[Show abstract][Hide abstract] ABSTRACT: Several circulating biomarkers have been implicated in carotid atherosclerotic plaque rupture and thrombosis; however, their clinical utility remains unknown. The aim of this study was to determine the role of a large biomarker panel in the discrimination of symptomatic (S) vs. asymptomatic (A/S) subjects in a contemporary population with carotid artery stenosis (CS).
Prospective sampling of circulating cytokines and blood lipids was performed in 300 unselected, consecutive patients with ≥50% CS, as assessed by duplex ultrasound (age 47-83 years; 110 with A/S and 190 with S) who were referred for potential CS revascularization.
CS severity and pharmacotherapy did not differ between the A/S and S patients. The median values of total cholesterol, low-density lipoprotein cholesterol, and lipoprotein(a) did not differ, but high-density lipoprotein (HDL) cholesterol was significantly higher (p<0.001) and triglycerides were lower (p=0.03) in the A/S-CS group than in the S-CS group. Interleukin-6 (IL-6) and high-sensitivity C-reactive protein were higher (p=0.04 and p=0.07, respectively) in the S-CS group. Circulating visfatin, soluble CD 40 receptor ligand, soluble vascular cell adhesion molecule, leptin, adiponectin, IL-1β, IL-8, IL-18, monocyte chemoattractant protein-1, myeloperoxidase, matrix metalloproteinases-8, -9, and -10, and fibrinogen were similar, but tissue inhibitor of matrix metalloproteinases-1 (TIMP) was reduced in S-CS compared to A/S-CS (p=0.02). Nevertheless, incorporation of TIMP and IL-6 did not improve the HDL-cholesterol receiver operating characteristics for S-CS status prediction. S-CS status was unrelated to angiographic stenosis severity or plaque burden, as assessed by intravascular ultrasound (p=0.16 and p=0.67, respectively). Multivariate logistic regression analysis revealed low HDL-cholesterol to be the only independent predictor of CS symptoms, with an odds ratio of 1.81 (95% confidence interval=1.15-2.84, p=0.01) for HDL <1.00 mmol/L (first quartile) vs. >1.37 (third quartile). In S-CS, osteoprotegerin and lipoprotein-associated phospholipase A2 (Lp-PLA2) were elevated in those with recent vs. remote symptoms (p=0.01 and p=0.02, respectively).
In an all-comer CS population on contemporary pharmacotherapy, low HDL-cholesterol (but not other previously implicated or several novel circulating biomarkers) is an independent predictor of S-CS status. In addition, an increase in circulating osteoprotegerin and Lp-PLA2 may transiently indicate S transformation of the carotid atherosclerotic plaque.
Journal of Clinical Neurology 07/2013; 9(3):165-75. · 1.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: -Effective progenitor cell recruitment to ischemic injury zone is a prerequisite for any potential therapeutic effect. Cell uptake determinants in humans with recent MI are not defined. We tested the hypothesis that myocardial uptake of autologous CD34(+) cells delivered intracoronary after recent MI is related to LVEF and infarct size (IS). METHODS AND RESULTS: -Thirty-one subjects (age 36-69 years, 28 men) with pPCI-treated anterior STEMI and significant myocardial injury (peak TnI 138 [58-356ng/dL]; median [limits]) and sustained LVEF depression at ≤45%) were recruited. On day 10 [7-12], 4.3x10(6) [0.7-9.9x10(6)] (99m)Tc-extametazime-labeled autologous bone-marrow CD34(+) cells (activity 77 [45.9-86.7]MBq) were administered transcoronary (LAD). (99m)Tc-MIBI-SPECT prior to cell delivery showed 7 [2-11] (of 17) segments with definitely-abnormal/absent perfusion. Gadolinium late-enhanced infarct core (LGE(CORE)) mass was 21.7 [4.4-45.9]g and infarct border-zone mass (LGE(IBZ)) was 29.8 [3.9-60.2]g (full-width-at-half-maximum, FWHM, signal intensity thresholding algorithm). One hour after administration, 5.2% [1.7-9.9%] of labeled cells activity localized in the myocardium (whole-body planar γ-scan). Image fusion of labeled cells SPECT with LV perfusion SPECT or with cMRI infarct imaging indicated cell uptake in the peri-infarct zone. Myocardial uptake of labeled cells activity correlated in particular with LGE(IBZ) (r=0.84, p<0.0001) and with peak TnI (r=0.76, p<0.001); it also correlated with severely-abnormal/absent perfusion segments number (r=0.45, p=0.008 and LGE(CORE) (r=0.58 and r=0.84, p<0.0001) but not with echo-LVEF (r=-0.07, p=0.68) or GSPECT-LVEF (r=-0.28, p=0.16). The correlation with cMRI-LVEF was weak (r=-0.38, p=0.04). CONCLUSIONS: -This largest human study with labeled bone marrow CD34(+) cells transcoronary transplantation after recent STEMI found that myocardial cell uptake is determined by infarct size rather than LVEF, and it occurs preferentially in the peri-infarct zone.
[Show abstract][Hide abstract] ABSTRACT: Significant atherosclerotic stenosis of internal carotid artery (ICA) origin is common (5-10% at ≥ 60 years). Intravascular ultrasound (IVUS) enables high-resolution (120 µm) plaque imaging, and IVUS-elucidated features of the coronary plaque were recently shown to be associated with its symptomatic rupture/thrombosis risk. Safety of the significant carotid plaque IVUS imaging in a large unselected population is unknown.
We prospectively evaluated the safety of embolic protection device (EPD)-assisted vs. unprotected ICA-IVUS in a series of consecutive subjects with ≥ 50% ICA stenosis referred for carotid artery stenting (CAS), including 104 asymptomatic (aS) and 187 symptomatic (S) subjects (age 47-83 y, 187 men). EPD use was optional for IVUS, but mandatory for CAS.
Evaluation was performed of 107 ICAs (36.8%) without EPD and 184 with EPD. Lesions imaged under EPD were overall more severe (peak-systolic velocity 2.97 ± 0.08 vs. 2.20 ± 0.08 m/s, end-diastolic velocity 1.0 ± 0.04 vs. 0.7 ± 0.03 m/s, stenosis severity of 85.7 ± 0.5% vs. 77.7 ± 0.6% by catheter angiography; mean ± SEM; p<0.01 for all comparisons) and more frequently S (50.0% vs. 34.6%, p=0.01). No ICA perforation or dissection, and no major stroke or death occurred. There was no IVUS-triggered cerebral embolization. In the procedures of (i) unprotected IVUS and no CAS, (ii) unprotected IVUS followed by CAS (filters - 39, flow reversal/blockade - 3), (iii) EPD-protected (filters - 135, flow reversal/blockade - 48) IVUS + CAS, TIA occurred in 1.5% vs. 4.8% vs. 2.7%, respectively, and minor stroke in 0% vs. 2.4% vs. 2.1%, respectively. EPD intolerance (on-filter ICA spasm or flow reversal/blockade intolerance) occurred in 9/225 (4.0%). IVUS increased the procedure duration by 7.27 ± 0.19 min.
Carotid IVUS is safe and, for the less severe lesions in particular, it may not require mandatory EPD use. High-risk lesions can be safely evaluated with IVUS under flow reversal/blockade.
Medical science monitor: international medical journal of experimental and clinical research 02/2012; 18(2):MT7-18. · 1.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We compared the effect of simvastatin versus simvastatin combined with ezetimibe on hemostasis and inflammation after acute coronary events [acute coronary syndromes (ACS)]. In an investigator-initiated, double-blind, placebo-controlled, randomized study, patients with ACS were assigned to 40 mg/d of simvastatin + 10 mg/d of ezetimibe (n = 26) or 40 mg/d of simvastatin + placebo (n = 28) administered for 2 months. Markers of coagulation (prothrombin fragments 1.2, thrombin-antithrombin complexes, free tissue factor pathway inhibitor), fibrinolysis [plasminogen activator inhibitor-1, clot lysis time (CLT)], platelet activation (soluble CD40 ligand, β-thromboglobulin, thromboxane B2), oxidative stress [8-iso-prostaglandin F2α (8-iso-PGF2α)], and inflammation (interleukin-6, interleukin-18, and interleukin-1β) were measured within the first 12 hours of ACS and at 1 and 2 months of therapy. A final analysis comprised 20 patients in the simvastatin + ezetimibe group and 26 patients in the simvastatin + placebo group. Both groups were similar with regard to demographics, risk factors, medications, and routine laboratory results. Inflammatory, coagulation, and platelet markers did not differ between both treatment groups at all time points. Reductions in low-density lipoprotein cholesterol, CLT, plasminogen activator inhibitor-1, and 8-iso-PGF2α were significantly greater (by 10%, 8.7%, 17.5%, and 22.4%) in the simvastatin + ezetimibe group after 1 month, with further decreases in CLT and 8-iso-PGF2α at 2 months (all P < 0.05). These changes were not associated with lipid and inflammatory parameters. In conclusion, compared with simvastatin alone, simvastatin + ezetimibe results in a greater suppression of oxidative stress and enhanced fibrinolysis in patients with ACS, indicating that ezetimibe might exert cholesterol-independent actions in humans (NCT00725829).
Journal of cardiovascular pharmacology 05/2011; 58(2):167-72. · 2.83 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The study aimed to determine the potential interrelations between left ventricle mass (LVM), LV diastolic function, systolic blood pressure (SBP) and diastolic blood pressure (DBP) and cardiovascular events in patients undergoing renal artery stenting [corrected] (RAS).
Prior to RAS, 3 and 12 months afterward, the change in LVM, left ventricular mass index (LVMI), diastolic function (E/A ratio, E' wave velocity, isovolumetric relaxation time [IVRT], E/E' ratio) on echocardiography and change in SBP and DBP on 24-hour monitoring were assessed in 84 patients, aged 63.7 ± 10 years, who underwent RAS for renal artery stenosis > 60%.
During 12 months, 12 (14.3%) cardiovascular (CV) events (five deaths) occurred. At 1 year, the mean LVM decreased from 179 ± 49 g to 141 ± 31 g (P < .001), LVMI in men decreased from 100 ± 20 g/m(2) to 79 ± 18 g/m(2) (P < .001), and the LVMI in women decreased from 96 ± 18 g/m(2) to 80 ± 17 g/m(2) (P < .001). No improvement in diastolic function parameters was seen. The mean SBP and DBP decreased from 133.5 ± 16.9 mm Hg to 127.9 ± 13.2 mm Hg (P = .007) and from 75.4 ± 10.2 mm Hg to 73.1 ± 8.8 mm Hg (P = .035), respectively. On multivariate logistic regression analysis, coronary artery disease (CAD) severity (relative risk [RR], 1.27; P = .023), smoking (RR, 1.29; P = .016), and baseline LVM (RR, 1.21; P = .07) were found as independent CV event risk factors. The independent factors associated with SBP and DBP improvement were grade of renal stenosis (RR, 1.28; P = .006), bilateral RAS procedure (RR, 1.17; P = .07), and baseline DBP value (RR, 1.74; P < .001). LVM reduction was associated with higher baseline ejection fraction (RR, 1.53; P < .001) and baseline LVM (RR, 1.7; P < 0.001). SBP and DBP value changes were independent of LVM change (r = 0.031; P = .796 and r = 0.098; P = .413, respectively).
RAS induced LVM and LVMI reduction, which is independent of the change in blood pressure. Baseline LVM is associated with higher CV event risk following RAS.
Journal of vascular surgery: official publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter 03/2011; 53(3):692-7. · 3.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: For 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.
To optimize cell directing toward the coronary endothelium under maintained flow, the authors developed a cell-delivery side-holed perfusion catheter (PC). Thirty-four patients (36-69 years, 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] × 10⁶) administration at 6-14 days after pPCI (LVEF 37.1 [24-44]%). Myocardial perfusion (⁹⁹(m)Tc-MIBI) and labeled cells' activity were evaluated (SPECT) at, respectively, 36-48 h prior to and 60 min after delivery.
In contrast to OTW coronary occlusions, no intolerance or ventricular arrhythmia occurred with PC cells' administration (P < .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, P = .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.
Irrespective 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.
Journal of Nuclear Cardiology 02/2011; 18(1):104-16. · 2.85 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A role of coagulation in the pathogenesis of aortic stenosis (AS) is unknown. The aim of this study was to investigate the fibrin (Fn) presence and its determinants in calcified stenotic aortic valve leaflets. Twenty-one patients with dominant AS and 17 well-matched patients with dominant aortic insufficiency (AI) undergoing aortic valve replacement were studied. Immunofluorescence analysis was performed on decalcified leaflets using antibodies against human Fn and tissue factor (TF). Fn-positive (41.4%) and TF-positive (25.3%) areas were increased in AS valves compared with AI valves (7.9% and 5.9%, respectively, both p<0.001). Patients with AS had elevated plasma D-dimer (236.4 ± 28 ng/ml, p=0.002) and prothrombin fragment 1+2 (F1.2) (261.7 ± 27.1 pM, p=0.005) compared to AI subjects (142.8 ± 10 ng/ml and 131.2 ± 1.3 pM, respectively). In AS patients Fn-positive areas correlated with TF-positive areas (r=0.68, p=0.0005), D-dimer (r=0.45, p=0.018), F1.2 (r=0.64, p=0.002), the time required for plasma fibrin clot formation (r=0.44, p=0.015) and maximum absorbance of fibrin clots (r=-0.38, p<0.0001), but not with clot permeability or lysis time. Thickness of Fn layer within AS valves was associated with maximum transvalvular gradient (r =0.41, p=0.048). Patients with maximal gradient above 75 mmHg (n=11) showed significant associations between Fn-positive area and both maximal (r =0.63) and mean (r =0.67) transvalvular gradients. Large fibrin amounts, mostly co-localised with TF, are present within the valve leaflets of patients with advanced AS. In vivo thrombin generation and fibrin clot formation are associated with the extent of Fn presence within leaflets, which might contribute to the AS progression.
Thrombosis and Haemostasis 11/2010; 105(2):254-60. · 5.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This prospective study aimed to determine whether carotid intima-media thickness (CIMT) and biomarkers can enhance the predictive value of classic atherosclerosis risk factors (RFs) for cardiovascular (CV) event risk in patients with confirmed atherosclerosis.
Baseline levels of hs-CRP, Tumor Necrosis Factor alpha (TNF-α), Transforming Growth Factor beta (TGF-β), Interleukin-6 (IL-6), Interleukin-10 (IL-10) and Nt-proBNP were measured in 304 subjects (189 men) aged 64.2±9.4 years, with confirmed atherosclerotic occlusive disease. Maximum CIMT values of common, bulb and internal carotid arteries were measured and expressed as mean CIMT value. The incidences of CV death, myocardial infarction (MI), ischemic stroke (IS) and symptomatic lesion progression were recorded.
During 44.7±12.1 months of follow-up, CV events occurred in 61 (20.1%) patients. Age (odds ratio: OR=1.04; p=0.013), diabetes (OR=2.01; p=0.007), LDL-cholesterol>3.35mmol/L (OR=2.03; p=0.007), previous MI (OR=2.14; p=0.003) and previous IS (OR=3.35; p<0.001) were found independent CV event RFs. Adding biomarkers or CIMT to classic RFs revealed that levels of TNF-α>6pg/mL (OR=1.77; p=0.024), hs-CRP>6mg/L (OR=1.69; p=0.009) or CIMT>1.25mm (OR=5.11; p<0.001) were independently associated with CV event risk. While Nt-proBNP was found RF of CV death (OR=1.19; p=0.003) and MI (OR=1.19; p=0.002). In patients with RFs plus TNF-α>6pg/mL and hs-CRP>6mg/L, a 2- and 5-year event-free survival was 8% and 4%, respectively, as compared to 42% and 33% in those with RFs but lower TNF-α and hs-CRP levels. While, CIMT<1.25mm increased a 2- and 5-year CV event-free survival probability to 79% and 73%, respectively, despite classic RFs presence.
Additive value of TNF-α, hs-CRP and CIMT to classic RFs in CV risk stratification was found in patients with confirmed atherosclerosis. Nt-proBNP was found an independent risk factor of CV death and MI.
[Show abstract][Hide abstract] ABSTRACT: To evaluate the possible role of transcranial color-coded Doppler ultrasonography (TCD) in predicting cerebral reperfusion injury (CRI) in patients undergoing carotid artery stenting (CAS) for internal carotid artery (ICA) stenosis.
TCD was obtained in 210 patients (149 men; mean age 64.2+/-8.4 years, range 44-83) who underwent CAS for ICA stenosis averaging 86.7%+/-8.4%. Contralateral ICA occlusion or near occlusion (stenosis >90%) was present in 67 (31.9%) patients. TCD was performed before and 24 hours after CAS with assessment of peak systolic velocities (PSVs) in the ipsilateral middle cerebral artery (iMCA) and contralateral middle cerebral artery (cMCA). PSV ratios (PSVR) in the iMCA and cMCA were calculated from the PSVs before and after CAS.
CRI syndrome occurred in 3 (1.4%) patients (2 intracranial bleedings, 1 subarachnoid hemorrhage). The mean iMCA and cMCA PSVRs were 2.66+/-0.19 and 4.16+/-2.77, respectively, in CRI patients, while the PSVRs in CAS patients without neurological sequelae were 1.56+/-0.46 and 1.21+/-0.39, respectively (both p<0.001). The combination of iPSVR>2.4 and cPSVR>2.4 occurred in 4 patients with bilateral ICA disease; 3 (75%) of them developed CRI (100% sensitivity and 99% specificity for CRI prediction). The following independent CRI predictors were identified: combined iPSVR>2.4 and cPSVR>2.4 (RR 2.06, CI 1.89 to 2.24; p<0.001), high cMCA PSV after CAS (RR 1.23, CI 1.13 to 1.34; p<0.001), and contralateral ICA occlusion (RR 1.13, CI 1.03 to 1.23; p = 0.007).
TCD is an important tool in CRI risk evaluation. The combination of iPSVR>2.4 and cPSVR>2.4 is an independent CRI risk factor, along with contralateral ICA occlusion and high cMCA PSVs after CAS.
Journal of Endovascular Therapy 08/2010; 17(4):556-63. · 2.70 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Thromboembolic complications occur more frequently in patients with chronic heart failure (CHF) than in the general population. Formation of a compact fibrin clot resistant to lysis has been shown in arterial and venous thrombosis.
To investigate fibrin clot properties in patients with CHF.
Plasma clot permeability, compaction, turbidity and fibrinolysis were assessed in 36 consecutive patients with stable CHF (30M, 6F; aged 64+/-10 years, left ventricular ejection fraction (LVEF) 34.9+/-6.7%) and 36 controls matched for age, sex, cardiovascular risk factors and medication. Exclusion criteria were LVEF >40%, anticoagulant therapy, previous thromboembolic events, atrial fibrillation.
Clots obtained from plasma of patients with CHF had 23% lower clot permeability (p<0.0001), 13% less clot compaction (p<0.001), 15% faster fibrin polymerisation (p<0.0001) and tended to have prolonged fibrinolysis time (p=0.1) compared with controls. C-reactive protein and fibrinogen were associated inversely with clot permeability (R(2)=0.84, p<0.0001 and R(2)=0.79, p<0.0001, respectively) and positively with fibrinolysis time (R(2)=0.88, p<0.0001 and R(2)=0.80, p<0.0001, respectively) in patients with CHF. Plasma thrombin-antithrombin complex concentrations were inversely correlated with clot permeability (R(2)=0.88, p<0.0001) and positively with fibrinolysis time (R(2)=0.91, p<0.0001). Left atrium diameter, but not LVEF, correlated with fibrinolysis time (R(2)=0.61, p=0.027).
Patients with CHF with sinus rhythm are characterised by faster formation of compact plasma fibrin clots, which might predispose to thromboembolic complications.
[Show abstract][Hide abstract] ABSTRACT: To evaluate right-ventricular (RV) function during stress echocardiography (SE) and to assess its relationship with exercise capacity in heart failure (HF) patients.
We included 88 patients aged 60.9 +/- 11.2 years with a mean LVEF of 27.2 +/- 9.5%. The following RV parameters were measured at baseline and peak exercise during semi-supine SE: velocity (IVV) and acceleration during isovolumic contraction (IVA), S', E', A', and ratio of early diastolic tricuspid velocity to E' (E/E') and longitudinal strain and strain rate. Patients were stratified into two groups according to their VO(2peak) values: group 1 (n = 35) with VO(2peak) <14 mL/kg/min and group 2 (n = 53) with VO(2peak) >or=14 mL/kg/min. At rest, all analysed variables were similar in the two groups, but during stress IVV, S', and E' were significantly higher and the E/E' ratio significantly lower in group 2. In broad terms, parameters measured at stress correlated much better with VO(2peak) than parameters assessed at baseline. However, results of multivariable analysis determined that the independent predictors of VO(2peak) were solely the left-ventricular (LV) parameters: E/E' and S'.
Right-ventricular function (whether at rest or during stress tests) was not significantly associated with exercise capacity in our patients with HF. In contrast, systolic and, to a greater extent, diastolic LV parameters during the stress tests emerged as the most important indicators linked to exercise capacity in HF.
European Journal of Heart Failure 03/2010; 12(3):260-7. · 5.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The clinical efficacy of transcatheter atrial septal defect (ASD) closure with the Amplatzer Septal Occluder (ASO) can only be judged against the results of contemporaneous surgery. The present study compared early and late results of ASD closure using ASO versus open-heart surgery.
Forty-eight adult patients were found eligible for transcatheter closure in transesophageal echocardiography. The surgical group consisted of 52 patients with isolated ostium secundum ASD. All patients underwent standard ECG, 24-hour ECG recording, and transthoracic echocardiography pre-procedure at 1-month and at 1-year follow-up. Physical fitness was assessed by cardiopulmonary exercise testing (CPX) prior to ASD closure and at 1-year follow-up.
ASD closure was successful in all surgical patients and in 94% of the ASO group (0% mortality). The total complication rate for surgical vs. device closure was not significantly different (19.2% vs. 26.7%; p=0.383), despite more serious complications in the surgical group. Hospital stay was significantly shorter in the ASO group (5.4+/-2.2 vs. 9.1+/-1.2 days; p<0.001). Although echocardiographic parameters did not differ significantly between the respective groups at 1-year follow-up, CPX revealed a higher decrease in the VE/VCO2 slope in the ASO group (-3.7+/-3.4 vs.-1.2+/-4.8; p=0.003).
As surgical and device closure appear similarly effective in adults with ASD, avoidance of thoracotomy and cardiopulmonary bypass, in conjunction with a shorter hospital stay, argues in favour of device closure in selected patients.
Medical science monitor: international medical journal of experimental and clinical research 12/2009; 15(12):CR612-7. · 1.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Increased risk of thrombotic events occurs in chronic obstructive pulmonary disease (COPD). Elevated fibrinogen and C-reactive protein (CRP), being common in COPD, are associated with formation of dense fibrin clots resistant to lysis. Statins have been found to display anti-inflammatory and antithrombotic effects. We investigated fibrin clot properties in COPD patients prior to and following statin therapy. Ex vivo plasma fibrin clot permeability, compaction, and fibrinolysis were assessed in 56 patients with stable COPD, aged 64.9 +/- 9.2 years (mean FEV(1), 54.7 +/- 15.9% predicted), versus 56 controls matched for age, sex and cardiovascular risk factors. Patients were then randomly assigned to receive simvastatin 40 mg/day (n = 28) or to remain without statins for three months (n = 28). Patients with COPD had lower clot permeability (6.1+/- 1.07 versus 9.2 +/- 0.9 10(-9) cm(2), p < 0.0001), decreased compaction (44.9 +/- 4.5 versus 63.9 +/- 6.1%, p < 0.0001), higher maximum D-dimer levels released from clots (4.23 +/- 0.55 versus 3.53 +/- 0.31 mg/l, p < 0.0001) with a decreased rate of this release (75.0 +/- 8.3 versus 80.9 +/- 8.0 microg/l/min, p = 0.03) and prolonged lysis time (9.84 +/- 1.33 versus 8.02 +/- 0.84 min, p < 0.0001) compared with controls. Scanning electron microscopy confirmed denser clot structure in COPD. Multiple linear regression analysis after adjustment for age and fibrinogen showed that in the COPD patients, CRP was the only independent predictor of permeability (R(2) = 0.47, p < 0.001) and lysis time (R(2) = 0.43, p < 0.001). Simvastatin improved clot properties (p < 0.05) despite unaltered CRP and irrespective of cholesterol reduction. Our study shows that fibrin clots in COPD patients are composed of much denser networks that are more resistant to lysis, and these properties can be improved by statin administration.
Thrombosis and Haemostasis 12/2009; 102(6):1176-82. · 5.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To assess changes of systolic function using tissue Doppler imaging (TDI) during stress echocardiography and its impact on exercise capacity in heart failure (HF) patients (pts).
80 pts (65 male), mean age of 59.3 +/- 10.9 years, NYHA class 1.95 +/- 0.8, left ventricle ejection fraction (LVEF) 27.2 +/- 9.5 (10-45%). The etiology of HF was ischemic (ICM) in 50 pts and dilated cardiomyopathy (DCM) in 30 pts. Peak myocardial velocity (IVV) and acceleration (IVA) during isovolumic contraction and peak myocardial velocity during ejection phase (S') were measured at baseline and peak exercise during semi-supine stress-echo (20 Watts, 2-min increments). Concurrently peak oxygen uptake (VO(2) peak) was measured.
Rest values of analyzed parameters were comparable in groups according to etiology of HF and physical capacity. However, peak stress parameters mainly S' were significantly higher in the DCM group and the group with better VO(2) peak. The best correlation with exercise capacity was S' at peak stress (r = 0.66; p < 0.0001). The most useful parameter for identifying severe exercise intolerance, VO(2) peak < 14 ml/kg/min, was S' with an area under ROC curve of 0.82 +/- 0.05 (95% CI 0.71-0.89). The cutoff of 5.75 cm/s for S' at peak stress showed a sensitivity of 61% with a specificity of 96%.
The evaluation of systolic function by means of TDI instead of LVEF shows more clearly that systolic function is at least partly responsible for exercise tolerance in HF. Assessment of echocardiographic systolic parameters at peak stress provides more accurate information about exercise capacity in HF pts.
[Show abstract][Hide abstract] ABSTRACT: In 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.
To evaluate the relationship between CIMT, atherosclerosis extent and CV event rates in patients with established atherosclerosis.
Baseline 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).
In 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.
[Show abstract][Hide abstract] ABSTRACT: Carotid intima-media thickness (CIMT) is an early marker of coronary artery disease (CAD). This study aimed to evaluate CIMT value for CAD prediction in pre-and postmenopausal women referred for coronary angiography with angina-like symptoms and a positive result of the treadmill test. The study comprised 321 women referred for coronary angiography with symptoms suggesting CAD. Carotid intima-media thickness was measured in common, bifurcation, and internal carotid artery, and expressed as the mean maximum value. Coronary angiography showed coronary stenosis > or = 50% in 211 (65.7%) women, including 27 with regular menses (47.3 +/- 3.4 years) and 184 postmenopausal (65.8 +/- 7.2 years). Normal coronary arteries were found in 110 women: 17 (47.3 +/- 4.9 years) with regular menses and 93 postmenopausal (64.3 +/- 6.5 years). The highest CIMT values were found in postmenopausal CAD women (1.360 +/- 0.32 mm), as compared to premenopausal with CAD (1.178 +/- 0.36 mm, P = 0.005), pre- (0.860 +/- 0.23 mm, P < 0.001) and postmenopausal (1.022 +/- 0.30 mm, P < 0.001) women without CAD. Carotid intima-media thickness (P < 0.001), hyperlipidemia (P = 0.018), and myocardial infarction (P < 0.001), but not menopause itself or the number of years since menses cessation, were found to be independent CAD predictors. By receiver operating characteristic calculation, the mean maximum CIMT cut-off values discriminating CAD were lower in premenopausal (> or = 0.933 mm) than in postmenopausal women (> or = 1.075 mm; P < 0.05) resulting in similar sensitivity (85.2% and 82.6%) and specificity (70.6% and 69.9%). Carotid intima-media thickness is a strong CAD predictor in both pre- and postmenopausal women, in contrast to the menopausal status.
Heart and Vessels 09/2008; 23(5):295-300. · 2.13 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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).
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.
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.
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.
Journal of Endovascular Therapy 07/2008; 15(3):249-62. · 2.70 Impact Factor