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Elena Tremoli

Publications and source records attributed to Elena Tremoli.

At least 37 records · Page 2Linked to original sources
PubMed2005

Proteome of endothelial cell-derived procoagulant microparticles.

Microparticles (MP) are small membrane vesicles that are released from cells upon activation or during apoptosis. Cellular MP in body fluids constitute a heterogeneous population, differing in cellular origin, numbers, size, antigenic composition and functional properties. MP support coagulation by exposure of tissue factor (TF), the initiator of coagulation in vivo. Moreover, MP may transfer bioactive molecules to other cells, thereby stimulating them to produce cytokines, cell-adhesion molecules, growth factors and TF, and modulate endothelial functions. However, a comprehensive characterization of the antigenic composition of MP has been poorly defined. This study describes the protein composition of endothelial cell (EC)-derived MP (EMP) using a proteomic approach. MS analysis indicated the presence of newly described protein such as metabolic enzymes, proteins involved in adhesion and fusion processes, members of protein folding event, cytoskeleton associated proteins and nucleosome. In conclusion, circulating EMP behave as an actual storage pool, able to disseminate blood-borne TF activity and other bioactive effectors, as confirmed by our experiments showing an increased procoagulant activity of EC exposed to EMP.

Amino Acid Sequence↗
PubMed2005

Correlation of parents' longevity with carotid intima-media thickness in patients attending a Lipid Clinic.

The relationship between carotid intima-media thickness (IMT) and the subject's parents' longevity has been investigated. The association between parents' age at death and IMT was estimated in 593 consecutive patients attending a Lipid Clinic by survival-analysis methods. Average maximum IMT (Avg-IMT), maximum IMT (Max-IMT), clinical and laboratory variables and parental age at death, were assessed. Kaplan-Meier analyses showed significant differences in survival curves, low IMTs being associated with long-lived parents (p=0.0003 and 0.001 by log-rank test for fathers and mothers, respectively). A Cox proportional hazards regression model showed that higher carotid IMT values were associated with father's and mother's deaths at an early age, even after adjusting for conventional cardiovascular risk factors. These data were confirmed after the stratification of patients into younger (<65 y) and older (>/=65 y) or into subjects with and without a family history of dyslipidemia or vascular diseases. In addition, by stratifying subjects into those with no, one or two long-lived parents, we observed a significant trend for the combination of father's and mother's longevity on their offspring's IMTs (p<0.01 and 0.05 for Avg-IMT and Max-IMT, respectively). These data highlight a significant relationship between carotid artery IMT and a familial predisposition to be long-lived that is independent of the individual's vascular risk profile.

Adolescent↗
PubMed2005

Meta-analysis of randomized trials comparing off-pump with on-pump coronary artery bypass graft patency.

BACKGROUND: Off-pump coronary artery bypass graft surgery (OPCAB) is increasingly becoming a widely used technique and challenges conventional on-pump coronary artery bypass grafting as the standard surgical therapy for coronary artery disease. Little information, however, is available concerning postoperative performance of bypass grafts done with this new technique. The aim of this study is to assess differences in graft patency between OPCAB and coronary artery bypass grafting by meta-analysis of data published in randomized trials. METHODS: A literature search for the period beginning January 1990 until December 2004 supplemented with manual bibliographic review was performed for all peer-reviewed English-language publications. A systematic overview (meta-analysis) of randomized trials was conducted to assess differences between OPCAB and coronary artery bypass grafting in graft occlusion rates. RESULTS: Literature search yielded five comparable randomized studies, for a total of 872 and 998 grafts performed during OPCAB and coronary artery bypass grafting procedures, respectively. Meta-analysis of these studies showed an increased risk of graft occlusion in the OPCAB group of patients, both when all the studies were analyzed together (odds ratio, 1.51; 95% confidence intervals, 1.15 to 1.99; p = 0.003), and when low-quality (odds ratio, 1.46; 95% confidence intervals, 1.05 to 2.03; p = 0.02) and high-quality (odds ratio, 1.65; 95% confidence intervals, 0.99 to 2.75; p = 0.05) studies were analyzed separately. CONCLUSIONS: Cumulative analysis of the few prospective randomized studies currently available in the literature documents a reduction in postoperative patency of coronary artery bypass grafts performed during OPCAB procedures. The risk of reduced graft patency needs to be considered when choosing OPCAB as tailored strategy for selected patients.

Coronary Artery Bypass↗
PubMed2005

Increased prothrombotic state lasting as long as one month after on-pump and off-pump coronary surgery.

OBJECTIVE: This study investigated whether the activation of coagulation, fibrinolysis, and endothelium occurring during the first postoperative month after on-pump coronary artery bypass surgery differs from that after off-pump coronary artery bypass grafting. METHODS: Thirty-five patients candidates to coronary surgery were randomized to undergo on-pump (n = 18) or off-pump (n = 17) coronary artery bypass grafting. Blood samples were collected before the intervention and to 1 month after surgery. RESULTS: Prothrombin fragment F1.2, thrombin-antithrombin complex, and D-dimer increased after surgery and were persistently higher than preoperative values as late as 30 postoperative days in both on- and off-pump groups; higher levels of these variables were detected after on-pump surgery relative to off-pump surgery only at the time point after termination of cardiopulmonary bypass (fragment F1.2 and thrombin-antithrombin complex) or from bypass end to 8 postoperative days (D-dimer). Fibrinogen levels decreased after surgery and then increased in parallel in both groups to 8 days after surgery. The von Willebrand factor level increased postoperatively in both groups and returned to baseline 30 days after surgery; it was higher after on-pump surgery from bypass end to 8 postoperative days. Soluble vascular cell adhesion molecule 1 was increased significantly from baseline in both groups 30 days after surgery, with no difference between groups. CONCLUSION: Patients undergoing off-pump surgery showed protection against activation of coagulation and fibrinolysis and against endothelial injury only during the intraoperative period; this was followed by the development of a prothrombotic pattern comparable to that of patients undergoing on-pump surgery lasting at least as late as 30 days after surgery.

Blood Coagulation↗
PubMed2005

The role of tissue factor and P-selectin in the procoagulant response that occurs in the first month after on-pump and off-pump coronary artery bypass grafting.

BACKGROUND: It has been previously shown that a persistent (up to 1 month) prothrombotic status occurs after coronary bypass surgery performed both on pump and off pump. To assess the pathways involved in the occurrence of postoperative prothrombotic state, in this study we evaluated plasma, monocyte-bound, and platelet-bound tissue factor expression, as well as platelet and soluble P-selectin expression, up to 1 month after off-pump and on-pump coronary artery bypass grafting. METHODS: Thirty patient candidates for coronary surgery were randomized to undergo off-pump coronary artery bypass grafting (n = 15) or on-pump coronary artery bypass grafting (n = 15). Blood samples were collected before the intervention, after protamine administration, and 4, 8, and 30 days after surgical intervention. RESULTS: Plasma tissue factor levels were significantly higher than baseline both in the on-pump coronary artery bypass grafting group (from protamine administration up to 4 postoperative days) and in the off-pump coronary artery bypass grafting group (at 4 postoperative days), with no differences between groups. Basal and lipopolysaccharide-stimulated monocyte tissue factor expression, as well as basal and adenosine diphosphate-stimulated platelet tissue factor expression, did not show significant variations over time and were similar in the on-pump and off-pump coronary artery bypass grafting groups throughout the course of the study. Platelet expression of P-selectin, both basal and after adenosine diphosphate stimulation, did not significantly change over time and was not different in the on-pump and off-pump coronary artery bypass grafting groups. Soluble P-selectin levels in plasma were significantly higher in patients receiving on-pump coronary artery bypass grafting only at the time point after protamine administration, whereas this variable behaved similarly in the on-pump and off-pump coronary artery bypass grafting groups for the whole postoperative period. CONCLUSIONS: The postoperative tissue factor and P-selectin expression did not differ between the on-pump and off-pump coronary artery bypass grafting groups. The distinct increase of plasma tissue factor occurring after both surgical procedures might represent a mechanism that might explain, in part, the early postoperative prothrombotic state occurring after on-pump and off-pump coronary artery bypass grafting.

Aged↗
PubMed2005

Reduced in vivo oxidative stress following 5-methyltetrahydrofolate supplementation in patients with early-onset thrombosis and 677TT methylenetetrahydrofolate reductase genotype.

The protective role of folate in vascular disease has been related to antioxidant effects. In 45 patients with previous early-onset (at age <50 years) thrombotic episodes and the 677TT methylenetetrahydrofolate reductase genotype, we evaluated the effects of a 28 d-course (15 mg/d) of 5-methyltetrahydrofolate (MTHF) on homocysteine metabolism and on in vivo generation of 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha), a reliable marker of oxidative stress. At baseline, patients' fasting total homocysteine (tHcy) was 11.5 micromol/l (geometric mean) and urinary excretion of 8-iso-PGF2alpha was 304 pg/mg creatinine, with the highest metabolite levels in the lowest quartile of plasma folate distribution (P < 0.05). After 5-MTHF supplementation, plasma folate levels increased approximately 13-fold (P < 0.0001 versus baseline); tHcy levels (6.7 micromol/l, P < 0.0001) and urinary 8-iso-PGF2alpha (254 pg/mg creatinine, P < 0.001) were both significantly lowered, their reduction being proportional to baseline values (r = 0.98 and r = 0.77, respectively) and maximal in patients with the lowest pre-supplementation folate levels (P < 0.05). The effects on folate (P < 0.0001) and tHcy (P = 0.0004) persisted for at least up to 2 months after withdrawing 5-MTHF. In parallel with long-lasting tHcy-lowering effects, a short-course 5-MTHF supplementation reduces in vivo formation of 8-iso-PGF2alpha in this population, supporting the antioxidant protective effects of folate in vascular disease.

Adult↗
PubMed2005

Anti-inflammatory properties of drugs acting on the renin-angiotensin system.

It is now well established that the activation of the renin-angiotensin system (RAS) is involved in the onset and progression of cardiovascular and renal diseases, and that its main effector, angiotensin II (Ang II) has major pro-inflammatory activity that induces the expression of cytokines, chemokines, adhesion molecules, growth factors and reactive oxygen species. By means of these actions, Ang II induces vascular inflammation, endothelial dysfunction and fibrosis, and participates in destabilizing atherosclerotic plaque and establishing chronic kidney diseases. Blocking the RAS by inhibiting Ang II generation or blocking angiotensin receptors reduces the morbidity and mortality associated with cardiovascular and renal disease beyond the levels due to the lowering of blood pressure, and these benefits are at least partially due to the reduction/prevention of both local and systemic inflammatory processes. The aim of this review is to describe the role of the RAS (and particularly Ang II) in initiating and maintaining these processes, and to summarize experimental and clinical evidence supporting the role of drugs acting on the RAS in preventing or modulating inflammation.

Angiotensin II↗
PubMed2004

Neurohormonal activation is associated with increased levels of plasma matrix metalloproteinase-2 in human heart failure.

AIMS: Development of heart failure depends on systemic and molecular abnormalities among which are the activation of neurohormonal systems and the increase of matrix metalloproteinases (MMPs). This study assessed the relationship between catecholamines and active MMPs in vivo in patients with severe congestive heart failure (CHF) and in vitro in human cardiac fibroblasts. METHODS AND RESULTS: Forty patients with CHF due to dilated cardiomyopathy, either idiopathic (n=20) or secondary to ischaemic heart disease (n=20), were compared with 20 healthy subjects. Plasma MMP-2 and MMP-9 activity, but not TIMP-2, were significantly higher in patients than in controls (median MMP-2, 270 vs. 214 ng/mL, P=0.006; MMP-9 16.3 vs. 8.7 ng/mL, P<0.0001). Similarly, noradrenaline, but not adrenaline, was significantly higher in patients (noradrenaline 645 vs. 157 pg/mL, P<0.0001; adrenaline 86.0 vs. 72.6 pg/mL, P=0.68). No difference in any parameter was observed between patient groups. The intra-group correlation between MMP-2 and noradrenaline was significant (r=0.33, P=0.01); indeed, noradrenaline appear to be a predictor of MMP-2. Moreover, this catecholamine increased MMP-2 in human cardiac fibroblasts. CONCLUSIONS: The positive correlation between noradrenaline and MMP-2 in severe CHF patients, together with the in vitro induction of MMP-2 by this catecholamine, suggests a potential biochemical link between noradrenaline and MMP-2.

Cardiomyopathy, Dilated↗
PubMed2004

Analysis of pathological events at the onset of brain damage in stroke-prone rats: a proteomics and magnetic resonance imaging approach.

Spontaneously hypertensive stroke-prone rats (SHRSP) develop brain abnormalities invariably preceded by the accumulation of acute-phase proteins in body fluids. This study describes the sequence of pathological events, and in particular the involvement of inflammation, at the onset of brain injury in this animal model. In SHRSP subjected to permissive dietary treatment, the appearance of brain damage and of altered permeability of the blood-brain barrier (BBB) was monitored over time by magnetic resonance imaging (MRI) after intravenous injection of gadolinium. The protein content in cerebrospinal fluid and brain extracts was analyzed by two-dimensional electrophoresis. Gadolinium diffusion showed impairment of the BBB after 42 +/- 3 days from the start of salt loading, simultaneously with the detection of brain abnormalities by MRI. Tissue lesions were initially localized at one or more small foci and then spread throughout the brain in the form of fibrinoid necrosis. This type of lesion is characterized by fibrin deposition, in particular around the vessels; loss of tissue texture; and infiltration of macrophages and lymphocytes. High levels of plasma-derived proteins of molecular mass up to >130 kDa were detected in the cerebrospinal fluid after MRI had revealed brain abnormalities. Plasma proteins extravasated from brain vessels were immunodetected in tissue homogenates from affected areas. The results obtained in this study provide new insights into the pathogenesis of the spontaneous brain damage in SHRSP and in particular on the involvement of the inflammatory cascade. These studies may be useful in evaluating new pharmacological strategies aimed at preventing/treating brain diseases.

Animals↗
PubMed2004

Anti-inflammatory effects of AT1 receptor blockade provide end-organ protection in stroke-prone rats independently from blood pressure fall.

Spontaneously hypertensive stroke-prone rats (SHRSP) develop hypertension and systemic inflammation, with subsequent brain and renal disorders and early death. We tested the hypothesis that valsartan, an angiotensin II type 1 (AT1) receptor antagonist, exerts protective effects in SHRSP through its anti-inflammatory properties, even in the absence of a blood pressure-lowering effect. SHRSP fed a high-salt diet were treated with vehicle or valsartan (1-10 mg/kg/day). The vehicle-treated rats developed hypertension, proteinuria, progressive kidney disease, and, 40 +/- 5 days from the beginning of the treatment, brain damage as visualized by magnetic resonance imaging. Rats treated with 1 mg/kg/day valsartan developed brain damage after 61 +/- 3 days (p <0.01 versus vehicle-treated rats). No damage showed after 100 days in 80% of the rats treated with 10 mg/kg/day. Valsartan treatment preserved renal structure, by preventing the infiltration of inflammatory cells, and lowered renal expression of monocyte chemoattractant protein-1, transforming growth factor-beta1, and interleukin-1beta, compared with vehicle-treated SHRSP. Urinary excretion of acute-phase proteins increased in the latter but remained negligible in the drug-treated animals. Furthermore, valsartan exerted protective effects also when given after established proteinuria. In SHRSP, blockade of AT1 receptor with valsartan prevents the development of proteinuria, delays the appearance of brain damage, preserves renal structure, and increases survival under stressful conditions. Valsartan exerts its beneficial effects independently of any blood pressure fall and by means of broad anti-inflammatory actions both at local and at systemic levels. These observations indicate that the administration of AT1 receptor antagonists may be useful in pathological situations in which an anti-inflammatory effect is required.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2004

Apocynin prevents cyclooxygenase 2 expression in human monocytes through NADPH oxidase and glutathione redox-dependent mechanisms.

In the present study we report the preventive effect of apocynin, an active constituent of the Himalayan herb Picrorhiza kurrooa, on cyclooxygenase-2 (Cox-2) synthesis and activity in human adherent monocytes exposed to serum treated zymosan (STZ) and phorbol myristate acetate (PMA). Apocynin markedly decreases the intracellular reduced/oxidized glutathione ratio (GSH/GSSG) and prevents nuclear factor-kappaB (NF-kappaB) activation in stimulated monocytes. Moreover, it reduces intracellular reactive oxygen species (ROS) generation, NADPH oxidase activity in monocyte homogenates and translocation of p47phox subunit in monocyte membranes. p47phox levels are also reduced in lysates of apocynin-treated monocytes. The inhibition of Cox-2 by apocynin is completely abrogated by GSH provision. Results from this study indicate that apocynin inhibits Cox-2 synthesis and activity induced in monocytes by an increased oxidative tone and provide an explanation for the protective effect exerted by this compound in numerous cell and animal models of inflammation. Attenuation of NADPH oxidase derived ROS coupled with GSH/GSSG reduction and suppression of NF-kappaB activation are highlighted as the molecular mechanisms responsible for Cox-2 inhibition.

Acetophenones↗
PubMed2004

Pentoxifylline prevents spontaneous brain ischemia in stroke-prone rats.

Anti-inflammatory properties of pentoxifylline (PTX) have recently been described. Spontaneously hypertensive stroke-prone rats (SHRSP) constitute an animal model that develops an inflammatory condition that precedes the appearance of brain abnormalities. The aim of the present investigation was to assess: 1) the efficacy of PTX treatment in protecting the neural system in SHRSP, and 2) how its anti-inflammatory properties might be involved in this effect. Male SHRSP fed with a permissive diet received no drug or PTX (100 or 200 mg/kg/day). Brain abnormalities detected by magnetic resonance imaging developed spontaneously in control rats after 42 +/- 3 days, whereas in rats treated with 100 mg/kg/day PTX, abnormalities developed in only 80% of the animals and only after 70 to 80 days. Treatment with a higher dose of PTX (200 mg/kg/day) completely protected the brain from abnormal development. The drug treatment prevented the accumulation of macrophages or CD4+ positive cells, the activation of glia in brain tissues, and the appearance of inflammatory proteins and thiobarbituric acid-reactive substances in body fluids. PTX treatment did induce a greater increase of serum tumor necrosis factor-alpha (TNF-alpha), but not of interleukin (IL)-1beta and IL-6 induced by in vivo administration of lipopolysaccharide (LPS), which suggests a protective role for TNF-alpha. PTX also exerted protective effects when it was administered after the first occurrence of proteinuria (>40 mg/day). These data indicate that PTX treatment dose-dependently prevents the occurrence of spontaneous brain damage by reducing inflammatory events. We also hypothesize that the increase of TNF-alpha by PTX treatment represents a protective mechanism in SHRSP.

Animals↗
PubMed2004

Statins in atherothrombosis.

Clinical studies have shown that hydroxy-methyl glutaryl coenzyme A reductase inhibitors (statins) may favorably affect atherothrombosis. In addition to their potent cholesterol-lowering properties, statins reduce atheroma progression as well as the incidence of acute thrombosis-related vascular events and their dreadful clinical consequences. Available data indicate that statins exert significant antithrombotic effects in clinical practice by reducing the occurrence of vascular atherothrombotic events, with a more prominent effect in high-risk patients. The mechanisms by which statins inhibit thrombosis have been extensively investigated, and several pathways appear to be involved. In particular, statins have been proposed to reduce platelet activation and to exert favorable effects on fibrinolysis, but no clear-cut conclusion can be drawn from available studies. Moreover, statins do not consistently influence fibrinogen or factor VII levels in plasma. In contrast, in vitro and in vivo data indicate that these compounds profoundly affect thrombin generation driven by tissue factor/factor VII pathway. In vitro studies indicate that this effect is not dependent on plasma cholesterol lowering but, rather, on the inhibition of isoprenoid biosynthesis. The relative contribution of reduced levels of prenylated proteins and of cholesterol pathway to the modulation of tissue factor expression is, however, hardly to be established in clinical settings.

Animals↗
PubMed2004

Recognition of patients with cardiovascular disease by artificial neural networks.

BACKGROUND: Artificial neural networks (ANNs) are computer algorithms inspired by the highly interactive processing of the human brain. When exposed to complex data sets, ANNs can learn the mechanisms that correlate different variables and perform complex classification tasks. AIMS: A database, of 949 patients and 54 variables, was analysed to evaluate the capacity of ANNs to recognise patients with (VE+, n = 196) or without (VE-, n = 753) a history of vascular events on the basis of vascular risk factors (VRFs), carotid ultrasound variables (UVs) or both. METHOD: The performance of ANN was assessed by calculating the percentage of correct identifications of VE+ and VE- patients (sensitivity and specificity, respectively) and the prediction accuracy (weighted mean between sensitivity and specificity). RESULTS: The results showed that ANNs can be trained to identify VE+ and VE- subjects more accurately than discriminant analyses. When VRFs and UVs were used as input variables, the prediction accuracies of the ANN providing the best results were 80.8% and 79.2%, respectively. The addition of gender, age, weight, height and body mass index to UVs increased accuracy of prediction to 83.0%. When the ANNs were allowed to choose the relevant input data automatically (I.S. system-Semeion), 37 variables were selected among 54, five of which were UVs. Using this set of variables as input data, the performance of the ANNs in the classification task reached a prediction accuracy of 85.0%. with the 92.0% correct classification of VE+ patients. CONCLUSIONS: Artificial neural network technology is highly promising in the development of accurate diagnostic tools designed to recognize patients at high risk of cardiovascular diseases.

Adult↗
PubMed2004

Oxidised-HDL3 induces the expression of PAI-1 in human endothelial cells. Role of p38MAPK activation and mRNA stabilization.

Modified lipoproteins have been suggested to modulate endothelial expression of plasminogen activator inhibitor-1 (PAI-1). As oxidized high-density lipoprotein (Ox-HDL) has been found in atheromatous plaques and receptors for modified HDL are present on endothelial cells, we investigated the role of Ox-HDL3 on the expression of PAI-1. Ox-HDL3 but not native HDL3, increased PAI-1 mRNA expression in endothelial cells. Furthermore, PAI-1 antigen expression and activity increased in the supernatant of cells incubated with Ox-HDL3. The intracellular pathways involved in this effect were investigated. Ox-HDL3 activated both extracellular signal-regulated kinases (ERK) 1/2 and p38 mitogen-activated protein kinase (MAPK). Moreover, incubation with specific inhibitors of these kinases showed that p38MAPK was mainly involved in the Ox-HDL3-dependent PAI-1 induction. Transient transfection experiments suggested that none of the response elements in the proximal promoter (-804 to 17) were involved in Ox-HDL3-mediated PAI-1 expression. mRNA stability experiments showed that Ox-HDL3 increased the PAI-1 mRNA half-life. In summary, Ox-HDL3 induced PAI-1 mRNA expression and antigen release through a molecular mechanism involving MAPK activation and mRNA stabilization. Thus, oxidative modification converts HDL to a prothrombotic lipoprotein species.

Cells, Cultured↗
PubMed2004

Effect of Interleukin-6 promoter polymorphisms in survivors of myocardial infarction and matched controls in the North and South of Europe. The HIFMECH Study.

Elevated plasma IL-6 levels have been implicated in the pathogenesis of coronary heart disease. We have investigated the association of two polymorphisms in the promoter of IL-6 (-572G>C and -174G>C) with levels of inflammatory markers and risk of myocardial infarction (MI) in a European study of MI survivors and age-matched controls from two high-risk centres in the North of Europe, and two low risk centres in the South. IL-6 and CRP levels were similar in controls in both regions, but were higher in cases. For the -174G>C polymorphism the rare -174C allele showed a regional difference in allele frequency, being more common in the North European group (0.43 vs 0.28; p < 0.0005), where -174C allele carriers showed an apparent reduced risk of MI compared to -174GG homozygotes (OR 0.53, 95%CI 0.32, 0.86). No such effect was observed in the South or with the -572G>C in either group. Neither genotype was associated with a significant effect on plasma IL-6 levels in either cases or controls. Furthermore, no regional difference was observed in the frequency of the -572G>C SNP, suggesting that these polymorphisms are unlikely to be contributing to the observed increased risk of cardiovascular disease in Northern Europe.

Adult↗
PubMed2004

Plasma fibrinogen concentration predicts the risk of myocardial infarction differently in various parts of Europe: effects of beta-fibrinogen genotype and environmental factors. The HIFMECH Study.

The propensity to atherothrombotic disease differs in Europe, with high-risk regions located in the North of Europe and lowrisk regions in the South of Europe. The HIFMECH study (Hypercoagulability and Impaired Fibrinolytic function MECHanisms predisposing to myocardial infarction (MI) study) was undertaken to elucidate genetic and environmental mechanisms underlying MI based on investigations of postinfarction patients and healthy individuals recruited from Stockholm, Sweden, London, England (North of Europe), Marseille, France and San Giovanni Rotondo, Italy (South of Europe). In the present report, emphasis was placed on fibrinogen, a multifunctional protein, widely recognized as an independent predictor of atherothrombotic disease. The adjusted plasma fibrinogen concentration was an independent discriminator between cases and controls in London (SOR 3.58; 95% CI 1.31; 9.83), but not in the other centres. Genotyping for six beta-fibrinogen promoter single nucleotide polymorphisms was performed of which -249C/T, -455G/A and -854G/A were used in analysis as a consequence of the linkage disequilibrium pattern. Four haplotypes, with similar distribution across Europe, were detected: CGG (46.7%), CAG (20.3%), TGG (18.2%) and CGA (14.8%). A significant haplotype effect on plasma fibrinogen concentration was observed in patients (p < 0.001) but not in controls (p = 0.08). The -455G/A genotype related to plasma fibrinogen concentration amongst patients along with centre and IL-6 concentration (together explaining 11.5% of the variation), whereas predictors amongst controls included centre, body mass index, IL-6 and smoking habit (explaining 15.7%). Thus, plasma fibrinogen concentration contributes differently to MI across Europe, and a disease-related stimulus is required to evoke allele-specific regulation of fibrinogen synthesis.

Aged↗