Activated leukocyte cell adhesion molecule and prognosis in acute ischemic stroke

Background and Purpose— Biomarkers predicting mortality and functional outcome in stroke may be clinically helpful in identification of patients likely to benefit from intervention. Activated leukocyte cell adhesion molecule (ALCAM) is upregulated during neuroinflammation; we investigated whether ALCAM concentrations are associated with long-term mortality after ischemic stroke. Methods— In 244 patients with acute ischemic stroke (age 69±13 years), samples of ALCAM were obtained serially from presentation to Day 5 and after 6 months. Patients with overt ischemic heart disease and atrial fibrillation were excluded. The patients were followed for 47 months with all-cause and cardiovascular mortality as end points. Results— At follow-up, 72 patients (29%) had died, 43 due to cardiovascular causes. Patients with ALCAM in the fourth quartile (&gt;46.8 ng/mL) at admission had a significantly poorer survival rate on univariate analysis ( P &lt;0.001); other time points did not add further but provided similar prognostic information. In multivariate analysis, after adjustment for age, stroke severity, C-reactive protein levels, troponin T levels, and heart and/or renal failure, ALCAM levels above the fourth quartile remained an independent predictor of long-term mortality (adjusted hazard ratio, 2.05; 95% CI, 1.11 to 3.76; P =0.021) and cardiovascular mortality (adjusted hazard ratio, 2.54; 95% CI, 1.06 to 6.07; P =0.028). Conclusions— ALCAM levels measured at admission of acute ischemic stroke are associated with long-term mortality. </jats:sec

Determinants and prognostic implications of Cardiac Troponin T measured by a sensitive assay in Type 2 Diabetes Mellitus

<p>Abstract</p> <p>Background</p> <p>The cardiac troponins are biomarkers used for diagnosis of myocardial injury. They are also powerful prognostic markers in many diseases and settings. Recently introduced high-sensitivity assays indicate that chronic cardiac troponin elevations are common in response to cardiovascular (CV) morbidity. Type 2 diabetes mellitus (T2DM) confers a high risk of CV disease, but little is known about chronic cardiac troponin elevations in diabetic subjects. Accordingly, we aimed to understand the prevalence, determinants, and prognostic implications of cardiac troponin T (cTnT) elevations measured with a high-sensitivity assay in patients with T2DM.</p> <p>Methods</p> <p>cTnT was measured in stored, frozen serum samples from 124 subjects enrolled in the Asker and Bærum Cardiovascular Diabetes trial at baseline and at 2-year follow-up, if availabe (96 samples available). Results were analyzed in relation to baseline variables, hospitalizations, and group assignment (multifactorial intensive versus conventional diabetes care for lowering CV risk).</p> <p>Results</p> <p>One-hundred thirteen (90 %) had detectable cTnT at baseline and of those, 22 (18 % of the total population) subjects had values above the 99th percentile for healthy controls (13.5 ng/L). Levels at baseline were associated with conventional CV risk factors (age, renal function, gender). There was a strong correlation between cTnT levels at the two time-points (r = 0.92, p > 0.001). Risk for hospitalizations during follow-up increased step-wise by quartiles of hscTnT measured at baseline (p = 0.058).</p> <p>Conclusions</p> <p>Elevations of cTnT above the 99th percentile measured by a highly sensitive assay were encountered frequently in a population of T2DM patients. cTnT levels appeared to be stable over time and associated with conventional CV risk factors. Although a clear trend was present, no statistically robust associations with adverse outcomes could be found.</p

Clinical and pathogenic significance of S100A4 overexpression in systemic sclerosis

Objectives: We have studied the damage-associated molecular pattern protein S100A4 as a driver of fibroblast activation in systemic sclerosis (SSc).// Methods: S100A4 protein concentration was measured by ELISA in serum of SSc (n=94) and healthy controls (n=15). Protein expression in skin fibroblast cultures from diffuse cutaneous SSc (SScF, n=6) and healthy controls (normal fibroblasts (NF), n=6) was assessed. Recombinant S100A4 and a high affinity anti-S100A4 neutralising monoclonal antibody (AX-202) were tested on SScF and NF.// Results: Median (range) S100A4 (ng/mL) was higher in serum of SSc (89.9 (15.0–240.0)) than healthy controls (71.4 (7.9–131.8); p=0.027). There was association with SSc-interstitial lung disease (p=0.025, n=55), scleroderma renal crisis (p=0.026, n=4). Median (range) S100A4 (ng/mL) was higher in culture supernatants of SScF (4.19 (0.52–8.42)) than NF controls (0.28 (0.02–3.29); p1.5) induced in NF by S100A4 were also constitutively overexpressed, and downregulated by AX-202, in SScF. Pathway mapping of these S100A4 dependent genes in SSc showed the most significant enriched Kegg pathways (FDR <0.001) were regulation of stem cell pluripotency (4.6-fold) and metabolic pathways (1.9-fold).// Conclusion: Our findings provide compelling evidence for a profibrotic role for S100A4 in SSc and suggest that serum level may be a biomarker of major organ manifestations and disease severity. This study supports examining the therapeutic potential of targeting S100A4 in SSc

Changes in Diagnosing Non-ST-Segment Elevation Myocardial Infarction after the Introduction of a New High-Sensitivity Cardiac Troponin T Assay: A Single-Centre Experience

Background: Cardiac troponins are the most sensitive and specific biochemical markers of myocardial injury and with the new high-sensitivity roponin methods very minor injuries of the heart muscle can be detected. The introduction of high-sensitivity assays has facilitated reference range adjustments and a revised cut-off point for myocardial infarction (MI) due to an improved performance in the lower concentration range. The objective of this study was to investigate whether implementing a high-sensitivity cardiac troponin T (hs-cTnT) assay with subsequent lowering of the cut-off point changed the hospital evaluation and diagnosis of acute non-ST-segment elevation myocardial infarction (NSTEMI) in a general hospital population. Methods: NSTEMI patients admitted to our hospital during two periods each lasting one year were retrospectively compared. During period 1 (August 2007 - July 2008) patients were diagnosed with a conventional troponin T assay, and during period 2 (August 2009 - July 2010) patients were diagnosed using an hs-cTnT assay. Results: A significant increase in the number of NSTEMI admissions was observed using the hs-cTnT assay (225 vs. 341, risk ratio 1.57, 95% confidence interval 1.33 to 1.85). The proportion of patients examined with acute coronary angiography was similar (25.8% vs. 23.8%). Due to the higher number of NSTEMI admissions the total number of angiographies was higher in period 2 (58 vs. 81, p < 0.05), and significantly more patients were examined without signs of coronary artery disease (CAD) (0% vs. 8.6%, p < 0.05). A smaller proportion diagnosed with the high-sensitivity assay had significant dynamic cTnT changes between the highest and lowest cTnT measurement during each admission (96.2% vs. 88.7%, p < 0.01). Conclusions: More patients were diagnosed with NSTEMI and underwent coronary angiography after introducing the hs-cTnT assay. At the same time there was an increase in the frequency of coronary angiograms without signs of CAD, and fewer had significant dynamic cTnT concentration changes

A nationwide registry study on heart failure in Norway from 2008 to 2018: variations in lookback period affect incidence estimates

Background The incidence of heart failure (HF) has declined in Europe during the past two decades. However, incidence estimates from registry-based studies may vary, partly because they depend on retrospective searches to exclude previous events. The aim of this study was to assess to what extent different lookback periods (LPs) affect temporal trends in incidence, and to identify the minimal acceptable LP. Further, we wanted to estimate temporal trends in incidence and prevalence of HF in a nationwide population, using the minimal acceptable LP. Methods We identified all in- and out-patient contacts for HF in Norway during 2008 to 2018 from the Norwegian Patient Registry. To calculate the influence of varying LP on incident cases, we defined 2018 with 10 years of LP as a reference and calculated the relative difference by using one through 9 years of lookback. Temporal trends in incidence rates were estimated with sensitivity analyses applying varying LPs and different case definitions. Standardised incidence rates and prevalence were calculated by applying direct age- and sex-standardization to the 2013 European Standard Population. Results The overestimation of incident cases declined with increasing number of years included in the LP. Compared to a 10-year LP, application of 4, 6, and 8 years resulted in an overestimation of incident cases by 13.5%, 6.2% and 2.3%, respectively. Temporal trends in incidence were affected by the number of years in the LP and whether the LP was fixed or varied. Including all available data mislead to conclusions of declining incidence rates over time due to increasing LPs. Conclusions When taking the number of years with available data and HF mortality and morbidity into consideration, we propose that 6 years of fixed lookback is sufficient for identification of incident HF cases. HF incidence rates and prevalence increased from 2014 to 2018. Trial registration Retrospectively registered