Vascular reactivity in patients with undifferentiated connective tissue diseases

Assessment of changes in plaque volume is increasingly used as a surrogate-endpoint in clinical trials testing the efficacy of anti-atherosclerotic interventions. Multi-detector computed tomography (MDCT) can detect and quantify non-calcified atherosclerotic plaques, but its ability to monitor changes in plaque volume has not yet been tested.We sought to test the ability of MDCT to detect and quantify serial changes in atheroma burden in comparison with magnetic resonance imaging (MRI).MethodsRabbits (n = 12) with experimentally induced abdominal atherosclerosis were randomized to receive a plaque-regressing agent (recombinant apoA-I_Milano, n = 8) or placebo (n = 4). All animals underwent two 64-slice MDCT angiography and MRI studies (pre- and post-treatment). The primary endpoint was the change in plaque burden (defined as vessel wall volume in the 5 cm distal to the left renal artery) between pre- and post-treatment MDCT in comparison with MRI.ResultsMDCT detected a significant decrease in plaque burden caused by recombinant apoA-I_Milano (464 [423–535] to 405 [363–435] mm³, p = 0.03) that was confirmed by MRI (324 [286–412] to 298 [282–399] mm³, p = 0.03). No significant effect was noted in the placebo group either by MDCT or MRI. There were strong correlations between both modalities for the quantification of plaque burden (r = 0.750, p < 0.001) and change in plaque burden (r = 0.657, p = 0.020). MDCT overestimated plaque burden compared to MRI.On MDCT, the mean interobserver variability for plaque burden was 2.5 ± 0.4%.ConclusionsIn an animal model of atherosclerosis, MDCT accurately documented serial changes in aortic plaque burden, demonstrating good correlation and agreement with MRI-derived measurements and low interobserver variability.     

CRP and CD14 polymorphisms correlate with coronary plaque volume in patients with coronary artery disease--IVUS substudy of the ENCORE trials

BackgroundSeveral proinflammatory single-nucleotide polymorphisms (SNPs) have been linked to the progression of atherosclerosis and coronary artery disease (CAD). Plaque size and its destabilization by inflammatory processes are major determinants of ischemia and acute coronary syndromes. Intravascular ultrasound (IVUS) allows for quantification of plaque size in vivo. We therefore investigated the relation of plaque size with mutations of proinflammatory genes in patients with CAD.MethodsIn 196 patients with stable CAD enrolled in the ENCORE trials coronary plaque and vessel volume was assessed by IVUS. 173 patients were successfully genotyped for polymorphisms of proinflammatory genes CD14 C(?260)T and CRP C(+1444)T using the single-nucleotide polymorphism polymerase chain reaction (SNP PCR) approach.ResultsBaseline characteristics were comparable for all genotype groups. Higher ratios of plaque volume/vessel volume were observed in patients with the CRP 1444TT (n = 11) and CD14 260TT (n = 33) genotypes (p = 0.016 and p = 0.026, respectively).ConclusionIn patients with stable coronary artery disease the CRP 1444TT and CD14 260TT variants are associated with larger coronary plaque volume independently of concomitant cardiovascular risk factors.     

A comparison between 40 MHz intravascular ultrasound iMap imaging system and integrated backscatter intravascular ultrasound

BackgroundiMap is a newly developed intravascular ultrasound (IVUS) tissue characterization system based on pattern recognition of the radio frequency (RF) signals.PurposeThe purpose of this study was to compare tissue characterization between iMap and another previously validated tissue characterization system, integrated backscatter (IB)-IVUS in vivo and to clarify similarities and differences between these two methods.MethodsA total of 31 lesions from 16 patients with ischemic heart disease were studied. IVUS imaging was performed using 40 MHz IVUS catheter. RF signals from each lesion were then exported to analyze tissue characterization using both iMap and IB-IVUS. By iMap, coronary plaque was classified into four categories, fibrotic, lipidic, necrotic, or calcified. By IB-IVUS, coronary plaque was classified into four categories, fibrosis, lipid pool, dense fibrosis, or calcification. After the images were acquired, IB-IVUS and iMap images were compared at exactly the same cross-sections. Because severe calcification is a perfect reflector, dense calcification lesions (>20%) were excluded.ResultsBoth fibrotic and calcified by iMap correlated well with fibrosis and calcification by IB-IVUS (fibrotic vs. fibrosis: r² = 0.522, p < 0.001, calcified vs. calcification: r² = 0.560, p < 0.001). Although lipidic by iMap did not correlate with lipid pool by IB-IVUS, necrotic by iMap correlated well with lipid pool by IB-IVUS (r² = 0.480, p < 0.001).ConclusionAlthough tissue types classified by iMap correlated well with corresponding tissue type by IB-IVUS, some discrepancy presented between the two systems. These results may call for careful interpretation of the tissue types obtained by the different IVUS tissue characterization systems.     

Epidemiology of fat replacement of the right ventricular myocardium determined by multislice computed tomography using a logistic regression model

PurposeWe frequently observe fat replacement (FR) of the anterior wall of the right ventricular myocardium (RVM), but its epidemiological significance is not clear.Methods and materials49 consecutive subjects (28 males, 36–83 years old, median 67) underwent enhanced ECG-gated multislice CT (Light speed ultra 16, General Electrics, WI) and we retrospectively analyzed the presence of FR of RVM. A logistic model for predicting FR of RVM was constructed using age, sex, hypertension [HT], diabetes mellitus [DM], hyperlipidemia [HL] smoking, obesity (body mass index > 25.0) and calcified and non-calcified plaques of coronary arteries (CA).ResultsFR of RVM was detected in 21 subjects (12 males, 51–78 years old, median 67), 76% of whom had HT, 38% DM, 43% HL, 48% smoking history, 52% were obese, and 76% had calcified and 24% had non-calcified plaques of CA. Only obesity was significantly higher in FR (p < 0.05). A logistic regression model showed, although there was a close association between obesity and an increased incidence of FR, it did not reach statistical significance (p = 0.0515, relative risk 5.11).ConclusionsObesity is significantly more common in cases of FR, and despite a negative multivariable analysis, may influence FR in the RVM. FR in obesity may occur independently of clinically-significant arrhythmia, which is different from ARVC. Thus, even with FR, obesity must be considered as a diagnosis before ARVC.     

Coronary microvascular dysfunction is associated with higher frequency of thin-cap fibroatheroma

ObjectiveBoth coronary microvascular dysfunction and epicardial plaque vulnerability have been associated with adverse cardiovascular outcomes. However, whether microvascular dysfunction is a predictor of plaque vulnerability is not known. We hypothesized that microvascular dysfunction is associated with greater systemic inflammation and is a predictor of virtual histology–intravascular ultrasound (VH–IVUS)-defined coronary thin-cap fibroatheromas.MethodsInvasive physiologic assessment and VH–IVUS were performed and serum high-sensitivity C-reactive protein (hs-CRP) was measured in 51 patients with non-obstructive CAD [fractional flow reserve (FFR) ≥ 0.75]. Microvascular dysfunction was defined as coronary flow velocity reserve (CFVR) < 2.0. Lumen area and plaque burden and composition were assessed in each VH–IVUS frame. Frequency of thin-cap fibroatheroma (TCFA) in each artery was defined as the percentage of VH–IVUS frames with plaque burden ≥ 40% and confluent necrotic core ≥ 10% in contact with lumen for at least 3 consecutive frames.ResultsMean age was 57 ± 12 years and 25% of patients presented with acute coronary syndrome. Despite similar amount of epicardial disease, characterized by lumen area (8.9 ± 3.0 vs. 10.1 ± 3.3 mm², p = 0.3) and FFR (0.90 ± 0.08 vs. 0.92 ± 0.07, p = 0.2), patients with microvascular dysfunction had greater hs-CRP (4.2 [2.3, 7.6] vs. 1.0 [0.4, 4.2] ng/ml, p = 0.006), greater plaque burden (47 ± 10 vs. 36 ± 13%, p = 0.004), and higher frequency of TCFA (17 ± 25 vs. 6 ± 9%, p = 0.02). After adjustment for cardiovascular risk factors, hs-CRP, and plaque burden, coronary microvascular dysfunction was an independent predictor of frequency of TCFA (β = +0.42, p = 0.033).ConclusionIn patients with non-obstructive CAD, coronary microvascular dysfunction is associated with higher serum hs-CRP and is an independent predictor of more TCFAs, a marker for increased epicardial plaque vulnerability.     

Association of pericardial fat and coronary high-risk lesions as determined by cardiac CT

ObjectivePericardial adipose tissue (PAT) is a pathogenic fat depot associated with coronary atherosclerosis and cardiovascular events. We hypothesized that higher PAT is associated with coronary high-risk lesions as determined by cardiac CT.MethodsWe included 358 patients (38% female; median age 51 years) who were admitted to the ED with acute chest pain and underwent 64-slice CT angiography. The cardiac CT data sets were assessed for presence and morphology of CAD and PAT. Coronary high-risk lesions were defined as >50% luminal narrowing and at least two of the following characteristics: positive remodeling, low-density plaque, and spotty calcification. PAT was defined as any pixel with CT attenuation of ?190 to ?30 HU within the pericardial sac.ResultsBased on cardiac CT, 50% of the patients (n = 180) had no CAD, 46% (n = 165) had CAD without high-risk lesions, and 13 patients had CAD with high-risk lesions. The median PAT in patients with high-risk lesions was significantly higher compared to patients without high-risk lesions and without any CAD (151.9 [109.0–179.4] cm³ vs. 110.0 [81.5–137.4] cm³, vs. 74.8 [58.2–111.7] cm³, respectively p = 0.04 and p < 0.0001). These differences remained significant after adjusting for traditional risk factors including BMI (all p < 0.05). The area under the ROC curve for the identification of high-risk lesions was 0.756 in a logistic regression model with PAT as a continuous predictor.ConclusionPAT volume is nearly twice as high in patients with high-risk coronary lesions as compared to those without CAD. PAT volume is significantly associated with high risk coronary lesion morphology independent of clinical characteristics and general obesity.     

Improved characterization of atherosclerotic plaques by gadolinium contrast during intravascular magnetic resonance imaging of human arteries

ObjectivesTo determine whether gadolinium-DTPA (Gd-DTPA) facilitates discrimination of fibrous, lipid or calcified constituents during intravascular magnetic resonance imaging (IVMRI) of human atherosclerotic arteries.BackgroundAtherosclerotic plaques that cause fatal thrombosis due to rupture have high content of lipid relative to fibrous tissue. We recently demonstrated that IVMRI identifies lipid, fibrous, and calcified components within atherosclerotic human arteries with favorable sensitivity and specificity. Gd-DTPA, a T1-shortening agent, selectively amplifies the signal from fibrous tissue on T1 weighted (T1w) surface MRI.MethodsA 0.030 in. diameter receiver coil coupled to a 1.5T MR scanner was positioned in iliac arteries of nine subjects with atherosclerosis. Previously validated multi-parametric analysis of T1w and moderate T2w images identified 137 fibrous, lipid and calcified regions of interest within 37 arterial segments. T1w imaging was repeated following 0.1 mmol/kg IV Gd-DTPA infusion.ResultsComputer-derived mean gray value in fibrous regions increased by 34.2% with Gd-DTPA (95% CI 24.3–43.5%, p = 0.0001) while lipid and calcified regions showed only a non-significant increase of 4.3% (95% CI ?0.6 to 9.2%, p = 0.0825) and 3.8% (95% CI ?1.1 to 7.7%, p = 0.103), respectively. The increase in mean gray value with Gd-DTPA was greater for fibrous than for lipid or calcified regions (p = 0.0001).ConclusionsGd-DTPA selectively enhances signal intensity of fibrous constituents during IVMRI of human atherosclerotic arteries and thus identifies key tissue characteristics associated with plaque stability. These findings have important implications for the assessment of plaque-stabilizing therapies and ultimately for reducing cardiovascular events.     

Characterization of non-calcified coronary atherosclerotic plaque by multi-detector row CT: comparison to IVUS

Multi-detector row Computed Tomography (MDCT) permits non-invasive visualization of the coronary arteries. The ability to visualize and, with limitations, to characterize non-calcified coronary atherosclerotic plaque has been described. We investigated the CT attenuation of non-calcified plaques as determined by 16-slice MDCT in comparison to intravascular ultrasound (IVUS). METHODS AND RESULTS: Thirty-two patients were investigated by contrast-enhanced 16-slice CT. In addition, IVUS of one coronary artery (motorized pullback) was performed (LM+LAD: 22, LM+LCX: 4, RCA: 6). At 252 sites within the coronary system, in which non-calcified atherosclerotic plaque could be identified both in MDCT and IVUS, the CT attenuation within the plaque was measured using a centrally placed region of interest and correlated to the appearance of the plaque in IVUS at the corresponding location. The mean CT attenuation within plaque that corresponded to hyper-echogenic appearance in IVUS was 121+/-34HU (n=76). The mean CT attenuation within plaque that corresponded to hypo-echogenic appearance was 58+/-43HU (n=176, p<0.001). However, there was substantial overlap of the density values measured by MDCT in the two groups. CONCLUSIONS: A significant difference of the mean CT attenuation within atherosclerotic lesions of hypo-echogenic and hyper-echogenic appearance in IVUS could be observed. However, we observed substantial overlap of attenuation values between plaque types so that the differentiation of "vulnerable" and "stable" plaques based on their CT attenuation is doubtful.     

Comparison of quantitative measurements between two different intravascular ultrasound systems: In vitro and in vivo studies

BackgroundAlthough intravascular ultrasound (IVUS) allows for precise measurements of coronary artery dimension, variability in quantitative measurements among currently available different IVUS systems is unknown. The aim of study was to compare two different IVUS catheters and consoles to verify their accuracy and compatibility.Methods(1) In vitro study: IVUS imaging was performed in a concentric cylindrical phantom with 6 sections of known, cross-sectional diameter ranging from 3.0 to 8.0 mm. The minimum lumen diameter (MLD) and lumen cross sectional area (CSA) were measured and compared. (2) In vivo study: IVUS imaging was performed in 69 coronary arterial segments from 20 patients. The external elastic membrane cross sectional area (EEM-CSA), lumen CSA, and plaque plus media (P + M) CSA were measured and compared between the two IVUS systems.Results(1) In vitro study: MLD and lumen CSA obtained by the two IVUS systems correlated well with the actual values. (2) In vivo study: EEM-, lumen and P + M CSA obtained by the two IVUS systems showed good correlations (R² = 0.973, p < 0.0001; R² = 0.938, p < 0.0001; R² = 0.949, p < 0.0001, respectively).ConclusionsQuantitative measurements by 2 different, currently available IVUS systems were accurate and comparable. These results suggest that the 2 different IVUS catheters/systems may be alternatively used during clinical studies assessing coronary arterial size.     

Placenta growth factor expression in human atherosclerotic carotid plaques is related to plaque destabilization

Background and purposePlacenta growth factor (PlGF) mediates angiogenesis and inflammation, but its role in human atherosclerosis is unknown. This study was designed to test the hypothesis that PlGF-expression in human atherosclerotic carotid plaques is related to inflammation, vascularization and clinical plaque instability.MethodsThe expression of PlGF, C-reactive protein (CRP) and CD40L was analyzed with Western blots in carotid plaques of 60 patients. Cellular infiltration (CD68, CD3) and vascularization (von-Willebrand-factor) was assessed by immunohistochemistry.ResultsSymptomatic patients showed higher levels of PlGF than asymptomatic patients (115.4 ± 8.2 versus 83.6 ± 10.5 densitometric units (DU), p < 0.05) and higher grading for inflammatory cells and microvessels (CD3: 2.3 ± 0.1 versus 0.6 ± 0.1, p < 0.001, CD68: 2.4 ± 0.1 versus 0.8 ± 0.1, p < 0.001, microvessels: 2.3 ± 0.1 versus 1.5 ± 0.1, p < 0.01). PlGF-expression showed a positive correlation to the expression of CRP (r = 0.5, p < 0.001) and CD40L (r = 0.4, p < 0.01).ConclusionsPlGF-expression within human atherosclerotic lesions is associated with plaque inflammation and microvascular density, suggesting a role for PlGF in plaque destabilization and, thus, in clinical manifestation of the disease.     

Four-year clinical outcomes of the OLIVUS-Ex (impact of Olmesartan on progression of coronary atherosclerosis: evaluation by intravascular ultrasound) extension trial

BackgroundThe previous OLIVUS trial reported a positive role in achieving a lower rate of coronary atheroma progression through the administration of Olmesartan, an angiotension-II receptor blocking agent (ARB), for stable angina pectoris (SAP) patients requiring percutaneous coronary intervention (PCI). However, the benefits between ARB administration on long-term clinical outcomes and serial atheroma changes by IVUS remain unclear. Thus, we examined the 4-year clinical outcomes from OLIVUS according to treatment strategy with Olmesartan.MethodsSerial volumetric IVUS examinations (baseline and 14 months) were performed in 247 patients with hypertension and SAP. When these patients underwent PCI for culprit lesions, IVUS was performed in their non-culprit vessels. Patients were randomly assigned to receive 20–40 mg of Olmesartan or control, and treated with a combination of β-blockers, calcium channel blockers, glycemic control agents and/or statins per physician's guidance. Four-year clinical outcomes and annual progression rate of atherosclerosis, assessed by serial IVUS, were compared with major adverse cardio- and cerebrovascular events (MACCE).ResultsCumulative event-free survival was significantly higher in the Olmesartan group than in the control group (p = 0.04; log-rank test). By adjusting for validated prognosticators, Olmesartan administration was identified as a good predictor of MACCE (p = 0.041). On the other hand, patients with adverse events (n = 31) had larger annual atheroma progression than the rest of the population (23.8% vs. 2.1%, p < 0.001).ConclusionsOlmesartan therapy appears to confer improved long-term clinical outcomes. Atheroma volume changes, assessed by IVUS, seem to be a reliable surrogate for future major adverse cardio- and cerebrovascular events in this study cohort.     

Deviation from Murray's law is associated with a higher degree of calcification in coronary bifurcations

ObjectiveMurray's law describes the optimal branching anatomy of vascular bifurcations. If Murray's law is obeyed, shear stress is constant over the bifurcation. Associations between Murray's law and intravascular ultrasound (IVUS) assessed plaque composition near coronary bifurcations have not been investigated previously.MethodsIn 253 patients plaque components (fibrous, fibro-fatty, necrotic core, and dense calcium) were identified by IVUS in segments proximal and distal to the bifurcation of a coronary side branch. The ratio of mother to daughter vessels was calculated according to Murray's law (Murray ratio) with a high Murray ratio indicating low shear stress. Analysis of variance was used to detect independent associations of Murray ratio and plaque composition.ResultsPatients with a high Murray ratio exhibited a higher relative amount of dense calcium and a lower amount of fibrous and fibro-fatty tissue than those with a low Murray ratio. After adjustment for age, sex, cardiovascular risk factors or concomitant medications, the Murray ratio remained significantly associated with fibrous volume distal (F-ratio 4.90, P = 0.028) to the bifurcation, fibro-fatty volume distal (F-ratio 4.76, P = 0.030) to the bifurcation, and dense calcium volume proximal (F-ratio 5.93, P = 0.016) and distal (F-ratio 5.16, P = 0.024) to the bifurcation.ConclusionThis study shows that deviation from Murray's law is associated with a high degree of calcification near coronary bifurcations. Individual deviations from Murray's law may explain why some patients are prone to plaque formation near vessel bifurcations.     

Single polymorphism nucleotide rs1333049 on chromosome 9p21 is associated with carotid plaques but not with common carotid intima-media thickness in older adults. A combined analysis of the Three-City and the EVA studies

ObjectivesTo address the relationship of rs1333049, the 9p21 variant showing the strongest association with coronary heart disease (CHD), with carotid plaques and plaque-free common carotid artery intima-media thickness (CCA-IMT) in older adults from 2 French population-based cohorts.MethodsWe genotyped for rs1333049, 4097 CHD-free participants including 3191 aged 65–86 years from the Three-City (3C) Study and 906 aged 59–71 years from the Vascular Aging Study (EVA). Plaque-free mean CCA-IMT and the presence of carotid plaques were assessed.ResultsIn multivariate analysis, each C allele copy of rs1333049 was associated with baseline carotid plaques (odds ratio (OR) = 1.24; 95% confidence interval (CI) = 1.13–1.36; p < 0.001) but not with baseline CCA-IMT (p = 0.19). Among the EVA participants, the C allele was associated with 4-year plaques progression (p = 0.04) but not with CCA-IMT progression.ConclusionThe chromosome 9p21 locus might influence CHD risk through carotid plaques development.     

Coronary calcification is more predictive of carotid intimal medial thickness in black compared to white middle aged men

BackgroundRace-specific data for the association between coronary artery calcification (CAC) and carotid intimal medial thickness (IMT) are limited. We sought to compare black-white specific associations of these two measures.MethodsWe conducted a population-based study of 379 randomly selected men aged 40–49 years (84 black and 295 white) from Allegheny County, US (2004–2006). Agatston CAC score was evaluated by electron-beam tomography and carotid IMT was evaluated by ultrasonography.ResultsCompared to white men, black men had similar prevalence of CAC (p = 0.56) and higher total carotid IMT (p < 0.001). In black and white men, CAC score had significant positive correlations with total carotid IMT (r = 0.47 and r = 0.24, respectively, p < 0.001 for both) as well as the IMT for the common carotid artery (CCA), internal carotid artery and carotid bulb. The associations of CAC with total and CCA IMT were significantly stronger in black (β = 0.07 and β = 0.05, respectively) than white men (β = 0.03 and β = 0.01, respectively) after adjustment for traditional coronary risk factors (p = 0.046 and p = 0.036, respectively).ConclusionsIn black and white middle aged men, CAC score had significant positive correlations with total and segmental carotid IMT. CAC was more predictive of total and CCA IMT in black than white men independent of coronary risk factors.     

iMap intravascular ultrasound evaluation of culprit and non-culprit lesions in patients with ST-elevation myocardial infarction

ObjectiveThe purpose of this study was to evaluate plaque characteristics of culprit and non-culprit lesions in ST-elevation myocardial infarction (STEMI) patients at the index procedure and 10 months later using iMap intravascular ultrasound (IVUS).BackgroundThe exact site of the plaque rupture or erosion in coronary arteries with subsequent thrombosis cannot be precisely defined. Our hypothesis is that in STEMI patients angiographically guided stenting could fail to identify necrotic tissue and thus may leave an uncovered significant amount of vulnerable plaque.MethodsIn 63 consecutive STEMI patients the culprit artery was analyzed with iMap IVUS at the time of the index procedure and 10 months later. The most stenotic culprit segment was compared to the segment proximal to the culprit lesion.ResultsA high percentage of necrotic tissue was observed in the culprit lesion and a comparatively lower percentage of necrotic tissue was observed in the non-culprit lesions proximal to the culprit at the index procedure by iMap IVUS (31.9% ± 10.0% vs 27.8% ± 11.8%, p = 0.012). The proportion of necrotic tissue in the segment proximal to the culprit lesion was unchanged at 10-month follow-up (27.1% ± 11.9% vs 25.5% ± 12.8%, p = 0.147). The percentage of lipidic tissue in the proximal segment decreased at 10-month follow-up (9.8% ± 2.9% vs 8.8 ± 3.0%, p = 0.009).ConclusionsIn STEMI patients, culprit lesion segments and non-culprit segments contain high proportions of necrotic tissue. However, a comparatively higher proportion of necrotic tissue was found in the culprit lesions according to iMap IVUS. The percentage of necrotic tissue remained high at 10-month follow-up in both culprit and non-culprit segments.     

Gender specific associations between matrix metalloproteinases and inflammatory markers in post myocardial infarction patients

ObjectiveAtherothrombotic disease in the coronary arteries leads to myocardial infarction (MI) through plaque rupture or erosion of the endothelium, the former mechanism predominating in men and the latter in women. Inflammation is a key feature of these processes, and the interplay between inflammation and matrix metalloproteinases (MMPs) in this context is not fully understood. In this study, we investigated the association between inflammatory markers and MMPs in men and women.MethodsBlood samples were drawn 3 months after a first MI in 387 patients and 387 sex- and age-matched controls (82% men). C-reactive protein (CRP), interleukin-6 (IL-6), IL-8, -18, tumour necrosis factor-α (TNF-α), macrophage chemoattractant protein-1 (MCP-1), MMP-1, -3 and -9 were measured. Coronary angiography was performed in 243 of the patients, and they were classified into 0-, 1-, 2- or 3-vessel disease groups.ResultsCRP, IL-6, -8, -18 and TNF-α were higher, and MMP-3 and -9 were lower, in patients than in controls. A greater proportion of women (49%) had 0-vessel disease than men (16%, p < 0.0001). A gender specific pattern of associations between inflammatory markers and MMPs was found as IL-6 (r_S = 0.29, p < 0.05), IL-18 (r_S = 0.34, p < 0.01) and MCP-1 (r_S = 0.35, p < 0.01) correlated with MMP-3 in female patients, whereas CRP (r_S = 0.23, p < 0.0001), IL-6 (r_S = 0.13, p < 0.05) and IL-8 (r_S = ?0.21, p < 0.01) correlated with MMP-9 in male patients.ConclusionsThe present study demonstrates different patterns of association between inflammatory markers and MMPs in men and women, strengthening the hypothesis of gender specific differences in pathophysiological mechanisms of MI.     

Implantation of paclitaxel-eluting stent impairs the vascular compliance of arteries in porcine coronary stenting model

BackgroundThe impaired compliance of large and medium-sized muscular arteries has been shown to correlate with the risk of adverse cardiovascular events. We assessed coronary artery distensibility using simultaneous intracoronary ultrasound and pressure wire measurements in porcine coronary arteries after implantation of paclitaxel-eluting (PES) and bare metal stents (BMS) and compared this with the histopathology of the arterial wall injury.MethodsPES and BMS were implanted into porcine left coronary arteries under general anesthesia. At 1-month follow-up (FUP) the endothelium-dependent and endothelium-independent vascular compliances were measured after intracoronary infusion of 10^?6 M acetylcholine for 2.5 min, and intracoronary bolus of 100 μg nitroglycerine, respectively. The arterial stiffness index, distensibility and reflexion index were calculated in stented arteries (n = 25 PES and n = 25 BMS), and correlated with histopathologic and histomorphometric changes of the vessel wall.ResultsIn spite of smaller neointimal area, the fibrin deposition, medial thickening, vascular wall inflammation scores and arterial remodeling index were elevated and endothelialization was impaired in arteries with PES. Arteries with PES exhibited significantly worse endothelium-dependent vascular compliance: the stiffness (p < 0.001) and reflexion index (p < 0.001) were significantly higher and the distensibility index (p < 0.001) lower as compared with the arteries with BMS. The endothelium-independent vascular reaction was similarly impaired in arteries with PES, as the stiffness index (p < 0.001) and the distensibility index (p < 0.001) differed significantly between the PES and BMS groups. Incomplete endothelialization (r = 0.617, p < 0.001) was significantly associated with the endothelium-dependent increased vascular stiffness. The increased fibrin score (r = 0.646, p < 0.001), vessel wall inflammation (r = 0.657, p < 0.001) and medial thickening (r = 0.672, p < 0.001) correlated significantly with the endothelium-independent stiffness index.ConclusionsImplantation of PES impairs the coronary artery wall structure and the endothelium-dependent and independent vessel wall dynamics more than does the implantation of BMS.     

Effect of statin therapy on coronary fibrous-cap thickness in patients with acute coronary syndrome: assessment by optical coherence tomography study

BackgroundThe thickness of coronary fibrous caps is a major determinant of vulnerable plaques. Several clinical trials have suggested that statin therapy could stabilize vulnerable plaques. Recently, optical coherence tomography (OCT) has been proposed as an effective histology-resolution imaging modality for assessing such micro-structural changes.MethodsForty AMI patients with hyperlipidemia were enrolled and underwent percutaneous coronary intervention (PCI). They were divided into two groups; statin treatment group (n = 23) or control group (n = 17). Serial OCT analyses were performed at baseline and 9-month follow-up for a non-PCI lipid-rich plaque lesion.ResultsThe LDL-cholesterol level in the statin group was significantly lower than that in the control group at follow-up. Although the fibrous-cap thickness was significantly increased in both the statin treatment group (151 ± 110 to 280 ± 120 μm, p < 0.01) and the control group (153 ± 116 to 179 ± 124 μm, p < 0.01) during follow-up period, the degree of increase was significantly greater in the statin treatment group than in the control group (188 ± 64% vs. 117 ± 39%, p < 0.01). Furthermore, when the patients in the statin treatment group were divided into two subgroups (fibrous-cap thickness ConclusionThe lipid-lowering therapy with statin for 9 months after the onset of acute myocardial infarction significantly increased the fibrous-cap thickness in patients with hyperlipidemia.     

Early detection of premature subclinical coronary atherosclerosis in systemic lupus erythematosus patients

ObjectiveTo elucidate early coronary atherosclerotic changes in premenopausal systemic lupus erythematosus (SLE) female patients without clinical cardiovascular manifestation using a 64-slice Multi-detector computed tomography (MDCT) scan to detect coronary calcification and measure coronary calcium score (CCS), and to find out its correlation to some traditional and non-traditional risk factors.MethodologySixty consecutive premenopausal SLE female patients, and sixty age and sex matched healthy subjects without known systemic, immunological, or cardiovascular disease (served as a control group) underwent clinical examination, serological analysis, and 64-slice MDCT-based coronary calcium scoring. All the clinical, serological, and MDCT parameters of the patients were correlated.ResultsCoronary calcification (CC) was seen in 21 patients (35%), the number of atherosclerotic calcified plaques ranged from 0 to 19. Calcium scores ranged from 0 to 843. In contrast to control subjects, SLE patients had significantly higher erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), total cholesterol level, low-density lipoprotein (LDL), immunoglobulin G (IgG) and IgM anti-cardiolipin antibodies, serum intracellular adhesion molecule (sICAM) and E-selectin levels. SLE patients had highly significantly more atherosclerotic plaques (3 ± 0.66 compared to 0.1 ± 0.07, p < 0.001) and higher CCS (59.2 ± 20.3 compared to 2.6 ± 1.85, p < 0.001). Significant positive correlation was found between both number of atherosclerotic plaques and CCS and total cholesterol level, LDL, cumulative prednisone dose, SLE disease activity index (SLEDAI), ESR, CRP, sICAM-1, E-Selectin, and anti-cardiolipin antibodies (p < 0.05 in all).ConclusionPre-menopausal SLE female patients free from clinical atherosclerotic vascular disease have an increased number of atherosclerotic plaques and CCS, which correlate positively with SLEDAI disease activity score, serum CRP, anticardiolipin antibodies, sICAM-1, E-Selectin, LDL level, total cholesterol level, and cumulative prednisone dose. In addition, we conclude that MDCT is a non-invasive, sensitive, reproducible, and reliable tool for accurate measurement of coronary calcification.     

Plaque rupture and morphological characteristics of the culprit lesion in acute coronary syndromes without significant angiographic lesion: analysis by intravascular ultrasound

PurposeTo evaluate by intravascular ultrasound (IVUS) the characteristics of the culprit lesion with plaque rupture without significant angiographic stenosis after acute coronary syndromes (ACS).Patients and methodsAfter ACS, IVUS was performed in 68 patients (46.8 years ± 11.9) without significant angiographic stenosis (31 ± 15%). Plaque rupture was defined as a cavity within the plaque, communicating with the arterial lumen and having an overlying residual fibrous cap fragment. Qualitative analysis defined the type of plaque, and quantitative analysis evaluated plaque plus media area, plaque volume, plaque burden, and arterial remodeling index. Patients were divided into two groups: Group I with plaque rupture (25 patients) and Group II without plaque rupture (43 patients).ResultsAll patients with rupture showed soft or mixed plaque but no calcified plaque. In Group I, plaque rupture was associated with a larger plaque burden (49.8 ± 12.3% vs. 39.8 ± 12.1%, P < .0005), a more significant plaque plus media area (7.44 ± 2.9 vs. 5.24 ± 2.4 mm², P < .001), a greater plaque volume (151.9 ± 103.4 vs. 99.2 ± 81.6 mm³, P < .007), and a higher ratio of plaque volume over length (8.0 ± 3.8 vs. 5.6 ± 3.7 mm³/mm, P < .003). In Group I, positive remodeling was more frequent than intermediate remodeling (P < .03) or negative remodeling (P < .005). In Group II, there was no significant difference between the three types of remodeling.ConclusionThe plaque ruptures responsible for ACS frequently appear on voluminous plaques with a large plaque burden and positive arterial remodeling.