Neutrophil/Lymphocyte Ratio Is Associated with Non-Calcified Plaque Burden in Patients with Coronary Artery Disease

Background: Elevations in soluble markers of inflammation and changes in leukocyte subset distribution are frequently reported in patients with coronary artery disease (CAD). Lately, the neutrophil/lymphocyte ratio has emerged as a potenti al marker of both CAD severity and cardiovascular prognosis. Objectives: The aim of the study was to investigate whether neutrophil/lymphocyte ratio and other immune-inflammatory markers were related to plaque burden, as assessed by coronary computed tomography angiography (CCTA), in patients with CAD. Methods: Twenty patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) and 30 patients with stable angina (SA) underwent CCTA at two occasions, immediately prior to coronary angiography and after three months. Atherosclerotic plaques were classified as calcified, mixed and non-calcified. Blood samples were drawn at both occasions. Leukocyte subsets were analyzed by white blood cell differential counts and flow cytometry. Levels of C-reactive protein (CRP) and interleukin(IL)-6 were measured in plasma. Blood analyses were also performed in 37 healthy controls. Results: Plaque variables did not change over 3 months, total plaque burden being similar in NSTE-ACS and SA. However, non-calcified/total plaque ratio was higher in NSTE-ACS, 0.25(0.09-0.44) vs 0.11(0.00-0.25), pless than0.05. At admission, levels of monocytes, neutrophils, neutrophil/lymphocyte ratios, CD4+ T cells, CRP and IL-6 were significantly elevated, while levels of NK cells were reduced, in both patient groups as compared to controls. After 3 months, levels of monocytes, neutrophils, neutrophil/lymphocyte ratios and CD4+ T cells remained elevated in patients. Neutrophil/lymphocyte ratios and neutrophil counts correlated significantly with numbers of non-calcified plaques and also with non-calcified/total plaque ratio (r = 0.403, p = 0.010 and r = 0.382, p = 0.024, respectively), but not with total plaque burden. Conclusions: Among immune-inflammatory markers in NSTE-ACS and SA patients, neutrophil counts and neutrophil/lymphocyte ratios were significantly correlated with non-calcified plaques. Data suggest that these easily measured biomarkers reflect the burden of vulnerable plaques in CAD

Quantitative Analysis of the Impact of Total Ischemic Time on Myocardial Perfusion and Clinical Outcome in Patients With ST-Elevation Myocardial Infarction

Early reperfusion of the infarct-related coronary artery is an important issue in improvement of outcomes after ST-segment elevation myocardial infarction (STEM!). In this study, the clinical significance of total ischemic time on myocardial reperfusion and clinical outcomes was evaluated in patients with STEMI treated with primary percutaneous coronary intervention and thrombus aspiration and additional triple-antiplatelet therapy. Total ischemic time was defined as time from symptom onset to first intracoronary therapy (first balloon inflation or thrombus aspiration). All patients with STEMI treated with primary percutaneous coronary intervention with total ischemic times >= 30 minutes and 2 to 3 hours, 26.8% >3 to 5 hours, and 23.5% >5 hours. Increased ischemic time was associated with age, female gender, hypertension, and diabetes. Patients with total ischemic times 5 hours. In addition, patients with total ischemic times 5 hours. In conclusion, in this contemporary cohort of patients with STEMI treated with primary percutaneous coronary intervention, triple-antiplatelet therapy, and thrombus aspiration, short ischemic time was associated with better myocardial reperfusion and decreased mortality. After a 5-hour period in which outcomes remain relatively stable, myocardial reperfusion becomes suboptimal and mortality increases. (C) 2011 Elsevier Inc. All rights reserved. (Am J Cardiol 2011;108:1536-1541

Computed tomography coronary angiography in patients with acute myocardial infarction and normal invasive coronary angiography

Background: Three to five percent of patients with acute myocardial infarction (AMI) have normal coronary arteries on invasive coronary angiography (ICA). The aim of this study was to assess the presence and characteristics of atherosclerotic plaques on computed tomography coronary angiography (CTCA) and describe the clinical characteristics of this group of patients. Methods: This was a multicentre, prospective, descriptive study on CTCA evaluation in thirty patients fulfilling criteria for AMI and without visible coronary plaques on ICA. CTCA evaluation was performed head to head in consensus by two experienced observers blinded to baseline patient characteristics and ICA results. Analysis of plaque characteristics and plaque effect on the arterial lumen was performed. Coronary segments were visually scored for the presence of plaque. Seventeen segments were differentiated, according to a modified American Heart Association classification. Echocardiography performed according to routine during the initial hospitalisation was retrieved for analysis of wall motion abnormalities and left ventricular systolic function in most patients. Results: Twenty-five patients presented with non ST-elevation myocardial infarction (NSTEMI) and five with ST-elevation myocardial infarction (STEMI). Mean age was 60.2 years and 23/30 were women. The prevalence of risk factors of coronary artery disease (CAD) was low. In total, 452 coronary segments were analysed. Eighty percent (24/30) had completely normal coronary arteries and twenty percent (6/30) had coronary atherosclerosis on CTCA. In patients with atherosclerotic plaques, the median number of segments with plaque per patient was one. Echocardiography was normal in 4/22 patients based on normal global longitudinal strain (GLS) and normal wall motion score index (WMSI); 4/22 patients had normal GLS with pathological WMSI; 3/22 patients had pathological GLS and normal WMSI; 11/22 patients had pathological GLS and WMSI and among them we could identify 5 patients with a Takotsubo pattern on echo. Conclusions: Despite a diagnosis of AMI, 80 % of patients with normal ICA showed no coronary plaques on CTCA. The remaining 20 % had only minimal non-obstructive atherosclerosis. Patients fulfilling clinical criteria for AMI but with completely normal ICA need further evaluation, suggestively with magnetic resonance imaging (MRI).Funding Agencies|Swedish Heart and Lung Foundation [20120449]; Region of Ostergotland [437491]; European Union FP 7 [223615]; Medical Research Council of Southeast Sweden [157921]</p

Characteristics of patients with false- ST-segment elevation myocardial infarction diagnoses

Background: A subgroup of patients presenting with suspected ST-elevation myocardial infarction (STEMI) have no culprit lesion during coronary angiography (false-positive STEMI). Little is known about patient- and system-related factors that are associated with false-positive STEMI. We evaluated the incidence, correlates, delay, final diagnosis, and outcome of patients with false-positive STEMI. Methods: We studied 827 consecutive patients presenting with suspected STEMI between January 2011-September 2012. Results: A false positive STEMI activation was identified in 68 patients (8.2%). Patients with false-positive STEMI were younger (57 vs 63 year; p=0.020), less often had hypercholesterolemia (19 vs 43%; p=0.001), and had a higher heart rate (82 vs 75 bpm; p=0.014). The association between these factors and false-positive STEMI activation persisted in multivariate analysis. The duration of symptoms to call was longer in false-positive STEMI patients (128 vs 83 min; p=0.030), although this did not reach statistical significance in multivariate analysis. Final diagnosis in patients with false-positive STEMI activation was particularly from unknown origin (41%). There were no significant differences in mortality at 30 days and one year between patients with STEMI and false-positive STEMI. Conclusion: The incidence of false-positive STEMI was 8.2% in patients suspected of STEMI. Patients with false-positive STEMI differ from STEMI patients in certain baseline characteristics and in patient delay. Interestingly, absence of coronary disease did not translate into better clinical outcome

Different plaque compositions as seen by CCTA.

<p>The different types of coronary plaque are shown in longitudinal views, with cross-sectional views at the level of the dotted line. A non-calcified plaque is shown on the left (A and B), with white arrowheads pointing at the non-calcified plaque component. A mixed plaque is shown in the middle (C and D), with a white arrowhead indicating the non-calcified plaque component and a black arrowhead indicating the calcified component. A large calcified plaque is shown on the right side (E and F), with black arrowhead indicating the calcifications.</p

Baseline clinical and biochemical characteristics of patients and controls.

<p>The data are presented as mean ±SD, median (25^th, 75^th percentile), or numbers (%). SA =  stable angina; ACS =  acute coronary syndrome; MI =  myocardial infarction; LDL =  low density lipoprotein, HDL =  high density lipoprotein. NS =  non-significant (p≥0.05). For comparisons between groups, p-values indicating significant differences are denoted by ψ (controls vs SA), γ (controls vs NSTE-ACS) and <i>Φ</i> (SA vs NSTE-ACS), respectively.</p><p>Baseline clinical and biochemical characteristics of patients and controls.</p

Baseline leukocyte subsets and plasma cytokines of patients and controls.

<p>The data are presented as mean ±SD or median (25^th, 75^th percentile). SA =  stable angina; NSTE-ACS =  non-ST-elevation acute coronary syndrome; CD19+ cells, B cells; CD4+ cells, T helper cells; CD8+ cell, cytotoxic T cell; NK =  Natural killer; IL =  interleukin; CRP =  C-reactive protein. NS =  non-significant (p≥0.05). For comparisons between groups, p-values indicating significant differences are denoted by ψ (controls vs SA), γ (controls vs NSTE-ACS) and <i>Φ</i> (SA vs NSTE-ACS), respectively.</p><p>Baseline leukocyte subsets and plasma cytokines of patients and controls.</p

Time of symptom onset and value of myocardial blush and infarct size on prognosis in patients with ST-elevation myocardial infarction

In patients with ST-segment elevation myocardial infarction (STEMI), the time of onset of ischemia has been associated with myocardial infarction (MI) size. Myocardial blush grade (MBG) reflects myocardial response to ischemia/reperfusion injury, which may differ according to time of the day. The aim of our study was to explore the 24-hour variation in MBG and MI size in relation to outcomes in STEMI patients. A retrospective multicenter analysis of 6970 STEMI patients was performed. Time of onset of STEMI was divided into four 6-hour periods. STEMI patients have a significant 24-hour pattern in onset of symptoms, with peak onset around 09: 00 hour. Ischemic time was longest and MI size, estimated by peak creatine kinase concentration, was largest in patients with STEMI onset between 00: 00 and 06: 00 hours. Both MBG and MI size were independently associated with mortality. Time of onset of STEMI was not independently associated with mortality when corrected for baseline and procedural factors. Interestingly, patients presenting with low MBG between 00: 00 and 06: 00 hours had a better prognosis compared to other groups. In conclusion, patients with symptom onset between 00: 00 and 06: 00 hours have longer ischemic time and consequently larger MI size. However, this does not translate into a higher mortality in this group. In addition, patients with failed reperfusion presenting in the early morning hours have better prognosis, suggesting a 24-hour pattern in myocardial protection

Chronic Metformin Treatment is Associated with Reduced Myocardial Infarct Size in Diabetic Patients with ST-segment Elevation Myocardial Infarction

Increased myocardial infarct (MI) size is associated with higher risk of developing left ventricular dysfunction, heart failure and mortality. Experimental studies have suggested that metformin treatment reduces MI size after induced ischaemia but human data is lacking. We aimed to investigate the effect of metformin on MI size in patients presenting with an acute MI. All consecutive patients (n = 3,288) presenting to our hospital with ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI between January 2004 and December 2010 were included in this retrospective analysis. Patients with diabetes were divided according to metformin versus non-metformin based pharmacotherapy. MI size was estimated using peak values of serum creatine kinase (CK), myocardial band of CK (CK-MB), and troponin-T. We identified 677 (20.6 %) patients with diabetes, of whom 189 (27.9 %) were treated with metformin. Chronic metformin treatment was associated with lower peak levels of CK (1,101 vs. 1,422 U/L, P = 0.005), CK-MB (152 vs. 182 U/L, P = 0.018) and troponin-T (2.5 vs. 4.0 ng/L, P = 0.021) compared to non-metformin using diabetics. After adjustment for age, sex, TIMI flow post PCI, and previous MI, the use of metformin treatment remained an independent predictor of smaller MI size. Patient with diabetes treated with metformin had even smaller MI size than patients without diabetes. Chronic metformin treatment is associated with reduced MI size compared to non-metformin based strategies in diabetic patients presenting with STEMI. Metformin might have additional beneficial effects beyond glucose lowering efficacy