Shuning Zhang

Aspirin for primary prevention of cardiovascular events in patients with diabetes: A meta-analysis.

BACKGROUND To systematically review trials concerning the benefit and risk of aspirin therapy for primary prevention of cardiovascular events in patients with diabetes mellitus. METHODS We searched MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials. Eligible studies were prospective, randomized controlled trials of aspirin therapy for primary cardiovascular prevention in patients with diabetes with follow-up duration at least 12 months. RESULTS 7 trials included 11,618 individuals with diabetes. Aspirin therapy was not associated with a statistically significant reduction in major cardiovascular events (relative risk [RR] 0.92, 95% confidence interval [CI] 0.83-1.02, p=0.11). Aspirin use also did not significantly reduce all-cause mortality (0.95, 95% CI 0.85-1.06; p=0.33), cardiovascular mortality (0.95, 95% CI 0.71-1.27; p=0.71), stroke (0.83, 95% CI 0.63-1.10; p=0.20), or myocardial infarction (MI) (0.85, 95% CI 0.65-1.11; p=0.24). There was no significant increased risk of major bleeding in aspirin group (2.46, 95% CI 0.70-8.61; p=0.16). Meta-regression suggested that aspirin agent could reduce the risk of stroke in women and MI in men. CONCLUSIONS In patients with diabetes, aspirin therapy did not significantly reduce the risk of cardiovascular events without an increased risk of major bleeding, and showed sex-specific effects on MI and stroke.

Administration of intracoronary bone marrow mononuclear cells on chronic myocardial infarction improves diastolic function

Background: Regeneration of the myocardium and improved ventricular function have been demonstrated in patients with acute myocardial infarction (MI) treated by intracoronary delivery of autologous bone marrow mononuclear cells (BMC) a few days after successful myocardial reperfusion by percutaneous coronary intervention (PCI); however, the effects of intracoronary cell infusion in chronic MI patients are still unknown. Aims: To investigate whether intracoronary infusion of BMC into the infarct-related artery in patients with healed MI could lead to improvement in left ventricular (LV) function. Methods: Among 47 patients with stable ischaemic heart disease due to a previous MI (13 (SD 8) months previously), 24 were randomised to intracoronary infusion of BMC (BMC group) and 23 to a saline infusion (control group) into the target vessel after successful PCI within 12 hours after chest pain occurred. LV systolic and diastolic function, infarct size and myocardial perfusion defect were assessed with the use of echocardiography, magnetic resonance imaging (MRI) or 201Tl single-photon-emission computed tomography (SPECT) at baseline and repeated at the 6-month follow-up examination. Results: BMC treatment did not result in a significant increase in LV ejection fraction in any of the groups by any of the methods used, and the apparent tendency of an improvement was not statistically different between the two groups. The two groups also did not differ significantly in changes of LV end-diastolic and systolic volume, infarct size or myocardial perfusion. However, there was an overall effect of BMC transfer compared with the control group with respect to early/late (E/A) (p<0.001), early diastolic velocity/late diastolic (Aa) velocity (Ea/Aa) ratio (p = 0.002) and isovolumetric relaxation time (p = 0.038) after 6 months, as evaluated by tissue Doppler echocardiography. We noted no complications associated with BMS transfer. Conclusion: Intracoronary transfer of autologous BMC in patients with healed MI did not lead to significant improvement of cardiac systolic function, infarct size or myocardial perfusion, but did lead to improvement in diastolic function.

Impact of Timing on Efficacy and Safetyof Intracoronary Autologous Bone Marrow Stem Cells Transplantation in Acute Myocardial Infarction: A Pooled Subgroup Analysis of Randomized Controlled Trials

Until now there were no clinical studies or systematic reviews to investigate the impact of timing on efficacy and safety of intracoronary bone marrow stem cell (BMSC) transfer in patients with acute myocardial infarction (AMI).

Repeated autologous bone marrow mononuclear cell therapy in patients with large myocardial infarction

We sought to determine whether repeat administration of bone marrow mononuclear cells (BMC) can improve left ventricular function compared with a single infusion in patients with large acute myocardial infarction (AMI).

Intracoronary autologous bone marrow stem cells transfer for patients with acute myocardial infarction: a meta-analysis of randomised controlled trials.

BACKGROUND Conflicting results existed now on the clinical utility of intracoronary bone marrow stem cells (BMSC) transfer for acute myocardial infarction (AMI). This study sought to analyze the efficacy and safety of autologous BMSC transfer in patients with AMI by performing a meta-analysis based on published randomised controlled trials. METHODS A systematic literature search of PubMed, MEDLINE, BIOSIS, EMBASE, and Cochrane EBM databases during the period of 1990-2007 was made, objective being the randomised controlled trials in patients with AMI who underwent primary percutaneous coronary intervention (PCI) and received intracoronary BMSC transfer, and were followed up for at least 3 months. RESULTS A total of 6 trials with 525 patients were available for analysis. The pooled statistics showed the mean increase in left ventricular ejection fraction (LVEF) from baseline was 7.05% in BMSC group (p=0.01), whereas only 2.46% in control group (p=0.02), and the effect on the absolute change in LVEF was an increase of 4.77% compared with the control (95% confidence interval [CI] 1.42% to 8.12%; p=0.005). The similar effect on left ventricular (LV) end-diastolic dimensions was demonstrated in inter-group comparison (standardized mean difference [SMD]=-0.15, 95%CI -0.50 to 0.20; p=0.41). The incidence of major adverse cardiac events was also similar in two groups but in favor of BMSC group (relative risk [RR]=0.85, 95%CI, 0.61 to 1.19; p=0.34). CONCLUSIONS Post PCI BMSC transplantation in patients with AMI significantly increases LVEF but has no effects on LV remodeling, and there is not an incremental effect on the occurrence of major adverse cardiac events in the observed period.

Deep magnetic capture of magnetically loaded cells for spatially targeted therapeutics

Magnetic targeting has recently demonstrated potential in promoting magnetically loaded cell delivery to target lesion, but its application is limited by magnetic attenuation. For deep magnetic capture of cells for spatial targeting therapeutics, we designed a magnetic pole, in which the magnetic field density can be focused at a distance from the pole. As flowing through a tube served as a model of blood vessels, the magnetically loaded mesenchymal stem cells (MagMSCs) were highly enriched at the site distance from the magnetic pole. The cell capture efficiency was positively influenced by the magnetic flux density, and inversely influenced by the flow velocity, and well-fitted with the deductive value by theoretical considerations. It appeared to us that the spatially-focused property of the magnetic apparatus promises a new deep targeting strategy to promote homing and engraftment for cellular therapy.

Efficacy of ACE inhibitors in chronic heart failure with preserved ejection fraction — A meta analysis of 7 prospective clinical studies

BACKGROUND The effect of ACE inhibitors on the prognosis of chronic heart failure patients with preserved left ventricular ejection fraction remains controversial. AIMS To assess the impact of ACE inhibitors on the prognosis of chronic heart failure patients with preserved left ventricular ejection fraction. METHODS AND RESULTS Seven prospective studies evaluating the effect of ACE inhibitors compared to placebo or other classes of drugs, such as monotherapy or first-line therapy, on the prognosis of chronic heart failure patients with preserved left ventricular ejection fraction were included. A total of 2554 patients (mean age: 75.1 years, female: 58%) were recruited with an average follow up of 20.9 months. The primary etiology of heart failure with preserved ejection fraction was ischemic heart disease (33.7%), hypertension (69.1%) and diabetes mellitus (25.8%). Our results demonstrated that ACE inhibitors significantly reduced all-cause mortality (odds ratio, OR = 0.52; 95% Confidence Interval (CI), 0.41 to 0.64; P<0.01). Furthermore, ACE inhibitors were able to reduce heart failure related rehospitalization or treatment over 20.9 months (p<0.05) in a subgroup of patients aged over 75 years. However, death due to worsening of heart failure, heart failure related rehospitalization and any-cause readmission were not affected (OR = 0.88; 95% CI: 0.66 to 1.17; P = 0.37 for death due to worsening of heart failure; OR = 0.81; 95% CI: 0.63 to 1.05; P = 0.11 for heart failure related rehospitalization and OR = 0.88; 95% CI: 0.68 to 1.14; P = 0.33 for any-cause readmission, respectively). CONCLUSIONS In patients with chronic heart failure with preserved ejection fraction, ACE inhibitors reduced all-cause mortality without affecting mortality due to heart failure and any-cause rehospitalization.

Efficacy and safety of intracoronary autologous bone marrow-derived cell transplantation in patients with acute myocardial infarction: insights from randomized controlled trials with 12 or more months follow-up.

Until now there was no systematic review concerning the chronic effects of intracoronary bone marrow‐derived cell (BMC) transplantation in patients with acute myocardial infarction (MI).

Effects of intensive glucose control on incidence of cardiovascular events in patients with type 2 diabetes: A meta-analysis

Abstract Background. The effects of intensive glucose control over conventional glucose control on cardiovascular outcomes of patients with type 2 diabetes remain uncertain. Methods. We searched MEDLINE, EMBASE, and the Cochrane database to identify randomized controlled trials that compared the effects of intensive glucose control and conventional glucose control, on cardiovascular events in patients with type 2 diabetes. Results. Seven trials involving 34,144 participants with type 2 diabetes were included. Intensive glucose control significantly reduced major cardiovascular events by 10% (relative risk (RR) 0.90, 95% CI 0.85–0.96; P = 0.0006), and non-fatal myocardial infarction by 16% (0.84, 95% CI 0.76–0.93; P = 0.0006) at the expense of increased incidence of severe hypoglycemia (2.30, 95% CI 1.74–3.03; P < 0.00001), while all-cause mortality, cardiovascular death, non-fatal stroke, and heart failure were similar between the two groups. Subgroup analyses showed that patients with longer follow-up duration, shorter diabetic duration, less glycosylated hemoglobin (HbA1c) reduction, higher HbA1c concentration at follow-up, and lower base-line HbA1c benefited more from intensive glucose control. Conclusion. An intensive glucose control strategy can effectively reduce the risk of major cardiovascular events but at the expense of a significantly increased risk of severe hypoglycemia in patients with type 2 diabetes.

Infarcted myocardium-like stiffness contributes to endothelial progenitor lineage commitment of bone marrow mononuclear cells

Optimal timing of cell therapy for myocardial infarction (MI) appears during 5 to 14 days after the infarction. However, the potential mechanism requires further investigation. This work aimed to verify the hypothesis that myocardial stiffness within a propitious time frame might provide a most beneficial physical condition for cell lineage specification in favour of cardiac repair. Serum vascular endothelial growth factor (VEGF) levels and myocardial stiffness of MI mice were consecutively detected. Isolated bone marrow mononuclear cells (BMMNCs) were injected into infarction zone at distinct time‐points and cardiac function were measured 2 months after infarction. Polyacrylamide gel substrates with varied stiffness were used to mechanically mimic the infarcted myocardium. BMMNCs were plated on the flexible culture substrates under different concentrations of VEGF. Endothelial progenitor lineage commitment of BMMNCs was verified by immunofluorescent technique and flow cytometry. Our results demonstrated that the optimal timing in terms of improvement of cardiac function occurred during 7 to 14 days after MI, which was consistent with maximized capillary density at this time domains, but not with peak VEGF concentration. Percentage of double‐positive cells for DiI‐labelled acetylated low‐density lipoprotein uptake and fluorescein isothiocyanate (FITC)‐UEA‐1 (ulex europaeus agglutinin I lectin) binding had no significant differences among the tissue‐like stiffness in high concentration VEGF. With the decrease of VEGF concentration, the benefit of 42 kPa stiffness, corresponding to infarcted myocardium at days 7 to 14, gradually occurred and peaked when it was removed from culture medium. Likewise, combined expressions of VEGFR2+, CD133+ and CD45– remained the highest level on 42 kPa substrate in conditions of lower concentration VEGF. In conclusion, the optimal efficacy of BMMNCs therapy at 7 to 14 days after MI might result from non‐VEGF dependent angiogenesis, and myocardial stiffness at this time domains was more suitable for endothelial progenitor lineage specification of BMMNCs. The results here highlight the need for greater attention to mechanical microenvironments in cell culture and cell therapy.