Vulnerable plaque burden post pharmacological and interventional treatments in patients with acute coronary syndrome and borderline lesion: intravascular ultrasound follow up results / 中华心血管病杂志

<p><b>OBJECTIVE</b>To compare the efficacy and safety between the interventional and conservative treatment options for borderline vulnerable plaque lesion in acute coronary syndrome (ACS) patients by intravascular ultrasound (IVUS).</p><p><b>METHODS</b>A total of 100 ACS patients [78 male, age 43 - 74 (60.4 ± 14.1) years] undergoing coronary angiography (CAG) with borderline lesion (coronary artery stenosis between 50% - 70%) were enrolled in May 2007 to February 2009, who were randomly divided into PCI group (50 patients) and conservative therapy group (50 patients). According to minimal lumen area (MLA) detected by IVUS, patients were further divided into MLA ≥ 4.0 mm(2) sub-group and MLA < 4.0 mm(2) sub-groups. Outcomes during hospitalization and after 10 - 12 month follow-up were compared.</p><p><b>RESULTS</b>IVUS was performed in 40 patients at 10 - 12 months post PCI, there was no in-stent thrombosis and the extent of stent neointimal hyperplasia was comparable as at the time of immediately post PCI. IVUS was performed in 35 patients at 10 - 12 months post conservative therapy, IVUS results showed that MLA increased significantly [(7.32 ± 1.42) mm(2) vs. (4.98 ± 0.89) mm(2), P < 0.01], while plaque area [(7.70 ± 2.09) mm(2) vs. (10.01 ± 2.55) mm(2), P < 0.05], plaque burden [(55.94 ± 8.36)% vs. (67.97 ± 9.36)%] and low echo area [(4.08 ± 0.80) mm(2) vs. (2.27 ± 0.79) mm(2)] were significantly decreased at follow up compared to those as baseline (all P < 0.01). There was one patient in PCI group with MLA ≥ 4.0 mm(2) developed acute in-stent thrombosis in left anterior descending artery two days after the procedure and 9 patients in conservative therapy and MLA < 4.0 mm(2) group received PCI due to recurrent angina pectoris during follow-up.</p><p><b>CONCLUSIONS</b>For the borderline lesion with MLA ≥ 4.0 mm(2) detected by IVUS, adequate medication could effectively attenuate and or reverse the plaque progression and stabilize plaque.</p>

Impact of CYP2C9 and VKORC1 polymorphism on warfarin response during initiation of therapy / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate potential contributions of genetic variants of cytochrome P-450 2C9 (CYP2C9) and vitamin K expoxide reductase (VKORC1) to the anticoagulation response during the initiation of warfarin therapy in the Han Chinese population.</p><p><b>METHODS</b>A total of 798 Han Chinese patients received long-term warfarin anticoagulant therapy orally after valve replacement in our hospital between 2000 and 2008 were included in this study. Nine single nucleotide polymorphism (SNP) loci [rs12572351 G > A, rs9332146 G > A, rs4917639 G > T, rs1057910 A > C (CYP2C9(*)3), rs1934967 G > T, rs1934968 G > A, rs9923231 C > T (VKORC1-1639 G > A), rs2359612 G > A and rs10871454 C > T] in 2 genes including CYP2C9 and VKORC1, which were possibly correlated with warfarin pharmacokinetics and pharmacodynamics through literature retrieval, were selected and analyzed. Warfarin steady-state dose requirement, time to the INR (the international normalized ratio) within the therapeutic range and percent of the INR of more than 3.5 were compared among genotype subgroups. SNaPshot technique was used to detect gene SNPs; Hardy-Weinberg genetic equilibrium test was used to test population representativeness.</p><p><b>RESULTS</b>CYP2C9(*)3 genotype did not affect the required warfarin dose while it was associated with increased risk of bleeding when treated with routine dosage regimen during the initiation of treatment. The allelic mutation frequency at VKORC1 gene rs10871454G > A and VKORC1-1639G > A SNP loci was 92.04% and 88.03%, respectively and rs10871454 was in perfect linkage disequilibrium with-1639. Patients with VKORC1 rs10871454 genetic mutation required lower warfarin dose in the first 28 days of therapy. VKORC1-1639 genetic polymorphism was also associated with shorter time to the INR within the therapeutic range and increased risk of over-anticoagulation.</p><p><b>CONCLUSION</b>Detecting genetic polymorphism of CYP2C9 and VKORC1 could guide clinical use of warfarin to reduce the risk of adverse reactions including bleeding in patients receiving chronic anticoagulation therapy.</p>

Effect of impaired glucose tolerance on cardiac dysfunction in a rat model of prediabetes / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The effect of impaired glucose tolerance (IGT) on cardiac function during the chronic prediabetes state is complicated and plays an important role in clinical outcome. However, the molecular mechanisms are not fully understood. This study was designed to observe cardiac dysfunction in prediabetic rats with IGT and to determine whether glucose metabolic abnormalities, inflammation and apoptosis are linked to it.</p><p><b>METHODS</b>The IGT rat models were induced by streptozocin, and the heart functions were assessed by echocardiography. Myocardial glucose metabolism was analyzed by glycogen periodic acid-Schiff staining, and the pro-apoptotic effect of IGT was evaluated by TUNEL staining. Additionally, caspase-3 activation, macrophage migration inhibitory factor (MIF) and G-protein coupled receptor kinase 2 (GRK2) were detected by Western blotting in cardiac tissue lysates.</p><p><b>RESULTS</b>Area-under-the-curve of blood glucose in rats injected with streptozotocin was higher than that in controls, increased by 16.28%, 38.60% and 38.61% at 2, 4 and 6 weeks respectively (F = 15.370, P = 0.003). Abnormal cardiac functions and apoptotic cardiomyocytes were observed in the IGT rats, the ejection fraction (EF) being (68.59 ± 6.62)% in IGT rats vs. (81.07 ± 4.59)% in controls (t = 4.020, P = 0.002). There was more glucose which was converted to glycogen in the myocardial tissues of IGT rats, especially in cardiac perivascular tissues. Compared to controls, the cleaved caspase-3, MIF and GRK2 were expressed at higher levels in the myocardial tissues of IGT rats.</p><p><b>CONCLUSIONS</b>IGT in the prediabetes period resulted in cardiac dysfunction linked to abnormal glycogen storage and apoptosis. Additionally, MIF and GRK2 may be involved in the pathogenesis of cardiac dysfunction in prediabetes and their regulation may contribute to the design of novel diagnostic and therapeutic strategies for those who have potential risks for diabetic cardiovascular complications.</p>

Effects of amlodipine plus telmisartan or amlodipine plus amiloride regimen on blood pressure control in hypertensive patients: preliminary report of Chinese Hypertension Intervention Efficacy (CHIEF) trial / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the effects of amlodipine-based antihypertensive combination regimen on blood pressure control and impact on cardiovascular events.</p><p><b>METHODS</b>From Oct. 2007 to Oct. 2008, a total of 13 542 hypertensive patients from 180 centers in China were included in this multi-centre randomized, controlled, blind-endpoint assessment clinical trial. Inclusion criteria were: essential hypertension, 50 - 79 years of age with at least one cardiovascular risk factor and signed consent forms. Patients were randomly assigned to receive low-dose amlodipine + diuretics (group A) or low-dose amlodipine + telmisartan (group T). The primary endpoints are composite of non-fatal stroke/myocardial infarction and cardiovascular death. All patients will be followed-up for 4 years.</p><p><b>RESULTS</b>The characteristics of patients between the two groups were similar: mean age (61.5 +/- 7.7) Yrs with 19% history of cerebrovascular diseases, 12% coronary diseases, 18% diabetes, 42% dyslipidemia, mean initial blood pressure 157/93 mm Hg. After 8-week treatment, mean blood pressure in group A and B were reduced to (133.0 +/- 11.0)/(81.0 +/- 7.6) mm Hg, (132.9 +/- 11.6)/(80.6 +/- 7.9) mm Hg respectively. Blood pressure control rates reached 72.1% and 72.6% in group A and T, respectively.</p><p><b>CONCLUSION</b>Amlodipine-based antihypertensive combination regimens achieved satisfactory blood pressure control rate in patients with essential hypertension in this patient cohort.</p>

Intravascular ultrasound-guided interventional therapy for borderline lesions in patients with acute coronary syndrome / 南方医科大学学报

<p><b>OBJECTIVE</b>To assess the efficacy and safety of intravascular ultrasound (IVUS)-guided interventional therapy for borderline lesions in patients with acute coronary syndrome (ASC).</p><p><b>METHODS</b>Thirty-one ASC patients with borderline lesions (coronary artery stenosis between 40%-70% confirmed by coronary arteriography [CAG]) and a minimal lumen area (MLA) of the infarction related artery(IRA) < or =4.0 mm(2) shown by IVUS underwent percutaneous coronary intervention (PCI). Another 31 PCI cases without IVUS were also enrolled as the control group. The minimal luminal diameter, cross section luminal area, total cross section, plaque area and area stenosis rate were measured before and after stent deployment at a conventional or higher pressure in the IVUS group. All the patients were followed up for 10-12 months and clinically evaluated 1, 3, 6 month and 12 months after the procedure to collect the data of angina recurrence, myocardial infarction and revascularization.</p><p><b>RESULTS</b>All the 31 cases were successfully stented with satisfied CAG results (with residual stenosis <0, TIMI flow grade III) and without dissection or any related complications. Among the 32 stents, 28 showed insufficient adherence or underexpansion (stent malapposition) to require 18-20 atm dilation or another high pressure balloon to attain the adequate IVUS results. CAG and IVUS were repeated in 22 patients (70.97%) of the IVUS group during the 10 to 12 months of follow up. No stent restenosis occurred with the in-stent diameter late loss >50%, nor was in-stent thrombus found by IVUS. Endomembrane proliferation was found but without any significant difference. Minimal stent lumen area were not significantly different from the immediate results after PCI (10.12-/+1.15 mm(2) vs 8.98-/+2.12 mm(2), P>0.05). The 31 patients in the control group were successfully stented with satisactory CAG results, but 3 suffered angina at 3-6 months who showed stent restenosis and insufficient stent adherence.</p><p><b>CONCLUSION</b>IVUS can more effectively guide the interventional therapy for ACS borderline lesions and assess the immediate efficacy of therapy than CAG. Post-dilation with higher pressure (16-20 atm) guided by IVUS can further improve the procedural results. IVUS-guided PCI for ACS borderline lesions ensures high immediate and long-term success rate.</p>

Human bone marrow mesenchymal stem cells cocultured with semi-permeable membrane separated neonatal rat ventricular myocytes differentiated into cardiomyocyte phenotype / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the ability of human bone marrow mesenchymal stem cells (hBMSCs), cocultured with semi-permeable membrane separated neonatal rat ventricular myocytes, to differentiate into cardiomyocytes.</p><p><b>METHODS</b>hBMSCs were isolated and purified by density gradient centrifugation and adherence screening method. Cells were expanded as undifferentiated cells in culture for more than 3 passages and their phenotypes were identified with flow cytometer. hBMSCs were cocultured with neonatal rat ventricular myocytes in a rate of 1:10 separated by semi-permeable membrane. GATA4 mRNA was detected by RT-PCR; Immunocytochemistry, and Immunostaining were used to detect sarcomeric alpha-actinin, desmin, cTnT, and cTnI protein level.</p><p><b>RESULTS</b>CD29 (98.64% +/- 0.80%) and CD44 (96.70% +/- 1.50%) were the major surface markers of hBMSCs. After coculturing with semi-permeable membrane separated neonatal rat ventricular myocytes, the first contraction of single cells was noted at day 7 and GATA4 expression was detected on these cells by RT-PCR after 1 to 3 weeks coculture. Desmin, sarcomeric alpha-actinin, cTnI and cTnT could be detected by immunocytochemistry and immunostaining on some of these cells.</p><p><b>CONCLUSION</b>hBMSCs possess the potential to differentiate into myocardial cell phenotype in the cardiac microenvironment. Direct contact with cardiomyocytes was not necessary required for hBMSCs differentiation.</p>

Effects of?1 adrenoceptor antisense on blood pressure and?1 adrenoceptor mRNA and protein in renal hypertension rats / 中华急诊医学杂志

Objective To evaluate the effects of 131 adrenoceptor anfisense on blood pressure and?1 adrenoceptor mRNA and protein levels in 2 kidney 1 clip(2K1C)rats.Method 2KIC hypertensive rots were produced by clipping renal artery of SD rats.Liposome/AS-ODNs 2.0 were tested intravenously in rats with 2KIC hypertension.Animals were divided into 5 groups(n=18 in each group):?1-AS-ODN group,?1-IN-ODN group,2K1C group,Sham group and SD group.Blood pressure was measured by tail-cuff method,the levels of myocardial?adreneceptor mRNA and protein were tested by RT-PCR and binding assay.Results On the basis of the magnitude and duration of hypotension,?1-AS-ODN decreased blood pressure by 39 mmHg at the most for 4 weeks.Compared with the 2KIC group,?1-AS-ODN did not significantly change the levels of myocardial?1 adrenoceptor mRNA but significantly decreased the levels of myocardial?1 adrenoceptor protein at 2,7,30 days (P

Association of the polymorphism of macrophage migration inhibitory factor gene with coronary heart disease in Chinese population / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>Inflammation is involved in the process of coronary heart disease (CHD). Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine which can inhibit the random migration of macrophages and concentrate macrophages at the inflammatory site, and is thought to play an important role in cell mediated immunity. The present study is to investigate the association of the -173 G/C polymorphism of MIF gene with the outcome of the CHD.</p><p><b>METHODS</b>One hundred and thirty-eight patients with coronary angiography (CAG) proved CHD were studied, and 163 healthy matched controls in Guangdong were studied. Patients and controls were genotyped for a single nucleotide polymorphism in the 5'-flanking region at position -173 of the MIF gene, using PCR-RFLP analysis, followed by DNA sequencing identification.</p><p><b>RESULTS</b>Only MIF -173G/G and MIF -173G/C genotypes were detected in CHD patients and controls. The MIF -173 G allele was detected in 0.966 of normal controls and 0.917 of patients, while MIF -173 C allele was detected in 0.034 of normal controls and 0.083 of patients. Individuals possessing a MIF-173*C genotype have an increased risk of CHD (16.7% versus 6.8%) (OR: 2.764, 95% CI: 1.295-5.899; P= 0.007).</p><p><b>CONCLUSION</b>These results suggest that MIF -173G /C polymorphism was associated with CHD in Chinese population, the MIF -173C allele might be a risk factor for CHD in Chinese Han nationality.</p>

The development of a new perimembranous ventricular septal defect occluder / 中华心血管病杂志

<p><b>OBJECTIVE</b>The aim of this study was to develop a new perimembranous VSD occluder and to evaluate it.</p><p><b>METHODS</b>The shape of VSD occluder was designed as fabric frame "I" shape that comprised two types: symmetric and asymmetric. The safety, efficacy, feasibility and complication were tested in 22 animal models and in 58 VSD patients in clinical trial. The device were compared with Amplatzer occluder in this study.</p><p><b>RESULTS</b>The new perimembranous VSD occluder was passed the national material test. In animal study, artificial VSD were all occluded by using the new devices with no complication in follow up except one pig expresented wound infection. In clinical trial, all 58 VSD cases were healing with the new device. One patient suffered with atria-ventricular block 5 days after procedure and was free from AV block with medicine therapy. Compared with Amplatzer perimembranous VSD occluder, the new devices had lower frequency of residual shunt.</p><p><b>CONCLUSION</b>The new perimembranous VSD occluder is a safe and effective perimembranous VSD interventional apparatus, and the effect of the new occluders seems not worse than that of the Amplatzer ones.</p>

The AGT genotype affects the antihypertensive effects of benazepril / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the association between M235T variant of angiotensinogen (AGT) gene and the blood pressure response to benazepril in a hypertensive cohort.</p><p><b>METHODS</b>Benazepril (10-20 mg/day) was administered for 6 weeks to 251 essential hypertensives. Polymerase chain reaction (PCR) combined with restriction enzyme digestion was used to detect the polymorphism and the patients were classified as MM, MT or TT genotype. The changes in systolic and diastolic blood pressure (SBP and DBP) were analyzed for association with genotypes at the AGT gene locus.</p><p><b>RESULTS</b>The MM genotype was observed in 23 patients (9.2%), the MT genotype in 104 patients (41.4%) and the TT genotype in 124 patients (49.4%). There was no association between these polymorphisms and the blood pressure responses in the total 251 patients. But based on the analysis stratified by age, the association between these polymorphism and the DBP responses was found in the old patients (> or = 60 years old) subgroup, the reduction in DBP was significantly greater in patients carrying the MM compared to MT or TT genotypes (14.8 +/- 4.8 mm Hg vs. 7.9 +/- 7.7 mm Hg or 9.8 +/- 6.4 mm Hg respectively; ANOVA, P = 0.034).</p><p><b>CONCLUSION</b>The M235T polymorphism of the AGT gene was shown to influence the responses to benazepril in old hypertensive patients (> or = 60 years old). Thus, specific genotypes might predict the response to specific antihypertensive treatment.</p>