Leukocyte Activity in Patients with ST-Segment Elevation Acute Myocardial Infarction Treated with Anakinra

Anakinra, the recombinant form of the human interleukin (IL)-1 receptor antagonist, blunts the acute systemic inflammatory response in patients with ST-segment elevation myocardial infarction (STEMI), by determining a fall in peripheral blood leukocyte and plasma C-reactive protein levels. The aim of the present study was to determine the effects of anakinra on the activity of leukocytes measured ex vivo. Blood was collected 72 h after admission in 17 patients enrolled in the Virginia Commonwealth University - Anakirna Remodeling Trial (2) (VCU-ART2) and randomly treated with anakinra (N = 7) or placebo (N = 10). Whole blood was cultured at 37°C for 24 h to measure spontaneous production of IL-6 or stimulated with Escherichia coli lipopolysaccharide (LPS) for toll-like receptor (TLR)-4 or heat-killed Staphylococcus epidermidis (SE) for TLR-2 activation. The cultures of anakinra-treated patients produced significantly less IL-6 spontaneously (71 pg/mL [27–114]) compared with placebo-treated patients (290 pg/mL [211–617], p = 0.005). LPS- or SE-induced IL-6 production, on the other hand, was not statistically different between anakinra-versus placebo-treated patients (344 pg/mL [94–560] versus 370 pg/mL [306–991], p = 0.32 for LPS, and 484 pg/mL [77–612] versus 615 pg/mL [413–871], p = 0.31 for SE, respectively). IL-1 blockade with anakinra in STEMI patients results in reduced spontaneous leukocyte activity ex vivo without impairing the responsiveness to bacterial stimuli.     

Circadian Variation in Patient Characteristics and Outcomes in ST-Segment Elevation Myocardial Infarction

A morning peak in ST-segment elevation myocardial infarction (STEMI) has been described. The authors explored the relationship between variation of symptom onset, patient characteristics, and outcomes in two worldwide fibrinolytic trials. A total of 35 492 patients with STEMI were grouped into 8-h intervals by time of symptom onset: early (06:00 to 13:59?h), late-day (14:00 to 21:59?h), overnight (22:00 to 05:59?h). The authors correlated timing with patient characteristics and outcomes (adjusted for thrombolysis in myocardial infarction [TIMI] risk score) first in InTIME II-TIMI 17 trial (N?=?15 031), and confirmed in the ExTRACT-TIMI 25 trial (N?=?20 461). Timing was similar in the derivation (early 49%, late-day 30%, and overnight 21%; p?<?.001) and validation set (48%, 31%, and 21%, respectively; p?<?.001). Some patient characteristics consistently varied with time of symptom onset. Patients in the early cohort were older with poorer renal function. The late-day group had more smokers with higher initial heart rate and systolic blood pressure. Those with overnight symptom onset had higher rates of obesity, prior myocardial infarction, and treatment delays. Prior use of aspirin and beta-blockers was also highest in the overnight group. Relative to the early cohort, adjusted mortality was higher with late-day onset (derivation odds ratio [OR]: 1.19, p?=?.04; validation OR: 1.18, p?=?.01), but there was no excess in mortality overnight compared with early (derivation OR: .97, p?=?.72; validation OR: 1.01, p?=?.90). Composite endpoints followed similar patterns. This study indicates that circadian patterns in onset of STEMI continue to exist with patient characteristics differing by time of day. Despite a potential physiologic resistance to morning thrombolysis, outcomes were best in the early cohort, intermediate overnight, and worst with late-day symptom onset. Efforts to reduce smoking and improve control of blood pressure could reduce the number of patients with late-day onset of STEMI who experience the worst outcomes. (Author correspondence: owen@mogabgab.com)     

Lipoprotein-Associated Phospholipase A2 Is Associated with Atherosclerotic Stroke Risk: The Northern Manhattan Study

Background

Lipoprotein-associated phospholipase A2 (LpPLA2) levels are associated with stroke, though whether this extends to all populations and stroke subtypes is unknown.

Methods

Serum samples from stroke-free community participants in the Northern Manhattan Study were assayed for LpPLA2 mass and activity. Participants were followed annually for stroke. Cox-proportional-hazard models were fitted to estimate hazard-ratios and 95% confidence intervals (HR, 95% CI) for the association of LpPLA2 levels with ischemic stroke (IS), after adjusting for demographic and medical risk factors.

Results

Serum samples were available in 1946 participants, of whom 151 (7.8%) experienced a first IS during median follow-up 11 years. Mean age was 69 (SD 10), 35.6% were men, 20% non-Hispanic Whites, 22% non-Hispanic Blacks, and 55% Hispanics. LpPLA2 mass and activity levels were not associated with overall IS risk.LpPLA2 mass but not activity levels were associated with strokes due to large artery atherosclerosis (LAA; adjusted HR per SD 1.55, 95% CI 1.17–2.04). There was a dose-response relationship with LAA (compared to first quartile, 2nd quartile HR = 1.43, 95% CI 0.23–8.64; 3rd quartile HR = 4.47, 95% CI 0.93–21.54; 4th quartile HR = 5.07, 95% CI 1.07–24.06). The associations between LpPLA2-mass and LAA-stroke risk differed by race-ethnicity (p = 0.01); LpPLA2-mass was associated with increased risk of LAA among non-Hispanic Whites (adjusted HR per SD 1.44, 95% CI 0.98–2.11), but not other race-ethnic groups.

Conclusion

LpPLA2-mass levels were associated with risk of atherosclerotic stroke among non-Hispanic White participants, but not in other race-ethnic groups in the cohort. Further study is needed to confirm these race-ethnic differences and the reasons for them.     

不同剂量氯吡格雷治疗急性ST段抬高心肌梗死的临床研究

目的:观察标准治疗基础上联合不同剂量氯吡格雷治疗急性ST段抬高心肌梗死的疗效及安全性。方法:2004年9月至2008年3月就诊我院的124例12小时以内发病的ST段抬高型心肌梗死患者,随机分为3组,3组均在入院后前3天给予阿司匹林300mg/d,此后给予阿司匹林100mg/d,A组常规不给予氯吡格雷治疗,B组给予氯吡格雷75mg/d,C组入院即刻给予氯吡格雷300mg,继之75 mg/d治疗,随访30天。观察溶栓血管再通率、梗死后心绞痛发作、心力衰竭事件及死亡、再发心肌梗死、或脑卒中的联合终点。结果:与A组相比,B组、C组患者溶栓成功率提高、梗死后心绞痛发作减少。P<0.05:进一步分析发现C组与B组差异无统计学意义,P>0.05。三组均无主要和次要出血事件发生,轻微出血发生率无统计学差异,P<0.05。结论:ST段抬高的急性心肌梗死患者在标准治疗的基础上早期加用氯吡格雷75 mg/d或先予300 mg负荷量,继之75 mg/d口服,均可提高溶栓成功率,降低梗死后心绞痛发生,而氯吡格雷负荷剂量组并不优于普通剂量组,且两组安全耐受性好。     

Longitudinal Strain Is a Marker of Microvascular Obstruction and Infarct Size in Patients with Acute ST-Segment Elevation Myocardial Infarction

Objectives

We assessed the value of speckle tracking imaging performed early after a first ST-segment elevation myocardial infarction (STEMI) in order to predict infarct size and functional recovery at 3-month follow-up.

Methods

44 patients with STEMI who underwent revascularization within 12 h of symptom onset were prospectively enrolled. Echocardiography was performed 3.9±1.2 days after myocardial reperfusion, assessing circumferential (CGS), radial (RGS), and longitudinal global (GLS) strains. Late gadolinium-enhanced cardiac magnetic imaging (CMR), for assessing cardiac function, infarct size, and microvascular obstruction (MVO), was conducted 5.6±2.5 days and 99.4±4.6 days after myocardial reperfusion.

Results

GLS was evaluable in 97% of the patients, while CGS and RGS could be assessed in 85%. Infarct size significantly correlated with GLS (R = 0.601, p<0.001), RGS (R = −0.405, p = 0.010), CGS (R = 0.526, p = 0.001), ejection fraction (R = −0.699, p<0.001), wall motion score index (WMSI) (R = 0.539, p = 0.001), and left atrial volume (R = 0.510, p<0.001). Baseline ejection fraction and GLS were independent predictors of 3-month infarct size. MVO mass significantly correlated with GLS (R = 0.376, p = 0.010), WMSI (R = 0.387, p = 0.011), and ejection fraction (R = −0.389, p = 0.011). In multivariate analysis, GLS was the only independent predictor of MVO mass (p = 0.015). Longitudinal strain >−6.0% within the infarcted area exhibited 96% specificity and 61% sensitivity for predicting the persistence of akinesia (≥3 segments) at 3-month follow-up.

Conclusions

Speckle-tracking strain imaging performed early after a STEMI is easy-to-use as a marker for persistent akinetic territories at 3 months. In addition, GLS correlated significantly with MVO and final infarct size, both parameters being relevant post-MI prognostic factors, usually obtained via CMR.     

IABP对急性ST段抬高与非ST段抬高心肌梗死患者疗效的比较

目的:探讨主动脉内球囊反搏术(IABP)在不同类型急性心肌梗死患者中的有效性及对预后的影响.方法:入选2010年1月至2011年06月应用IABP治疗的急性心肌梗死患者62例,分为两组:A组为ST段抬高组,共34人;B组为非ST段抬高组,共28人.收集并观察两组的即刻病情改善率、术后30天、3月的左室射血分数(LVEF)及室壁运动积分指数(WMSI)、主要心血管事件(MACE)发生率.结果:B组IABP即刻有效性显著优于A组(10/25比8/30,P＜0.05).术后30天,A、B两组LVEF均较术前增加,且组间具有统计学差异(35.5％±5.2％比40.6％±4.9％,P＜0.05);在MACE事件上,A组仅在死亡例数一项明显高于B组(10/30比6/25,P＜0.05).术后3月,A、B两组LVEF、WMSI有统计学差异(37.0％±6.9％比44.2％±5.2％;1.7±0.4比1.3±0.5,P均＜0.05).A组MACE事件发生率明显高于B组,主要表现在非致死性心肌梗死和死亡两方面(3/30比1/25;15/30比8/25,P均＜0.01).结论:IABP对于不同类型急性心肌梗死疗效存在差异,非ST段抬高心肌梗死疗效尤为显著.     

Detection of Tissue Factor Antigen and Coagulation Activity in Coronary Artery Thrombi Isolated from Patients with ST-Segment Elevation Acute Myocardial Infarction

Introduction

Although ruptured atherosclerotic plaques have been extensively analyzed, the composition of thrombi causing arterial occlusion in patients with ST-segment elevation acute myocardial infarction has been less thoroughly investigated. We sought to investigate whether coagulant active tissue factor can be retrieved in thrombi of patients with STEMI undergoing primary percutaneous coronary intervention.

Methods

Nineteen patients with ST-segment elevation acute myocardial infarction referred for primary percutaneous coronary intervention were enrolled in this study. Coronary thrombi aspirated from coronary arteries were routinely processed for paraffin embedding and histological evaluation (4 patients) or immediately snap frozen for evaluation of tissue factor activity using a modified aPTT test (15 patients). Immunoprecipitation followed by immunoblotting was also performed in 12 patients.

Results

Thrombi aspirated from coronary arteries showed large and irregular areas of tissue factor staining within platelet aggregates, and in close contact with inflammatory cells. Some platelet aggregates stained positive for tissue factor, whereas others did not. Monocytes consistently stained strongly for tissue factor, neutrophils had a more variable and irregular tissue factor staining, and red blood cells did not demonstrate staining for tissue factor. Median clotting time of plasma samples containing homogenized thrombi incubated with a monoclonal antibody that specifically inhibits tissue factor-mediated coagulation activity (mAb 5G9) were significantly longer than their respective controls (88.9 seconds versus 76.5 seconds, respectively; p<0.001). Tissue factor was also identified by immunoprecipitation in 10 patients, with significant variability among band intensities.

Conclusions

Active tissue factor is present in coronary artery thrombi of patients with ST-segment elevation acute myocardial infarction, suggesting that it contributes to activate the coagulation cascade ensuing in coronary thrombosis.     

Adjunctive Manual Thrombus Aspiration during ST-Segment Elevation Myocardial Infarction: A Meta-Analysis of Randomized Controlled Trials

Objective

The aim of this study was to synthesize evidence by examining the effects of manual thrombus aspiration on clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI).

Methods and Results

A total of 26 randomized controlled trials (RCTs), enrolling 11,780 patients, with 5,869 patients randomized to manual thrombus aspiration and 5,911 patients randomized to conventional percutaneous coronary intervention (PCI), were included in the meta-analysis. Separate clinical outcome analyses were based on different follow-up periods. There were no statistically reductions in the incidences of mortality (risk ratio [RR], 0.86 [95% confidence interval [CI]: 0.73 to 1.02]), reinfarction (RR, 0.62 [CI, 0.31 to 1.32]) or target vessel revascularization (RR, 0.89 [CI, 0.75 to 1.05]) in the manual thrombus aspiration arm at 12 to 24 months of follow-up. The composite major adverse cardiac events (MACEs) outcomes were significantly lower in the manual thrombus aspiration arm over the long-term follow-up (RR, 0.76 [CI, 0.63 to 0.91]). A lower incidence of reinfarction was observed in the hospital to 30 days (RR, 0.59 [CI, 0.37 to 0.92]).

Conclusion

The present meta-analysis suggested that there was no evidence that using manual thrombus aspiration in patients with STEMI could provide distinct benefits in long-term clinical outcomes.     

Combined Biomarker Analysis for Risk of Acute Kidney Injury in Patients with ST-Segment Elevation Myocardial Infarction

Background

Acute kidney injury (AKI) complicating ST-segment elevation myocardial infarction (STEMI) increases subsequent morbidity and mortality. We combined the biomarkers of heart failure (HF; B-type natriuretic peptide [BNP] and soluble ST2 [sST2]) and renal injury (NGAL [neutrophil gelatinase-associated lipocalin] and cystatin C) in predicting the development of AKI in patients with STEMI undergoing primary percutaneous coronary intervention (PCI).

Methods and Results

From March 2010 to September 2013, 189 STEMI patients were sequentially enrolled and serum samples were collected at presentation for BNP, sST2, NGAL and cystatin C analysis. 37 patients (19.6%) developed AKI of varying severity within 48 hours of presentation. Univariate analysis showed age, Killip class ≥2, hypertension, white blood cell counts, hemoglobin, estimated glomerular filtration rate, blood urea nitrogen, creatinine, and all the four biomarkers were predictive of AKI. Serum levels of the biomarkers were correlated with risk of AKI and the Acute Kidney Injury Network (AKIN) stage and all significantly discriminated AKI (area under the receiver operating characteristic [ROC] curve: BNP: 0.86, sST2: 0.74, NGAL: 0.75, cystatin C: 0.73; all P < 0.05). Elevation of ≥2 of the biomarkers higher than the cutoff values derived from the ROC analysis improved AKI risk stratification, regardless of the creatine level (creatinine < 1.24 mg/dL: odds ratio [OR] 11.25, 95% confidence interval [CI] 1.63-77.92, P = 0.014; creatinine ≥ 1.24: OR 15.0, 95% CI 1.23-183.6, P = 0.034).

Conclusions

In this study of STEMI patients undergoing primary PCI, the biomarkers of heart failure (BNP and sST2) and renal injury (NGAL and cystatin C) at presentation were predictive of AKI. High serum levels of the biomarkers were associated with an elevated risk and more advanced stage of AKI. Regardless of the creatinine level, elevation of ≥2 of the biomarkers higher than the cutoff values indicated a further rise in AKI risk. Combined biomarker approach may assist in risk stratification of AKI in patients with STEMI.     

Percutaneous Coronary Intervention after Fibrinolysis for ST-Segment Elevation Myocardial Infarction Patients: An Updated Systematic Review and Meta-Analysis

BackgroundPercutaneous coronary intervention (PCI), fibrinolysis and the combination of both methods are current therapeutic options for patients with ST-segment elevation myocardial infarction (STEMI).MethodsWe searched PubMed, EMBASE, Google scholar and Cochrane Controlled Trials Register for randomized controlled trials (RCTs) evaluating the efficacy and safety of PCI after fibrinolysis within 24 hours, which was compared with primary PCI alone and ischemia-guided or delayed PCI. Meta-analysis was conducted using Review Manager 5.30 following the methods described by the Cochrane library.ResultsA total of 16 studies including 10,034 patients were enrolled. As compared with primary PCI alone group, the short-term mortality (5.8% vs 4.5%, RR 1.29, 95% confidence interval [CI] 1.00–1.65) and re-infarction rate (4.1% vs 2.7%, RR 1.46, 95%CI 1.05–2.03) were higher in the immediate PCI group (median/mean time ≤ 2 h after fibrinolysis). However, the short-term mortality and re-infarction rate showed no statistically significant differences in the early PCI group (2–24 hours after fibrinolysis). The rate of major bleeding events was higher both in the immediate PCI (6.3% vs 4.4%, RR 1.43, 95%CI 1.11–1.85) and the early PCI group (6.4% vs 4.4%, RR 1.46, 95%CI 1.03–2.06) as compared with primary PCI alone group. As compared with ischemia-guided or delayed PCI, early PCI was associated with significantly reduced re-infarction (2.4% vs 4.0%, RR 0.61, 95%CI 0.41–0.92) and recurrent ischemia (1.5% vs 5.3%, RR 0.29, 95%CI 0.12–0.70) at short-term. And the reduced re-infarction rate was also observed at long-term.ConclusionsEarly PCI after fibrinolysis, with a relatively broader time for PCI preparation, can bring the similar effects with primary PCI alone and is better than ischemia-guided or delayed PCI in STEMI patients with symptom onset < 12 h who cannot receive timely PCI. However, immediate PCI after fibrinolysis is detrimental.     

Lipoprotein-Associated Phospholipase A2 Activity Predicts Cardiovascular Events in High Risk Coronary Artery Disease Patients

Objective

Lipoprotein-associated phospholipase A2 (Lp-PLA2) is deemed to play a role in atherosclerosis and plaque destabilization as demonstrated in animal models and in prospective clinical studies. However, most of the literature is either focused on high-risk, apparently healthy patients, or is based on cross sectional studies. Therefore, we tested the hypothesis that serum Lp-PLA2 mass and activity are useful for predicting cardiovascular (CV) events over the coronary atherosclerotic burden and conventional risk factors in high-risk coronary artery disease patients.

Methods and Results

In a prospective cohort study of 712 Caucasian patients, who underwent coronary angiography and measurement of both Lp-PLA2 mass and activity at baseline, we determined incident CV events at follow-up after splitting the patients into a high and a low Lp-PLA2 mass and activity groups based on ROC analysis and Youden index. Kaplan-Meier and propensity score matching analysis were used to compare CV event-free survival between groups. Follow-up data were obtained in 75% of the cohort after a median of 7.2 years (range 1–12.7 years) during which 129 (25.5%) CV events were observed. The high Lp-PLA2 activity patients showed worse CV event-free survival (66.7% vs. 79.5%, p = 0.023) and acute coronary syndrome-free survival (75.4% vs. 85.6%, p = 0.04) than those in low Lp-PLA2 group.

Conclusions

A high Lp-PLA2 activity implies a worse CV prognosis at long term follow up in high-risk Caucasian patients referred for coronary angiography.     

Mannose-Binding Lectin Deficiency Is Associated with Myocardial Infarction: The HUNT2 Study in Norway

Objectives

Mannose-binding lectin (MBL) and ficolins activate the complement cascade, which is involved in atherogenesis. Based on a pilot study, we hypothesized that functional polymorphisms in the MBL gene (MBL2) leading to dysfunctional protein are related to development of myocardial infarction (MI). The aim of the present study was to study polymorphisms in MBL2 and ficolin genes in relation to the risk of MI.

Methods and Results

Using the population-based HUNT Study in Norway, 57133 persons were followed up for a first-time MI from 1995–1997 until the end of 2008. The 370 youngest MI patients were matched by age (range 29–62 years) and gender to 370 controls. A younger population was selected because disease in this group might be less dependent on non-genetic risk factors. The study size was based on power calculation. Polymorphisms in MBL2 and in the genes of ficolin-1, ficolin-2 and ficolin-3 were genotyped by pyrosequencing and related to the risk of MI, estimated as odds ratios (OR). Functional haplotypes were analyzed and stringent alpha levels of significance were set by permutation testing. Variant MBL2 haplotypes causing MBL deficiency were associated with a two-fold higher risk of MI (OR 2.04, 95%CI 1.29–3.24). Adjustments for conventional cardiovascular risk factors did not substantially influence the association. The ficolins were not associated with MI risk.

Conclusion

In a young to middle aged and relatively healthy Caucasian population, MBL2 variants related to functional MBL deficiency were associated with a doubling of the risk for MI, independent of conventional risk factors. This supports that MBL deficiency may lead to increased atherosclerosis or development of vulnerable plaques.     

Depressive Symptoms Are Associated with Mental Stress-Induced Myocardial Ischemia after Acute Myocardial Infarction

Objectives

Depression is an adverse prognostic factor after an acute myocardial infarction (MI), and an increased propensity toward emotionally-driven myocardial ischemia may play a role. We aimed to examine the association between depressive symptoms and mental stress-induced myocardial ischemia in young survivors of an MI.

Methods

We studied 98 patients (49 women and 49 men) age 38–60 years who were hospitalized for acute MI in the previous 6 months. Patients underwent myocardial perfusion imaging at rest, after mental stress (speech task), and after exercise or pharmacological stress. A summed difference score (SDS), obtained with observer-independent software, was used to quantify myocardial ischemia under both stress conditions. The Beck Depression Inventory-II (BDI-II) was used to measure depressive symptoms, which were analyzed as overall score, and as separate somatic and cognitive depressive symptom scores.

Results

There was a significant positive association between depressive symptoms and SDS with mental stress, denoting more ischemia. After adjustment for demographic and lifestyle factors, disease severity and medications, each incremental depressive symptom was associated with 0.14 points higher SDS. When somatic and cognitive depressive symptoms were examined separately, both somatic [β = 0.17, 95% CI: (0.04, 0.30), p = 0.01] and cognitive symptoms [β = 0.31, 95% CI: (0.07, 0.56), p = 0.01] were significantly associated with mental stress-induced ischemia. Depressive symptoms were not associated with ischemia induced by exercise or pharmacological stress.

Conclusion

Among young post-MI patients, higher levels of both cognitive and somatic depressive symptoms are associated with a higher propensity to develop myocardial ischemia with mental stress, but not with physical (exercise or pharmacological) stress.     

Culprit Vessel Only versus Multivessel Percutaneous Coronary Intervention in Patients Presenting with ST-Segment Elevation Myocardial Infarction and Multivessel Disease

BackgroundThe best strategy for ST-segment elevation myocardial infarction (STEMI) patients with multivessel disease (MVD), who underwent primary percutaneous coronary intervention (PCI) in the acute phase, is not well established.ObjectivesOur goal was to conduct a meta-analysis comparing culprit vessel only percutaneous coronary intervention (culprit PCI) with multivessel percutaneous coronary intervention (MV-PCI) for treatment of patients with STEMI and MVD.MethodsPubmed, Elsevier, Embase, and China National Knowledge Infrastructure (CNKI) databases were systematically searched for randomized and nonrandomized studies comparing culprit PCI and MV-PCI strategies during the index procedure. A meta-analysis was performed using Review Manager 5.1 (Cochrane Center, Denmark).ResultsFour randomized and fourteen nonrandomized studies involving 39,390 patients were included. MV-PCI strategy is associated with an increased short-term mortality (OR: 0.50, 95% CI: 0.32 to 0.77, p = 0.002), long-term mortality (OR: 0.52, 95% CI: 0.36 to 0.74, p<0.001), and risk of renal dysfunction (OR: 0.77, 95% CI: 0.61 to 0.97, p = 0.03) compared with culprit PCI strategy, while it reduced the incidence of revascularization (OR: 2.65, 95% CI: 1.80 to 3.90, p<0.001).ConclusionsThis meta-analysis supports current guidelines which indicate that the non-culprit vessel should not be treated during the index procedure.     

血浆磷脂酶A2与糖尿病合并心肌梗死患者预后的临床研究

目的:研究血浆磷脂酶A2(plasma phospholipase A2,PLA2)与糖尿病合并心肌梗死(myocardial infarction,MI)患者预后关系。方法:前瞻性研究分析2009年6月至2012年9月期间入住我院心内科或内分泌科158例半年内有MI病史的患者根据有无2型糖尿病分为糖尿病合并MI患者组(80例)与单纯MI患者组(对照组,78例)。两组患者均在6个月内因急性MI在我院行经皮冠状动脉介入治疗(percutaneous coronary intervention,PCI)并置入药物涂层支架。观察两组患者PLA2的水平,分析其与患者心功能的变化及预后的相关性。两组患者行2年随访,随访结束后通过K-M模型观察组间心血管不良事件(major adverse cardiovascular events,MACE)的发生率,将单因素分析有意义的变量包括,PLA2、高血压、低密度脂蛋白、吸烟、性别、年龄、超敏C反应蛋白、肾小球滤过率、白细胞计数等纳入Cox比例风险回归模型对预后进行多因素分析。结果:糖尿病合并MI组患者PLA2的水平显著高于单纯心肌梗死组(11.67±4.26μg/L vs.5.36±1.1μg/L,P0.001)。这些患者外周血中CD14+单核细胞亦显著高于单纯心肌梗死组(53.36%±17.41%vs.35.23%±11.57%,P0.001)。糖尿病合并MI组患者血浆磷脂酶A2的水平与患者心功能呈负相关(r=-0.25,P=0.02),而单纯MI患者组未显示统计学意义(r=-0.20,P=0.07)。Kaplan-Meier生存分析显示糖尿病合并MI患者主要心血管不良事件的发生率明显高于单纯心肌梗死组(P=0.046)。通过COX模型分析影响生存因素发现血浆磷脂酶A2(HR:4.29,95%CI:2.305-7.975,P0.001)仍与这些患者心血管不良事件发生显著相关。结论:血浆磷脂酶A2反应糖尿病合并MI患者体内的炎症剧烈程度,高水平的血浆高磷脂酶A2与糖尿病合并MI患者的预后密切相关。     

Impact of Heart Rate on Myocardial Salvage in Timely Reperfused Patients with ST-Segment Elevation Myocardial Infarction: New Insights from Cardiovascular Magnetic Resonance

Background

Previous studies evaluating the progression of the necrotic wave in relation to heart rate were carried out only in animal models of ST-elevated myocardial infarction (STEMI). Aim of the study was to investigate changes of myocardial salvage in relation to different heart rates at hospital admission in timely reperfused patients with STEMI by using cardiovascular magnetic resonance (CMR).

Methods

One hundred-eighty-seven patients with STEMI successfully and timely treated with primary coronary angioplasty underwent CMR five days after hospital admission. According to the heart rate at presentation, patients were subcategorized into 5 quintiles: <55 bpm (group I, n = 44), 55–64 bpm (group II, n = 35), 65–74 bpm (group III, n = 35), 75–84 bpm (group IV, n = 37), ≥85 bpm (group V, n = 36). Area at risk, infarct size, microvascular obstruction (MVO) and myocardium salvaged index (MSI) were assessed by CMR using standard sequences.

Results

Lower heart rates at presentation were associated with a bigger amount of myocardial salvage after reperfusion. MSI progressively decreased as the heart rates increased (0.54 group I, 0.46 group II, 0.38 group III, 0.34 group IV, 0.32 group V, p<0.001). Stepwise multivariable analysis showed heart rate, peak troponin and the presence of MVO were independent predictor of myocardial salvage. No changes related to heart rate were observed in relation to area at risk and infarct size.

Conclusions

High heart rates registered before performing coronary angioplasty in timely reperfused patients with STEMI are associated with a reduction in salvaged myocardium. In particular, salvaged myocardium significantly reduced when heart rate at presentation is ≥85 bpm.     

The Relation between Serum Phosphorus Levels and Clinical Outcomes after Acute Myocardial Infarction

Background

Elevated serum phosphorus levels have been linked with cardiovascular disease and mortality with conflicting results, especially in the presence of normal renal function.

Methods

We studied the association between serum phosphorus levels and clinical outcomes in 1663 patients with acute myocardial infarction (AMI). Patients were categorized into 4 groups based on serum phosphorus levels (<2.50, 2.51–3.5, 3.51–4.50 and >4.50 mg/dL). Cox proportional-hazards models were used to examine the association between serum phosphorus and clinical outcomes after adjustment for potential confounders.

Results

The mean follow up was 45 months. The lowest mortality occurred in patients with serum phosphorus between 2.5–3.5 mg/dL, with a multivariable-adjusted hazard ratio of 1.24 (95% CI 0.85–1.80), 1.35 (95% CI 1.05–1.74), and 1.75 (95% CI 1.27–2.40) in patients with serum phosphorus of <2.50, 3.51–4.50 and >4.50 mg/dL, respectively. Higher phosphorus levels were also associated with increased risk of heart failure, but not the risk of myocardial infarction or stroke. The effect of elevated phosphorus was more pronounced in patients with chronic kidney disease (CKD). The hazard ratio for mortality in patients with serum phosphorus >4.5 mg/dL compared to patients with serum phosphorus 2.50–3.50 mg/dL was 2.34 (95% CI 1.55–3.54) with CKD and 1.53 (95% CI 0.87–2.69) without CKD.

Conclusion

We found a graded, independent association between serum phosphorus and all-cause mortality and heart failure in patients after AMI. The risk for mortality appears to increase with serum phosphorus levels within the normal range and is more prominent in the presence of CKD.     

血清ANGPTL4联合Nesfatin-1对急性ST段抬高型心肌梗死患者PCI术后无复流的预测价值研究

摘要 目的：探讨血清血管生成素样蛋白 4（ANGPTL4）联合摄食抑制因子1（Nesfatin-1）对急性ST段抬高型心肌梗死（ASTEMI）患者经皮冠状动脉介入（PCI）术后无复流的预测价值。方法：选择2017年2月至2020年10月我院收治的339例ASTEMI患者,根据术后心肌梗死溶栓治疗（TIMI）分级将患者分为无复流组（TIMI血流0～2级,61例）和正常血流组（TIMI血流3级,278例）。比较两组患者基线资料、血清ANGPTL4和Nesfatin-1水平、实验室指标。多因素Logistic回归分析ASTEMI患者PCI术后发生无复流的影响因素,受试者工作特征（ROC）曲线分析血清ANGPTL4、Nesfatin-1预测ASTEMI患者PCI术后发生无复流的效能。结果：无复流组年龄、PCI术前心率、左室重量指数（LVMI）、休克指数、冠脉痉挛、血糖、冠脉病变长度、冠脉病变支数、白细胞计数、中性粒细胞计数、肌酸激酶同工酶（CK-MB）、心肌肌钙蛋白I（cTnI）高于正常血流组（P＜0.05）,收缩压、左心室射血分数（LVEF）、血清ANGPTL4和Nesfatin-1水平低于正常血流组（P＜0.05）。低水平Nesfatin-1、低水平ANGPTL4、高休克指数、冠脉痉挛是ASTEMI患者PCI术后发生无复流的危险因素（P＜0.05）。联合ANGPTL4、Nesfatin-1预测ASTEMI患者PCI术后发生无复流的曲线下面积（AUC）为0.885,高于ANGPTL4、Nesfatin-1单独预测的0.751、0.725。结论：PCI术后无复流ASTEMI患者血清ANGPTL4、Nesfatin-1水平降低,且血清Nesfatin-1、ANGPTL4水平降低与ASTEMI患者PCI术后无复流的发生密切相关,对ASTEMI患者PCI术后无复流具有一定的预测价值。     

Elevation in Sphingomyelin Synthase Activity Is Associated with Increases in Amyloid-Beta Peptide Generation

A pathological hallmark of Alzheimer’s disease (AD) is the presence of amyloid-beta peptide (Aβ) plaques in the brain. Aβ is derived from a sequential proteolysis of the transmenbrane amyloid precursor protein (APP), a process which is dependent on the distribution of lipids present in the plasma membrane. Sphingomyelin is a major membrane lipid, however its role in APP processing is unclear. Here, we assessed the expression of sphingomyelin synthase (SGMS1; the gene responsible for sphingomyelin synthesis) in human brain and found that it was significantly elevated in the hippocampus of AD brains, but not in the cerebellum. Secondly, we assessed the impact of altering SGMS activity on Aβ generation. Inhibition of SGMS activity significantly reduced the level of Aβ in a dose- and time dependent manner. The decrease in Aβ level occurred without changes in APP expression or cell viability. These results when put together indicate that SGMS activity impacts on APP processing to produce Aβ and it could be a contributing factor in Aβ pathology associated with AD.