Hongya Han

Influence of abnormal fasting plasma glucose on left ventricular function in older patients with acute myocardial infarction.

We assessed whether the admission fasting plasma glucose (FPG) levels were associated with all-cause mortality and left ventricular (LV) function in older patients with acute myocardial infarction (AMI). A total of 1854 consecutive patients were categorized into 4 groups: hypoglycemia, euglycemia, mild hyperglycemia, and severe hyperglycemia. The primary outcomes were in-hospital/3-year mortality and LV function. There was a near-linear relationship between FPG and Killip class. However, no significant correlation was found between FPG levels and LV ejection fraction. Both FPG levels and Killip classes were all independent significant predictors of mortality. Compared with the euglycemia group, both the hypo- and hyperglycemia groups were associated with higher in-hospital and 3-year mortality. In older patients with AMI, the FPG values had differential influences on LV function and mortality. There was a U-shaped relationship between FPG and in-hospital/3-year mortality, and a near-linear relationship between increased admission glucose levels and higher Killip classification.

Rapamycin Affects Tissue Plasminogen Activator and Plasminogen Activator Inhibitor 1 Expression: A Potential Prothrombotic Mechanism of Drug-Eluting Stents

Although drug-eluting stents (DESs) can decrease the risk of restenosis, this benefit is tempered by a possible increased risk of in-stent thrombosis. We assessed the effects of rapamycin on human umbilical vein endothelial cells (HUVECs) to identify the alterations in gene expression associated with thrombosis. Expression of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1) was assessed in HUVECs treated with rapamycin (final concentrations: 1, 10, 100, and 1000 ng/mL) for 24 and 48 hours. Incubation of HUVECs with rapamycin strongly reduced the expression of t-PA in a concentrationdependant manner (P < .05 to < .01). However, the expression of PAI-1 was induced by rapamycin (P < .05 to < .01). The increase in PAI-1 induction was up to 3.3-fold. In conclusion, rapamycin inhibited t-PA and induced PAI-1 expression in HUVECs. This effect may contribute to in-stent thrombosis associated with DESs.Although drug-eluting stents (DESs) can decrease the risk of restenosis, this benefit is tempered by a possible increased risk of in-stent thrombosis. We assessed the effects of rapamycin on human umbilical vein endothelial cells (HUVECs) to identify the alterations in gene expression associated with thrombosis. Expression of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1) was assessed in HUVECs treated with rapamycin (final concentrations: 1, 10, 100, and 1000 ng/mL) for 24 and 48 hours. Incubation of HUVECs with rapamycin strongly reduced the expression of t-PA in a concentration-dependant manner (P < .05 to < .01). However, the expression of PAI-1 was induced by rapamycin (P < .05 to < .01). The increase in PAI-1 induction was up to 3.3-fold. In conclusion, rapamycin inhibited t-PA and induced PAI-1 expression in HUVECs. This effect may contribute to in-stent thrombosis associated with DESs.

Effect of Abnormal Fasting Plasma Glucose Level on All-Cause Mortality in Older Patients With Acute Myocardial Infarction: Results From the Beijing Elderly Acute Myocardial Infarction Study (BEAMIS)

OBJECTIVE To assess whether the relationship between abnormal fasting plasma glucose (FPG) levels and patient outcomes holds for both older men and older women with acute myocardial infarction (AMI). PATIENTS AND METHODS From April 1, 2004, to October 31, 2006, a total of 2016 consecutive older patients (age ≥65 years) presenting with AMI were screened. Of these patients, 1854 were consecutively enrolled in the study. Patients were categorized into 4 groups: the hypoglycemic group (FPG, ≤90.0 mg/dL [to convert to mmol/L, multiply by 0.0555]; n=443, 23.9%), the euglycemic group (FPG, 90.1-126.0 mg/dL; n=812, 43.8%), the mildly hyperglycemic group (FPG, 126.1-162.0 mg/dL; n=308, 16.6%), and the severely hyperglycemic group (FPG, ≥162.1 mg/dL; n=291, 15.7%). The primary outcomes were rates of in-hospital and 3-year mortality. RESULTS Female patients were older and had a higher incidence of diabetes mellitus but lower rates of smoking and use of invasive therapy. Men tended to have a higher frequency of hypoglycemia, whereas women tended to have a higher frequency of hyperglycemia. No significant difference was found in in-hospital (10.9% vs 9.1%; P=.36) or 3-year (24.5% vs 24.5%; P=.99) mortality between male and female patients, and FPG-associated mortality did not vary significantly by sex. CONCLUSION An increased FPG level was associated with a relatively higher risk of in-hospital mortality in men but not in women. Nonetheless, increased and decreased FPG levels at admission could predict higher mortality rates regardless of sex. There was a striking U-shaped relationship between FPG levels and in-hospital and 3-year mortality. The effect of abnormal FPG level on outcomes among older patients with AMI did not vary significantly by sex.

Preconditioning With Tauroursodeoxycholic Acid Protects Against Contrast-Induced HK-2 Cell Apoptosis by Inhibiting Endoplasmic Reticulum Stress.

To investigate whether tauroursodeoxycholic acid (TUDCA) could attenuate contrast media (CM)-induced renal tubular cell apoptosis by inhibiting endoplasmic reticulum stress (ERS), we exposed HK-2 cells to increasing doses of meglumine diatrizoate (20, 40, and 80 mg I/mL) for 2 to 16 hours, with/without TUDCA preconditioning for 24 hours. Cell viability test, Hoechst 33258 staining, and flow cytometry were used to detect meglumine diatrizoate-induced cell apoptosis, while real-time polymerase chain reaction and Western blot analysis were used to measure the expressions of ERS markers of glucose-regulated protein 78 (GRP78), activating transcription factor 4 (ATF4), and the apoptosis-related marker of caspase 12. Cell apoptosis and messenger RNA (mRNA) expression of GRP78 (P = .005), ATF4 (P = .01), and caspase 12 (P = .001) were significantly higher in the CM 4 hours group than the control as well as the protein expressions. The TUDCA preconditioning reduced the mRNA expression of GRP78, ATF4, and caspase 12 in the CM 4 hours groups (P = .009, .019, and .003, respectively) as well as the protein expression. In conclusion, TUDCA could protect renal tubular cells from meglumine diatrizoate-induced apoptosis by inhibiting ERS.

Valsartan protects HK-2 cells from contrast media-induced apoptosis by inhibiting endoplasmic reticulum stress.

Contrast‐induced acute kidney injury (CI‐AKI) is associated with increasing in‐hospital and long‐term adverse clinical outcomes in high‐risk patients undergoing percutaneous coronary intervention (PCI). Contrast media (CM)‐induced renal tubular cell apoptosis is reported to participate in this process by activating endoplasmic reticulum (ER) stress. An angiotensin II type 1 receptor (AT1R) antagonist can alleviate ER stress‐induced renal apoptosis in streptozotocin (STZ)‐induced diabetic mice and can reduce CM‐induced renal apoptosis by reducing oxidative stress and reversing the enhancement of bax mRNA and the reduction of bcl‐2 mRNA, but the effect of the AT1R blocker on ER stress in the pathogenesis of CI‐AKI is still unknown. In this study, we explored the effect of valsartan on meglumine diatrizoate‐induced human renal tubular cell apoptosis by measuring changes in ER stress‐related biomarkers. The results showed that meglumine diatrizoate caused significant cell apoptosis by up‐regulating the expression of ER stress markers, including glucose‐regulated protein 78 (GRP78), activating transcription factor 4 (ATF4), CCAAT/enhancer‐binding protein‐homologous protein (CHOP) and caspase 12, in a time‐ and dose‐dependent manner, which could be alleviated by preincubation with valsartan. In conclusion, valsartan had a potential nephroprotective effect on meglumine diatrizoate‐induced renal cell apoptosis by inhibiting ER stress.

Safety and feasibility of transradial approach for coronary bypass graft angiography and intervention.

The transradial approach (TRA) is commonly applied for coronary catheterization. However, there are few reports on the safety and feasibility of transradial catheterization in patients with prior coronary artery bypass graft (CABG) surgery. We retrospectively evaluated 124 consecutive patients who underwent graft angiography and intervention via the transradial (TRA group, n = 68) or transfemoral approach (TFA group, n = 56). The baseline clinical characteristics between the 2 groups were similar except for prior myocardial infarction. No significant difference (P > .05)was observed in procedure time, the success rate of puncture, angiography, and intervention procedure between the 2 groups. There was no significant difference in major adverse cardiac and cerebrovascular events during hospitalization. However, the vascular access site complications were significantly lower (P = .021) and the duration of hospitalization was shorter (P = .007) in the TRA group. The TRA for coronary bypass graft angiography and intervention was safe and feasible.

High Clopidogrel Dose in Patients With Chronic Kidney Disease Having Clopidogrel Resistance After Percutaneous Coronary Intervention

We evaluated the impact of clopidogrel 150 mg/d in patients with chronic kidney disease (CKD) having clopidogrel resistance (CR) after percutaneous coronary intervention (PCI); 1076 consecutive patients with coronary artery disease (CAD) having CKD were enrolled. Maximal platelet aggregation (MPA) was assessed before, 24 hours, and 30 days after a 300-mg loading dose of clopidogrel prior to PCI. After PCI, 370 patients with CR were randomized to receive clopidogrel 75 mg/d (n = 184) or 150 mg/d (n = 186) for 30 days. Stent thrombosis (ST), major adverse cardiac events (MACEs), and bleeding were analyzed after 1 month. Patients in the 150 mg group had significant lower rates of ST and MACE. There was no significant difference in major or minor bleeding. Patients in the 150 mg group had lower MPA and greater inhibition of platelet aggregation. One-month administration of 150 mg/d of clopidogrel decreases the rate of ST and MACE without increasing bleeding in patients with CKD having CR after PCI.

Clinical predictors for progression of nonintervened nonculprit coronary lesions despite low-density lipoprotein cholesterol less than 1.8 mmol/l after successful stent implantation.

ObjectiveDespite achieving very low levels of low-density lipoprotein cholesterol (LDL-C), many patients continue to show disease progression. We sought to characterize the clinical factors that correlate with nonculprit lesion plaque progression in patients with LDL-C level less than 1.8 mmol/l. MethodsBetween May 2006 and December 2009, 653 patients met the following criteria: (i) underwent coronary angiograms again with a time interval from 6 months to 2 years after successful stent implantation, (ii) less than 50% stenoses of nonintervened nonculprit coronary lesions (NCLs), (iii) follow-up LDL-C levels less than 1.8 mmol/l. Patients were classified as progressors [NCL–percutaneous coronary intervention (PCI)] or nonprogressors (non-NCL-PCI). ResultsFive patients with de novo NCL and 87 patients with preexisting NCL developed progression. Progressors had higher percentage of acute coronary syndrome (ACS), multivessel diseases and triglycerides (TGs) at baseline PCI. At follow-up, a significant difference was observed between progressors and nonprogressors in TG (1.73 vs. 1.32 mmol/l, P<0.001), change in TG (−0.18±1.01 vs. −0.42±1.02 mmol/l, P=0.032), high-density lipoprotein cholesterol (HDL-C) (0.98±0.22 vs. 1.08±0.25 mmol/l, P=0.001) and change in HDL-C (0.11±0.17 vs. 0.19±0.27 mmol/l, P<0.001). Multivariate logistic regression analysis revealed that ACS, multivessel diseases, on-treatment TG and HDL-C and smaller increases in HDL-C were independent predictors for progression. ConclusionDespite attainment of LDL-C level less than 1.8 mmol/l, NCL had still progressed, mainly in preexisting NCL rather than de novo NCL. ACS, multivessel diseases, on-treatment TG, HDL-C and smaller increases in HDL-C were associated with the NCL progression. This finding highlights the need for intensive modification of global risk in patients with coronary artery disease.

Protective Role of Statins in Patients With Acute Coronary Syndrome Aged ≥75 Years With Low LDL-C Who Underwent Percutaneous Coronary Intervention

The effect of statins in patients with acute coronary syndrome (ACS) at advanced age with lower low-density lipoprotein cholesterol (LDL-C) levels undergoing percutaneous coronary intervention (PCI) remains unknown. We evaluated the effect of statins in 220 Chinese patients with ACS aged ≥75 years with low LDL-C undergoing PCI. Biomarkers were measured before and 6 hours after PCI, and patients were followed up for 1 year. Biomarkers in the statin group at 6 hours post-PCI were lower than controls (creatine kinase-myocardial band 14.2 ± 5.78 vs 47.3 ± 16.4 IU/L, P = .03; cardiac troponin I 0.36 ± 0.12 vs 1.33 ± 0.47 ng/mL, P = .01; and high-sensitivity C-reactive protein 7.6 ± 4.3 vs 13.6 ± 4.5 mg/L, P = .001, respectively). Significant differences were found in major adverse cardiac events at 1 year (P = .02-.01), while target lesion revascularization alone was less at 3 months between the 2 groups (P = .03). This study demonstrates that elderly patients with ACS having low LDL-C benefit from statins regardless of type, dosage, and duration of statin administration prior to PCI.

Optimal Revascularization Threshold of Fractional Flow Reserve and its Effect on Outcomes: Perspectives From a High-Volume Center in China

This study aimed to investigate the favorable revascularization threshold for fractional flow reserve (FFR) in daily practice. Between March 2013 and March 2017 in a high-volume center in China, 903 patients with 1210 lesions underwent coronary intervention with adjunctive FFR and were consecutively enrolled. The mean FFR was 0.80 ± 0.11, revascularization was deferred for 68% of lesions, and the median follow-up period was 21 months. For lesions with an FFR > 0.80, deferral of revascularization appeared safe. In contrast, for lesions with an FFR ≤ 0.80, deferral of revascularization was associated with a greater risk of target lesion failure (TLF) than revascularization (hazard ratio [HR] 4.63, 95% confidence interval [CI] 2.02-10.06, P < .001). For lesions with an FFR value in the gray-zone (0.76-0.80), medical treatment alone was less effective than revascularization (P = .020). For deferred lesions, FFR was an independent predictor for the future risk of TLF, when data were categorized (HR [FFR ≤ 0.75 vs FFR ≥ 0.86] 3.35, 95% CI 1.13-9.97, P = .030; HR [FFR 0.76-0.80 vs FFR ≥ 0.86] 4.01, 95% CI 1.73-9.31, P = .001) or continuous (HR 0.004, 95% CI 0.00-0.13, P = .002). Thus, an FFR value of 0.80 appears to be the optimal threshold for decision-making regarding revascularization and risk stratification.