Antiplatelet Therapy, Clinical Characters and Long-term Outcomes of Patients With Angiography-documented Stent Thrombosis / 中国循环杂志

Objectives: To describe the differences between patients with angiography confirmed stent thrombosis in antiplatelet therapy and long term outcomes. Methods: We analyzed data from 1 204 patients with angiography – documented stent thrombosis between January 2008 to December 2016 in Beijing Anzhen Hospital. According to the timing of stent thrombosis post stent implantation, patients were divided into acute stent thrombosis (<24 h, n=106), subacute stent thrombosis(24 h~30 d, n=206), late stent thrombosis (>30 d~1y, n=268), and very late stent thrombosis (>1 y, n=624) groups. Death, recurrent stent thrombosis, recurrent myocardial infarction, target vessel revascularization, stroke and antiplatelet treatment during In-hospital or long-term clinical follow-up were compared among groups. Results: Prevalence of stent thrombosis was the highest in the left anterior descending artery (51.9%) in acute stent thrombosis group. Subjects with subacute stent thrombosis had a higher prevalence rate of LVEF<50% (28.2%), and subjects with very late stent thrombosis had a higher prevalence rate of diabetes (34.1%). All patients in acute stent thrombosis group received aspirin + clopidogrel, 96.5% patients in subacute stent thrombosis group and 94.5% patients in late stent thrombosis group were treated with double or triple antiplatelet therapy, while 95.2% patients in the very late stent thrombosis group were treated with double or mono antiplatelet therapy. During the follow up, mortality was 23.6%, 26.7%, 26.3% and 18.9% in acute stent thrombosis, subacute stent thrombosis, late stent thrombosis, and very late stent thrombosis groups, respectively. Conclusions: Most patients with angiography–documented stent thrombosis are treated with recommended antiplatelet therapy. Development of stent thrombosis is associated with poor outcomes.

Effects of thyroid hormone on macrophage dysfunction induced by oxidized low-density lipoprotein / 生理学报

It has been recognized that patients with hypothyroidism have higher risks of atherosclerosis and coronary heart disease, however, the mechanisms are largely unknown. Considering that macrophage dysfunction plays an important role in the formation and development of atherosclerosis plaques, this study aimed to investigate the direct effects of thyroid hormone on macrophage functions and to provide new insight for the mechanism of hypothyroid atherosclerosis. RAW264.7 cells (mouse leukaemic monocyte macrophage cell line) were incubated with oxidized low-density lipoprotein (oxLDL) to establish macrophage foam cells model in vitro, and the protective effects of different concentration of thyroxine (T4) on the macrophage foam cells function were explored. The proliferation, migration and cell aging of macrophages were detected by MTT method, scratch test and β-galactosidase staining respectively. The ELISA method was used to detect the secretion of tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), and interleukin-1β (IL-1β). Western blot analysis was applied to measure the phosphorylation of focal adhesion kinase (FAK), which was required for the process of proliferation and migration of macrophages. The results showed that oxLDL significantly inhibited the macrophage proliferation and migration, induced cell senescence, and promoted the secretion of TNF-α, MCP-1, and IL-1β; while T4 reversed those effects of oxLDL on macrophage in a concentration-dependent manner. Moreover, oxLDL increased the phosphorylation of FAK in macrophage, while T4 concentration-dependently reversed the effect. These results suggest that T4 modulates macrophage proliferation, migration, senescence, and secretion of inflammation factors in a concentration-dependent way.

Magnetic resonance imaging features of vulnerable plaques in an atherosclerotic rabbit model / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Noninvasive detection of vulnerable plaque has a significant implication for prevention and treatment of atherosclerotic diseases. The aim of this study is to investigate the difference between vulnerable plaques and stable plaques in magnetic resonance (MR) images.</p><p><b>METHODS</b>Atherosclerosis was induced in twenty male New Zealand white rabbits by high cholesterol diet and balloon injury of the abdominal aorta. After baseline (pre-triggering) MR imaging (MRI) scan, the rabbits underwent pharmaceutical triggering with Russell's viper venom and histamine to induce atherothrombosis, followed by another MRI scan 48 hours later (post-triggering). Rabbits were euthanized to obtain pathological and histological data. The results of MRI were compared with those of pathology and histology.</p><p><b>RESULTS</b>MRI showed that abdominal aorta of the rabbits had pathological change of atherosclerosis in different degrees. Seventy-five plaques were analysed, among which 14 had vulnerable thrombi and 61 stable. Thrombosis was identified in 7 of 11 rabbits by post-triggering MRI, the sensitivity and K value of MR in detection of vulnerable plaque was 71% and 0.803 (P < 0.05). MRI data significantly correlated with the histopathological data in fibrous cap thickness (r = 0.749) plaque area (r = 0.853), lipid core area (r = 0.900). Compared with stable plaques, vulnerable plaques had a significantly thinner fibrous cap ((0.58 ± 0.27) mm vs. (0.95 ± 0.22) mm), larger lipid core area ((7.56 ± 2.78) mm(2) vs. (3.29 ± 1.75) mm(2)), and a higher ratio of lipid core area/plaque area ((55 ± 16)% vs. (27 ± 17)%), but plaque area was comparable in two groups on MRI. The ratio of lipid core area/plaque area was a strong predictor of vulnerable plaques.</p><p><b>CONCLUSION</b>MRI could distinguish vulnerable plaques from stable plaques in a rabbit model of atherothrombosis and may thus be useful as a noninvasive modality for detection of vulnerable plaques in humans.</p>

Impact of anemia on long-term outcome in elderly patients with acute coronary syndrome undergoing percutaneous coronary interventions / 中华心血管病杂志

<p><b>OBJECTIVE</b>To assess the impact of pre-procedure anemia on the long-term mortality in elderly patients with acute coronary syndrome (ACS) after percutaneous coronary interventions.</p><p><b>METHODS</b>A total of 1014 ACS patients (≥ 60 years of age) with hemoglobin data and without previous treatment with thrombolytic agents and without end-stage renal failure before the interventional procedure were included. Patients were classified as anemia using the definition of World Health Organization: hemoglobin < 130 g/L in men, and < 120 g/L in women. A total of 253 patients were anemia. The clinical features of patients with and without anemia and association of pre-procedure anemia with long-term mortality were analyzed.</p><p><b>RESULTS</b>Incidence of diabetes and serum creatinine level were significantly higher in anemia patients than in non-anemia patients while systolic blood pressure and low-density lipoprotein cholesterol were significantly lower in anemia patients than in non-anemia patients (P < 0.05 or P < 0.01). The patients were followed up for 528 (178 - 675) days. After adjustment for potential co-variants in Cox regression analysis, pre-procedure anemia was associated with a significantly higher long-term mortality (RR: 3.293, 95%CI: 1.431 - 7.578, P < 0.01).</p><p><b>CONCLUSION</b>Pre-procedure anemia is an independent predictor of long-term mortality in elderly patients with acute coronary syndrome after percutaneous coronary interventions.</p>

Detection of atherosclerotic plaque progression in the abdominal aorta of rabbits with 3T magnetic resonance imaging / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>With features of high tissue contrast, MRI can be used for the qualitative and quantitative evaluation of atherosclerosis plaques. In this study we investigated the development of atherosclerosis plaque with high resolution 3T MRI in a rabbit model and compared the findings with the histopathological results.</p><p><b>METHOD</b>Twenty male New Zealand white rabbits were randomly allocated into an experimental group (n = 16) and a control group (n = 4). Atherosclerotic lesions were induced in the abdominal aorta by balloon injury and cholesterol feeding. Multiple sequences MRI examination (ToF, T1WI, T2WI, and CE T1WI) were performed at the 2nd, 3rd, and 4th months after aortic denudation. Vessel wall thickness, total vessel area, lumen area, and vessel wall area were recorded. Plaque components were analyzed using histological results as a standard reference.</p><p><b>RESULTS</b>Seventeen rabbits (14 in the experimental group and 3 in the control group) received all three MR examinations. Gradually, from 2 months to 4 months, vessel wall thickness and area in the experimental group increased significantly compared with the control group (P < 0.01). In the lumen area progressive stenosis was not found, even a slight dilation had developed in the experimental group. Lipid, fibrotic and calcified plaques can be differentiated by MR image. According to histological results, MRI had good performance in detection of lipid plaque.</p><p><b>CONCLUSION</b>MRI can be used to monitor progression of atherosclerosis and differentiate plaque components.</p>

Procedural results and 30-day clinical events analysis following Edwards transcatheter aortic valve implantation in 48 consecutive patients: initial experience / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Transcatheter aortic valve implantation (TAVI) is a rapidly evolving strategy for therapy of aortic stenosis. We presented the procedural results and analyzed the death causes of 30-day mortality and clinical events in patients who underwent TAVI with Edwards prosthetic valves in University Hospital of Caen, France.</p><p><b>METHODS</b>The patients with severe aortic stenosis but at high surgical risk or inoperable were considered as candidates for TAVI. Forty-eight patients undergoing TAVI from July 2010 to September 2011 were enrolled in this registry. The Edwards prosthetic valves were solely used in this clinical trial.</p><p><b>RESULTS</b>Overall 48 patients underwent TAVI, 28 of which accepted TAVI by trans-femoral (TF) approaches, 20 by trans-apical approaches (TA). The aortic valve area (AVA) was (0.70 ± 0.23) cm(2), left ventricular ejection fraction (LVEF) was (57.4 ± 17.6)%, Log EuroSCORE was (19.2 ± 15.8)%, mean gradient was (47.0 ± 16.6) mmHg. There were no significant differences between TF and TA groups in all these baseline parameters. Device success rate was 95.8%, and procedural success rate was 93.7% in total. Procedural mortality was 6.7% (3/48): two deaths in TA group (10%), and one death in TF group (3.6%). Forty-six Edwards valves were implanted: 10 Edwards Sapien and 36 Edwards XT. Procedure-related complications included cardiac tamponade in 2 cases (4.2%), acute myocardial infarction (AMI) in 1 case (2.1%), permanent pacemaker implantation in 1 case (2.1%), life-threatening and major bleeding in 3 cases; access site related major complication in 1 case, AKI stage 3 in 3 cases (6.3%), minor stroke in 1 case (2.1%). Thirty-day survival rate was 89.6%. There were 5 deaths in total (10.4%): 4 in TA group (20%) and 1 in TF group (3.6%).</p><p><b>CONCLUSION</b>The procedural success rate and 30-day mortality were acceptable in these high risk patients with Edwards prosthetic valves in the first 48 TAVI.</p>

Imaging of atherosclerotic aorta of rabbit model by detection of plaque inflammation with fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Atherosclerotic plaque rupture is the primary mechanism of thrombosis which plays a key role in the onset of acute coronary syndromes. Detection of these plaques prone to rupture (vulnerable plaque) could be clinically significant for prevention of cardiac events. It has been shown that high metabolism cells have a high uptake of fluorine-18 fluorodeoxyglucose ((18)F-FDG). The objective of this study was to investigate the correlation of FDG uptake and the immuno-histochemistry parameters of plaques, and the effect of atorvastatin on vulnerable atherosclerotic plaque in a rabbit model.</p><p><b>METHODS</b>Ten male New Zealand White rabbits were divided into three groups as follows: (1) normal control group (n = 2, C group): the animals were fed a standard diet at 120 g/d and were given water ad labium; (2) atherosclerosis group (n = 4, As group): animals were fed with high fat diet for 5 months after aortic endothelia damage; (3) treatment group (atherosclerosis + atorvastatin, n = 4, Statin group): animals were fed with high fat diet for 5 months and then changed into normal chow plus atorvastatin (2.5 mg·d(-1)·kg(-1)) treatment for another 4 months. Then these four rabbits were imaged with fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) and sacrificed for pathohistologic studies. FDG uptake by the aorta was expressed as target-to-background ratio (TBR). Maximal standardized uptake value (SUV) was measured over the thoracic and abdominal aortas. The aortic smooth muscle cell (SMC) number, CD-14 antibody positive cell (macrophage) number and the ratio of the thickness of fibrous cap to the thickness of lipid core (cap-to-core ratio) in atherosclerotic plaques were analyzed.</p><p><b>RESULTS</b>As group showed significantly higher uptake of FDG than C group (SUVs: 0.746 ± 0.172 vs. 0.286 ± 0.073, P < 0.001). After 4 months of atorvastatin treatment and the modification of diet, SUVs decreased significantly (Statin group: 0.550 ± 0.134, compared to As group, P < 0.001). However, no marked difference was found in TBR, the number of macrophages, the number of SMC and the cap-to-core ratio in the aortic segments between Statin group and As group. The correlation of aortic FDG uptake with SMC assessed by histopathology was negatively significant (r = -0.57, P < 0.001). When aortic FDG uptake was expressed as TBR, it correlated significantly (r = 0.69, P < 0.001) with the macrophage number, and also correlated significantly (r = -0.78, P < 0.001) with the cap-to-core ratio.</p><p><b>CONCLUSION</b>(18)F-FDG PET/CT might serve as a useful non-invasive imaging technique for detection of atherosclerotic plaque and potentially permit monitoring of relative changes in inflammation within the atherosclerotic lesion.</p>

In vivo noninvasive detection of vulnerable atherosclerotic plaque by (99)Tc(m)-Annexin V imaging in an atherosclerotic rabbit model / 中华心血管病杂志

<p><b>OBJECTIVE</b>Apoptosis contributes to the instability of the atherosclerotic (AS) lesions. The vulnerable plaque was identified in vivo by detecting the apoptosis with radiolabeled annexin V in an atherosclerotic rabbit model.</p><p><b>METHODS</b>Eight male New Zealand white rabbits on 2% cholesterol diet for 2 weeks had abdominal aortic balloon injury and fed a 2% cholesterol diet for another 15 weeks (AS group), 3 rabbits fed a normal rabbit chow for 17 weeks without balloon injury served as controls. Annexin V labeled with (99)Tc(m) was then intravenously administered and planar whole-body images were captured using a gamma camera in the left lateral position. The entire length of the abdominal aorta was explanted for ex vivo imaging with gamma camera. The aorta then was divided into several segments according to the severity of AS. The segments were separated weighted and counted in an gamma counter for the absorptive dose of annexin per gram of tissue. Histology examinations were made on specimens.</p><p><b>RESULTS</b>At 2 hours post annexin V injection, clear delineation of radiolabel within the abdominal aorta could be evidenced in vivo gamma imaging. After explanation of the aorta, ex vivo imaging showed a robust uptake of radiotracer in the infradiaphragmatic aorta corresponding to the in vivo images and conforming to the macroscopic distribution of atherosclerotic lesions. The uptake of radiolabel was absent in areas without grossly visible atherosclerotic lesions. The in vivo and ex vivo images identified plaque areas were identical and corresponded histological results on the explanted specimen. The aortic specimen was divided into 18 segments on lesions. The magority of the lesions (14/18) manifested as type IV or type V lesions of AHA classification (vulnerable lesions), except segments 1 - 4, which manifested as type I or type II lesions. The thickness of fibrous cap (TFC) and the ratio of cap and lipid nuclear (RCN) were significantly reversely correlated to the unit radioactivity counts, and the correlation between RCN and the unit radioactivity counts was more significant than that between TFC and the unit radioactivity counts (r = -0.904, P < 0.01, and r = -0.8, P < 0.01). Apoptosis detection (TUNEL): annexin V intake in plaques was positively correlated to apoptotic index(r = 0.651, P = 0.012).</p><p><b>CONCLUSION</b>Noninvasive Annexin V imaging could be used to detect vulnerable atherosclerotic plaques in vivo.</p>

Rosiglitazone inhibits atherosclerosis in apolipoprotein E-knockout mice / 中华心血管病杂志

<p><b>OBJECTIVE</b>To study the effect of rosiglitazone on atherosclerosis and potential mechanism in ApoE-knockout mice.</p><p><b>METHODS</b>Thirty-two 6-week-old ApoE-knockout mice were used as atherosclerosis model in two groups: rosiglitazone group (n = 18) and control group (n = 14). Each group contained equal numbers of male and female mice. All mice were fed with normal chow diet. In addition to normal diet, rosiglitazone group received rosiglitazone 17 mg/kg of body weight/day. Venous bloods were collected for plasma glucose and lipid analysis, and aorta were prepared for morphologic and immunohistochemical analysis after 14 weeks. Aortic root (1 cm) was cut and prepared for paraffin slice. The histomorphometric analysis of atherosclerotic lesion was performed by means of HE; positive percentage of macrophage cell and tumor necrosis factor-alpha were measured by means of immunohistochemistry in cross section. The ratio of lesion/aortic wall surface in the rest aorta was measured by means of Sudan IV staining in longitudinal section.</p><p><b>RESULTS</b>The amount of fatty streak in rosiglitazone group was significantly greater than that of control group; the gross number of lesions and the number of fibrous plaque and atheromatous plaque were similar in two groups. There were no differences in percentage of lesions in cross section in two groups. Rosiglitazone could significantly reduce the extend of atherosclerosis of longitudinal section, decrease the amount of macrophage cell and the level of tumor necrosis factor-alpha in lesions. The plasma glucose was normal and similar in two groups, and total cholesterol, LDL-cholesterol and triglyceride were significantly higher in rosiglitazone group.</p><p><b>CONCLUSION</b>Rosiglitazone suppresses the expression of tumor necrosis factor-alpha, reduces the number of macrophage cell in lesion, and inhibits the development of atherosclerosis.</p>

Rosiglitazone promotes atherosclerotic plaque stability in apolipoprotein e-knockout mice / 中华老年医学杂志

Objective To study the effect of rosiglitazone on plaque stability in ApoE-knockout mice. Methods Thirty-two 6-week-old ApoE knockout mice were used as atherosclerosis models in two groups: rosiglitazonegroup (n=18) and control group (n=14). Male and female mice were half separated into two groups. All mice were fed normal chow diet. Rosiglitazone group received rosiglitazone 17 mg/kg of body weight/day. The animals were sacrificed and aortae were prepared for analysis after fourteen weeks. Aortic root were cutted and prepared for paraffin section. The positive percentage of macrophage cells, smooth muscle cells, tumor necrosis factor-? and matrix metalloproteinase-9 in aortic lesions were measured by immunohistochemistry. The changes of grey gradient of collagen in lesion of both groups were measured by Masson stain. Results The positive percentage of smooth muscle cells [(38.5?7.2)%vs(18.6?6.7)%,P