Kallirroi Kalantzi

Adherence to the Mediterranean diet in relation to acute coronary syndrome or stroke nonfatal events: a comparative analysis of a case/case-control study.

BACKGROUND Although the role of Mediterranean diet on cardiovascular disease prevention has long been evaluated and understood, its association with the development of stroke has been rarely examined. The aim of the present work was to comparatively evaluate the association between adherence to the Mediterranean diet and the development of an acute coronary syndrome (ACS) or ischemic stroke. METHODS During the period from 2009 to 2010, 1,000 participants were enrolled; 250 were consecutive patients with a first ACS, 250 were consecutive patients with a first ischemic stroke, and 500 population-based, control subjects, 1-for-1 matched to the patients by age and sex. Sociodemographic, clinical, psychological, dietary, and other lifestyle characteristics were measured. Adherence to the Mediterranean diet was assessed by the validated MedDietScore (theoretical range 0-55). RESULTS After various adjustments were made, it was observed that for each 1-of-55-unit increase of the MedDietScore, the corresponding odds ratio for having an ACS was 0.91 (95% CI 0.87-0.96), whereas regarding stroke, it was 0.88 (95% CI 0.82-0.94). CONCLUSIONS The present work extended the current knowledge about the cardioprotective benefits from the adoption of the Mediterranean diet by showing an additional protective effect on ischemic stroke development.

Pharmacodynamic properties of antiplatelet agents: current knowledge and future perspectives

Platelets play an important role in atherothrombotic disease. The currently available antiplatelet drugs target key steps of platelet activation including thromboxane A2 synthesis, ADP-mediated signaling, and glycoprotein IIb/IIIa-mediated platelet aggregation. The improvement of our understanding on the pharmacokinetic and pharmacodynamic characteristics of these drugs enables the tailoring of the most appropriate anti-thrombotic therapy to the individual patient and risk situation in the daily clinical practice. However, current antiplatelet therapies are associated with increased bleeding risk. Thus, further research on platelet functions may give rise to numerous new antiplatelet agents with high anti-thrombotic efficiency and low adverse hemorrhagic side effects.

Comparative analysis of a-priori and a-posteriori dietary patterns using state-of-the-art classification algorithms: A case/case-control study

OBJECTIVE To compare the accuracy of a-priori and a-posteriori dietary patterns in the prediction of acute coronary syndrome (ACS) and ischemic stroke. This is actually the first study to employ state-of-the-art classification methods for this purpose. METHODS AND MATERIALS During 2009-2010, 1000 participants were enrolled; 250 consecutive patients with a first ACS and 250 controls (60±12 years, 83% males), as well as 250 consecutive patients with a first stroke and 250 controls (75±9 years, 56% males). The controls were population-based and age-sex matched to the patients. The a-priori dietary patterns were derived from the validated MedDietScore, whereas the a-posteriori ones were extracted from principal components analysis. Both approaches were modeled using six classification algorithms: multiple logistic regression (MLR), naïve Bayes, decision trees, repeated incremental pruning to produce error reduction (RIPPER), artificial neural networks and support vector machines. The classification accuracy of the resulting models was evaluated using the C-statistic. RESULTS For the ACS prediction, the C-statistic varied from 0.587 (RIPPER) to 0.807 (MLR) for the a-priori analysis, while for the a-posteriori one, it fluctuated between 0.583 (RIPPER) and 0.827 (MLR). For the stroke prediction, the C-statistic varied from 0.637 (RIPPER) to 0.767 (MLR) for the a-priori analysis, and from 0.617 (decision tree) to 0.780 (MLR) for the a-posteriori. CONCLUSION Both dietary pattern approaches achieved equivalent classification accuracy over most classification algorithms. The choice, therefore, depends on the application at hand.

Influence of high‐density lipoprotein and paraoxonase‐1 on platelet reactivity in patients with acute coronary syndromes receiving clopidogrel therapy

Summary.  Background: The paraoxonase activity of the enzyme paraoxonase‐1 (PON‐1) associated with high‐density lipoprotein (HDL) may significantly influence clopidogrel’s antiplatelet and clinical efficacy as a result of its involvement in the clopidogrel biotransformation to the pharmacologically active thiol metabolite. We evaluated the possible relationships of HDL levels as well as PON‐1 activities and the Q192R genotype with clopidogrel’s antiplatelet efficacy in acute coronary syndrome (ACS) patients. Methods and results: The platelet aggregation, P‐selectin expression and platelet/leukocyte conjugates as well as the clopidogrel response variability (evaluated by the VASP phosphorylation test and expressed as platelet reactivity index, PRI) were assessed in 74 ACS patients undergoing percutaneous coronary intervention (PCI) in relation to the PON‐1 Q192R genotype and to serum HDL‐cholesterol levels, and PON‐1 (paraoxonase and arylesterase) activities. Patients were loaded with 600 mg of clopidogrel followed by 75 mg per day. HDL‐cholesterol levels and PON‐1 activities at baseline (before clopidogrel loading) were not altered at 5‐ and 30‐day post‐clopidogrel loading, whereas baseline platelet activation parameters were significantly attenuated. At 5 days, 17 patients were clopidogrel non‐responders (PRI: 64.2 ± 11.1%). HDL‐cholesterol was inversely associated with platelet activation parameters independently on platelet response variability to clopidogrel whereas a negative association between platelet activation parameters and paraoxonase activity was observed in patients adequately responding to clopidogrel but not in clopidogrel non‐responders. Similarly, the platelet activation markers were significantly higher in PON‐1 Q192Q genotype carriers compared with those having one or two R alleles only in patients adequately responding to clopidogrel. Conclusions: PON‐1 is an important determinant of clopidogrel antiplatelet efficacy only in patients adequately responding to clopidogrel. These findings may be clinically important in ACS patients receiving clopidogrel therapy, especially the first days after the episode.

Association Between Serum γ-Glutamyltransferase and Acute Ischemic Nonembolic Stroke in Elderly Subjects

BACKGROUND AND AIMS Elevated serum gamma-glutamyltransferase (GGT) levels have been proposed as an independent predictor for cardiovascular morbidity and mortality. The aim of this study was to determine whether GGT levels are associated with acute ischemic/nonembolic stroke in a case-control study of elderly subjects. METHODS A total of 163 patients >70 years of age (88 men) admitted due to a first-ever acute ischemic/nonembolic stroke and 166 volunteers (87 men) without a history of cardiovascular disease were included. The association between GGT and stroke was determined by multivariate logistic regression modelling after adjusting for potential confounding factors. RESULTS GGT levels were higher in subjects with metabolic syndrome (MetS) and correlated with MetS individual components including insulin resistance. Stroke patients showed higher concentrations of GGT compared with controls. In univariate analysis, crude odds ratio (OR) for GGT was 1.06/1 IU/L increase (95% CI, 1.03-1.09; p<0.001). Compared to subjects with GGT levels in the lowest quartile, those within the highest quartile had a 4.7-times increase in the odds of experiencing an ischemic stroke (95% CI 2.39-9.11, p<0.001). This association remained significant after controlling for all potential confounders (adjusted OR, 2.90, 95% CI, 1.35-6.27; p=0.007). Analysis of interaction between MetS and GGT showed that subjects with MetS had a 1.08 higher odds/1 IU/L increase in GGT to experience an ischemic stroke [adjusted OR, 1.08 (95% CI, 1.04-1.12; p<0.001). CONCLUSIONS There are positive associations between serum GGT and first ischemic/nonembolic stroke in individuals >70 years of age independent of established risk factors for cardiovascular disease and concurrent metabolic abnormalities.

Exercise-induced repolarization changes in patients with stable coronary artery disease.

Exercise is a classic trigger of ventricular arrhythmias in the setting of coronary artery disease (CAD). The aim of this study was to examine the changes of novel indexes of repolarization in patients with stable CAD who underwent exercise stress testing. Sixty-seven consecutive patients (mean age 62 ± 9 years, 60 men) who underwent treadmill exercise stress testing according to the Bruce protocol and completed the test without evidence of ischemia were enrolled. Baseline clinical and demographic characteristics were recorded, and indexes of repolarization such as corrected QT (QTc) interval, T peak-to-end (Tpe) interval, and Tpe/QT ratio were assessed at baseline and at peak exercise. A similar group of control subjects without CAD (n = 68, mean age 60 ± 11 years, 52 men) were also studied. All participants successfully completed the test. In the patient group, the QTc interval significantly increased from baseline to peak exercise (median 385 ms [25th percentile 357 ms, 75th percentile 407 ms] vs 418 ms [381 ms, 447 ms], p <0.001). The Tpe interval and the Tpe/QT ratio were also significantly increased at peak exercise (42 ms [36 ms, 60 ms] vs 78 ms [60 ms, 84 ms], p <0.001; and 0.17 [0.14, 0.22] vs 0.21 [0.16, 0.25], p = 0.015). In the control group, the QTc interval did not change significantly, the Tpe interval decreased at peak exercise (62 ms [41 ms, 80 ms] vs 48 ms [40 ms, 78 ms], p = 0.05), and the Tpe/QT ratio did not show a significant change (0.18 [0.12, 0.22] vs 0.16 [1.14, 0.21], p = 0.39). In patients with stable CAD and normal treadmill exercise stress test results, the QTc interval, the Tpe interval, and the Tpe/QT ratio increased during exercise. In conclusion, it is reasonable to assume that despite the absence of inducible ischemia, the spatial dispersion of repolarization is increased during exercise, exposing these patients to increased arrhythmic risk.

The platelet hyporesponsiveness to clopidogrel in acute coronary syndrome patients treated with 75 mg/day clopidogrel may be overcome within 1 month of treatment

Platelets are involved in thrombus formation and inflammation following vascular injury, while clopidogrel exerts antithrombotic and anti-inflammatory actions. We investigated various platelet-derived prothrombotic and proinflammatory mediators as well as the platelet aggregatory response in patients with acute coronary syndromes (ACS) receiving clopidogrel, as a function of the patient responsiveness to drug treatment. Blood samples were obtained from 40 patients with recent (<24 h) ACS before clopidogrel loading 600 mg (followed by a maintenance dose of 75 mg/day) as well as 5-days and 30-days afterwards. Twelve patients exhibited platelet reactivity index (PRI) values higher than 50% evaluated by the Vasodilator Stimulated Phosphoprotein (VASP) test at 5 days and were characterized as nonresponders. The platelet response to adenosine diphosphate (ADP) and thrombin receptor agonist peptide-14 (TRAP) was studied by flow cytometry and light transmission aggregometry. A maximum reduction of ADP- or TRAP-induced platelet aggregation in 28 clopidogrel responding patients was observed at 5 days postclopidogrel loading, whereas in nonresponders, it was achieved at 30-days along with a significant decrease in the PRI values. Similar results were obtained for the membrane expression of CD40L and the production of platelet-derived microparticles. By contrast, the maximum inhibition of P-selectin expression and platelet–leukocyte conjugate formation was observed at 30-days in both patient groups. A maintenance dose of 75 mg clopidogrel differentially affects the platelet aggregation and platelet-derived prothrombotic and proinflammatory mediators in ACS patients within the first month of the treatment, a phenomenon that is highly influenced by the drug response variability. Since these factors may be involved in the major adverse cardiovascular events in ACS patients, especially in those undergoing percutaneous coronary intervention, the above findings may be clinically important.

Platelet-Mediated Inflammation in Cardiovascular Disease. Potential Role of Platelet-Endothelium Interactions

Inflammation of the vascular wall is considered as the principal underlying mechanism in the development of atherosclerosis. Besides their specific functions in haemostasis via thrombus formation after an endothelial injury, a growing body of evidence indicates that platelets play an important role in the inflammatory reactions occurring in the vascular wall as well as in the subsequent tissue repair mechanisms. Platelets interact with activated endothelium as well as with circulating leukocytes and progenitor cells. These interactions, involve direct cell-to-cell interactions as well as autocrine and paracrine pathways, which lead to activation of platelets and their respective cellular counterpart. An increasing body of evidence suggests that antiplatelet therapy may reduce vascular inflammation primarily by inhibiting platelet activation. The aim of the present review is to highlight the molecular basis of platelet-mediated inflammatory response, focusing on the mechanisms underlying the platelet-endothelial cell interaction. The anti-inflammatory effects of current antiplatelet therapies will be also discussed.

Effect of clopidogrel besylate on platelet reactivity in patients with acute coronary syndromes. Comparison with clopidogrel hydrogen sulfate

Objective: The efficacy of clopidogrel therapy in patients with an acute coronary syndrome (ACS) has been established using the clopidogrel hydrogen sulfate (CHS) formulation. In this study we compared the antiplatelet effectiveness of a generic clopidogrel salt, clopidogrel besylate (CB), with the original CHS in patients with an ACS. Research design and methods: Ninety-six ACS patients were randomized to receive a 600-mg loading dose of either CHS (n = 45) or CB (n = 51), followed by 75 mg/day. Sixty-eight patients underwent a percutaneous coronary intervention (PCI), whereas 28 were treated conservatively. Platelet aggregatory response, vasodilator-stimulated phosphoprotein (VASP) phosphorylation, P-selectin expression and platelet–leucocyte conjugates were determined before clopidogrel loading (baseline), as well as at 5 days and at 1 month afterwards. Results: No difference in the clopidogrel response variability was observed between patients receiving CHS or CB either at 5 days or at 1 month of follow-up. Similarly, no difference in the inhibition of platelet aggregation, P-selectin expression or in the platelet–leucocyte conjugates was observed between CHS and CB group during the follow-up. Conclusions: There is no overall significant difference in the antiplatelet efficacy between CB and CHS during their administration in ACS patients for up to 1 month after the episode.

Clopidogrel differentially affects platelet-mediated thrombosis and inflammatory response in patients with acute coronary syndromes.

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