Age-Related Utilization of Thrombus Aspiration in Patients With ST-Segment Elevation Myocardial Infarction: Findings From the Improving Care for Cardiovascular Disease in China Project.

Background: There are some controversies on the utilization and benefits of thrombus aspiration in patients with ST-segment elevation myocardial infarction (STEMI). However, a few studies investigated this issue and the age-associated effects among the large population in China. Hence, we aimed to figure out the age-associated utilization and in-hospital outcomes of thrombus aspiration to improve therapeutic decisions in clinical routine. Methods: We retrospectively recruited 13,655 eligible STEMI patients from the database of the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome project. These subjects were allocated into primary percutaneous coronary intervention (PPCI)-only group and thrombus aspiration group after being subdivided into three age groups (G21-50, G51-75, and G76-95). After 1:1 propensity score matching for PPCI-only and thrombus aspiration groups, a total of 8,815 matched patients were enrolled for the subsequent analysis. The primary outcome was in-hospital cardiovascular death, and the key safety outcome was in-hospital stroke. Results: We observed that the ratio of STEMI patients undergoing thrombus aspiration to PPCI-only reduced with aging. For patients ≤ 75 years, the culprit lesion suffered from thrombus aspiration was mainly located in the left anterior descending branch, and left-ventricular ejection fraction (LVEF) was lower (G21-50: 54.9 ± 8.9 vs. 56.0 ± 8.7%, P = 0.01; G51-75: 53.9 ± 9.6 vs. 54.8 ± 9.0%, P = 0.001) and the rate of regional wall motion abnormality was higher (G21-50: 75.7 vs. 66.5%, P < 0.001; G51-75: 75.4 vs. 69.1%, P < 0.001) in the thrombus aspiration group. By contrast, for patients > 75 years, the right coronary artery was the predominant culprit lesion undergoing thrombus aspiration, LVEF (63.1 ± 10.5 vs. 53.1 ± 9.5%, P = 0.985) and the regional wall motion abnormality (79.2 vs. 74.2%, P = 0.089) were comparable between the two treatment groups. Thrombus aspiration neither reduced the in-hospital risk of cardiovascular death, all-cause death, recurrent myocardial infarction, acute stent thrombosis, heart failure, cardiogenic shock, and sudden cardiac arrest nor increased stroke risk compared with the PPCI-only group. However, after adjustment for age, thrombus aspiration presented the tendency to reduce the incidence of sudden cardiac arrest (4.9 vs. 2.5%, P = 0.06) and in-hospital cardiovascular death at 3 days (hazard ratio 0.46; 95% CI, 0.20-1.06; log-rank P = 0.08) in G76-95 group and tended to increase the incidence of heart failure in G51-75 (5.7 vs. 6.9%, P = 0.07). Conclusion: The thrombus aspiration neither significantly reduced the in-hospital incidence of major adverse cardiac events nor increased stroke risk. However, it might play a protective role in reducing in-hospital sudden cardiac arrest and increasing survival from cardiovascular death at 3 days for the elderly.

Outcomes after percutaneous coronary intervention and comparison among scoring systems in predicting procedural success in elderly patients (≥ 75 years) with chronic total occlusion.

BACKGROUND: Evidence-based data on percutaneous coronary intervention in elderly patients with chronic total occlusion (CTO) and comparison among different scoring systems have not been well established. PATIENTS AND METHODS: A total of 246 consecutive patients were stratified into two groups according to the age: elderly group (age≥ 75 years, n = 68) and nonelderly group (age < 75 years, n = 178). Clinical and angiographic characteristics including the Synergy Between PCI With TAXUS and Cardiac Surgery score, in-hospital major adverse cardiac events, procedural success rates, and predictive capacity of four scoring systems [J-CTO, Prospective Global Registry for the Study of Chronic Total Occlusion Intervention (PROGRESS CTO), clinical and lesion-related (CL), and ostial location, Rentrop grade < 2, age ≥ 75 years (ORA) scores] were examined. RESULTS: Triple-vessel disease and the Synergy Between PCI With TAXUS and Cardiac Surgery score in the elderly group were significantly higher than those in the nonelderly group (73.53 vs. 53.93%, P = 0.005; 31.39 ± 7.68 vs. 27.85 ± 7.16, P = 0.001, respectively). The in-hospital major adverse cardiac event rates, vascular access complication rates, and major bleeding rates were similar between the elderly and the nonelderly group (2.94 vs. 2.25%, P = 0.669; 1.47 vs. 0.56%, P = 0.477; 2.94 vs. 1.12%, P = 0.306, respectively). By contrast, the procedural success rate was statistically lower in the elderly group than that in the nonelderly group (73.53 vs. 84.83%, P = 0.040). All the four scoring systems showed a moderate predictive capacity [area under the curve (AUC) for J-CTO score: 0.806, P < 0.0001; AUC for PROGRESS CTO score: 0.727, P < 0.0001; AUC for CL score: 0.800, P < 0.0001; AUC for ORA score: 0.672, P < 0.0001, respectively]. Compared with the ORA score, the J-CTO score, and the CL score showed a significant advantage in predicting procedural success among overall patients (ΔAUC = 0.134, P = 0.0122; ΔAUC = 0.128, P = 0.0233, respectively). CONCLUSION: Despite the lower procedural success rate, percutaneous coronary intervention in elderly patients with CTO is feasible and safe. J-CTO, PROGRESS, ORA, and CL scoring systems have moderate discriminatory capacity.

Triglyceride to high-density lipoprotein cholesterol ratio as a risk factor of repeat revascularization among patients with acute coronary syndrome after first-time percutaneous coronary intervention.

BACKGROUND: It is clinically important to identify high-risk patients with acute coronary syndrome (ACS) who may require repeat revascularization. This retrospective study identified risk factors for repeat revascularization among ACS patients after first-time successful percutaneous coronary interventions (PCIs). The predictive value of the triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio for repeat revascularization was also evaluated. METHODS: We enrolled consecutive ACS patients who had coronary angiography performed during the period from 6 to 12 months after a first-time successful PCI. The primary outcome of the study was to identify the risk factors of repeat revascularization. The subjects were stratified based on repeat PCI events. After comparing various clinical characteristics, univariate and multivariate Cox proportional hazard model analyses were adopted to evaluate the effects of risk factors on repeat revascularization. RESULTS: The patients (n=271) were divided into the event (+) group (n=101) and the event (-) group (n=170). In the event (+) group, target lesion revascularization (TLR) accounted for 20.79% and target vessel revascularization (TVR) accounted for 50.49% of the patients. In contrast, 52.47% of the patients required de novo vessel revascularization (DVR). After adjustment for confounding factors, the TG/HDL-C ratio [hazard ratio (HR) =1.206, 95% confidence interval (CI): 1.016-1.431, P=0.032 for each higher TG/HDL-C ratio unit] and the Gensini score (HR =1.012, 95% CI: 1.005-1.018, P<0.001 for each higher Gensini score unit) were independent risk factors for a repeat PCI. Subgroup analyses showed that higher TG/HDL-C ratios were associated with a significantly higher risk of repeat PCIs in the male, hypertensive, and diabetes mellitus subgroups. CONCLUSIONS: The TG/HDL-C ratio and Gensini score could serve as risk factors for repeat revascularization in ACS patients after a first-time successful PCI.

Curcumin protects cardiac myocyte against hypoxia-induced apoptosis through upregulating miR-7a/b expression.

OBJECTIVE: Curcumin has properties of anti-inflammation, anti-oxidation, anti-infection and anti-tumor, benefiting for the treatment of many diseases. The present study was aimed to investigate the role of curcumin in myocardial infarction (MI) and its potential mechanism involving transcription factor specific protein 1 (SP1). METHODS: After receiving curcumin, C57BL/6 mice subjected to left anterior descending (LAD) coronary artery occlusion to induce MI model. Infarct size was measured by triphenyl tetrazolium chloride staining. In vitro experiments, mouse cardiac myocytes (MCM) subjected to hypoxia after the incubation of curcumin, miR-7a/b and SP1 expression levels were detected by real-time PCR and western blot. Caspase-3 activity and TUNEL assay were performed to assess the cell apoptosis. RESULTS: In animal experiments, curcumin significantly reduced the infarct size compared with the control. It also up-regulated miR-7a/b expression and down-regulated SP1 expression. In hypoxia-induced MCM, curcumin led to the decrease of cell apoptosis. Transfected MCM with miR-7a/b inhibitor, curcumin induced the decrease of cell apoptosis and SP1 expression was reversed. Transfected with pcDNA-SP1, the decrease of cardiac myocytes apoptosis after the treatment of curcumin was also reversed. CONCLUSION: Curcumin pre-treatment protected against hypoxia-induced cardiac myocytes apoptosis through the up-regulation of miR-7a/b and the down-regulation of SP1 expression.

The Circular RNA Cdr1as Promotes Myocardial Infarction by Mediating the Regulation of miR-7a on Its Target Genes Expression.

OBJECTIVES: Recent studies have demonstrated the role of Cdr1as (or CiRS-7), one of the well-identified circular RNAs (circRNAs), as a miR-7a/b sponge or inhibitor in brain tissues or islet cells. This study aimed to investigate the presence of Cdr1as/miR-7a pathway in cardiomyocytes, and explore the mechanism underlying the function of miR-7a in protecting against myocardial infarction (MI)-induced apoptosis. METHODS: Mouse MI injury model was established and evaluated by infarct size determination. Real-time PCR was performed to quantify the expression of Cdr1as and miR-7a in cardiomyocytes. Cell apoptosis was determined by caspase-3 activity analysis and flow cytometry assays with Annexin V/PI staining. Transfection of Cdr1as overexpressing plasmid and miR-7a mimic were conducted for gain-of-function studies. Luciferase reporter assay and western blot analysis were performed to verity potential miR-7a targets. RESULTS: Cdr1as and miR-7a were both upregulated in MI mice with increased cardiac infarct size, or cardiomyocytes under hypoxia treatment. Cdr1as overexpression in MCM cells promoted cell apoptosis, but was then reversed by miR-7a overexpression. The SP1 was identified as a new miR-7a target, in line with previously identified PARP, while miR-7a-induced decrease of cell apoptosis under hypoxia treatment was proven to be inhibited by PARP-SP1 overexpression. Moreover, Cdr1as overexpression in vivo increased cardiac infarct size with upregulated expression of PARP and SP1, while miR-7a overexpression reversed these changes. CONCLUSIONS: Cdr1as also functioned as a powerful miR-7a sponge in myocardial cells, and showed regulation on the protective role of miR-7a in MI injury, involving the function of miR-7a targets, PARP and SP1.

A Functional Single-Nucleotide Polymorphism in Pre-microRNA-196a2 is Associated with Atrial Fibrillation in Han Chinese.

BACKGROUND: MicroRNAs are small, single-stranded, non-protein-coding RNAs of about 22 nucleotides. MicroRNA molecules have been identified to play key roles in a broad range of physiologic and pathologic processes. Polymorphisms in the corresponding sequence space are likely to make a significant contribution to phenotypic variation. A T/C genetic variant (rs11614913) in the pre-miR-196a2 sequence could alter mature miR-196a expression and target mRNA binding. The aim of the present study is to evaluate the relationship between this polymorphism and atrial fibrillation (AF). METHODS: A total of 123 participants were enrolled, 65 AF patients were confirmed with electrocardiogram (ECG) or dynamic electrocardiography, 58 normal individuals were assigned to the control group. Genotypes of the premiR-196a2 were distinguished using the method of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. RESULTS: The distribution of the pre-miR-196a2 genotypes (TT, TC, and CC) was 15.38%, 46.15%, and 38.46% in the AF group and 39.66%, 46.55%, and 13.79% in the controls, respectively (p = 0.0011). Compared with the TT genotype, the C allele carriers (TC+CC genotypes) had a 3.968-fold increased risk of AF (adjusted OR = 3.968, 95% CI = 1.633 - 9.644, p = 0.002). AF patients with the TC+CC genotype had greater left atrial dimension than did patients with the TT genotype (42.10 ± 8.74 vs. 35.13 ± 8.16, p = 0.0224). CONCLUSIONS: Our data support that the pre-miR-196a2 polymorphism is associated with AF, and the C allele is a risk factor for AF.

Clinical Outcomes of Revascularization Strategies for Patients With MVD/LMCA Disease: A Systematic Review and Network Meta-Analysis.

Hybrid coronary revascularization (HCR), a new minimally invasive procedure for patients requiring revascularization for multivessel coronary lesions, combines coronary artery bypass grafting (CABG) for left anterior descending (LAD) lesions and percutaneous coronary intervention (PCI) for non-LAD coronary lesions. However, available data related to outcomes comparing the 3 revascularization therapies is limited to small studies.We conducted a search in MEDLINE, EMBASE, and the Cochrane Library of Controlled Trials up to December 31, 2014, without language restriction. A total of 16 randomized trials (n=4858 patients) comparing HCR versus PCI or off-pump CABG (OPCAB) were included in this meta-analysis. The primary outcomes were major adverse cardiac and cerebrovascular events (MACCE), all-cause death, myocardial infarction (MI), cerebrovascular events (CVE), and target vessel revascularization (TVR). Odds ratios (OR) and 95% confidence intervals (CI) were calculated using random-effect and fixed-effect models. Ranking probabilities were used to calculate a summary numerical value: the surface under the cumulative ranking (SUCRA) curve.No significant differences were seen between the HCR and PCI in short term (in hospital and 30 days) with regard to MACCE (odds ratio [OR] = 0.51, 95% confidence interval [CI] 0.00-2.35), all-cause death (OR = 2.09, 95% CI 0.34-7.66), MI (OR = 1.02, 95% CI 0.19-2.95), CVE (OR = 4.45, 95% CI 0.39-19.16), and TVR (OR = 6.99, 95% CI 0.17-39.39). However, OPCAB had lower MACCE than HCR (OR = 0.19, 95% CI 0.00-0.95). In midterm (1 year and 3 year), in comparison with HCR, PCI had higher all-cause death (OR = 5.66, 95% CI 0.00-13.88) and CVE (OR = 4.40, 95% CI 0.01-5.68), and lower MI (OR = 0.51, 95% CI 0.00-2.86), TVR (OR = 0.53, 95% CI 0.05-2.26), and thus the MACCE (OR = 0.51, 95% CI 0.00-2.35). Off-pump CABG presented a better outcome than HCR with significant lower MACCE (OR = 0.17, 95% CI 0.01-0.68). Surface under the cumulative ranking probabilities showed that HCR may be the superior strategy for MVD and LMCA disease when regarded to MACCE (SUCRA = 0.84), MI (SUCRA = 0.76) in short term, and regarded to MACCE (SUCRA = 0.99), MI (SUCRA = 0.94), and CVE (SUCRA = 0.92) in midterm.Hybrid coronary revascularization seemed to be a feasible and acceptable option for treatment of LMCA disease and MVD. More powerful evidences are required to precisely evaluate risks and benefits of the 3 therapies for patients who have different clinical characteristics.

In-hospital clinical outcomes of elderly patients (≥60 years) undergoing primary percutaneous coronary intervention.

Elderly patients are at high risk of mortality when they present with ST-elevation myocardial infarction (STEMI). However, the clinical outcomes of this sub-group undergoing primary percutaneous coronary intervention (PPCI) have not been well established, despite recent advances in both devices and techniques. In the present retrospective cohort study from a Chinese single center, we assessed the clinical outcomes and predictors of mortality in elderly patients (≥60 years) underwent with PPCI. The primary endpoints were immediate angiographic success and in-hospital procedural success. The secondary endpoints were all-cause death in hospital. Between January 2011 and December 2013, a total of 184 consecutive patients with acute STEMI underwent PPCI were enrolled. 116 (63.04%) patients were in the elderly group. Despite the difference in lesion complexity between groups, the immediate angiographic success rate was similar (93.97% in the elderly group, and 94.12% in the non-elderly group, P=0.966). The procedural success rate were not significantly different between the two groups (90.52% in the elderly group, and 94.12% in the non-elderly group, P=0.389). However, in-hospital mortality was statistically higher in elderly group than in the non-elderly group (8.62% Vs 1.47%, P=0.048). The major causes of death were cardiac shock and malignant arrhythmias (ventricular tachycardia and fibrillation). Our results indicate that PPCI in the elderly is feasible and has a high likelihood of immediate angiographic and procedural success.

Interleukin-10 promotor -592A/C polymorphism is associated with slow coronary flow in Han Chinese.

An accumulating body of evidence suggests that slow coronary flow (SCF) phenomenon seems to be an early-form of atherosclerosis and low-grade inflammation plays a major role in the atherosclerotic vascular processes. Interleukin (IL)-10 is a multifunctional cytokine involved in both innate and adaptive immune response. The aim of the present study is to investigate the association of IL-10 gene -592A/C polymorphism with SCF in Han Chinese. 250 patients who underwent coronary angiography and had angiographically normal coronary arteries of varying coronary flow rates without any atherosclerotic lesion were enrolled in this study. Patients who had thrombolysis in myocardial infarction frame counts (TFC) above the normal cutoffs were considered to have SCF and those within normal limits were considered to have normal coronary flow (NCF). The PCR-based restriction fragment length polymorphism (PCR-RFLP) technique was used to assess the genotypes frequencies. The distribution of the IL-10 -592A/C genotypes (AA, AC, and CC) was 46.34%, 41.46%, and 12.20% in the NCF group, and 66.51%, 28.71%, and 4.78% in SCF subjects, respectively (P = 0.0280). The frequency of the A allele in the SCF group was significantly higher than that in the NCF group (80.86% vs. 67.07%, P = 0.0054). Compared with the CC genotype, the AA genotype had increased risk of SCF in both unadjusted and adjusted analyses. In SCF patients, the average serum IL-10 levels in AA genotype were statistically lower than in AC + CC genotype (P = 0.0000). These findings suggest that IL-10 -592A/C polymorphism is associated with SCF and the A allele has increased risk for SCF in Han Chinese.

Serum YKL-40 is increased in patients with slow coronary flow.

OBJECTIVES: There is accumulating evidence that inflammation plays a major role in the development of the slow coronary flow (SCF) phenomenon. YKL-40 has been suggested to be a potential biomarker of inflammation. In this study, we aimed to study YKL-40 as it relates to SCF. MATERIALS AND METHODS: Patients who underwent coronary angiography before and had angiographically normal coronary arteries of varying coronary flow rates without any atherosclerotic lesion were enrolled in this study. Patients who had thrombolysis in myocardial infarction frame counts (TFC) above the normal cutoffs were considered to have SCF and those within normal limits were considered to have normal coronary flow (NCF). The YKL-40 levels and biochemical profiles of all patients were studied and analyzed. RESULTS: There were 41 patients in the SCF group and 209 patients in the NCF group. Compared with the NCF patients, SCF patients had higher serum high-sensitivity C-reactive protein (hs-CRP) (P=0.0003) and YKL-40 (P=0.0007) levels. A positive correlation was detected between the YKL-40 levels and hs-CRP (r=0.7021, P<0.001), and the mean TFC (r=0.4038, P=0.0088) in SCF patients. CONCLUSION: Our study showed that YKL-40 levels are higher and correlated positively with TFC and hs-CRP in SCF patients. This finding suggests that YKL-40 may be a useful marker and predictor for SCF.

Interleukin-6 promotor polymorphisms and coronary vasospastic angina in Han Chinese.

There is an accumulating body of evidence indicating association between inflammation and the pathogenesis of coronary vasospastic angina (CVA). Interleukin-6 (IL-6) is a pleiotropic cytokine, functions as a mediator of inflammatory response and has both pro-inflammatory and anti-inflammatory properties. The aim of the present study is to investigate the association of -634C/G polymorphism of IL-6 gene with CVA in Han Chinese. A total of 27 CVA patients and 232 healthy controls were eligible for this study. The PCR-based restriction fragment length polymorphism (PCR-RFLP) technique was used to assess the genotypes frequencies. The distribution of the IL-6 -634C/G genotypes (CC, CG, and GG) was 59.48%, 37.07%, and 3.45% in the controls, and 37.04%, 48.15%, and 14.81% in CVA group, respectively (P = 0.0080). The frequency of the G allele in the CVA group was significantly higher than that in the control group (38.89% vs 21.98%, P = 0.0057). Compared with the wild type CC, the G allele carriers (CG + GG genotypes) had increased risk of CVA in both unadjusted and adjusted analyses. These findings suggest that IL-6 -634C/G polymorphism is associated with CVA and the G allele is an independent risk for CVA in Han Chinese.

Association of Interleukin-10 promotor polymorphisms with atrial fibrillation in Han Chinese.

There is an accumulating body of evidence indicating strong association between inflammation and the pathogenesis of atrial fibrillation (AF). IL-10 is a multifunctional anti-inflammatory cytokine that down-regulates cell-mediated immune responses and cytotoxic inflammatory responses. The aim of the present study is to investigate the association of IL-10 gene -592A/C polymorphism with AF in Han Chinese. 117 AF patients and 100 healthy volunteers were eligible for this study. The PCR-based restriction fragment length polymorphism (PCR-RFLP) technique was used to assess the genotypes frequencies. The distribution of the IL-10 -592A/C genotypes (AA, AC, and CC) was 55.00%, 35.00%, and 10.00% in the controls, and 71.79%, 23.08%, and 5.13% in AF subjects, respectively (p = 0.0335). The frequency of the A allele in the AF group was significantly higher than that in the control group (83.33% vs 72.50%, p = 0.0063). Compared with the CC genotype, the AA genotype had increased risk of AF in both unadjusted and adjusted analyses. The average serum IL-10 levels in AA genotype were statistically lower than in AC + CC genotype (p = 0.0000). These findings suggest that IL-10 -592A/C polymorphism is associated with AF and the A allele has increased risk for AF in Han Chinese.

A functional single-nucleotide polymorphism in interleukin-6 promoter is associated with p wave dispersion in hypertensive subjects with atrial fibrillation.

Inflammation has been shown to be implicated in the pathophysiology of atrial fibrillation (AF). Interleukin-6 (IL-6) is a pleiotropic cytokine, functions as a mediator of inflammatory response and has both pro-inflammatory and anti-inflammatory properties. Little is known about genetic factors of inflammation in the accompanying atrial electrical remodeling expressed by P wave dispersion (Pdisp). The aim of the present study is to evaluate the association of -634C/G polymorphism of IL-6 gene with Pdisp in Han Chinese hypertensive patients with AF. A total of 100 patients with essential hypertension (EH) were eligible for this study. Patients with paroxysmal AF (n=50) were allocated to the AF group, and 50 subjects without AF to the control group. The PCR-based restriction fragment length polymorphism (PCR-RFLP) technique was used to assess the genotypes frequencies. The distribution of the IL-6 -634C/G genotypes (CC, CG, and GG) was 68.00%, 28.00%, and 4.00% in the controls, and 44.00%, 40.00%, and 16.00% in AF subjects, respectively (P=0.0269). The frequency of the G allele in the AF group was significantly higher than that in the control group (36.00% vs 18.00%, P=0.0041). Compared to the wild type CC, the G allele carriers (CG + GG genotypes) had a 2.7045-fold increased risk of AF (odds ratio =2.7045, 95% confidence interval =1.1966-6.1126, P=0.0156). AF patients with the CG + GG genotype had longer Pdisp (P=0.0032) than did patients with the CC genotype. The longer Pdisp in the subjects with the CG + GG genotype was also found in the control group (P=0.0016). These findings support that IL-6 -634C/G polymorphism is associated with Pdisp and AF, suggesting an active implication of inflammation in the atrial electrophysiological remodeling predisposing to AF.

Angiotensin-converting enzyme gene 2350 G/A polymorphism and susceptibility to atrial fibrillation in Han Chinese patients with essential hypertension.

OBJECTIVE: The angiotensin-converting enzyme gene is one of the most studied candidate genes related to atrial fibrillation. Among the polymorphisms of the angiotensin-converting enzyme gene, the 2350 G/A polymorphism (rs4343) is known to have the most significant effects on the plasma angiotensin-converting enzyme concentration. The aim of the present study was to investigate the association of the angiotensin-converting enzyme 2350 G/A polymorphism with atrial fibrillation in Han Chinese patients with essential hypertension. METHODS: A total of 169 hypertensive patients were eligible for this study. Patients with atrial fibrillation (n = 75) were allocated to the atrial fibrillation group, and 94 subjects without atrial fibrillation were allocated to the control group. The PCR-based restriction fragment length polymorphism technique was used to assess the genotype frequencies. RESULTS: The distributions of the angiotensin-converting enzyme 2350 G/A genotypes (GG, GA, and AA, respectively) were 40.43%, 41.49%, and 18.08% in the controls and 18.67%, 46.67%, and 34.66% in the atrial fibrillation subjects (p = 0.037). The frequency of the A allele in the atrial fibrillation group was significantly greater than in the control group (58.00% vs. 38.83%, p = 0.0007). Compared with the wild-type GG genotype, the GA and AA genotypes had an increased risk for atrial fibrillation. Additionally, atrial fibrillation patients with the AA genotype had greater left atrial dimensions than the patients with the GG or GA genotypes (p<0.01 and p<0.05, respectively). CONCLUSIONS: The results obtained in this study indicate that the angiotensin-converting enzyme 2350 G/A polymorphism is associated with atrial fibrillation and that the A allele shows an increased risk for atrial fibrillation in Han Chinese patients with essential hypertension.

Angiotensin-converting enzyme gene 2350 G/A polymorphism and susceptibility to atrial fibrillation in Han Chinese patients with essential hypertension

OBJECTIVE: The angiotensin-converting enzyme gene is one of the most studied candidate genes related to atrial fibrillation. Among the polymorphisms of the angiotensin-converting enzyme gene, the 2350 G/A polymorphism (rs4343) is known to have the most significant effects on the plasma angiotensin-converting enzyme concentration. The aim of the present study was to investigate the association of the angiotensin-converting enzyme 2350 G/A polymorphism with atrial fibrillation in Han Chinese patients with essential hypertension. METHODS: A total of 169 hypertensive patients were eligible for this study. Patients with atrial fibrillation (n = 75) were allocated to the atrial fibrillation group, and 94 subjects without atrial fibrillation were allocated to the control group. The PCR-based restriction fragment length polymorphism technique was used to assess the genotype frequencies. RESULTS: The distributions of the angiotensin-converting enzyme 2350 G/A genotypes (GG, GA, and AA, respectively) were 40.43%, 41.49%, and 18.08% in the controls and 18.67%, 46.67%, and 34.66% in the atrial fibrillation subjects (p = 0.037). The frequency of the A allele in the atrial fibrillation group was significantly greater than in the control group (58.00% vs. 38.83%, p = 0.0007). Compared with the wild-type GG genotype, the GA and AA genotypes had an increased risk for atrial fibrillation. Additionally, atrial fibrillation patients with the AA genotype had greater left atrial dimensions than the patients with the GG or GA genotypes (p<0.01 and p<0.05, respectively). CONCLUSIONS: The results obtained in this study indicate that the angiotensin-converting enzyme 2350 G/A polymorphism is associated with atrial fibrillation and that the A allele shows an increased risk for atrial fibrillation in Han Chinese patients with essential hypertension. .

[Therapeutic effects of magnetically labeled mononuclear and mesenchymal stem cells transplantation in a swine myocardial infarction model assessed by magnetic resonance imaging].

OBJECTIVE: To evaluate the therapeutic effects of magnetically labeled mononuclear stem cells (MR-MNC) and mesenchymal stem cells (MR-MSC) transplantation in a swine acute myocardial infarction (AMI) model by MR imaging. METHODS: AMI model was established in swines by balloon occlusion of the left anterior descending coronary artery, 10(7) autologous MR-MSC (n = 7), MR-MNC (n = 6) or PBS (n = 6) were delivered via intracoronary infusion within 1 week after AMI [(4.8 +/- 1.3) days]. Changes of infarct size and cardiac function were assessed with the use of 3.0T MR scanner before AMI, at 1 and 8 weeks post AMI. RESULTS: Magnetically labeled stem cells could be identified in the region of AMI by cardiac MR imaging. Eight weeks post transplantation, infarct size was significantly reduced in MR-MSC transplantation group (8.5% +/- 0.5% vs. 24.7% +/- 3.1%, P < 0.05) and in MR-MNC transplantation (12.3% +/- 1.5% vs. 26.1% +/- 1.5%, P < 0.05) while infarct size remained unchanged in PBS group (P > 0.05) compared to values at 1 week post AMI, left ventricular ejection fraction (LVEF) was also significantly higher in MR-MSC transplantation group (56.9% +/- 1.3% vs. 40.7% +/- 2.0%, P < 0.05) and MR-MNC transplantation group (52.8% +/- 1.4% vs. 41.9% +/- 3.3%, P < 0.05) compared to LVEF at 1 week post AMI. LVEF increase was more significant in swines received MR-MSC transplantation than MR-MNC transplantation (16.2% +/- 1.2% vs. 10.9% +/- 3.0%, P < 0.05). Prussian blue staining identified stem cells in corresponding myocardial regions with as by MRI. Western blot analysis demonstrated that cardiac expressions of myosin heavy chain (MHC) in MR-MSC group (100.3 +/- 5.5) and in MR-MNCs group (95.5 +/- 4.2) were significantly higher than that in PBS group (75.7 +/- 5.7, P < 0.05), myocardial troponin T (cTNT) expression in MR-MSC group (124.0 +/- 5.8) and MR-MNC group (118.4 +/- 4.4) were also significantly higher than in PBS group (93.3 +/- 3.9, P < 0.05) while MMP2/TIMP1 ratios in MR-MSC group (0.6 +/- 0.1) and MR-MNC group (0.6 +/- 0.1) were significantly lower than that in PBS group (4.2 +/- 0.2, P < 0.05). CONCLUSIONS: Magnetically labeled MR-MSC and MR-MNC homed to heart post myocardial infarction and reduced infarct size, improved cardiac function. MR-MSC is superior to MR-MNC on improving cardiac function.

[MR imaging of injected magnetically labeled stem cells in myocardial infarction: experiment with pigs].

OBJECTIVE: To investigate the efficacy of magnetic resonance imaging (MRI) in tracking bone marrow derived mononuclear cells (BM-MNCs) labeled with superparamagnetic iron oxide (SPIO) nanoparticles. METHODS: BM-MNCs were isolated from the bone marrow of 14 pigs. These 14 pigs underwent occlusion of the left anterior descending coronary artery (LAD) to establish myocardial infarction (MI) models and then randomly divided into 2 groups: experimental group (n = 9) to be injected with BM-MNCs labeled with SPIO intracoronarily under X-ray fluoroscopy, and control group (n = 5), to be injected with unlabelled BM-MNCs MRI was performed with a 1.5T MR scanner to demonstrate the location of the BM-MNCs once a week. T pigs were killed when no labeled BM-MSC was detected. The hearts were taken out to undergo HE staging and Prussian blue staining. Immunohistochemistry was used to detect the desmin and myosin. RESULTS: The cell labeling efficiency was almost 100%. Contrast-enhanced MRI demonstrated successful establishment of MI models. Effective MRI tracking findings were obtained in 8 pigs, 7 of the experimental group and 3 of the control group. In 3 pigs T2* weighted MRI showed the zone of labeled cell accumulation shows vague low-signal area around the infarction area and much better conspicuity of the zone of hypoenhancement was shown under contrast-enhanced MRI. The hypoenhancement zone disappeared 14 - 21 days after the injection of BM-MSCs. Histological analyses showed that most Prussian blue positive cells were well correlated with the area where a signal intensity loss was observed in MRI. CONCLUSION: 1.5T MR imaging can monitor the magnetically labeled BM-MNC in vivo in myocardial infarction provided the number of injected is nor less than 10(6).