Krzysztof Zmudka

Peristent Remodeling and Neointimal Suppression 2 Years After Polymer-Based, Paclitaxel-Eluting Stent Implantation: Insights From Serial Intravascular Ultrasound Analysis in the TAXUS II Study

Background— The purpose of this study was to evaluate long-term vascular responses as long as 2 years after implantation of polymer-based, paclitaxel-eluting stents in contrast to uncoated stents. Methods and Results— TAXUS II is a randomized, double-blind trial comparing slow-release (SR) and moderate-release (MR) TAXUS stents with bare-metal control stents (BMSs). One hundred sixty-one event-free patients (SR, 43; MR, 41; and BMS, 77) underwent serial intravascular ultrasound (IVUS) analysis after the procedure and at 6 months and 2 years. At 2 years, neointimal responses continued to be significantly suppressed in the SR and MR groups when compared with the BMS group (BMS, 1.49±1.12 mm2; SR, 0.94±0.76 mm2 [P=0.004]; and MR, 1.06±0.90 mm2 [P=0.02]). Between 6 months and 2 years, the BMS group showed compaction of the neointima (&Dgr;, −0.22±1.05 mm2 [P=0.08]). In contrast, both the SR and MR groups exhibited an increase (&Dgr; SR, 0.30±0.76 mm2 (P=0.01); MR, 0.41±0.94 mm2 [P=0.009]). Between 6 months and 2 years, the initial increase in plaque outside the stent regressed in the BMS and SR groups to levels comparable to those after the procedure, whereas expansive remodeling partially regressed in the MR group (&Dgr; between after the procedure and 2 years BMS, −0.34±1.28 mm2 [P=0.05]; SR, −0.02±1.40 mm2 [P=0.93]; MR, 0.32±1.56 mm2 [P=0.27]). Conclusions— The 2-year follow-up demonstrates that neointimal suppression was dose independent and that this effect was still sustained at 2 years. However, the increase in area outside the stent seen at 6 months regressed to different extents in a dose-dependent manner at 2 years.

Hyperglycemia Is Associated With Enhanced Thrombin Formation, Platelet Activation, and Fibrin Clot Resistance to Lysis in Patients With Acute Coronary Syndrome

OBJECTIVE—Acute hyperglycemia on admission for acute coronary syndrome worsens the prognosis in patients with and without known diabetes. Postulated mechanisms of this observation include prothrombotic effects. The aim of this study was to evaluate the effect of elevated glucose levels on blood clotting in acute coronary syndrome patients. RESEARCH DESIGN AND METHODS—We studied 60 acute coronary syndrome patients within the first 12 h after pain onset, including 20 subjects with type 2 diabetes, 20 subjects with no diagnosed diabetes but with glucose levels >7.0 mmol/l, and 20 subjects with glucose levels <7.0 mmol/l. We determined generation of thrombin-antithrombin complexes (TATs) and soluble CD40 ligand (sCD40L), a platelet activation marker, at the site of microvascular injury, together with ex vivo plasma fibrin clot permeability and lysis time. RESULTS—The acute coronary syndrome patients with no prior diabetes but elevated glucose levels had increased maximum rates of formation and total production of TATs (by 42.9%, P < 0.0001, and by 25%, P < 0.0001, respectively) as well as sCD40L release (by 16.2%, P = 0.0011, and by 16.3%, P < 0.0001, respectively) compared with those with normoglycemia, whereas diabetic patients had the highest values of TATs and sCD40L variables (P < 0.0001 for all comparisons). Patients with hyperglycemia, with no previously diagnosed diabetes, had longer clot lysis time (by ∼18%, P < 0.0001) similar to that in diabetic subjects, but not lower clot permeability compared with that in normoglycemic subjects. CONCLUSIONS—Hyperglycemia in acute coronary syndrome is associated with enhanced local thrombin generation and platelet activation, as well as unfavorably altered clot features in patients with and without a previous history of diabetes.

Carotid artery stenting with patient- and lesion-tailored selection of the neuroprotection system and stent type: early and 5-year results from a prospective academic registry of 535 consecutive procedures (TARGET-CAS).

Purpose: To develop and prospectively evaluate the safety and efficacy of an algorithm for tailoring neuroprotection devices (NPD) and stent types to the patient/lesion in carotid artery stenting (CAS). Methods: From November 2002 to October 2007, 499 patients (360 men; mean age 65.2±8.4 years, range 36–88) were prospectively enrolled in a safety and efficacy study of tailored CAS using proximal (flow blockade or reversal) or distal (filters or occlusion) NPDs and closed- or open-cell self-expanding stents. Of the 535 lesions treated in the study, 175 (32.7%) were “high risk” by morphology. Half (50.1%) the patients were symptomatic. Results: A quarter (137, 25.6%) of the procedures were performed under proximal protection and the remainder (398, 74.4%) with distal NPDs; the direct stenting rate was 66.9%. High-risk lesions were treated predominantly with a proximal NPD and closed-cell stent (77.1% and 82.9%, respectively) and less frequently by direct stenting (37.1%, p<0.0001 versus non-high-risk lesions). The in-hospital death/stroke rate was 2.0% (95% CI 0.85% to 3.23%), and the death/major stroke rate was 0.7% (95% CI 0.02% to 1.48%). There were no myocardial infarctions, but there was 1 (0.2%) further death within 30 days. With the tailored approach, symptom status and high-risk lesion morphology were not risk factors for an adverse outcome after CAS; only age >75 years (p<0.001) was a predictor of short-term death. Long-term survival (95.4% at 1 and 88.3% at 5 years) was similar for symptomatic versus asymptomatic patients, direct stenting versus predilation, and closed-vs. open-cell stent design; only coronary artery disease adversely impacted survival (p=0.04). The rates of freedom from death/ipsilateral stroke were 94.9% at 1 year and 85.9% at 5 years. Conclusion: Tailored CAS is associated with a low complication rate and high long-term efficacy. CAS operators should have a practical knowledge of different NPDs, including at least one proximal type.

Randomized transcoronary delivery of CD34+ cells with perfusion versus stop-flow method in patients with recent myocardial infarction: Early cardiac retention of 99mTc-labeled cells activity

BackgroundFor transcoronary progenitor cells’ administration, injections under flow arrest (over-the-wire balloon technique, OTW) are used universally despite lack of evidence for being required for cell delivery or being effective in stimulating myocardial engraftment. Flow-mediated endothelial rolling is mandatory for subsequent cell adhesion and extravasation.MethodsTo optimize cell directing toward the coronary endothelium under maintained flow, the authors developed a cell-delivery side-holed perfusion catheter (PC). Thirty-four patients (36-69xa0years, 30 men) with primary stent-assisted angioplasty-treated anterior MI (peak TnI 151 [53-356]ng/dL, mean[range]) were randomly assigned to OTW or PC autologous 99Tc-extametazime-labeled bone marrow CD34+ cells (4.34 [0.92-7.54]xa0×xa0106) administration at 6-14xa0days after pPCI (LVEF 37.1 [24-44]%). Myocardial perfusion (99mTc-MIBI) and labeled cells’ activity were evaluated (SPECT) at, respectively, 36-48xa0h prior to and 60xa0min after delivery.ResultsIn contrast to OTW coronary occlusions, no intolerance or ventricular arrhythmia occurred with PC cells’ administration (Pxa0<xa0.001). One hour after delivery, 4.86 [1.7-7.6]% and 5.05 [2.2-9.9]% activity was detected in the myocardium (OTW and PC, respectively, Pxa0=xa0.84). Labeled cell activity was clearly limited to the (viable) peri-infarct zone in 88% patients, indicating that the infarct core zone may be largely inaccessible to transcoronary-administered cells.ConclusionsIrrespective of the transcoronary delivery method, only ≈5% of native (i.e., non-engineered) CD34+ cells spontaneously home to the injured myocardium, and cell retention occurs preferentially in the viable peri-infarct zone. Although the efficacy of cell delivery is not increased with the perfusion method, by avoiding provoking ischemic episodes PC offers a rational alternative to the OTW delivery.

Direct stenting with TAXUS stents seems to be as safe and effective as with predilatation: A post hoc analysis of TAXUS II

Background and Method:Although direct coronary stenting does not improvenangiographic outcome, it makes sense by reducing procedurentimes, radiation exposure and costs. Other potential advantagesnof direct stenting may be a reduction of myocardial ischemiantime, which could be clinically relevant in high-risk patients.nWith the introduction of drug-eluting stents, however, concernnarose that direct stenting would possibly damage the polymerncoating and change or diminish the efficacy of the programmedndrug release. Also, concerns about safety by preventing optimalnapposition of single stent struts developed. It is the purposenof this paper to retrospectively analyze the data from thenTAXUS-II Trial (536 patients) regarding patients with andnwithout direct stenting. While predilatation was recommended pernprotocol, direct stenting was not forbidden: thus, directnstenting was performed in 49 patients (TAXUS n = 23, control n =n26).Results:In the TAXUS groups, there was no significant differencenregarding major adverse cardiac events (MACE; 7.5% vs. 4.3%),nangiographic restenosis in the analysis segment (4.8% vs. 4.3%),nlate loss (0.28 ± 0.36 vs. 0.33 ± 0.30 mm) or intravas- cularnultrasound-(IVUS-)measured volume obstruction (7.95 ± 9.84% vs.n5.61 ± 7.91%) at six months between the predilated and directlynstented patients. The same was true for the patients receivingnthe control stent. Compared with the directly stented controlngroup, the statistically significant positive effects of TAXUSndirect stenting were maintained, regarding angiographicnrestenosis in the analysis segment (4.3% vs. 30.8%), late lossn(0.33 ± 0.30 vs. 0.80 ± 0.62 mm) or IVUS-measured volumenobstruction (5.61 ± 7.91% vs. 22.50 ± 21.62%) at six months.nMACE was reduced from 19.2% to 4.3%; due to the small number ofnpatients this trend did not reach statistical significance.nAfter predilatation, all parameters were significantly improvednby the TAXUS stent.Conclusion:Comparison of patients receiving TAXUS stents with ornwithout predilatation revealed no differences in clinical,nangiographic or IVUS parameters at six months. This suggestsnthat direct stenting with the polymer-based paclitaxelelutingnTAXUS stent is feasible, safe and equally effective. Randomizedntrials comparing stenting after predilatation versus directnstenting with drug-eluting stents are warranted.Hintergrund und Methodik:Obwohl das koronare Direkt-Stenting das angiographischenKurz- und Langzeitergebnis nicht verbessert, macht es dennochnSinn, da es die Prozedurzeiten, Strahlenexposition und dienKosten reduzieren kann. Andere mögliche Vorteile desnDirekt-Stentings liegen in einer Reduktion der myokardialennIschämiezeit, was bei Hochrisikopatienten klinisch relevant seinnkönnte. Mit der Einführung der Medikamente freisetzenden Stentsnkamen jedoch Bedenken auf, dass ein Direkt-Stentingnmöglicherweise die Polymerbeschichtung beschädigen könnte undnsomit die Wirksamkeit vermindert. Auch eine eventuellenBeeinträchtigung der Sicherheit und Wirksamkeit durchnMalapposition einzelner Stentstreben wurde diskutiert. Zielndieser Arbeit ist es, die Daten der TAXUS-II Studie (536nPatienten) hinsichtlich des Direkt-Stentings retrospektiv zunanalysieren. In dieser Studie war die Vordehnung zwar empfohlen,nein Direkt-Stenting aber nicht unerlaubt. Insgesamt wurde einnDirekt-Stenting bei 49 Patienten (23 in der TAXUS-Gruppe, 26 innder Kontrollgruppe) durchgeführt.Ergebnisse:In der TAXUS-Gruppe war nach 6 Monaten zwischen dennprädilatierten und den direkt-gestenteten Patienten keinnsignifikanter Unterschied hinsichtlich MACE (7,5 % vs. 4,3 %),nangiographischer Restenose im analysierten Gesamtsegment (4,8 %nvs. 4,3 %), late loss (0,28 ± 36 mm vs. 0,33 ± 30 mm) und in dernIVUS-gemessenen prozentualen Obstruktion des Stentvolumens (7,95n± 9,84 vs. 5,61 ± 7,91) erkennbar. Dasselbe galt auch für dienPatienten, die einen unbeschichteten Kontrollstent erhielten. ImnVergleich zur direkt gestenteten Kontrollgruppe waren dienstatistisch signifikanten positiven Effekte desnTAXUS-Direkt-Stentings unverändert erhalten: angiographischenRestenose im gesamten analysierten Segment (4,3 % vs. 30,8 %),nlate loss (0,33 ± 0,30 vs. 0,80 ± 0,62 mm) und IVUS-gemessenenVolumenobstruktion (5,61 ± 7,91% vs. 22,50 ± 21,62%). MACE wurdenvon 19,2 % auf 4,3 % reduziert, allerdings erreichte dieserneindeutige Trend aufgrund der kleinen Patientenzahl keinenstatistische Signifikanz. Nach Vordehnung waren in dernTAXUS-Gruppe alle Parameter signifikant besser als in dernKontrollgruppe.Schlussfolgerung:Der Vergleich von Patienten, die einen TAXUS-Stent mitnoder ohne Vordehnung erhielten, ließ keinen Unterschied in dennklinischen, angiographischen oder IVUSParametern nach 6-Monatennerkennen. Die Ergebnisse zeigen, dass das Direkt-Stenting mitndem Polymer-basierten, Paclitaxel-freisetzenden TAXUS-Stent gutndurchführbar, sicher und genauso wirksam ist wie nachnVordehnung. Randomisierte Studien zum Vergleich desnDirekt-Stentings mit Stenting nach Vordehnung für Medikamentenfreisetzende Stents sind wichtig.

No-Reflow Phenomenon After Acute Myocardial Infarction Is Associated With Reduced Clot Permeability and Susceptibility to Lysis

Objective— We assessed the relationship between fibrin clot properties and the no-reflow phenomenon after primary coronary intervention (PCI). Methods and Results— Epicardial blood flow was assessed by TIMI scale and corrected TIMI frame count (cTFC), and perfusion by TIMI Myocardial Perfusion Grade (TMPG) after PCI during ST-segment elevation myocardial infarction (STEMI). Fibrin clot permeability (Ks) and susceptibility to lysis in assays using exogenous thrombin (t50%) and without thrombin (tTF) were determined in 30 no-reflow patients (TIMI ≤2) and in 31 controls (TIMI-3) after uneventful 6 to 14 months from PCI. Patients with TIMI ≤2 had lower Ks by 18% (P<0.0001) and prolonged fibrinolysis by 33% for t50% (P<0.0001) and by 45% for tTF (P<0.0001). cTFC was correlated with Ks (r=−0.56, P<0.0001), t50% (r=0.49, P<0.001), and tTF (r=0.54, P<0.001). Ks increased in a stepwise fashion with TIMI flow (P<0.0001) and TMPG (P<0.0001), whereas both fibrinolysis times decreased with TIMI flow (P<0.0001 for both) and TMPG (P<0.01 for both). Multiple regression models showed that only Ks and fibrinogen were independent predictors of cTFC (P<0.05 for both), TIMI ≤2 flow (P<0.05 for both) and TMPG-0/1 (P<0.05 for both). Conclusions— Survivors of myocardial infarction with a history of the no-reflow after PCI are characterized with more compact fibrin network and its resistance to lysis.

Direct Stenting with TAXUS Stents Seems to be as Safe and Effective as with Predilatation

Background and Method:Although direct coronary stenting does not improvenangiographic outcome, it makes sense by reducing procedurentimes, radiation exposure and costs. Other potential advantagesnof direct stenting may be a reduction of myocardial ischemiantime, which could be clinically relevant in high-risk patients.nWith the introduction of drug-eluting stents, however, concernnarose that direct stenting would possibly damage the polymerncoating and change or diminish the efficacy of the programmedndrug release. Also, concerns about safety by preventing optimalnapposition of single stent struts developed. It is the purposenof this paper to retrospectively analyze the data from thenTAXUS-II Trial (536 patients) regarding patients with andnwithout direct stenting. While predilatation was recommended pernprotocol, direct stenting was not forbidden: thus, directnstenting was performed in 49 patients (TAXUS n = 23, control n =n26).Results:In the TAXUS groups, there was no significant differencenregarding major adverse cardiac events (MACE; 7.5% vs. 4.3%),nangiographic restenosis in the analysis segment (4.8% vs. 4.3%),nlate loss (0.28 ± 0.36 vs. 0.33 ± 0.30 mm) or intravas- cularnultrasound-(IVUS-)measured volume obstruction (7.95 ± 9.84% vs.n5.61 ± 7.91%) at six months between the predilated and directlynstented patients. The same was true for the patients receivingnthe control stent. Compared with the directly stented controlngroup, the statistically significant positive effects of TAXUSndirect stenting were maintained, regarding angiographicnrestenosis in the analysis segment (4.3% vs. 30.8%), late lossn(0.33 ± 0.30 vs. 0.80 ± 0.62 mm) or IVUS-measured volumenobstruction (5.61 ± 7.91% vs. 22.50 ± 21.62%) at six months.nMACE was reduced from 19.2% to 4.3%; due to the small number ofnpatients this trend did not reach statistical significance.nAfter predilatation, all parameters were significantly improvednby the TAXUS stent.Conclusion:Comparison of patients receiving TAXUS stents with ornwithout predilatation revealed no differences in clinical,nangiographic or IVUS parameters at six months. This suggestsnthat direct stenting with the polymer-based paclitaxelelutingnTAXUS stent is feasible, safe and equally effective. Randomizedntrials comparing stenting after predilatation versus directnstenting with drug-eluting stents are warranted.Hintergrund und Methodik:Obwohl das koronare Direkt-Stenting das angiographischenKurz- und Langzeitergebnis nicht verbessert, macht es dennochnSinn, da es die Prozedurzeiten, Strahlenexposition und dienKosten reduzieren kann. Andere mögliche Vorteile desnDirekt-Stentings liegen in einer Reduktion der myokardialennIschämiezeit, was bei Hochrisikopatienten klinisch relevant seinnkönnte. Mit der Einführung der Medikamente freisetzenden Stentsnkamen jedoch Bedenken auf, dass ein Direkt-Stentingnmöglicherweise die Polymerbeschichtung beschädigen könnte undnsomit die Wirksamkeit vermindert. Auch eine eventuellenBeeinträchtigung der Sicherheit und Wirksamkeit durchnMalapposition einzelner Stentstreben wurde diskutiert. Zielndieser Arbeit ist es, die Daten der TAXUS-II Studie (536nPatienten) hinsichtlich des Direkt-Stentings retrospektiv zunanalysieren. In dieser Studie war die Vordehnung zwar empfohlen,nein Direkt-Stenting aber nicht unerlaubt. Insgesamt wurde einnDirekt-Stenting bei 49 Patienten (23 in der TAXUS-Gruppe, 26 innder Kontrollgruppe) durchgeführt.Ergebnisse:In der TAXUS-Gruppe war nach 6 Monaten zwischen dennprädilatierten und den direkt-gestenteten Patienten keinnsignifikanter Unterschied hinsichtlich MACE (7,5 % vs. 4,3 %),nangiographischer Restenose im analysierten Gesamtsegment (4,8 %nvs. 4,3 %), late loss (0,28 ± 36 mm vs. 0,33 ± 30 mm) und in dernIVUS-gemessenen prozentualen Obstruktion des Stentvolumens (7,95n± 9,84 vs. 5,61 ± 7,91) erkennbar. Dasselbe galt auch für dienPatienten, die einen unbeschichteten Kontrollstent erhielten. ImnVergleich zur direkt gestenteten Kontrollgruppe waren dienstatistisch signifikanten positiven Effekte desnTAXUS-Direkt-Stentings unverändert erhalten: angiographischenRestenose im gesamten analysierten Segment (4,3 % vs. 30,8 %),nlate loss (0,33 ± 0,30 vs. 0,80 ± 0,62 mm) und IVUS-gemessenenVolumenobstruktion (5,61 ± 7,91% vs. 22,50 ± 21,62%). MACE wurdenvon 19,2 % auf 4,3 % reduziert, allerdings erreichte dieserneindeutige Trend aufgrund der kleinen Patientenzahl keinenstatistische Signifikanz. Nach Vordehnung waren in dernTAXUS-Gruppe alle Parameter signifikant besser als in dernKontrollgruppe.Schlussfolgerung:Der Vergleich von Patienten, die einen TAXUS-Stent mitnoder ohne Vordehnung erhielten, ließ keinen Unterschied in dennklinischen, angiographischen oder IVUSParametern nach 6-Monatennerkennen. Die Ergebnisse zeigen, dass das Direkt-Stenting mitndem Polymer-basierten, Paclitaxel-freisetzenden TAXUS-Stent gutndurchführbar, sicher und genauso wirksam ist wie nachnVordehnung. Randomisierte Studien zum Vergleich desnDirekt-Stentings mit Stenting nach Vordehnung für Medikamentenfreisetzende Stents sind wichtig.

Infarct size determines myocardial uptake of CD34+ cells in the peri-infarct zone: results from a study of (99m)Tc-extametazime-labeled cell visualization integrated with cardiac magnetic resonance infarct imaging.

Background— Effective progenitor cell recruitment to the ischemic injury zone is a prerequisite for any potential therapeutic effect. Cell uptake determinants in humans with recent myocardial infarction are not defined. We tested the hypothesis that myocardial uptake of autologous CD34+ cells delivered via an intracoronary route after recent myocardial infarction is related to left ventricular (LV) ejection fraction (LVEF) and infarct size. Methods and Results— Thirty-one subjects (age, 36–69 years; 28 men) with primary percutaneous coronary intervention–treated anterior ST-segment–elevation myocardial infarction and significant myocardial injury (median peak troponin I, 138 ng/mL [limits, 58–356 ng/mL]) and sustained LVEF depression at ⩽45% were recruited. On day 10 (days 7–12), 4.3×106 (0.7–9.9×106) 99mTc-extametazime–labeled autologous bone marrow CD34+ cells (activity, 77 MBq [45.9–86.7 MBq]) were administered transcoronarily (left anterior descending coronary artery). 99mTc-methoxyisobutyl isonitrile (99mTc-MIBI) single-photon emission computed tomography before cell delivery showed 7 (2–11) (of 17) segments with definitely abnormal/absent perfusion. Late gadolinium-enhanced infarct core mass was 21.7 g (4.4–45.9 g), and infarct border zone mass was 29.8 g (3.9–60.2 g) (full-width at half-maximum, signal intensity thresholding algorithm). One hour after administration, 5.2% (1.7%–9.9%) of labeled cell activity localized in the myocardium (whole-body planar &ggr; scan). Image fusion of labeled cell single-photon emission computed tomography with LV perfusion single-photon emission computed tomography or with cardiac magnetic resonance infarct imaging indicated cell uptake in the peri-infarct zone. Myocardial uptake of labeled cells activity correlated in particular with late gadolinium-enhanced infarct border zone mass (r=0.84, P<0.0001); it also correlated with peak TnI (r=0.76, P<0.001), severely-abnormal/absent perfusion segment number (r=0.45, P=0.008), and late gadolinium-enhanced infarct core (r=0.58, P=0.0003) but not with echocardiography LVEF (r=−0.07, P=0.68) or gated single-photon emission computed tomography LVEF (r=−0.28, P=0.16. The correlation with cardiac magnetic resonance imaging-LVEF was weak (r=−0.38; P=0.04). Conclusions— This largest human study with labeled bone marrow CD34+ cell transcoronary transplantation after recent ST-segment–elevation myocardial infarction found that myocardial cell uptake is determined by infarct size rather than LVEF and occurs preferentially in the peri-infarct zone.

Prior simvastatin treatment is associated with reduced thrombin generation and platelet activation in patients with acute ST-segment elevation myocardial infarction

BACKGROUNDnIt has been reported that statin therapy produces additional effects including impaired activation of blood coagulation. It is not clear whether statins can affect hemostasis in patients with acute coronary syndrome. The aim of this study was to investigate the effect of prior statin treatment on thrombin generation and platelet activation in patients with ST-segment elevation myocardial infarction (STEMI).nnnMETHODSnWe studied 53 consecutive STEMI patients admitted within 12 hours of pain onset, including 19 treated with simvastatin (40 mg/d) (simvastatin group) at least one month prior to STEMI, and 34 not receiving any statins (no-statin group) on admission. Thrombin-antithrombin (TAT) complexes generation and soluble CD40 ligand (sCD40L) release were determined in 60-second blood samples collected at the site of microvascular injury.nnnRESULTSnThere were no significant intergroup differences with respect to clinical and laboratory variables, including plasma TAT and sCD40L levels, except lower total cholesterol and low-density lipoprotein cholesterol in the simvastatin group. The mean maximum rate of TAT generation was 47.5% lower (p=0.0002) and sCD40L release 33.3% lower (p=0.0006) in the simvastatin group. Total amounts of TAT (p<0.0001) and sCD40L (p=0.002) collected within 5 minutes of bleeding were lower in simvastatin-pretreated patients. By multivariate regression analysis, variables describing local TAT and sCD40L profiles in the whole group were independently associated with simvastatin pretreatment (p<0.0001), but not with cholesterol, platelet count or troponin levels.nnnCONCLUSIONSnPrior simvastatin use is associated with lower thrombin generation and platelet activation following vascular injury in the early phase of STEMI.

The role of carotid intima-media thickness assessment in cardiovascular risk evaluation in patients with polyvascular atherosclerosis.

UNLABELLEDnIn populational studies, carotid intima-media thickness (CIMT) is a valuable tool in the evaluation of cardiovascular (CV) risk. However, there is not much evidence on the relation between CIMT, and CV events in patients who have already undergone revascularization procedures.nnnAIMnTo evaluate the relationship between CIMT, atherosclerosis extent and CV event rates in patients with established atherosclerosis.nnnMETHODS AND RESULTSnBaseline mean-CIMT was assessed in 652 patients, including 195; 191; 112; 29 with angiographic arterial stenosis >or=50% in 1; 2; 3 or 4 territories (coronary, supraaortic, renal and/or lower limb arteries), who underwent revascularization procedure in >or=1 arterial territory, and in 125 control subjects without significant lesions. For CIMT >or=1.25mm (>or=3rd quartile), the sensitivity and specificity of >or=2-territory involvement were 81.6% and 81.9%. CV events occurred in 91(14%) subjects. The Kaplan-Meier 2-year CV event-free survival was 95.6%; 93.1%; 83.8%; 77% in patients with mean-CIMT values in the 1st; 2nd; 3rd and 4th quartile. The independent CV adverse event predictors identified in the multivariate Cox proportional hazard model were: mean-CIMT >or=1.25mm (RR=2.52; CI=1.5-4.24; p=0.001); hs-CRP (RR=1.02; CI=1.0-1.03; p=0.011), claudication (RR=1.58; CI=0.98-2.57; p=0.062), accumulation of >or=4 traditional risk factors (RR=2.02; CI=1.31-3.12; p=0.002), 2-3-vessel coronary artery disease (RR=1.95; CI=1.21-3.14; p=0.006). Inclusion of CIMT into the stratification model significantly improved the prediction of CV event risk (DeltaChi(2)=13.27, p=0.0003).nnnCONCLUSIONSnIn patients undergoing revascularization procedure(s), CIMT has an important and independent contribution to further CV risk stratification. The mean-CIMT value >or=1.25mm is associated with 2.5-fold increased risk of adverse CV events.