phosphaditylinositol (P<0.05) 2 and HDL phosphatidylethanolamine (P<0.01) compared with 2 controls (baseline). In the same group, HDL phosphatidylcholine 3 increased (P<0.01) and HDL phosphatidylethanolamine decreased (P<0.05). In group B (oestrogen plus progestogens), HDL phosphatidylcholine increased (P<0.001) while there were 2 decreases in HDL sphingomyelin (P<0.01), HDL 2 2 phosphatidylserine (P<0.05), HDL phosphatidylethanolamine 2 (P<0.01) and HDL diphosphatidylglycerol (P<0.05). In the 2 same group, an increase in HDL phosphatidylcholine (P<0.01) 3 and HDL phosphatidylserine (P<0.01) were observed, as well 3 as a decrease in HDL phosphatidylethanolamine (P<0.001). 3 The significance of these results is discussed.The beneficial effect of hormone replacement therapy (HRT) in reducing the risk of cardiovascular disease may be partly mediated by favourable changes in the phospholipid composition of high density lipoprotein (HDL) subclasses. In group A(oestrogen alone) HDL phosphatidylcholine increased (P<0·01), while 2 there was a decrease in HDL phosphaditylinositol (P<0·05) 2 and HDL phosphatidylethanolamine (P<0·01) compared with 2 controls (baseline). In the samegroup, HDL phosphatidylcholine 3 increased (P<0·01) and HDL phosphatidylethanolamine de3 creased (P<0·05). In group B (oestrogen plus progestogens), HDL phosphatidylcholine increased (P<0·001) while there were 2 decreases in HDL sphingomyelin (P<0·01), HDL 2 2 phosphatidylserine (P<0·05), HDL phosphatidylethanolamine 2 (P<0·01) and HDL diphosphatidylglycerol (P<0·05). In the 2 same group, an increase in HDL phosphatidylcholine (P<0·01) 3 and HDL phosphatidylserine (P<0·01) were observed, as well 3 as a decrease in HDL phosphatidylethanolamine (P<0·001). 3 The significance of these results is discussed.

Recurrent inguinal hernia repair: what is the evidence of case series? A meta-analysis and metaregression analysis.

To examine, if case series considered together with observational studies tend to produce similar results as randomized-controlled trials (RCTs), on recurrent hernia repair. A systematic literature review and meta-analysis between 1990 and 2013 revealed 46 nonrandomized studies (NRCTs) and 5 RCTs including 25,730 patients. A direct comparison of the summary estimates between RCTs and NRCTs is presented. Outcomes, within or across studies, were compared. Comparisons of all outcomes in NRCTs and RCTs failed to show statistical significance. Prospective/retrospective cohort studies, case series, and RCTs did not differ significantly in their estimates. Adjusted testing for metaregression disclosed that rerecurrence among NRCTs was independent of the study design. The number of included patients and study setting were independent predictors of outcome. Our proposed methodology for a systematic review could potentially give answers where level I evidence is missing or could be a tool for optimization of a RCT design.

Associations between Adiponectin Gene Variability, Pro-inflammatory and Angiogenetic Markers: Implications for Microvascular Disease Development in Type 2 Diabetes Mellitus?

BACKGROUND Adiponectin gene (ADIPOQ) variability may affect the risk for type 2 diabetes mellitus (T2DM) but it remains unclear whether it is involved in microvascular complications. OBJECTIVE To explore the impact of ADIPOQ variability on markers of inflammation and angiogenesis in T2DM. METHODS Overall, 220 consecutive T2DM patients from our outpatient diabetic clinic were genotyped for G276T (rs1501299) and T45G (rs2241766) single nucleotide polymorphisms of ADIPOQ gene. Serum levels of interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1), vascular endothelial growth factor (VEGF) were measured by enzyme-linked immunosorbent assay and high sensitivity Creactive protein (hsCRP) by immunonephelometry. RESULTS Homozygosity for the G allele on rs2241766 was associated with significantly lower serum VEGF and ICAM-1 levels compared with other genotype groups, but had no effect on IL-6. Genetic variability on rs1501299 was not associated with either VEGF or ICAM-1 levels, but T homozygotes for rs1501299 had significantly lower IL-6 concentrations compared with G carriers. Furthermore, the presence of the G allele on rs2241766 was associated with significantly lower HbA1c, whereas no associations were observed for both body mass index and hsCRP with either rs2241766 or rs1501299. CONCLUSION Genetic variability on adiponectin gene was associated with serum levels of inflammatory and angiogenetic markers. Further research is required to elucidate the role of adiponectin in the development and/or progression of microvascular disease in T2DM patients.

Development of HLA-matched vascular grafts utilizing decellularized human umbilical artery

Worldwide, there is a great need of small diameter vascular grafts that can be used in human disorders such as cardiovascular and peripheral vascular disease. Until now, severe adverse reactions are caused from the use of synthetic or animal derived grafts, while the use of autologous vessels is restricted only in a small number of patients. The limited availability of the vessels might be resolved by the use of HLA-matched vascular grafts utilizing the decellularized human umbilical arteries. In this study, human umbilical arteries were decellularized and then repopulated with Mesenchymal Stem Cells. The HLA-genotype of the repopulated grafts, analyzed by Next Generation Sequencing technology, indicated their successful production. The HLA-matched vascular grafts could be generated efficiently and might be used in personalized medicine.