High levels of interleukin-6 are associated with final infarct size and adverse clinical events in patients with STEMI

Objective Inflammation has emerged as a new treatment target in patients with coronary artery disease and inflammation seems to play an important role in ischaemia/reperfusion injury that follows ST-elevation myocardial infarction (STEMI). We aimed to explore the role of acute and sustained interleukin 6 (IL-6) signalling, including soluble IL-6 receptor (IL-6R), with regard to infarct size, adverse remodelling and future cardiovascular events in patients with STEMI. Methods We included 269 patients with first-time STEMI, symptom duration <6 hours and treated with percutaneous coronary intervention. Blood sampling and cardiac MRI were performed in the acute phase and after 4 months. Clinical events and all-cause mortality were registered during 12-month and 70-month follow-up, respectively. Results IL-6 levels above median at all sampling points were significantly associated with increased infarct size and reduced left ventricular ejection fraction (LVEF). IL-6 levels in the highest quartile were at all sampling points associated with an increased risk of having an adverse clinical event during the first 12 months and with long-term all-cause mortality. IL-6R was not associated with infarct size, LVEF, myocardial salvage or long-term all-cause mortality. Conclusion Acute and sustained elevation of IL-6 measured 4 months after STEMI were associated with larger infarct size, reduced LVEF and adverse clinical events including all-cause mortality. The results add important information to the sustained role of inflammation in patients with STEMI and IL-6 as a potential target for long-term intervention

MR findings of microvascular perfusion in infarcted and remote myocardium early after successful primary PCI

Objectives The aim of the study was to evaluate CMR myocardial first-pass perfusion in the injured region as well as the non-infarcted area in ST-elevation myocardial infarction (STEMI) patients few days after successful primary percutaneous coronary intervention (PCI). Materials and methods 220 patients with first time STEMI successfully treated with PCI (with or without postconditioning) were recruited from the Postconditioning in STEMI study. Contrast enhanced CMR was performed at a 1.5 T scanner 2 (1–5) days after PCI. On myocardial first-pass perfusion imaging signal intensity (SI) was measured in the injured area and in the remote myocardium and maximum contrast enhancement index (MCE) was calculated. MCE = (peak SI after contrast—SI at baseline) / SI at baseline x 100. Results There were no significant differences in first-pass perfusion between patients treated with standard PCI and patients treated with additional postconditioning. The injured myocardium showed a significantly lower MCE compared to remote myocardium (94 ± 55 vs. 113 ± 49; p < 0.001). When patients were divided into four quartiles of MCE in the injured myocardium (MCE injured myocardium), patients with low MCE injured myocardium had: significantly lower ejection fraction (EF) than patients with high MCE injured myocardium, larger infarct size and area at risk, smaller myocardial salvage and more frequent occurrence of microvascular obstruction on late gadolinium enhancement. MCE in the remote myocardium revealed that patients with larger infarction also had significantly decreased MCE in the non-infarcted, remote area. Conclusion CMR first-pass perfusion can be impaired in both injured and remote myocardium in STEMI patients treated with primary PCI. These findings indicate that CMR first-pass perfusion may be a feasible method to evaluate myocardial injury after STEMI in addition to conventional CMR parameters

Osteoprotegerin levels in ST-elevation myocardial infarction: Temporal profile and association with myocardial injury and left ventricular function

Background Elevated levels of osteoprotegerin (OPG) have been associated with adverse outcomes in ST-elevation myocardial infarction (STEMI). However, the role of OPG in myocardial injury and adverse remodeling in STEMI patients remains unclear. The aims of this observational cohort study were to evaluate: 1) the temporal profile of OPG during STEMI, 2) possible associations between OPG measured acutely and after 4 months, with infarct size, adverse left ventricular (LV) remodeling, microvascular obstruction (MVO) and myocardial salvage and 3) the effect of heparin administration on OPG levels. Methods Blood samples were drawn repeatedly from 272 STEMI patients treated with primary percutaneous coronary intervention (PCI). Cardiac magnetic resonance imaging (CMR) was performed in the acute phase and after 4 months. The effect of heparin administration on OPG levels was studied in 20 patients referred to elective coronary angiography. Results OPG levels measured acutely were significantly higher than Day 1 and during follow-up. OPG levels were correlated with age. No association was found between early OPG levels and CMR measurements at 4 months. Patients with >median OPG levels measured at Day 1 had larger final infarct size, lower LV ejection fraction (LVEF) at 4 months and higher frequency of MVO. There were no associations between OPG and change in end-diastolic volume or myocardial salvage. OPG remained associated with infarct size and LVEF after adjustment for relevant covariates, except peak troponin T and CRP. A 77% increase in OPG levels following heparin administration was found in patients undergoing elective coronary angiography. Conclusions OPG was found to be associated with myocardial injury, but not with LV remodeling or myocardial salvage. The use of OPG as a biomarker in STEMI patients seems to be limited by a strong association with age, confounding effect of heparin administration, and little additive value to established biomarkers

Evaluation of circulating levels of CCN2/connective tissue growth factor in patients with ST-elevation myocardial infarction

CCN2/Connective tissue growth factor seems to be involved in development of cardiac hypertrophy and fibrosis, but a possible cardioprotective role in left ventricular (LV) remodelling following myocardial infarction has also been suggested. The main objectives of the study were therefore to investigate whether circulating CCN2 levels were associated with infarct size, LV function, adverse remodelling or clinical outcome in two cohorts of patients with ST-elevation myocardial infarction (STEMI). CCN2 was measured in 988 patients 18 hours after PCI and clinical events were recorded after 55 months in the BAMI cohort. In the POSTEMI trial, serial measurements of CCN2 were performed in 258 STEMI patients during index hospitalisation and cardiac magnetic resonance imaging was performed in the acute phase and after 4 months. Clinical events were also recorded. There were no significant associations between levels of CCN2 and infarct size, LV ejection fraction, changes in LV end-diastolic or end-systolic volume, myocardial salvage or microvascular obstruction. There were no significant associations between CCN2 levels and clinical events including mortality, in either of the study cohorts. In conclusion, circulating levels of CCN2 measured in the acute phase of STEMI were not associated with final infarct size, left ventricular function or new clinical events

Neutrophil extracellular trap components associate with infarct size, ventricular function, and clinical outcome in STEMI

Background. The relevance of neutrophil extracellular traps (NETs) in acute ST-elevation myocardial infarction (STEMI) is unclear. We explored the temporal profile of circulating NET markers and their associations to myocardial injury and function and to adverse clinical events in STEMI patients. Methods and Results. In 259 patients, blood samples were drawn before and after PCI, on day 1, and after 4 months. Double-stranded deoxyribonucleic acid (dsDNA) and myeloperoxidase-DNA (MPO-DNA) were measured in serum by a nucleic acid stain and ELISA. Cardiac magnetic resonance imaging assessed microvascular obstruction (MVO), area at risk, infarct size, myocardial salvage index, left ventricular ejection fraction (LVEF), and change in indexed left ventricular end-diastolic volume (LVEDVi). Clinical events were registered after 12 months. dsDNA and MPO-DNA levels were highest before PCI, with reduced levels thereafter (all p ≤ 0:02). Patients with high vs. low day 1 dsDNA levels (>median; 366 ng/ml) more frequently had MVO, larger area at risk, larger infarct size acutely and after 4 months, and lower myocardial salvage index (all p 75th percentile) and low LVEF (≤49%) after 4 months when adjusted for gender, time from symptoms to PCI, and infarct localization (OR 2.3 and 3.0, both p < 0:021), and patients with high day 1 dsDNA levels were more likely to experience an adverse clinical event, also when adjusting for peak troponin T (hazard ratio 5.1, p = 0:012). No such observations were encountered for MPO-DNA. Conclusions. High day 1 dsDNA levels after STEMI were associated with myocardial infarct size, adverse left ventricular remodeling, and clinical outcome. Although the origin of dsDNA could be discussed, these observations indicate a potential role for dsDNA in acute myocardial ischemia. This trial is registered with S-08421d, 2008/10614 (Regional Committee for Medical Research Ethics in South-East Norway (2008))

Osteoprotegerin (OPG) levels in patients with stable coronary artery disease (CAD) before and after heparin administration.

<p>Blood samples were drawn from patients (n = 20) during elective coronary angiography. A venous sample was taken before angiography (<b>A</b>, median 72 min before heparin). Arterial samples were taken immediately after cannulation (<b>B</b>, 1 min before heparin), and at the end of the angiography procedure (<b>C</b>, 20 min after heparin). Data are presented as boxplots, with median (line), 25^th and 75^th percentile (box) and range (whiskers).</p

Soluble IL-1 receptor 2 is associated with left ventricular remodelling in patients with ST-elevation myocardial infarction

Background The inflammatory response following myocardial infarction (MI) is prerequisite for proper healing of infarcted tissue, but can also have detrimental effects on cardiac function. Interleukin (IL)-1α and IL-1β are potent inflammatory mediators and their bioactivity is tightly regulated by IL-1 receptor antagonist (IL-1ra) and soluble (s) IL-1 receptors (R). We aimed to examine whether levels of soluble regulators of IL-1 signalling are changed during ST-elevation MI (STEMI) and their associations with parameters of cardiac injury and ventricular remodelling. Methods Plasma levels of IL-1Ra, sIL-1R1, sIL-1R2 and sIL-1R accessory protein (sIL-1RAcP) were measured by immunoassays in repeated samples from patients with STEMI (n = 255) and compared to healthy controls (n = 65). Results IL-1Ra, sIL-1R1 and sIL-1R2 levels were all significantly elevated after STEMI, while levels of sIL-1RAcP were lower compared to controls. sIL-1R2 levels (at different time points) correlated positively with C-reactive protein, myocardial infarct size and change in indexed left ventricular end-diastolic and end-systolic volume (LVEDVi and LVESVi) measured by cardiac MR acutely and after 4 months, and negatively with LV ejection fraction. Patients with >median levels of sIL-1R2 in the acute phase were more likely to have increased change in LVEDVi and LVESVi. Importantly, sIL-1R2 remained significantly associated with change in LVEDVi and LVESVi also after adjustment for clinical covariates. Conclusion Levels of sIL-1R2 are independently associated with parameters of LV adverse remodelling following STEMI

Soluble IL-1 receptor 2 is associated with left ventricular remodelling in patients with ST-elevation myocardial infarction

Background: The inflammatory response following myocardial infarction (MI) is prerequisite for proper healing of infarcted tissue, but can also have detrimental effects on cardiac function. Interleukin (IL)-1α and IL-1β are potent inflammatory mediators and their bioactivity is tightly regulated by IL-1 receptor antagonist (IL-1ra) and soluble (s) IL-1 receptors (R). We aimed to examine whether levels of soluble regulators of IL-1 signalling are changed during ST-elevation MI (STEMI) and their associations with parameters of cardiac injury and ventricular remodelling. Methods: Plasma levels of IL-1Ra, sIL-1R1, sIL-1R2 and sIL-1R accessory protein (sIL-1RAcP) were measured by immunoassays in repeated samples from patients with STEMI (n = 255) and compared to healthy controls (n = 65). Results: IL-1Ra, sIL-1R1 and sIL-1R2 levels were all significantly elevated after STEMI, while levels of sIL-1RAcP were lower compared to controls. sIL-1R2 levels (at different time points) correlated positively with C-reactive protein, myocardial infarct size and change in indexed left ventricular end-diastolic and end-systolic volume (LVEDVi and LVESVi) measured by cardiac MR acutely and after 4 months, and negatively with LV ejection fraction. Patients with >median levels of sIL-1R2 in the acute phase were more likely to have increased change in LVEDVi and LVESVi. Importantly, sIL-1R2 remained significantly associated with change in LVEDVi and LVESVi also after adjustment for clinical covariates. Conclusion: Levels of sIL-1R2 are independently associated with parameters of LV adverse remodelling following STEMI.</p

Baseline characteristics of the study population related to osteoprotegerin (OPG) levels measured at Day 1 (above or below median value).

<p>Baseline characteristics of the study population related to osteoprotegerin (OPG) levels measured at Day 1 (above or below median value).</p