Clinical Efficacy of Pre-Hospital Electrocardiogram Transmission in Patients Undergoing Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction.

Rapid reperfusion by primary percutaneous coronary intervention (pPCI) is an established strategy for the treatment of patients with ST-segment elevation myocardial infarction (STEMI). Pre-hospital electrocardiogram (PH-ECG) transmission by the emergency medical services (EMS) facilitates timely reperfusion in these patients. However, evidence regarding the clinical benefits of PH-ECG in individual hospitals is limited.This retrospective, observational study investigated the clinical efficacy of PH-ECG in STEMI patients who underwent pPCI. Of a total of 382 consecutive STEMI patients, 237 were enrolled in the study and divided into 2 groups: a PH-ECG group (n = 77) and non-PH-ECG group (n = 160). Door-to-balloon time (D2BT) was significantly shorter in the PH-ECG group (66 [52-80] min), compared to the non-PH-ECG group (70 [57-88] minutes, P = 0.01). The 30-day all-cause mortality rate was 6% in the PH-ECG group, which was significantly lower than that in the non-PH-ECG group (16%) (P = 0.037, hazard ratio [HR]: 0.38, 95% CI: 0.15-0.98). This trend was particularly evident in severely ill patients when stratified by GRACE score.The use of PH-ECG improved the survival rate of STEMI patients undergoing pPCI due to the improved pre-arrival preparation based on the EMS information. Coordination between EMS and PCI-capable institutes is essential for the management of PH-ECG.

Safety and efficacy of uninterrupted treatment with edoxaban or warfarin during the peri-procedural period of catheter ablation for atrial fibrillation.

BACKGROUND: The real-world safety and efficacy of uninterrupted anticoagulation treatment with edoxaban (EDX) or warfarin (WFR) during the peri-procedural period of catheter ablation (CA) for atrial fibrillation (AF) are yet to be investigated. METHODS: We conducted a two-center experience, observational study to retrospectively investigate consecutive patients who underwent CA for AF and received EDX or WFR. We examined the incidence of thromboembolic and bleeding complications during the peri-procedural period. RESULTS: The EDX and WFR groups included 153 and 103 patients, respectively (total: 256 patients). Demise or thromboembolic events did not occur in either of the groups. The incidence of major bleeding in the EDX and WFR groups was 0.7% and 2.9%, respectively. The total incidence of major/minor bleeding in the EDX and WFR groups was 7.8% and 8.7%, respectively. Of note, the incidence of bleeding complications in the uninterrupted WFR strategy group was markedly high in patients with an estimated glomerular filtration rate (eGFR) <30 (75%) or a HAS-BLED score ≥3 (60%). Patients with eGFR ≥30 and a HAS-BLED score ≤2 had a lower incidence of bleeding (<10%), regardless of the administered anticoagulation drug (EDX or WFR). CONCLUSIONS: This study confirmed the safety and efficacy of uninterrupted anticoagulation therapy using EDX or WFR in real-world patients undergoing CA for AF. Patients with severely impaired renal function and/or a higher bleeding risk during uninterrupted therapy with WFR were at a prominent risk of bleeding. Therefore, particular attention should be paid in the treatment of these patients.

Effect of Smoking Status on Monocyte Tissue Factor Activity, Carotid Atherosclerosis and Long-Term Prognosis in Metabolic Syndrome.

BACKGROUND: Smoking increases the risk of atherothrombotic events. Tissue factor (TF) mainly expressed on monocytes plays an important role in thrombosis and atherosclerosis. Metabolic syndrome (MetS) is being increasingly recognized as a major atherothrombotic risk factor, but the effects of smoking on monocyte TF activity (MTFA), carotid atherosclerosis estimated on carotid intima-media thickness (CIMT), and long-term prognosis in MetS remain unclear.Methods and Results:A total of 301 MetS patients lacking any known cardiovascular disease were prospectively investigated and classified into 4 groups according to smoking status at entry and at 12 months as follows: never smokers, past smokers, quitters, and persistent smokers. Peripheral blood mononuclear cells (PBMC) were isolated, and MTFA was measured using a coagulation assay. Linear trends for higher baseline MTFA and CIMT were observed among persistent smokers, quitters, and past smokers compared with never smokers. At 12 months, MTFA and CIMT decreased in never and past smokers and quitters but increased in persistent smokers. Six acute myocardial infarctions and 8 strokes occurred during a median follow-up of 66.0 months. Persistent smoking was associated with an increased risk of events (P<0.001). CONCLUSIONS: Smoking is associated with upregulated MTFA and progression of CIMT, which may be related to the risk of atherothrombotic events in MetS patients.

Serum Tartrate-resistant Acid Phosphatase-5b Levels are Associated with the Severity and Extent of Coronary Atherosclerosis in Patients with Coronary Artery Disease.

AIMS: Tartrate-resistant acid phosphatase (TRACP)-5b and osteoprotegerin (OPG) are specific and sensitive markers of bone resorption in patients with rheumatoid arthritis (RA) and chronic kidney disease (CKD). The TRACP-5b level is associated with the severity of RA and CKD, while the OPG level is associated with the severity of coronary atherosclerosis and calcification, and can predict a poor outcome in patients with coronary artery disease (CAD). However, the impact of TRACP-5b on coronary atherosclerosis in CAD patients remains unclear. METHODS: A total of 71 CAD patients (57 men, 14 women; mean age: 69.0±9.7 years) and 28 age- and gender- matched healthy subjects were investigated. The number of diseased vessels (a marker of the severity of coronary atherosclerosis) and the Gensini score (a marker of the extent of coronary atherosclerosis), as well as the OPG and TRACP-5b levels were measured in CAD patients. The TRACP-5b levels were classified into quartiles. RESULTS: The TRACP-5b levels were significantly higher in CAD patients than in healthy subjects. Patients with higher TRACP-5b levels had higher OPG levels and Gensini scores than those with lower TRACP-5b levels. Higher TRACP-5b levels were associated with an increased number of diseased vessels. A multivariate linear regression analysis showed that the OPG level and the number of diseased vessels or the Gensini score were significantly and independently associated with the TRACP-5b level. CONCLUSIONS: These data indicate that the TRACP-5b level is significantly associated with the OPG level and with the severity and extent of coronary atherosclerosis in CAD patients.

Nutritional Status is Associated with Inflammation and Predicts a Poor Outcome in Patients with Chronic Heart Failure.

AIM: Malnutrition has been identified to be an independent predictor of morbidity and mortality in patients with chronic heart failure (CHF). However, the pathophysiological mechanisms underlying this pathway remain unclear. METHODS: Nutritional screening was performed using the controlling nutritional status (CONUT) score, which was calculated using the serum albumin and total cholesterol levels and lymphocyte number, in 114 CHF patients with a mean left ventricular ejection fraction of 26.6%±6.4%. The carotid intima-media thickness (CIMT) is correlated with carotid atherosclerosis and is a significant predictor of future cardiovascular events. Peripheral blood mononuclear cells (PBMCs) were isolated, and the production of monocyte tumor necrosis factor (TNF)-α was measured and expressed as mean±SD (pg/mL/10(6) PBMCs). RESULTS: A multivariate linear regression analysis showed that the production of monocyte TNF-α (ß coefficient=0.434, p＜0.001) and mean CIMT (ß coefficient=0.204, p=0.006) were independent determinants of the CONUT score. During a median follow-up of 67.5 months, 45 patients experienced cardiac events, including 16 cardiac deaths and 29 readmissions for worsening CHF. A multivariate Cox hazard analysis demonstrated that a monocyte TNF-α level of ≥4.1 pg/mL/10(6) PBMCs (hazard ratio (HR), 14.10; 95% confidence interval (CI), 2.55-77.92; p=0.002) and CONUT score of ≥3 (HR, 11.97; 95% CI, 2.21-64.67; p=0.004) were independently associated with the incidence of cardiac events. CONCLUSIONS: These data indicate that a poor nutritional status as assessed using the CONUT score and atherosclerosis as indicated by CIMT is significantly associated with inflammation and predicts poor outcomes in patients with CHF.

Osteoprotegerin is Associated With Endothelial Function and Predicts Early Carotid Atherosclerosis in Patients With Coronary Artery Disease.

Osteoprotegerin (OPG) is a soluble glycoprotein belonging to the tumor necrosis factor receptor superfamily and is linked to vascular atherosclerosis and calcification. The carotid intima-media thickness (CIMT) correlates with carotid atherosclerosis and is a significant predictor of cardiovascular events. The OPG levels are associated with the CIMT in coronary artery disease (CAD) patients. However, the pathophysiological mechanisms underlying this pathway remain unclear. We investigated 114 CAD patients (89 men, 25 women; mean age: 68.7 ± 10.3 years) and measured the Gensini score (a marker of the extent of coronary atherosclerosis), the mean CIMT and the plasma levels of OPG and asymmetric dimethylarginine (ADMA; a marker of endothelial function). Early carotid atherosclerosis was defined as a mean CIMT > 1.0 mm. Only 33 of the 114 patients (28.9%) had early carotid atherosclerosis. Patients with early carotid atherosclerosis had higher OPG levels than those without. The OPG levels were found to be significantly associated with ADMA (r = 0.191, P = 0.046) and the mean CIMT (r = 0.319, P = 0.001), but not with the Gensini score. A receiver operating curve analysis revealed the optimal cut-off value of the OPG levels for predicting early carotid atherosclerosis to be 100 pmol/L. A multivariate logistic regression analysis showed OPG ≥ 100 pmol/L to be significantly and independently associated with early carotid atherosclerosis (odds ratio: 2.98, 95% confidence interval: 1.22-7.20, P = 0.017). These data indicate that OPG is significantly associated with endothelial function and predicts early carotid atherosclerosis in patients with CAD.

Differential Effects of Atorvastatin and Pitavastatin on Inflammation, Insulin Resistance, and the Carotid Intima-Media Thickness in Patients with Dyslipidemia.

AIMS: 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have multiple pleiotropic effects, such as anti-inflammatory and vascular endothelium protection, that are independent of their low-density-lipoprotein (LDL) cholesterol lowering effects. However, whether different statins exert diverse effects on inflammation, insulin resistance, and the progression of carotid atherosclerosis [as indicated by the intima-media thickness (CIMT)] in patients with dyslipidemia remains unclear. METHODS: A total of 146 patients with hypercholesterolemia without known cardiovascular disease were randomly assigned to receive 5 mg/day of atorvastatin (n=73) or 1 mg/day of pitavastatin (n=73). RESULTS: At baseline, age, gender, blood pressure, lipid profiles, and the serum monocyte chemoattractant protein (MCP)-1, homeostasis model assessment of insulin resistance (HOMA-IR) and CIMT values were comparable between the groups. After 12 months of treatment, atorvastatin and pitavastatin equally reduced the LDL cholesterol levels; however, atorvastatin increased the HOMA-IR by ＋26% and pitavastatin decreased this parameter by －13% (p＜0.001). The MCP-1 values were reduced by －28% in the patients treated with pitavastatin and only －11% in those treated with atorvastatin (p=0.016). A greater percent decrease in the mean CIMT from baseline was observed in the patients treated with pitavastatin than in those treated with atorvastatin (－4.9% vs. －0.5%, p=0.020). CONCLUSIONS: These data indicate that, while these agents significantly and equally reduce the LDL cholesterol levels, atorvastatin and pitavastatin have different effects on inflammation, insulin resistance, and the progression of carotid atherosclerosis in patients with dyslipidemia.

Relationships between the serum cholesterol levels, production of monocyte proinflammatory cytokines and long-term prognosis in patients with chronic heart failure.

OBJECTIVE: Low serum cholesterol is associated with a poor prognosis in patients with chronic heart failure (CHF). However, the relationships between the serum cholesterol level, production of monocyte proinflammatory cytokines and long-term prognosis in CHF patients remain unclear. METHODS: A total of 95 CHF patients who had not been treated with statins and had a mean left ventricular ejection fraction of 26.0±6.0% were examined. Peripheral blood mononuclear cells (PBMCs) were isolated, and the production of monocyte tumor necrosis factor (TNF)-α and interleukin (IL)-6 was measured and expressed as the mean ± SD (pg/mL/10(6) PBMCs). RESULTS: The production of monocyte TNF-α and IL-6 was found to be significantly and negatively associated with the serum low-density lipoprotein (LDL)-cholesterol level (TNF-α: r=-0.515, p<0.001, IL-6: r=-0.419, p<0.001). During a median follow-up of 66.0 months, 49 patients developed cardiac events, including 21 cardiac deaths and 28 readmissions for worsening CHF. A multivariate Cox hazard analysis showed that a monocyte TNF-α level of ≥4.9 pg/mL/10(6) PBMCs [hazard ratio (HR) 187.38, 95% confidence interval (CI) 7.92-4,434.94, p=0.001] and LDL-cholesterol level of <120 mg/dL (HR 9.41, 95% CI 1.02-86.66, p=0.048) were independently associated with the incidence of cardiac events. CONCLUSION: Low LDL-cholesterol and the upregulation of monocyte proinflammatory cytokine production are both significantly and independently associated with poor outcomes in CHF patients.

Effects of eicosapentaenoic acid on the levels of inflammatory markers, cardiac function and long-term prognosis in chronic heart failure patients with dyslipidemia.

AIMS: The effects of eicosapentaenoic acid (EPA) on the levels of inflammatory markers, cardiac function and long-term prognosis in chronic heart failure (CHF) patients with dyslipidemia remain unclear. METHODS: A total of 139 CHF patients with a mean left ventricular ejection fraction (LVEF) of 37.6± 8.0% were divided into two groups based on whether EPA was included in their treatment regimen: the EPA group (n=71) and the no EPA group (n=68). Only patients with dyslipidemia at baseline (entry) were treated with EPA. The monocyte chemoattractant protein (MCP)-1 and asymmetric dimethylarginine (ADMA) levels were measured at baseline and after 12 months of treatment. RESULTS: At 12 months, in the EPA group, the LVEF had improved and the MCP-1 and ADMA levels had decreased (respectively, p＜0.001); however, in the no EPA group, the LVEF had worsened, while the MCP-1 and ADMA levels had increased (respectively, p＜0.001). Fifty-five patients experienced cardiac events, including 15 cardiac deaths and 40 readmissions for worsening of CHF during a median follow-up period of 28.0 months. The percent change in LVEF from baseline was found to be significantly associated with the percent change in ADMA (r=-0.462, p＜0.001). A multivariate Cox hazard analysis showed EPA treatment (hazard ratio: 0.21, 95% confidence interval: 0.05-0.93, p=0.031) to be an independent predictor of cardiac events. CONCLUSIONS: These data indicate that EPA treatment may improve the cardiac function and long-term prognosis of CHF patients with dyslipidemia, at least in part, due to reductions in inflammation and improvements in the endothelial function.

Effect of insulin resistance associated with compensatory hyperinsulinemia on the long-term prognosis in patients with vasospastic angina.

BACKGROUND: Insulin resistance associated with compensatory hyperinsulinemia plays a significant role in the pathogenesis of cardiovascular diseases, including vasospastic angina (VSA). However, the effects of insulin resistance associated with hyperinsulinemia on the long-term prognosis in patients with VSA remain unclear. METHODS: A total of 265 selected patients with VSA and 56 control subjects with atypical chest pain were enrolled in the present study. Patients with VSA had a positive acetylcholine (ACh) provocation test with normal coronary angiograms, and control subjects had a negative ACh test and normal coronary angiograms. A 75-g oral glucose tolerance test was performed, and the plasma glucose and immunoreactive insulin (IRI) levels were measured before, and 30 min and 120 min (IRI 120) after the 75-g glucose load. RESULTS: During the median follow-up period of 90.0 months, thirty-one patients developed cardiac events, including 6 sudden cardiac deaths and 25 readmissions for acute coronary syndrome. Cardiac events occurred in 38.9% of the patients with an IRI 120 ≥ 80 µU/ml and only 1.6% of the patients with an IRI 120<80 µU/ml (log rank 77.220, p<0.001). A multivariate analysis showed that an IRI 120 ≥ 80 µU/ml (hazard ratio 27.49, 95% confidence interval: 4.66-162.10, p<0.001) was an independent predictor of cardiac events. CONCLUSIONS: These data indicate that insulin resistance associated with compensatory hyperinsulinemia increases the risk of cardiac events in VSA patients.

Effects of statin therapy on the production of monocyte pro-inflammatory cytokines, cardiac function, and long-term prognosis in chronic heart failure patients with dyslipidemia.

BACKGROUND: The effects of statin therapy on the production of monocyte pro-inflammatory cytokines, cardiac function and the long-term prognosis in chronic heart failure (CHF) patients with dyslipidemia remain unclear. METHODS AND RESULTS: A total of 146 CHF patients with a mean left ventricular ejection fraction (LVEF) of 26.9 ± 6.6% were divided into 2 groups based on whether or not statins were included in their treatment: a statin group (n=63) and a no statin group (n=83). Only patients with dyslipidemia were treated with statins. Peripheral blood mononuclear cells (PBMCs) were isolated, and the production of monocyte tumor necrosis factor (TNF)-α and interleukin (IL)-6 were measured at baseline and after 6 months of treatment, and the data expressed as mean ± SD (pg·ml(-1)·10(-6) PBMCs). The LVEF in the statin group improved, and the monocyte TNF-α and IL-6 production decreased (respectively, P<0.001), but the LVEF and cytokine production remained unchanged in the no statin group. Multivariate Cox hazard analysis showed that statin therapy (hazard ratio, 0.14; 95% confidence interval: 0.02-0.97, P=0.046) was an independent predictor of cardiac events. CONCLUSIONS: Statin therapy attenuates the production of monocyte pro-inflammatory cytokines, and ameliorates the cardiac function and may improve long-term prognosis in CHF patients with dyslipidemia.