The available data are not sufficient to understand the clinical impact of statin intensity in elderly patients who undergo percutaneous coronary intervention (PCI) due to acute myocardial infarction ...(AMI).
Using the COREA-AMI registry, we sought to compare the clinical impact of high- versus low-to-moderate-intensity statin in younger (<75 years old) and elderly (≥75 years old) patients. Of 10,719 patients, we included 8,096 patients treated with drug-eluting stents. All patients were classified into high-intensity versus low-to-moderate-intensity statin group according to statin type and dose at discharge. The primary end point was target-vessel failure (TVF), a composite of cardiovascular death, target-vessel MI, or target-lesion revascularization (TLR) from 1 month to 12 months after index PCI.
In younger patients, high-intensity statin showed the better clinical outcomes than low-to-moderate-intensity statin (TVF: 79 5.4% vs. 329 6.8%, adjusted hazard ratio aHR 0.76; 95% confidence interval CI 0.59-0.99; P = 0.038). However, in elderly patients, the incidence rates of the adverse clinical outcomes were similar between two statin-intensity groups (TVF: 38 11.4% vs. 131 10.6%, aHR 1.1; 95% CI 0.76-1.59; P = 0.63).
In this AMI cohort underwent PCI, high-intensity statin showed the better 1-year clinical outcomes than low-to-moderate-intensity statin in younger patients. Meanwhile, the incidence rates of adverse clinical events between high- and low-to-moderate-intensity statin were not statistically different in elderly patients. Further randomized study with large elderly population is warranted.
Background: Atrial fibrillation (AF) has been identified as a major risk factor for mortality after acute coronary syndrome (ACS). However, the long-term risk of ischemic stroke associated with ...new-onset atrial fibrillation (NOAF) in ACS remains controversial, and its gender-specific association is unknown. Methods: We analyzed the data of 10,137 ACS survivors included in a multicenter, prospective registry for Korean patients with acute myocardial infarction (AMI) between January 2004 and August 2014. Subjects were categorized into three groups (non-AF vs. NOAF vs. previous AF) based on medical history and electrocardiographic evidence of AF, either at admission or during hospitalization. Results: Among the total study population (72.3% men), 370 patients (3.6%) had NOAF and 130 (1.3%) had previous AF. During a median follow-up of 61 months (interquartile range, 38.8 to 89.3 months), 245 (2.4%) patients (218 (2.3%) non-AF vs. 15 (4.1%) NOAF vs. 12 (9.2%) previous AF, p < 0.001) experienced ischemic stroke. After adjustment for confounding variables, both NOAF (adjusted hazard ratio (HR) 1.87, 95% confidence interval (CI) 1.09–3.24, p = 0.024) and previous AF (adjusted HR 4.00, 95% CI 2.03–7.87, p < 0.001), along with older age, diabetes, current smoker, and previous stroke were independent risk factors of ischemic stroke. In the gender-stratified analysis, men with previous AF but not NOAF had a significantly higher risk of ischemic stroke (adjusted HR 4.14, 95% CI 1.79–9.55, p = 0.001) than those without AF. In women, NOAF (adjusted HR 2.54, 95% CI 1.21–5.35, p = 0.014) as well as previous AF (adjusted HR 3.72, 95% CI 1.16–11.96, p = 0.028) was a strong predictor of ischemic stroke, and the predictive value was comparable to that of previous AF among patients with a CHA2DS2-VASc score ≥ 2. Conclusions: Both NOAF and previous AF were associated with ischemic stroke after AMI, but the impact of NOAF as a risk factor of ischemic stroke was significant only in women.
Background Real‐world data on low baseline low‐density lipoprotein cholesterol (LDL‐C) levels and long‐term postdischarge cardiovascular outcomes in patients with acute coronary syndrome are limited. ...Methods and Results Of the 10 719 patients enrolled in the Korean registry of acute myocardial infarction between January 2004 and August 2014, we identified 5532 patients who were event free from death, recurrent myocardial infarction, or stroke during the in‐hospital period after successful percutaneous coronary intervention. The co–primary outcomes were 3‐point major adverse cardiovascular events (a composite of nonfatal stroke, nonfatal myocardial infarction, and cardiovascular death) and cardiovascular death at 5 years. Of 5532 patients with acute myocardial infarction (mean age, 62.1±12.8 years; 75.0% men), 446 cardiovascular deaths (8.1%) and 695 three‐point major adverse cardiovascular events (12.6%) occurred at 5 years. In the continuous analysis of LDL‐C, the risk of cardiovascular events increased steeply as LDL‐C levels decreased from 100 mg/dL. For categorical analysis of LDL‐C (<70, 70–99, and ≥100 mg/dL), as LDL‐C levels decreased, clinical outcomes worsened (237/3759 6.3% in LDL‐C ≥100 mg/dL versus 123/1291 9.5% in LDL‐C 70–99 mg/dL versus 86/482 17.8% in LDL‐C <70 mg/dL for cardiovascular death; P ‐trend<0.001; and 417/3759 11.1% in LDL‐C ≥100 mg/dL versus 172/1291 13.3% in LDL‐C 70–99 mg/dL versus 106/482 22.2% in LDL‐C <70 mg/dL for 3‐point major adverse cardiovascular event; P ‐trend<0.001). In a Cox time‐to‐event multivariable model with LDL‐C levels ≥100 mg/dL as the reference, the baseline LDL‐C level <70 mg/dL was independently associated with an increased incidence of cardiovascular death (adjusted hazard ratio, 1.68 95% CI, 1.30–2.17) and 3‐point major adverse cardiovascular event (adjusted hazard ratio, 1.37 95% CI, 1.10–1.71). Conclusions In this Korean acute myocardial infarction registry, the baseline LDL‐C level <70 mg/dL was significantly associated with an increased incidence of long‐term cardiovascular events after discharge. (COREA Cardiovascular Risk and Identification of Potential High‐Risk Population‐Acute Myocardial Infarction Registry; NCT02806102). Registration URL: https://www.clinicaltrials.gov/ ; Unique identifier: NCT02806102.
Background The benefits of long-term maintenance beta-blocker (BB) therapy in patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI) have not been well ...established. Methods and Results Using the Korean nationwide registry, a total of 7159 patients with AMI treated with PCI who received BBs at discharge and were free from death or cardiovascular events for 3 months after PCI were included in the analysis. Patients were divided into 4 groups according to BB maintenance duration: <12 months, 12 to <24 months, 24 to <36 months, and ≥36 months. The primary outcome was the composite of all-cause death, recurrent MI, heart failure, or hospitalization for unstable angina. During a mean 5.0±2.8 years of follow-up, over half of patients with AMI (52.5%) continued BB therapy beyond 3 years following PCI. After propensity score matching and propensity score marginal mean weighting through stratification, a stepwise inverse correlation was noted between BB duration and risk of the primary outcome (<12 months: hazard ratio HR, 2.19 95% CI, 1.95-2.46; 12 to <24 months: HR, 2.10 95% CI, 1.81-2.43;, and 24 to <36 months: HR, 1.68 95%CI, 1.45-1.94; reference: ≥36 months). In a 3-year landmark analysis, BB use for <36 months was associated with an increased risk of the primary outcome (adjusted HR, 1.59 95% CI, 1.37-1.85) compared with BB use for ≥36 months. Conclusions Among stabilized patients with AMI following PCI, longer maintenance BB therapy, especially for >36 months, was associated with better clinical outcomes. These findings might imply that a better prognosis can be expected if patients with AMI maintain BB therapy for ≥36 months after PCI. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02806102.
There are limited data regarding the role of coronary computed tomographic angiography (CCTA) in asymptomatic patients with type 2 diabetes mellitus. We analyzed 557 asymptomatic type 2 diabetic ...patients who underwent CCTA. Cardiac event was defined as a composite of cardiac death, nonfatal myocardial infarction, acute coronary syndrome requiring hospitalization, or late revascularization. Atherosclerotic plaques were observed in 395 patients (70.9%), and 170 patients (30.5%) showed significant coronary artery disease (CAD) on CCTA. Ninety-two patients (16.5%) were associated with a significant stenosis in the left main or proximal left anterior descending artery. During the follow-up period (33.7 ± 7.8 months), although an excellent prognosis was observed in patients without significant CAD on CCTA, those with significant CAD showed more cardiac events (7.1% vs 0.5%) and lower 3-year event-free survival rates (99.2 ± 0.6% vs 90.9 ± 2.6%, p <0.001). Furthermore, in group with significant CAD, patients with significant CAD in the left main or proximal left anterior descending artery had more cardiac events (10.9% vs 2.6%) and lower 3-year event-free survival rates (97.4 ± 1.8% vs 86.1 ± 4.2%, p = 0.049). On multivariate analysis, family history of premature CAD, previous history of stroke, higher UK Prospective Diabetes Study 10-year risk scores, neuropathy, and retinopathy were independent clinical predictors of having significant CAD and left main or proximal left anterior descending artery significant CAD on CCTA. In conclusion, about 1/3 of asymptomatic type 2 diabetic patients had significant CAD on CCTA with a subsequent high risk for cardiac events. These findings suggest that CCTA may have a potential role in identifying patients with high cardiovascular risks in asymptomatic type 2 diabetes.
There are limited data on the impact of diabetes mellitus (DM) on the risk of subclinical atherosclerosis. Therefore, we sought to investigate the impact of DM on the risk of subclinical ...atherosclerosis in asymptomatic subjects. We analyzed 2,034 propensity score–matched asymptomatic subjects who underwent coronary computed tomographic angiography (mean age 55.9 ± 8.2 years; men 1,725 84.8%). Coronary artery calcium score, degree and extent of coronary artery disease (CAD), and clinical outcomes were assessed. High-risk CAD was defined as at least 2-vessel coronary disease with proximal left anterior descending artery involvement, 3-vessel disease, or left main disease. Compared with subjects without DM, those matched with DM had higher coronary artery calcium score (89.9 ± 240.4 vs 62.8 ± 179.5, p = 0.004) and more significant CAD (≥50% diameter stenosis, 15.2% vs 10.2%, p = 0.001), largely in the form of 1-vessel disease (10.8% vs 7.3%, p = 0.007). However, there were no significant differences between matched pairs in significant CAD in the left main or proximal left anterior descending artery (5.3% vs 3.8%, p = 0.138), multivessel disease (4.4% vs 2.9%, p = 0.101), and high-risk CAD (4.3% vs 2.7%, p = 0.058). During the follow-up period (median 21.8, interquartile range 15.2 to 33.4 months), there was no significant difference in the composite of all-cause death, myocardial infarction, acute coronary syndrome, and coronary revascularization between 2 groups (hazard ratio 1.438, 95% confidence interval 0.844 to 2.449, p = 0.181). In asymptomatic subjects, those matched with DM have more subclinical atherosclerosis, mainly confined to non–high-risk CAD, than those matched without DM, and there are no differences in high-risk CAD and clinical outcomes.
Background The immune and inflammatory responses play a considerable role in left ventricular remodeling after myocardial infarction (MI). Binding of AhR (aryl hydrocarbon receptor) to its ligands ...modulates immune and inflammatory responses; however, the effects of AhR in the context of MI are unknown. Therefore, we evaluated the potential association between AhR and MI by treating mice with a nontoxic endogenous AhR ligand, ITE (2-1'H-indole-3'-carbonyl-thiazole-4-carboxylic acid methyl ester). We hypothesized that activation of AhR by ITE in MI mice would boost regulatory T-cell differentiation, modulate macrophage activity, and facilitate infarct healing. Methods and Results Acute MI was induced in C57BL/6 mice by ligation of the left anterior descending coronary artery. Then, the mice were randomized to daily intraperitoneal injection of ITE (200 µg/mouse, n=19) or vehicle (n=16) to examine the therapeutic effects of ITE during the postinfarct healing process. Echocardiographic and histopathological analyses revealed that ITE-treated mice exhibited significantly improved systolic function (
<0.001) and reduced infarct size compared with control mice (
<0.001). In addition, we found that ITE increased regulatory T cells in the mediastinal lymph node, spleen, and infarcted myocardium, and shifted the M1/M2 macrophage balance toward the M2 phenotype in vivo, which plays vital roles in the induction and resolution of inflammation after acute MI. In vitro, ITE expanded the Foxp3
(forkhead box protein P3-positive) regulatory T cells and tolerogenic dendritic cell populations. Conclusions Activation of AhR by a nontoxic endogenous ligand, ITE, improves cardiac function after MI. Post-MI mice treated with ITE have a significantly lower risk of developing advanced left ventricular systolic dysfunction than nontreated mice. Thus, the results imply that ITE has a potential as a stimulator of cardiac repair after MI to prevent heart failure.
The expression of myogenic regulatory factors (MRFs) consisting of MyoD, Myf5, myogenin (MyoG) and MRF4 characterizes various phases of skeletal muscle development including myoblast proliferation, ...cell-cycle exit, cell fusion and the maturation of myotubes to form myofibers. Although it is well known that the function of MyoG cannot be compensated for other MRFs, the molecular mechanism by which MyoG controls muscle cell differentiation is still unclear. Therefore, in this study, RNA-Seq technology was applied to profile changes in gene expression in response to MyoG knock-down (MyoGkd) in primary bovine muscle satellite cells (MSCs).
About 61-64% of the reads of over 42 million total reads were mapped to more than 13,000 genes in the reference bovine genome. RNA-Seq analysis identified 8,469 unique genes that were differentially expressed in MyoGkd. Among these genes, 230 were up-regulated and 224 were down-regulated by at least four-fold. DAVID Functional Annotation Cluster (FAC) and pathway analysis of all up- and down-regulated genes identified overrepresentation for cell cycle and division, DNA replication, mitosis, organelle lumen, nucleoplasm and cytosol, phosphate metabolic process, phosphoprotein phosphatase activity, cytoskeleton and cell morphogenesis, signifying the functional implication of these processes and pathways during skeletal muscle development. The RNA-Seq data was validated by real time RT-PCR analysis for eight out of ten genes as well as five marker genes investigated.
This study is the first RNA-Seq based gene expression analysis of MyoGkd undertaken in primary bovine MSCs. Computational analysis of the differentially expressed genes has identified the significance of genes such as SAP30-like (SAP30L), Protein lyl-1 (LYL1), various matrix metalloproteinases, and several glycogenes in myogenesis. The results of the present study widen our knowledge of the molecular basis of skeletal muscle development and reveal the vital regulatory role of MyoG in retaining muscle cell differentiation.
Intensive glycemic control is generally recommended for diabetic patients to reduce complications. However, the role of glycemic control in the mortality in diabetic patients with acute myocardial ...infarction (AMI) remained unclear.
We selected diabetic patients who measured HbA1c more than 3 times after AMI among 10,719 patients enrolled in the multicenter AMI registry. Patients (n = 1384) were categorized into five groups: according to mean HbA1c level: ≤ 6.5%, > 6.5 to ≤ 7.0%, > 7.0 to ≤ 7.5%, > 7.5 to ≤ 8.0% and > 8.0%. The primary endpoint was all-cause mortality.
During a median follow-up of 6.2 years, the patients with a mean HbA1c of 6.5 to 7.0% had the lowest all-cause mortality. Compared to patients with mean HbA1c of 6.5 to 7.0%, the risk of all-cause mortality increased in subjects with mean HbA1c ≤ 6.5% (adjusted hazard ratio HR 2.00, 95% confidence interval CI 1.02-3.95) and in those with mean HbA1c > 8.0% (adjusted HR 3.35, 95% CI 1.78-6.29). In the subgroup analysis by age, the J-curve relationship between mean HbA1c and all-cause mortality was accentuated in elderly patients (age ≥ 65 years), while there was no difference in all-cause mortality across the HbA1c groups in younger patients (age < 65 years).
The less strict glycemic control in diabetic patients with AMI would be optimal for preventing mortality, especially in elderly patients.
Background: The roles of soluble and endogenous secretory receptors for advanced glycation endproducts (sRAGE and esRAGE, respectively) in plaque vulnerability are unknown in patients with acute ...myocardial infarction (AMI). Methods and Results: We enrolled 54 patients with AMI (27 patients had type 2 diabetes mellitus DM) who had undergone primary percutaneous coronary intervention, and 54 controls who were matched for age, gender and the presence of DM. Plasma levels of s/esRAGE and matrix metalloproteinase (MMP)-9 were measured at the time of coronary angiography. There were no significant differences in the baseline characteristics of the AMI and control groups, except for the C-reactive protein levels (CRP: 14.1±14.2mg/L vs. 3.7±5.2mg/L, P<0.001). The plasma levels of MMP-9 (28.6±21.4 vs. 14.3±8.5ng/ml P<0.001) and sRAGE (0.61±0.28 vs. 0.41±0.17ng/ml, P<0.001) were higher in the AMI group than in the controls. In multivariate logistic regression analysis, the plasma levels of MMP-9 and sRAGE above the median (odds ratio OR, 2.39; 95% confidence interval CI, 1.02-5.58; P=0.044; OR, 2.47; 95%CI, 1.05-5.80; P=0.039, respectively) were independent predictors of AMI, as well as being a current smoker (OR, 2.98; 95%CI, 1.18-7.55; P=0.021) and CRP≥3.0mg/L (OR, 3.08; 95%CI, 1.25-7.59; P=0.015). Conclusions: An elevated plasma level of sRAGE might be independently associated with plaque vulnerability, as well as MMP-9, in patients with AMI. (Circ J 2011; 75: 1685-1690)
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