Wen-Shu Zhao

Comparison of glucose-insulin-potassium and insulin-glucose as adjunctive therapy in acute myocardial infarction: a contemporary meta-analysis of randomised controlled trials

Background There is conflicting evidence regarding two different insulin regimens for acute myocardial infarction (AMI), one focusing on delivering insulin (‘insulin focus’, glucose-insulin-potassium (GIK)) and one focusing on tight glycaemic control (‘glycaemia focus’, insulin-glucose). A longstanding controversy has focused on which strategy provides the greatest reduction in mortality. The aim of this study was to perform a meta-analysis of randomised controlled trials (RCTs) comparing GIK or insulin-glucose therapy versus standard therapy for AMI in the reperfusion era. Methods A MEDLINE/EMBASE/CENTRAL search was conducted of RCTs evaluating GIK or insulin-glucose as adjunctive therapy for AMI. The primary endpoint was all-cause mortality. The data were analysed with a random effect model. Results A total of 11 studies (including 23 864 patients) were identified, eight evaluating insulin focus with GIK and three evaluating glycaemia focus with insulin-glucose. Overall, insulin focus with GIK was not associated with a statistically significant effect on mortality (RR 1.07, 95% CI 0.89 to 1.29, p=0.487). Before the use of reperfusion, GIK also had no clear impact on mortality (RR 0.92, 95% CI 0.70 to 1.20, p=0.522). Pooled data from the three studies evaluating glycaemia focus showed that insulin-glucose did not reduce mortality in the absence of glycaemia control in patients with AMI with diabetes (RR 1.07, 95% CI 0.85 to 1.36, p=0.547). Conclusions Current evidence suggests that GIK with insulin does not reduce mortality in patients with AMI. However, studies of glycaemia are inconclusive and it remains possible that glycaemic control is beneficial.

The correlation between peripartum cardiomyopathy and autoantibodies against cardiovascular receptors.

Background Peripartum cardiomyopathy (PPCM) is characterized by left ventricular systolic dysfunction and heart failure. However, its pathogenesis is not clear. Our preliminary study revealed that autoantibodies against β1-adrenergic receptors (β1R-AABs) and M2-muscarinic receptors (M2R-AABs) participated in heart failure regardless of primary heart disease. Whether β1R-AABs and M2R-AABs participate in the pathogenesis of PPCM is still unknown. Methods Totally 37 diagnosed PPCM patients and 36 normal pregnant women were enrolled in this study. Clinical assessment and 2-dimensional echocardiographic studies as well as the measurement of β1R-AABs or M2R-AABs by enzyme linked immunosorbent assay (ELISA) were performed. Results The positive rates for β1R-AABs and M2R-AABs were 59.5% (22/37) and 45.9% (17/37) in PPCM patients, and 19.4% (7/36) (P<0.001) and 16.67% (6/36) (P<0.001) in normal pregnant women, respectively. Both β1R-AABs and M2R-AABs had a positive correlation with serum expression level of NT-proBNP, left ventricular dimension and NYHA FC (rs: 0.496–0.892, P<0.01). In addition, a negative correlation between the activity of β1R-AABs and M2R-AABs and LVEF, LVFS was observed (rs: −0.488–0.568, P<0.01). Moreover, autoantibodies against cardiovascular receptors increased the risk of the onset of PPCM (OR = 18.786, 95% confidence interval 1.926–183.262, P = 0.012). Conclusions The β1R-AABs and M2R-AABs reveal a significant elevation and are correlated with the increased left ventricular dimension and worse cardiac contraction function. The autoantibodies of cardiovascular receptors are independent risk factors for the onset of PPCM.

Modification of the association between smoking status and severity of coronary stenosis by vitamin D in patients suspected of coronary heart disease

AbstractGiven both smoking and vitamin D are associated with coronary heart disease (CHD) via inflammation and smoking may interfere with the local antiinflammatory effects of vitamin D. We hypothesized that the relationship between smoking and severity of CHD may be modified by vitamin D.A cross-sectional study was conducted. 25-OH vitamin D values were determined in 348 consecutive patients (mean age 62.4 ± 10.5 years; 56.3% male) undergoing coronary angiography at the Heart Center of Chaoyang Hospital affiliated to Capital Medical University between the period of September 2014 and May 2015. We categorized the patients into 2 groups based on 25-OH vitamin D levels, that is, severe hypovitaminosis D (25-OH vitamin D < 10 ng/mL) and higher vitamin D (25-OH vitamin D > =  10 ng/mL). Multivariable logistic regression models were used to estimate odds ratios (ORs) of severe coronary stenosis or higher Gensini score across three smoking status, that is, never smokers, former smokers, and current smokers in severe hypovitaminosis D and higher vitamin D groups, respectively.Of these patients, we identified 212 (60.9%) cases of severe CHD and 161 (46.3%) cases of severe hypovitaminosis D. Multivariable logistic regression model showed the ORs of severe CHD were 1.94 (95% confidence interval [CI]: 0.47, 7.98) for former smokers and 2.62 (95% CI: 0.83, 8.24) for current smokers, compared with never smokers in group with severe hypovitaminosis D (P-trend = 0.005). In contrast, smoking was not found to be significantly associated with severe CHD in group with higher 25-OH vitamin D (P-trend = 0.115). We found a significant interaction between smoking status and vitamin D on presence of severe CHD (P-interaction = 0.015). In terms of Gensini score as a dependent variable, similar results were identified.Our finding indicated the association between smoking and severity of CHD appeared to be substantially stronger among patients with severe hypovitaminosis D as compared with those with higher vitamin D levels. This suggests vitamin D sufficiency may have a protective effect against the damaging effects of smoking on coronary artery. Future cohort studies are warranted to confirm this finding.

Autoantibodies against β1-adrenergic receptor: response to induction therapy with bortezomib-containing regimens for multiple myeloma patients

Abstract This study aims to investigate the predictive value of pre-chemotherapy β1R-AABs by evaluating the response of newly diagnosed symptomatic multiple myeloma (MM) patients to their treatment with a bortezomib-containing regimen. Forty-five de novo MM patients and 50 normal controls (NCs) were prospectively enrolled in this study. Serum titers of β1R-AABs were detected by ELISA. These 45 MM patients were divided into two groups (positive and negative groups) according to their β1R-AABs. Follow-up examinations were performed on these patients during chemotherapy induction. The final analysis covered all 45 MM patients, including 19 patients who were positive for MM and 26 patients who were negative for MM. Multivariate analysis revealed that pre-chemotherapy β1R-AABs are possibly independent predictors for less than very good partial response (VGPR) after the bortezomib-containing regimen treatment (odds ratio: 5.967, 95% confidence interval: 1.513–23.531; p = .011). This study demonstrates for the first time that the presence of β1R-AABs is associated with MM. Pre-chemotherapy β1R-AABs are independent predictors for less than VGPR in de novo MM patients after the bortezomib-containing regimen was administrated. Bortezomib might not significantly give rise to cardiac impairment in MM patients.

Progress in Therapies for Myocardial Ischemia Reperfusion Injury.

BACKGROUND Experimental studies of acute myocardial infarction have revealed that up to half of the final infarct size may be due to reperfusion injury rather than the initial ischemic incident. Research over the past three decades has deepened our understanding of the molecular mechanisms underlying ischemic reperfusion injury and several therapeutic strategies to decrease the incidence and severity of reperfusion injury have been explored. OBJECTIVE To discuss the promising therapies and future perspectives on methods to attenuate myocardial reperfusion injury. RESULTS Existing therapies that address reperfusion can be divided into two major groups comprising nonpharmacological and pharmacological interventions. Myriad pharmacological and nonpharmacological approaches to reduce lethal reperfusion injury have been employed. Although many initial clinical studies were negative, more recent proof-of-concept clinical trials are promising. To date, the most encouraging results are with ischemic postconditioning, remote ischemic preconditioning, ANP, adenosine, cyclosporine and exenatide. CONCLUSION Studies demonstrate that nonpharmacological and pharmacological conditioning can be used together as part of a multifaceted approach to improve clinical outcomes in patients with ischemic heart disease.

Palmitic Acid Increases Endothelin-1 Expression in Vascular Endothelial Cells through the Induction of Endoplasmic Reticulum Stress and Protein Kinase C Signaling

Objective: We investigated the regulation of endothelin-1 (ET-1) expression in in vivo high-fat diet (HFD)-fed mice and in vitro cultured human aortic endothelial cells (HAECs). Methods: Male C57BL/6 mice were fed on standard chow, serum was prepared, and ET-1 levels were analyzed using an ELISA kit. Quantitative PCR was performed using iQ SYBR Green Supermix. Statistical significance was assessed using SPSS, with p < 0.05 considered significant. Results: The serum ET-1 content and endothelial expression of ET-1 mRNA were increased in the HFD-fed mice compared to the chow-fed control mice. Moreover, the mRNA expression of ET-1 was significantly increased in cultured HAECs in response to acute (< 24 h) and chronic (12–16 days) treatments with palmitic acid (PA), one of the most abundant saturated fatty acids in obesity. We found that the induction of ET-1 expression by PA was abolished by pretreating the cells with the endoplasmic reticulum (ER) stress inhibitor 4-phenylbutyric acid or the protein kinase C (PKC) inhibitor Gö 6850. Conclusion: Our findings demonstrate for the first time that PA increases ET-1 expression in endothelial cells through the induction of ER stress and the activation of PKC, providing novel mechanistic insights into the pathogenesis of obesity-associated hypertension and cardiovascular diseases.

A severity index study of long-term prognosis in patients with chronic heart failure

Aims: The present study describes the derivation and validation of the Chronic Heart Failure Severity Index (CHFSI). Main methods: The CHFSI was derived using data obtained from a single‐center prospective cohort study (2000–2014) that enrolled 756 patients. Logistic regression was used to identify independent predictors of mortality and quality of life over a 15‐year follow‐up period. Key findings: The score was validated at the first 5‐year (n = 644), second 5‐year (n = 364), and third 5‐year (n = 262). Independent predictors of mortality were older age (OR = 2.04, P < 0.001), etiology score (OR = 2.61, P < 0.001), faster heart rate (OR = 1.46, P = 0.027), higher systolic blood pressure (OR = 2.35, P < 0.001), and left ventricular ejection fraction ≤45% (OR = 1.97, P = 0.018). The derived CHFSI predicted the mortality, and the AUC for the logistic model was 0.78 (95% confidence interval = 0.74–0.81, P < 0.001). Based on the logistic model, an integer scoring system was derived. Patients were classified into three groups: low risk (0–7 points), intermediate risk (8–11 points) and high risk (≥12 points) groups. The cumulative mortality for 15 years was 45.5% (125/275), 84.0% (204/243), and 100% (99/99), respectively (P < 0.001). The 6‐min walk test revealed a significant difference in quality of life among patients in the low, medium and high risk groups (all, P < 0.0001). Significance: The CHFSI is a very useful clinical predictive tool that identifies patients at risk of future mortality and their quality of life across healthcare systems.

Effect modification of hypertension on the association of vitamin D deficiency with severity of coronary stenosis

Abstract Aims: There may exist an effect modification of hypertension on the relation of vitamin D deficiency with cardiovascular disease. The aim of this study was to investigate this interaction on coronary heart disease. Methods: We investigated 348 consecutive patients (mean age 62.4 ± 10.5 years; 56.3% male) who underwent coronary angiography because of chest discomfort at our heart center. Serum 25-OH vitamin D was also detected by ELISA method in these patients. Multivariable logistic regression models were used to estimate odd ratios (ORs) of CHD across vitamin D levels in hypertensives and normotensives, respectively. Results: We found the multivariable-adjusted ORs of CHD in the bottom(≤8.5 ng/ml) and middle tertiles (8.5–13 ng/ml) of 25-OH vitamin D were 2.86 (95% confidence interval [CI]: 1.38, 5.92) and 1.63 (0.83, 3.20), respectively, compared with those in top tertiles (>13ng/ml) among hypertensives (Ptrend=0.005). In contrast, the corresponding ORs of the above two groups were 0.88 (0.28, 2.74) and 1.23 (0.42, 4.00), respectively, in the normotensives (Ptrend = 0.800; Peffect modification = 0.020). The multivariable-adjusted OR of CHD in patients with severe hypovitaminosis D (<10 ng/ml) versus those with higher vitamin D (≧10 ng/ml) was also greater in hypertensives (2.76; 95% CI: 1.51, 5.04) than that in normotensives (0.92; 95% CI: 0.37, 2.33; Peffect modification=0.013). Similar results were observed when Gensini Score was treated as a dependent variable. Conclusion: Our finding suggests the presence of hypertension may modify the association of vitamin D deficiency with severity of coronary stenosis.