High levels of interleukin-6 are associated with final infarct size and adverse clinical events in patients with STEMI.
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.
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.
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.
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.
NCT00922675.
Tøllefsen IM
，Shetelig C
，Seljeflot I
，Eritsland J
，Hoffmann P
，Andersen GØ
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《Open Heart》
Association of IL-8 With Infarct Size and Clinical Outcomes in Patients With STEMI.
Little is known about the role of interleukin (IL)-8 in patients with acute ST-segment elevation myocardial infarction (STEMI).
The aims of this study were to evaluate, in STEMI patients, the temporal profile of IL-8 and possible associations with left ventricular (LV) function and remodeling, infarct size, microvascular obstruction, myocardial salvage, and future clinical events.
A total of 258 patients with STEMI were included. Blood samples were drawn before and immediately after percutaneous coronary intervention (PCI), at day 1, and after 4 months. Cardiac magnetic resonance imaging was performed in the acute phase and after 4 months. Clinical events were registered during 12 months' follow-up and all-cause mortality after median 70 months' follow-up.
Patients with IL-8 levels greater than the median measured both immediately after PCI and at day 1 had larger final infarct size, lower LV ejection fraction, larger increase in LV end-diastolic volume, and higher frequency of microvascular obstruction. After multivariate adjustment, high IL-8 levels at day 1 were associated with an increased risk of developing a large MI and having reduced LV ejection fraction at 4 months, also after adjustment for peak troponin value. Patients with IL-8 levels in the highest quartile measured at all sampling points were more likely to have a clinical event during the first 12 months after the MI and had lower overall survival during long-term follow-up.
High levels of circulating IL-8 were associated with large infarct size, impaired recovery of LV function, and adverse clinical outcome in patients with STEMI, suggesting IL-8 as a future therapeutic target based on its important role in post-infarction inflammation.
Shetelig C
，Limalanathan S
，Hoffmann P
，Seljeflot I
，Gran JM
，Eritsland J
，Andersen GØ
... -
《-》
Association of plasma interleukin-6 with infarct size, reperfusion injury, and adverse remodelling after ST-elevation myocardial infarction.
Little is known about the clinical relevance of interleukin (IL)-6 in patients with acute ST-elevation myocardial infarction (STEMI). This study examined the possible associations of plasma IL-6 concentrations with infarct size (IS), reperfusion injury and adverse left ventricular remodelling (LVR), in STEMI patients treated with primary percutaneous coronary intervention (PCI).
We prospectively included 170 consecutive STEMI patients (median age 57 years, 14% women) treated with primary PCI between 2017 and 2019. Blood samples for biomarker analyses including IL-6 were collected on Day 2. Left ventricular ejection fraction (LVEF), IS, and reperfusion injury [microvascular obstruction (MVO) and intramyocardial haemorrhage (IMH)] were determined using cardiac magnetic resonance (CMR) imaging on Day 4. Left ventricular remodelling was defined as ≥10% increase in left ventricular end-diastolic volume from baseline to 4 months CMR follow-up. Patients with IL-6 concentrations ≥median (17 ng/L) showed a significantly lower LVEF (43% vs. 52%, P < 0.001), larger IS (22% vs. 13%, P < 0.001), larger MVO (1.9% vs. 0.0%, P < 0.001), and more frequent IMH (52% vs. 18%, P < 0.001). Left ventricular remodelling was more common in patients with IL-6 ≥ median (24% vs. 9%, P = 0.005). In both linear and binary multivariable regression analyses, IL-6 remained independently associated with lower LVEF [odds ratio (OR): 0.10, 95% confidence interval (CI) 0.02-0.42, P = 0.002], larger IS (OR: 5.29, 95% CI 1.52-18.40, P = 0.009), larger MVO (OR: 5.20, 95% CI 1.30-20.85, P = 0.020), with presence of IMH (OR: 3.73, 95% CI 1.27-10.99, P = 0.017), and adverse LVR (OR: 2.72, 95% 1.06-6.98, P = 0.038).
High concentrations of circulating plasma IL-6 on Day 2 after STEMI were independently associated with worse myocardial function, larger infarct extent, more severe reperfusion injury, and a higher likelihood for LVR, suggesting IL-6 as a useful biomarker of more serious outcome and potential therapeutic target.
https://clinicaltrials.gov/ct2/show/NCT04113356;NCT04113356.
Tiller C
，Reindl M
，Holzknecht M
，Lechner I
，Schwaiger J
，Brenner C
，Mayr A
，Klug G
，Bauer A
，Metzler B
，Reinstadler SJ
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《-》
Neprilysin levels at the acute phase of ST-elevation myocardial infarction.
Several preliminary analyses suggested an association between neprilysin (NEP) levels and myocardial infarction.
The objective was to assess whether NEP plasma levels following reperfusion might be a surrogate for infarct size (IS) or predict adverse outcomes in acute ST-segment elevation myocardial infarction (STEMI) patients.
We measured NEP levels in a prospective cohort of 203 patients with STEMI referred for primary percutaneous coronary intervention. Circulating soluble NEP was measured by enzyme-linked immunosorbent assay at admission (t0) and 4 hours later (t4) following reperfusion and on 7 times points (t0, t4, t12, t24, t48, day 7 and day 30) in a subset of 21 patients. IS and left ventricular ejection fraction (LVEF) were measured at 1 month by cardiac magnetic resonance. Adverse cardiovascular outcomes were collected at 12-month follow-up.
Median t0 and t4 NEP levels in 203 patients were respectively 88.3 pg/mL (interquartile range [IQR] [14; 375.4]) and 101.5 pg/mL (IQR [18.5; 423.8]). These levels remained unchanged over 1 month (P = 0.70). NEP levels did not correlate significantly with IS (P = 0.51) or LVEF (P = 0.34). There was no correlation between NEP and troponin, creatine kinase and interleukin-6 levels at h0 and h4. NEP levels above the median were not associated with adverse outcomes at follow-up (hazard ratio = 1.28, 95% confidence interval [0.69; 2.37]; P = 0.42).
NEP serum levels were widely distributed and did not change significantly in the first hours and 1-month period following reperfusion in STEMI patients. There was no significant relationship with markers of infarct size and inflammation, and 1-year adverse outcomes.
Bernelin H
，Mewton N
，Si-Mohamed S
，Croisille P
，Rioufol G
，Bonnefoy-Cudraz E
，Douek P
，Dufay N
，Amaz C
，Jossan C
，Ovize M
，Bochaton T
... -
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