Novel association patterns of cardiac remodeling markers in patients with essential hypertension and atrial fibrillation

Abstract Background Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are essential for the cardiac extracellular matrix (ECM) remodeling. We investigated differences in serum levels of these markers between patients with atrial fibrillation (AF) and sinus rhythm (SR). Methods Serum levels of MMP-2, MMP-3, MMP-9 and TIMP-1 were measured in 86 patients: 27 on SR without any AF history, 33 with paroxysmal and 26 with permanent AF. All subjects had essential hypertension, normal systolic function and no coronary artery disease. Results Patients with AF had higher MMP-2, MMP-3 and MMP-9 and lower TIMP-1 compared to SR subjects (all p Conclusions In hypertensives, paroxysmal AF and permanent AF differ with respect to serum MMPs. Increased MMP-2 is associated with paroxysmal, whereas increased MMP-9 with permanent AF. Additionally, lower levels of TIMP-1 had a strong association with AF incidence.</p

Novel association patterns of cardiac remodeling markers in patients with essential hypertension and atrial fibrillation

Background: Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are essential for the cardiac extracellular matrix (ECM) remodeling. We investigated differences in serum levels of these markers between patients with atrial fibrillation (AF) and sinus rhythm (SR). Methods: Serum levels of MMP-2, MMP-3, MMP-9 and TIMP-1 were measured in 86 patients: 27 on SR without any AF history, 33 with paroxysmal and 26 with permanent AF. All subjects had essential hypertension, normal systolic function and no coronary artery disease. Results: Patients with AF had higher MMP-2, MMP-3 and MMP-9 and lower TIMP-1 compared to SR subjects (all p &lt; 0.001). Paroxysmal AF was associated with higher MMP-2 levels compared to permanent AF (p &lt; 0.001). Matrix metalloproteinase-9 but not MMP-3 was higher in permanent compared to paroxysmal AF group (p &lt; 0.001). Patients with AF had lower levels of TIMP-1 compared to those with SR while permanent AF subjects had lower TIMP-1 levels than those with paroxysmal AF (p &lt; 0.001 for both comparisons). Lower TIMP-1 was the only independent factor associated with AF (OR: 0.259, 95% CI: 0.104-0.645, p = 0.004). Conclusions: In hypertensives, paroxysmal AF and permanent AF differ with respect to serum MMPs. Increased MMP-2 is associated with paroxysmal, whereas increased MMP-9 with permanent AF. Additionally, lower levels of TIMP-1 had a strong association with AF incidence

Coronary artery ectasia and inflammatory cytokines: Link with a predominant Th-2 immune response?

Objective: The role of inflammation in coronary artery ectasia (CAE) remains controversial. We evaluated the hypothesis that CAE might be associated with a specific pattern of T helper (Th) lymphocyte activation by measuring the Th-1 cytokine, interleukin-2 (IL-2) and the Th-2 cytokines, interleukin-4 (IL-4) and interleukin-6 (IL-6) in patients with CAE, obstructive coronary artery disease (CAD) and controls. Methods: Serum levels of IL-2, IL-4 and IL-6 were measured in 74 patients undergoing an elective cardiac catheterization due to angina pectoris and positive or equivocal non-invasive screening for cardiac ischaemia: 34 had CAE and non-obstructive CAD (Group A), 22 had obstructive CAD (Group B) and 18 had normal coronaries (Group C). Results: Group A had significantly higher IL-4 than Group B and Group C (p &lt; 0.001 and p = 0.006, respectively). In contrast, Group A had markedly lower IL-2 than Group B and Group C (p &lt; 0.001 for both comparisons). Group C had higher IL-4 and lower IL-2 than Group B (p &lt; 0.001 for both comparisons). Interleukin-6 was significantly higher in Groups A and B compared to Group C (p &lt; 0.001 for both comparisons), whilst it was comparable between Group A and Group B. Multivariate logistic regression analysis showed that higher levels of IL-4 and lower levels of IL-2 were the strongest independent predictors associated with CAE (OR: 3.846, CI: 1.677-8.822, p = 0.001 and OR: 0.567, Cl: 0.387-0.831, p = 0.004, respectively). Conclusions: Our data demonstrates that Th-2 immune response, exhibited through increased IL-4 and low IL-2, constitutes a fundamental feature of CAE. (C) 2013 Elsevier Ltd. All rights reserved

Heat Shock Protein 70 Is Associated With Cardioversion Outcome and Recurrence of Symptomatic Recent Onset Atrial Fibrillation in Hypertensive Patients

Accumulating evidence indicates that heat shock proteins (HSPs) may represent a suitable biomarker to predict atrial fibrillation (AF). We investigated the relation of circulating serum HSP70 (sHSP70) with inflammatory cytokines and recurrence of symptomatic recent onset AF (ROAF). We enrolled 90 patients with ROAF (the duration from onset of symptoms &lt;= 24 hours) and 30 controls. Patients received amiodarone for cardioversion and rhythm control. The association of serum HSP70, serum interleukin-2 (sIL-2), and serum interleukin-4 (sIL-4) with the presence of cardioversion and AF recurrence within a year was investigated. Toll-like receptor 4 (TLR4) signaling dependence for IL-2 and IL-4 induction in response to stimulation with HSP70 was tested in rat aortic vascular smooth muscle cell cultures. Patients had higher sHSP70 and sIL-2 and lower sIL-4 compared with controls. Serum HSP70 was independently associated with ROAF (P = 0.005) and correlated with sIL-2 (r = 0.494, P &lt; 0.001) and sIL-4 (r = -0.550, P &lt; 0.001). By 48 hours, 71 of the 90 patients were cardioverted, with noncardioverted patients having higher sHSP70 and sIL-2 and lower sIL-4, which were the only independent factors associated with cardioversion. AF recurred in 38 of the 71 cardioverted patients in 1 year. A cutoff value of sHSP70 &gt;= 0.65 ng/mL and sIL-2 &gt;= 0.21 pg/mL was the only independent factor associated with AF recurrence (hazard ratio: 3.311, 95% confidence interval: 1.503-7.293, P = 0.003 and hazard ratio: 3.144, 95% confidence interval: 1.341-7.374, P = 0.008, respectively). The exposure of smooth muscle cell to HSP70 in vitro increased the expression of IL-2 (5x) and IL-4 (1.5x) through TLR4-dependent and receptor-independent mechanisms. In conclusion, sHSP70 and sIL-2 might constitute a prognostic tool for determining the cardioversion and recurrence likelihood in ROAF