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Dimitri P Mikhailidis

Publications and source records attributed to Dimitri P Mikhailidis.

At least 73 records · Page 4Linked to original sources
PubMed2004

Effect of fenofibrate on serum inflammatory markers in patients with high triglyceride values.

BACKGROUND: Atherosclerosis is the leading cause of death in developed countries. Although the mechanisms that underlie this process are not well defined, it has been proposed that atherosclerosis is mainly an inflammatory disease. In this context, a number of inflammatory markers have been studied for their ability to predict future cardiovascular events in asymptomatic individuals or patients with established atherosclerotic disease. METHODS AND RESULTS: The aim of our study was to evaluate the effect of micronized fenofibrate on serum inflammatory markers, such as C-reactive protein, fibrinogen, and plasma platelet-activating factor acetylhydrolase (PAF-AH) in patients with high triglyceride values. An analysis of baseline values revealed that hypertriglyceridemic patients (n = 58) exhibit an atherogenic phenotype, characterized not only by elevated lipid values but also by high concentrations of serum inflammatory markers. Along with the improvement in serum lipid profile (reduction in triglycerides and total cholesterol, low-density lipoprotein, and non-high-density lipoprotein-cholesterol, with a concomitant increase in high-density lipoprotein-cholesterol levels), fenofibrate administration significantly reduced the values of serum inflammatory markers by 34%, 9.5%, and 24.8% for C-reactive protein, fibrinogen, and plasma PAF-AH, respectively. However, with the exception of PAF-AH, these reductions in inflammatory markers were not correlated with the changes in lipid values. CONCLUSIONS: In addition to its well-known hypolipidemic effects, fenofibrate may also possess significant anti-inflammatory properties that can contribute its antiatherogenic effect.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed2004

Combination antiplatelet therapy in patients with peripheral vascular bypass grafts.

Peripheral bypass graft occlusion occurs in approximately 25% of cases in the 5 years following surgery; hence, therapies directed at reducing the tendency toward thrombotic occlusion are of clinical importance. This trial was conducted to determine if the addition of clopidogrel to aspirin enhances antiplatelet therapy in patients with infrainguinal bypass grafts. A randomized placebo-controlled study was performed on 20 patients over 3 months following infrainguinal bypass surgery. In addition to their regular aspirin therapy, patients were randomized to receive either clopidogrel (group 1) or placebo (group 2) for 1 week. Platelet activation was measured ex vivo by platelet aggregometry and flow cytometry. In group 1, there was a significant reduction in spontaneous (SP), adenosine diphosphate (ADP), and arachidonic acid (AA)-induced platelet aggregation compared with group 2; SP -17% (CI -33, -0.2 p = 0.048), ADP -39%, (CI -56, -22 p = 0.001), AA -21% (CI -39, -4 p = 0.023). Flow cytometry demonstrated a significant reduction in ADP-induced platelet P-selectin expression and GPIIb/IIIa activation following treatment with clopidogrel but not with placebo. This study demonstrated that the addition of clopidogrel to aspirin reduces platelet activation measured by platelet aggregation and flow cytometry, supporting a long-term trial with clinical endpoints.

Adenosine Diphosphate↗
PubMed2004

Erectile dysfunction: a need for greater awareness.

Research has led to effective treatment regimes for erectile dysfunction (ED). Convincing evidence links vascular risk factors (hypertension, diabetes mellitus, hyperlipidaemia and smoking) with ED. This association is not surprising since the corpus cavernosum is a modified vascular tissue. This review presents a brief account of the aetiology, diagnosis and treatment of ED. There is a need to raise awareness of this condition and to make appropriate treatment available to patients.

Awareness↗
PubMed2004

Effect of atorvastatin on high density lipoprotein cholesterol and its relationship with coronary events: a subgroup analysis of the GREek Atorvastatin and Coronary-heart-disease Evaluation (GREACE) Study.

OBJECTIVE: To investigate the relationship between changes in high density lipoprotein cholesterol(HDL-C) levels after statin treatment and the risk for coronary heart disease (CHD)-related events in the secondary CHD prevention GREek Atorvastatin and Coronary heart disease Evaluation (GREACE) Study. These findings suggested that dose titration with atorvastatin (10-80 mg/day, mean 24 mg/day)achieves the National Cholesterol Educational Program treatment goals and significantly reduces morbidity and mortality, in comparison to usual care. METHODS: Analysis of variance was used to assess the effect of atorvastatin on HDL-C over time (up to 48 months) in 1600 CHD patients. The time-dependent multivariate Cox predictive model,involving backward stepwise logistic regression,was used to evaluate the relation between coronary events and HDL-C changes. RESULTS: The mean increase in HDL-C levels during the study was 7%. All doses of atorvastatin significantly increased HDL-C levels. Increases were greater in men (7.8 vs 6.1%; p = 0.02), in combined hyperlipidaemia (7.9 vs 6.4% for hypercholesterolaemia; p = 0.04), and in the lower baseline HDL-C quartile (9.2 vs 5.3%, 1st vs 4th quartile; p = 0.001). After adjustment for 24 predictors of coronary events, multivariate analysis revealed a Hazards Ratio of 0.85 (95% confidence interval 0.76-0.94; p = 0.002) for every 4 mg/dL(0.1 mmol/L) increase in HDL-C. CONCLUSIONS: There was a significant beneficial effect on HDL-C levels across the dose range of atorvastatin. Clinical outcomes in the structured care arm of GREACE were determined in part by the extent of atorvastatin-induced HDL-C increase. This effect was independent from benefit induced by low density lipoprotein cholesterol (LDL-C)reduction, suggesting that the CHD risk reduction associated with a rise in a low HDL-C at baseline remains significant under aggressive (-46%) LDL-C lowering conditions. However, the relationship between HDL-C and vascular risk may be weaker when LDL-C levels are aggressively lowered.

Adult↗
PubMed2004

Relationship between LDL-C and non-HDL-C levels and clinical outcome in the GREek Atorvastatin and Coronary-heart-disease Evaluation (GREACE) Study.

BACKGROUND: Although available guidelines suggest reducing low-density lipoprotein cholesterol (LDL-C) to below 100 mg/dL (2.6 mmol/L), the importance of target-oriented therapy remains controversial. To assess whether achieving guideline-based targets is of benefit, the relationship between clinical outcomes and lipid levels (baseline and on-study) was evaluated in the GREek Atorvastatin and Coronary-heart-disease Evaluation (GREACE) study. This study demonstrated significant reductions in morbidity and mortality associated with active dose titration of atorvastatin and structured management of dyslipidaemia. METHODS AND RESULTS: Intention-to-treat analysis (Cox proportional hazards model) was used to assess the relationship between lipid values and coronary events. Higher levels of LDL-C at baseline were associated with a greater risk of subsequent events among patients randomized to usual care. Reducing the LDL-C and the non-high density lipoprotein cholesterol (non-HDL-C) level to the National Cholesterol Educational Program (NCEP) Adult Treatment Panel (ATP) III goals required greater doses of atorvastatin for the higher baseline quartile of LDL-C. During the study there was a greater reduction in the risk of coronary heart disease (CHD) events in atorvastatin-treated patients who were in the highest quartile of LDL-C at baseline, after achieving the LDL-C treatment goal, in comparison to the usual care patients in the highest baseline LDL-C quartile. CONCLUSIONS: Achieving the NCEP ATP III LDL-C and non-HDL-C goals by titrating up the dose of atorvastatin was associated with a significant reduction in vascular events in patients with CHD. The greatest benefit was seen in those patients with the highest baseline LDL-C levels.

Aged↗
PubMed2004

Clopidogrel and vascular disease prevention.

In this editorial we consider some aspects of the use of clopidogrel in current clinical practice. Clopidogrel has replaced ticlopidine as an alternative to aspirin. Among the problems with the use of antiplatelet agents is aspirin intolerance. The options for these patients are discussed; these include using clopidogrel. Clopidogrel may be especially effective in patients with peripheral arterial disease. However, this impression requires confirmation in appropriately designed trials. We also consider the effect of antiplatelet agents on growth factor release by platelets and of clopidogrel on the inflammatory process. Clopidogrel is a useful, evidence-based, antiplatelet agent.

Clopidogrel↗
PubMed2004

Prevalence of atherosclerotic vascular disease among subjects with the metabolic syndrome with or without diabetes mellitus: the METS-GREECE Multicentre Study.

AIMS: To estimate the prevalence of vascular disease (coronary heart disease/stroke/peripheral arterial disease) in individuals with the metabolic syndrome (MetSyn) with or without diabetes mellitus (DM) when compared with subjects without the MetSyn. PATIENTS AND METHODS: A cross-sectional analysis of a representative sample of Greek adults (n = 4153), men and women (49% and 51%, respectively), living in urban, semi-urban and rural areas (54%, 25% and 21%, respectively). The National Cholesterol Education Program-Adult Treatment Panel III definition of the MetSyn was used. RESULTS: The age-adjusted prevalence of the MetSyn was 23.6% [95% confidence interval (CI) = 22.4%-25.1%]; this was similar in men and women. The fully adjusted prevalence of vascular disease in those with the MetSyn (n = 984) was 29.4%, significantly higher than in those without (n = 3169, 9.6%, p < 0.0001), while subjects without both the MetSyn and DM had the lowest vascular disease prevalence (n = 3035, 8.9%). Subjects with the MetSyn but no DM (n = 674) had a vascular disease prevalence of 24.1% (p < 0.0001 vs. those without the MetSyn), which was similar to that in subjects with DM without the MetSyn (n = 134, 25.4%), but lower than in those with both the MetSyn and DM (n = 310, 40.7%, p < 0.0001 vs. all). In comparison to those without the MetSyn [odds ratio (OR) = 1], the ORs of prevalent vascular disease, after multivariate analysis for age, sex and components of the MetSyn, and antiatherosclerotic drugs were: all MetSyn = 1.94 (95% CI = 1.35-2.47), with both MetSyn and DM = 3.04 (95% CI = 1.98-4.11) and with MetSyn but no DM = 1.48 (95% CI = 1.12-1.92). CONCLUSIONS: The prevalence of vascular disease was markedly increased in the presence of the MetSyn. Those with both the MetSyn and DM had the highest prevalence of vascular disease, followed by those with the MetSyn without DM. Probably MetSyn without DM should be considered as a coronary heart disease-risk equivalent in future guidelines. This initiative would reset treatment targets and potentially provide additional benefit in patients with the MetSyn.

Arteriosclerosis↗
PubMed2003

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Age Factors↗
PubMed2003

Ghrelin can bind to a species of high density lipoprotein associated with paraoxonase.

Ghrelin is a 28-residue peptide hormone that is principally released from the stomach during fasting and prior to eating. Two forms are present in human plasma: the unmodified peptide and a less abundant acylated version, in which octanoic acid is attached to the third residue, a serine, via an ester linkage. The acylated form of ghrelin acts as a ligand for the growth hormone secretagogue receptor and can stimulate the release of growth hormone from the pituitary gland. It also initiates behavioral and metabolic adaptations to fasting. Here we show that an immobilized form of ghrelin specifically binds a species of high density lipoprotein associated with the plasma esterase, paraoxonase, and clusterin. Both free ghrelin and paraoxon, a substrate for paraoxonase, can inhibit this interaction. An endogenous species of ghrelin is found to co-purify with high density lipoprotein during density gradient centrifugation and subsequent gel filtration. This interaction links the orexigenic peptide hormone ghrelin to lipid transport and metabolism. Furthermore, the interaction of the esterified hormone ghrelin with a species of HDL containing an esterase suggests a possible mechanism for the conversion of ghrelin to des-acyl ghrelin.

Aryldialkylphosphatase↗
PubMed2003

Direct measurement of hepatic tissue hypoxia by using a novel tcpO2/pCO2 monitoring system in comparison with near-infrared spectroscopy.

BACKGROUND/AIMS: Hepatic hypoxia occurs during liver surgery and transplantation and it may also appear within liver tumours, correlating with prognosis and efficacy of the treatment. The present study measured liver tissue hypoxia by directly using near-infrared spectroscopy (NIRS) and a novel tcpO2/pCO2 monitoring system. METHODS: Graded hypoxia was achieved in a rabbit model by a stepwise reduction of the fraction of inspired oxygen (FiO2) from 0.3 to 0.0. Animals were allowed to recover from hypoxia at FiO2 of 3.0 indicated by normalised arterial blood gas values. Hepatic tissue oxyhaemoglobin (HbO2), deoxyhaemoglobin (Hb), cytochrome oxidase (Cyt Ox), oxygen partial pressure (pO2) and carbon dioxide partial pressure (pCO2) were measured continuously with the help of NIRS and a Clark-type surface tcpO2/pCO2 monitoring system, throughout the period of hypoxaemia. RESULTS: There was an immediate reduction in hepatic HbO2 with hypoxia and a simultaneous increase in hepatic Hb. Similarly, hepatic tissue pO2 decreased significantly but tissue pCO2 remained unchanged until the FiO2 was below 0.1. Hepatic HbO2 showed a positive correlation with tissue pO2 (r = 0.53, P < 0.001). Hepatic Hb showed a negative correlation with tissue pO2 (r = 0.47, P < 0.001). Hepatic Cyt Ox decreased significantly with an FiO2 of 0.1 or less and showed a positive correlation with hepatic tissue pO2 (r = 0.64, P < 0.001). A significant correlation was found between hepatic tissue pO2 and arterial blood pO2 (r = 0.44, P < 0.001). Arterial blood pCO2 also correlated with hepatic tissue pCO2 (r = 0.53, P < 0.001) measured by the tcpO2/pCO2 monitoring system. CONCLUSION: The data from the present study suggest that, like NIRS, the tcpO2/pCO2 monitoring system can be reliably used for the direct monitoring of hepatic tissue oxygenation in vivo.

Animals↗
PubMed2003

Both the ADP receptors P2Y1 and P2Y12, play a role in controlling shape change in human platelets.

Two types of ADP receptors, P2Y(1) and P2Y(12) are involved in platelet aggregation. The P2X(1) receptor is also present but its role, in terms of platelet function, is not yet defined. The aim of this study was to establish if the ADP receptors, P2Y(1,) P2Y(12) and P2X(1) play a role in controlling platelet shape change (PSC) in human platelets. PSC is an early phase of platelet activation that precedes aggregation. Using a high-resolution channelyzer, PSC was assessed by measuring the median platelet volume (MPV). The P2Y(1) receptor antagonist MRS 2179 (1.06 - 10.25 micro mol/l) blocked ADP-induced PSC (by 100%). The median IC(50) was 3.16 micro mol/l. MRS 2179 also significantly (P = 0.01) inhibited PSC induced by the combination of ADP + serotonin (5HT). The P2Y(12) receptor antagonist AR-C69931MX significantly inhibited (at 10s, P = 0.009; 15 s, P = 0.001 and 30 s, P = 0.015) ADP-induced PSC. The P2X(1) receptor antagonist TNP-ATP had no significant effect on ADP- or ADP + 5HT-induced PSC. We conclude that the IC(50) of a P2Y(1)-blocker can be derived because of the high-resolution and reproducibility of the channelyzer technique. In addition to the P2Y(1) purinoceptor, the P2Y(12)receptor appears to be involved in ADP-induced PSC since this process was significantly inhibited by AR-C69931MX. The channelyzer technique may be more reliable than optical aggregometry to assess PSC.

Adenosine Diphosphate↗
PubMed2003

Influence of platelet count and activity on thromboelastography parameters.

It has been suggested that thromboelastography TEG) can help in limiting or directing the appropriate use of blood products during surgery. However, the contribution of platelets to the TEG profile has not been studied in detail. Blood was taken from eight healthy subjects and eight patients with peripheral arterial disease (PAD). Immunomagnetic separation was achieved by the addition of Dynabeads labeled with a CD41 murine antibody (to the GPIIb/IIIa receptor) to achieve 90-100% depletion of platelets from blood. This was then titrated with whole blood to achieve platelet counts of approximately 0, 25 and 50% of the original count to compare with whole blood using TEG. Platelet function was also assessed by spontaneous platelet aggregometry (SPA) at baseline and at the 50% dilution. SPA, maximum amplitude (MA) and K time were significantly different in PAD patients compared to controls (P < 0.05). In both controls and PAD patients there was a strong linear correlation between Log10 [platelet count] and MA (r = 0.97 for controls, r = 0.89 for PAD) and K time (r = -0.86 for controls, r = -0.68 for PAD). Correlation between Log10 [platelet count] and R time was poor in both groups. The MA and K TEG parameters may be most useful for assessing platelet transfusion requirements.

Aged↗
PubMed2003

The epsilon 2 and 4 alleles of apolipoprotein E and ischemic vascular events in the Greek population--implications for the interpretation of similar studies.

The authors investigated whether apolipoprotein (apo) E polymorphism has an allelic and/or genotypic impact on the risk of an ischemic vascular event (IVE) in Greek patients with cardiovascular diseases (CVD). They compared apo E polymorphisms in 1) a group of 165 patients with IVE [IVE(+)], of whom 107 had survived a myocardial infarction and 58 an ischemic stroke; 2) a group of 165 patients, matched with the first group for age and gender, with angiographically confirmed coronary artery disease but without IVE [IVE(-)]; 3) a group of 240 healthy younger individuals with no family history of CVD. The apo epsilon2 allele was 5.2-fold less frequent in the IVE(+) group compared to the IVE(-) group (1.2% vs 6.2%, p = 0.001). The frequency of the epsilon2 allele in healthy subjects was 8.1%, which is 6.7-fold higher than in the IVE(+) group (p < 0.001), and more than twice as high compared to all CVD patients (p = 0.001). No significant differences in epsilon4 allele frequencies were observed between IVE(+) and IVE(-) patients (9.8% vs 8.4%) or between patients with CVD and healthy subjects (9.1% vs 10.2%). The epsilon4 allele was not associated with an increased risk for CVD or IVE. In contrast, an inverse and beneficial association of the epsilon2 allele with IVE was observed among Greek patients with CVD. These results suggest that the epsilon4 and epsilon2 alleles have a variable significance in terms of predicting the risk of vascular events in different populations. Therefore, it is important to carry out "local" studies.

Adult↗
PubMed2003

Apolipoprotein E polymorphism and atherosclerosis.

The relationship between apolipoprotein (apo) E and vascular disease has been the subject of a considerable amount of research. However, this relationship is far from clearly defined. This deficiency appears to be due to a multitude of factors. Among these are differences in ethnicity, age (and possibly gender), diagnostic criteria, and environmental factors (eg, diet and smoking) that have contributed to the contradictory findings. Several diseases and their treatment may also influence this relationship. There are also documented interactions between apo E genotypes and other genes or vascular risk factors. One possible clinically relevant application of identifying the apo E genotype could be to assess the response to a particular drug treatment. It may also be that apo E polymorphism will become a good predictor of vascular death (eg, from myocardial infarction or stroke) rather than an indicator of the risk of developing vascular disease but without an acute ischemic event. More research is required to define the place of apo E genotyping in the management of vascular disease in its various forms. Whatever the future brings, the evaluation of apo E genotypes will need to be rapid, cheap, and technically undemanding before this investigation becomes widely available and clinically relevant.

Apolipoproteins E↗
PubMed2003

The effect of a loading dose (300 mg) of clopidogrel on platelet function in patients with peripheral arterial disease.

Clopidogrel acts on the P2Y12 adenosine diphosphate (ADP) purinergic receptors on human platelets. The aim of this study was to establish if a loading dose of clopidogrel inhibits platelet activation in patients with peripheral arterial disease (PAD). Two indices of platelet activation were considered: platelet shape change (PSC) and aggregation. Citrated blood was collected from ten PAD patients who were not on aspirin, at baseline (0 hours) and 2 and 4 hours after these patients ingested a loading dose (300 mg) of clopidogrel. ADP (5 micromo/L)-induced platelet aggregation in whole blood was inhibited after 2 hours (free platelet count, 47% +/- 19% vs. 68% +/- 15%; p < or = 0.001) and 4 hours (47% +/- 19% vs. 66% +/- 16%; p < or = 0.001). There was also a significant inhibition of 5- hydroxytryptamine (SHT, 5.0 micromol/L)-induced platelet aggregation at 2 hours. This trend was also observed for 10-micomol/L ADP-induced aggregation. ADP (0.3-0.4 micromol/L)-induced PSC was significantly inhibited at 4 hours (increase in median platelet volume, 6.3%, 1.8-10.7 vs. 1.2%, 0-5.3; p = 0.01). 5HT (0.5 micromol/L)-induced PSC at 4 hours was also significantly inhibited (8.1, 5.3-10.6 vs. 3.0, 0-8.2; p = 0.03). A loading dose of clopidogrel (300 mg) inhibits platelet activation in PAD patients, as early as 2 hours. To the authors' knowledge, no other study considered the effect of a loading dose of clopidogrel in PAD.

Aged↗
PubMed2003

Value of thromboelastography in the assessment of platelet function.

Thromboelastography (TEG) is a useful measure of coagulation. Modified TEG (that is with the addition of a GP IIb/IIIa receptor antagonist) has been used to assess the contribution of the fibrinogen-platelet interaction to TEG parameters (in particular the maximum amplitude, MA). Modified TEG was compared with other investigations of platelet function to assess its sensitivity in both normal subjects and in patients with peripheral arterial disease (PAD), a condition associated with activated platelets. Blood was collected from eight healthy subjects and 12 PAD patients. Platelet function was measured by TEG, flow cytometry (using PAC-1, P-selectin, GP IIIa and GP Ib murine antibodies) and platelet aggregometry (spontaneous and ADP-induced) in the presence and absence of tirofiban (a GP IIb/IIIa receptor antagonist). TEG showed a statistically significant reduction in MA with tirofiban at 0.4 mg/L and an increase in k (kinetic time; which indicates how fast clot strength is increasing once clotting starts) at 0.2 and 0.4 mg/L of tirofiban in both healthy subjects and PAD patients. Flow cytometry showed a significant decrease in the PAC-1 binding index (at 0.2 mg/L). This finding was compatible with the significant reductions found in spontaneous and ADP-induced platelet aggregation. However, aggregometry and flow cytometry were more sensitive indicators of platelet inhibition than the TEG parameters. TEG does not provide a comprehensive or sensitive reflection of impaired platelet function. If TEG is used as an index of severely impaired platelet function, we recommend that the k parameter should be used as well as MA. TEG should be supplemented by other methods of platelet function assessment wherever possible.

Adenosine Diphosphate↗