Impact of Pharmacist Interventions on the Long-Term Clinical Outcomes in Patients with Myocardial Infarction.

BACKGROUND: Controlling modifiable risk factors (MRFs) in patients with cardiovascular diseases has been shown to be effective in reducing re-hospitalization rates. The aim of this study was to investigate the rates of controlled MRFs and clinical outcomes after pharmacist interventions in patients with myocardial infarction (MI) after hospital discharge. METHODS: This prospective randomized clinical study was conducted at one medical center in Taiwan, and enrolled patients with MI from January 1, 2012 to December 31, 2014. Patients received medication reconciliation and education from a pharmacist before hospital discharge. The intervention group (IG) received continuous consultations from the pharmacist after discharge, whereas the control group (CG) did not. Primary outcomes included achieving blood pressure < 140/70 mmHg, low-density lipoprotein-cholesterol (LDL-C) < 70 mg/dL, and hemoglobin A1c (HbA1c) < 7% targets. The secondary outcome was major adverse cardiac events (MACEs), defined as re-hospitalization due to MI, unstable angina and stroke. RESULTS: Two hundred and eight patients completed the study protocol (106 in the IG and 102 in the CG). The rate of achieving blood pressure goal was similar between the two groups. More patients in the IG achieved LDL-C and HbA1c goals than those in the CG at 1 year and 2 years post discharge. However, there was no significant difference in the cumulative incidence of MACEs between the two groups (5.7% vs. 9.8%) (p = 0.262). Diabetes was the only independent predictor of re-hospitalization due to a MACE. CONCLUSIONS: Pharmacist interventions led to a higher rate of optimal controlled MRFs but did not significantly reduce the MACE rate in the patients with MI.

Deletion of RasGRF1 Attenuated Interstitial Fibrosis in Streptozotocin-Induced Diabetic Cardiomyopathy in Mice through Affecting Inflammation and Oxidative Stress.

BACKGROUND: Diabetic cardiomyopathy (DCM) is characterized by cardiac fibrosis and stiffness, which often develops into heart failure. This study investigated the role of Ras protein-specific guanine nucleotide releasing factor 1 (RasGRF1) in the development of DCM. METHODS: Forty-eight mice were divided into four groups (n = 12 per group): Group 1: Wild-type (WT) mice, Group 2: RasGRF1 deficiency (RasGRF1-/-) mice. Group 3: Streptozotocin (STZ)-induced diabetic WT mice, Group 4: STZ-induced diabetic RasGRF1-/- mice. Myocardial functions were assessed by cardiac echography. Heart tissues from all of the mice were investigated for cardiac fibrosis, inflammation, and oxidative stress markers. RESULTS: Worse impaired diastolic function with elevation serum interleukin (IL)-6 was found in the diabetic group compared with the non-diabetic groups. Serum IL-6 levels were found to be elevated in the diabetic compared with the non-diabetic groups. However, the diabetic RasGRF1-/- mice exhibited lower serum IL-6 levels and better diastolic function than the diabetic WT mice. The diabetic RasGRF1-/- mice were associated with reduced cardiac inflammation, which was shown by lower invading inflammation cells, lower expression of matrix metalloproteinase 9, and less chemokines compared to the diabetic WT mice. Furthermore, less oxidative stress as well as extracellular matrix deposition leading to a reduction in cardiac fibrosis was also found in the diabetic RasGRF1-/- mice compared with the diabetic WT mice. CONCLUSION: The deletion of RasGRF1 attenuated myocardial fibrosis and improved cardiac function in diabetic mice through inhibiting inflammation and oxidative stress.

The prognostic value of atrial fibrillation on 30-day clinical outcome in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.

This study evaluated the association between atrial fibrillation (AF) and 30-day clinical outcome in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Between January 2005 and October 2009, 783 consecutive patients with acute STEMI undergoing primary PCI were enrolled. Of these patients, 85 (10.9%) with AF during admission were categorized into group 1, while the remaining 698 (89.1%) with sinus rhythm during admission served as group 2. The results demonstrated that the incidence of advanced Killip score (defined as ≥ score 3) and advanced congestive heart failure (defined as ≥ NYHA class 3) were significantly higher, whereas the left ventricular ejection fraction (LVEF) was notably lower in group 1 than in group 2 (all P < 0.003). Additionally, the normal blood flow in the infarct-related artery was notably lower in group 1 than in group 2 (P = 0.003). Moreover, the incidences of new-onset stroke and 30-day mortality were remarkably higher in group 1 than in group 2 (all P < 0.003). Furthermore, Kaplan-Meier analysis demonstrated that the 30-day survival rate was markedly lower in AF patients than in those with sinus rhythm. However, multivariate stepwise Cox regression analysis demonstrated that the advanced Killip score and low LVEF were significantly and independently predictive of 30-day mortality (all P < 0.004). In conclusion, AF was significantly associated with 30-day mortality.

Correction: Melatonin attenuated the brain damage and cognitive impairment partially through MT2 melatonin receptor in mice with chronic cerebral hypoperfusion.

[This corrects the article DOI: 10.18632/oncotarget.20382.].

Calcitriol Attenuates Doxorubicin-Induced Cardiac Dysfunction and Inhibits Endothelial-to-Mesenchymal Transition in Mice.

Doxorubicin (Dox) is an effective anti-neoplasm drug, but its cardiac toxicity limits its clinical use. Endothelial-to-mesenchymal transition (EndMT) has been found to be involved in the process of heart failure. It is unclear whether EndMT contributes to Dox-induced cardiomyopathy (DoIC). Calcitriol, an active form Vitamin D3, blocks the growth of cancer cells by inhibiting the Smad pathway. To investigate the effect of calcitriol via inhibiting EndMT in DoIC, C57BL/6 mice and endothelial-specific labeled mice were intraperitoneally administered Dox twice weekly for 4 weeks (32 mg/kg cumulative dose) and were subsequently treated with or without calcitriol for 12 weeks. Echocardiography revealed diastolic dysfunction at 13 weeks following the first Dox treatment, accompanied by increased myocardial fibrosis and up-regulated pro-fibrotic proteins. Calcitriol attenuated Dox-induced myocardial fibrosis, down-regulated pro-fibrotic proteins and improved diastolic function. Endothelial fate tracing revealed that EndMT-derived cells contributed to Dox-induced cardiac fibrosis. In vitro, human umbilical vein endothelial cells and mouse cardiac fibroblasts were treated with Transforming growth factor (TGF)-ß with or without calcitriol. Morphological, immunofluorescence staining, and Western blot analyses revealed that TGF-ß-induced EndMT and fibroblast-to-myofibroblast transition (FMT) were attenuated by calcitriol by the inhibition of the Smad2 pathway. Collectively, calcitriol attenuated DoIC through the inhibition of the EndMT and FMT processes.

Diabetes Mellitus: An Independent Risk Factor of In-Hospital Mortality in Patients with Infective Endocarditis in a New Era of Clinical Practice.

Infective endocarditis (IE) is a severe disease with a hospital mortality rate of 17%-25%. Early identification of IE patients with high risk of mortality may improve their clinical outcomes. Patients with diabetes mellitus (DM) who develop infective diseases are associated with worse outcomes. This study aimed to define the impact of DM on long-term mortality in IE patients. A total of 412 patients with definite IE from February 1999 to June 2012 were enrolled in this observational study and divided into 2 groups: group 1, patients with DM (n = 72) and group 2, patients without DM (n = 340). The overall in-hospital mortality rate for both groups combined was 20.2% and was higher in group 1 than in group 2 (41.7% vs. 16.5%, p < 0.01). Compared to patients without DM, patients with DM were older and associated with higher incidence of chronic diseases, less drug abuse, higher creatinine levels, and increased risk of Staphylococcus aureus infection (all p < 0.05). Moreover, they were more likely to have atypical clinical presentation and were associated with longer IE diagnosis time (all p < 0.05). In multivariable analysis, DM is an independent and significant predictor of mortality. The prognosis of IE patients with DM is still poor. Early identification and more aggressive treatment may be considered in IE patients with DM.

Liraglutide Inhibits Endothelial-to-Mesenchymal Transition and Attenuates Neointima Formation after Endovascular Injury in Streptozotocin-Induced Diabetic Mice.

Hyperglycaemia causes endothelial dysfunction, which is the initial process in the development of diabetic vascular complications. Upon injury, endothelial cells undergo an endothelial-to-mesenchymal transition (EndMT), lose their specific marker, and gain mesenchymal phenotypes. This study investigated the effect of liraglutide, a glucagon-like peptide 1 (GLP-1) receptor agonist, on EndMT inhibition and neointima formation in diabetic mice induced by streptozotocin. The diabetic mice with a wire-induced vascular injury in the right carotid artery were treated with or without liraglutide for four weeks. The degree of neointima formation and re-endothelialisation was evaluated by histological assessments. Endothelial fate tracing revealed that endothelium-derived cells contribute to neointima formation through EndMT in vivo. In the diabetic mouse model, liraglutide attenuated wire injury-induced neointima formation and accelerated re-endothelialisation. In vitro, a high glucose condition (30 mmol/L) triggered morphological changes and mesenchymal marker expression in human umbilical vein endothelial cells (HUVECs), which were attenuated by liraglutide or Activin receptor-like 5 (ALK5) inhibitor SB431542. The inhibition of AMP-activated protein kinase (AMPK) signaling by Compound C diminished the liraglutide-mediated inhibitory effect on EndMT. Collectively, liraglutide was found to attenuate neointima formation in diabetic mice partially through EndMT inhibition, extending the potential therapeutic role of liraglutide.

Melatonin attenuated the brain damage and cognitive impairment partially through MT2 melatonin receptor in mice with chronic cerebral hypoperfusion.

BACKGROUND: Vascular cognitive impairment (VCI) is a spectrum of cognitive impairment caused by various chronic diseases including aging, hypertension, and diabetes mellitus. Oxidative and inflammatory reactions induced by chronic cerebral hypoperfusion (CHP) are believed to cause VCI. Melatonin is reported to possess anti-oxidation and anti-inflammation effects. This study was designed to investigate the effect and mechanisms of melatonin in CHP mice model. RESULTS: The behavioral function results revealed that CHP mice were significantly impaired when compared with the control. Melatonin improved the cognitive function, but the addition of MT2 receptor antagonist reversed the improvement. The IHC staining showed melatonin significantly improved WM lesions and gliosis in CHP mice. Again, the addition of MT2 receptor antagonist to melatonin worsened the WM lesion and gliosis. Similar results were also found for mRNA and protein expressions of oxidative reaction and inflammatory cytokines. MATERIALS AND METHOD: Forty C57BL/6 mice were divided into four groups: Group 1: sham control; Group 2: CHP mice; Group 3: CHP with melatonin treatment; Group 4: CHP-melatonin and MT2 receptor antagonist (all groups n = 10). Working memory was assessed with Y-arm test at day-28 post-BCAS (bilateral carotid artery stenosis). All mice were sacrificed at day-30 post-BCAS. The immunohistochemical (IHC) staining was used for white matter (WM) damage and gliosis. The expression of mRNA and proteins about inflammatory and oxidative reaction were measured and compared between groups. CONCLUSIONS: Partially through MT2 receptor, melatonin is effective for CHP-induced brain damage.

No correlation between body mass index and 30-day prognostic outcome in Asians with acute ST-elevation myocardial infarction undergoing primary coronary intervention.

BACKGROUND: This study investigated whether body mass index (BMI) was a risk factor predictive of 30-day prognostic outcome in Asians with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). MATERIAL AND METHODS: Data regarding the impact of BMI on the prognostic outcome in Asian populations after acute STEMI is scarce. A number of 925 STEMI patients were divided into three groups according to the BMI: normal weight (<25 kg/m2), overweight (≥25.0 to <30.0 kg/m2) and obese (≥30.0 kg/m2). RESULTS: The obese group was significantly younger with significantly higher incidences of smoking and diabetes mellitus. The incidences of multi-vessel disease, final thrombolysis in myocardial infarction (TIMI)-3 flow, advanced Killip score, advance congestive heart failure, 30-day mortality and combined 30-day major adverse clinical outcome (MACO) did not differ among the three groups. Multiple regression analysis showed the age, unsuccessful reperfusion and lower left ventricular ejection fraction were most significant and independent predictor of 30-day mortality. CONCLUSION: BMI is not a predictor of 30-day prognostic outcome in Asians with STEMI undergoing primary PCI.

The risk of atrial fibrillation in patients with gout: a nationwide population-based study.

Many studies have found that systemic inflammation plays an important role in the pathogenesis of atrial fibrillation (AF). Gout is a chronic systemic inflammatory disorder, but little evidence exists regarding whether the risk of AF is increased in patients with gout. The National Health Insurance Research Database in Taiwan was used in this study, and gout was defined as the occurrence of at least one episode of an acute gout attack requiring medical treatment. A total of 63264 gout and 63264 age- and gender-matched patients were included as the study population. The Cox model was used to evaluate the risk of AF in patients with gout. Patients with gout experienced a greater frequency of co-morbidities compared to patients without gout. The cumulative incidences of AF were 4.61% and 3.04% in patients with and without gout, respectively (log-rank test, P < 0.001). After adjusting for co-morbidities and prescription medication use, gout was found to be associated with AF [hazard ratio (HR), 1.38]. Moreover, the HR for AF decreased with increasing age in our study. Gout was found to be associated with an increased risk of developing AF after adjusting for potential confounders.

Validation of Scoring Systems That Predict Outcomes in Patients With Coronary Artery Disease Undergoing Coronary Artery Bypass Grafting Surgery.

Several risk stratification scores, based on angiographic or clinical parameters, have been developed to evaluate outcomes in patients with left main coronary artery disease (LMCAD) who undergo coronary artery bypass grafting (CABG). This study aims to validate the predictive ability of different risk scoring systems with regard to long-term outcomes after CABG. This single-center study retrospectively re-evaluated the Synergy Between PCI with TAXUS and Cardiac Surgery (SYNTAX) score; EuroSCORE; age, creatinine, and ejection fraction (ACEF) score; modified ACEF score; clinical SYNTAX; logistic clinical SYNTAX score (logistic CSS); and Parsonnet scores for 305 patients with LMCAD who underwent CABG. The endpoints were 5-year rate of all-cause death and major adverse cardio-cerebral events (MACCEs), including cardiovascular (CV) death, myocardial infarction (MI), and stroke and target vessel revascularization (TVR). Compared with the SYNTAX score, other scores were significantly higher in discriminative ability for all-cause death (SYNTAX vs others: P < 0.01). The EuroSCORE ≥6 showed significant outcome difference on all-cause death, CV death, MI, and MACCE (P < .01). Multivariate analysis indicated the SYNTAX score was a non-significant predictor for different outcomes. Adjusted multivariate analysis revealed that the EuroSCORE was the strongest predictor of all-cause death (hazard ratio[HR]: 1.17; P < 0.001), CV death (HR: 1.16; P < 0.001), and MACCE (HR: 1.09; P = 0.01). The ACEF score and logistic CSS were predictive factors for TVR (HR: 0.25, P = 0.03; HR: 0.85, P = 0.01). The EuroSCORE scoring system most accurately predicts all-cause death, CV death, and MACCE over 5 years, whereas low ACEF score and logistic CSS are independently associated with TVR over the 5-year period following CABG in patients with LMCAD undergoing CABG.

Safety and feasibility of coronary stenting in unprotected left main coronary artery disease in the real world clinical practice--a single center experience.

BACKGROUND: This study evaluated the feasibility, safety, and prognostic outcome in patients with significant unprotected left main coronary artery (ULMCA) disease undergoing stenting. METHOD AND RESULTS: Between January 2010 and December 2012, totally 309 patients, including those with stable angina [13.9% (43/309)], unstable angina [59.2% (183/309)], acute non-ST-segment elevation myocardial infarction (NSTEMI) [24.3% (75/309)], and post-STEMI angina (i.e., onset of STEMI<7 days) [2.6% (8/309)] with significant ULMCA disease (>50%) undergoing stenting using transradial arterial approach, were consecutively enrolled. The patients' mean age was 68.9±10.8 yrs. Incidences of advance congestive heart failure (CHF) (defined as ≥ NYHA Fc 3) and multi-vessel disease were 16.5% (51/309) and 80.6% (249/309), respectively. Mechanical supports, including IABP for critical patients (defined as LVEF <35%, advanced CHF, or hemodynamically unstable) and extra-corporeal membrane oxygenator (ECMO) for hemodynamically collapsed patients, were utilized in 17.2% (53/309) and 2.6% (8/409) patients, respectively. Stent implantation was successfully performed in all patients. Thirty-day mortality rate was 4.5% (14/309) [cardiac death: 2.9% (9/309) vs. non-cardiac death: 1.6% (5/309)] without significant difference among four groups [2.3% (1) vs. 2.7% (5) vs. 9.3% (7) vs. 12.5% (1), p = 0.071]. Multivariate analysis identified acute kidney injury (AKI) as the strongest independent predictor of 30-day mortality (p<0.0001), while body mass index (BMI) and white blood cell (WBC) count were independently predictive of 30-day mortality (p = 0.003 and 0.012, respectively). CONCLUSION: Catheter-based LM stenting demonstrated high rates of procedural success and excellent 30-day clinical outcomes. AKI, BMI, and WBC count were significantly and independently predictive of 30-day mortality.