Background and aims Myocardial infarction triggers an inflammatory response involved in cardiac repair. We studied the association of the interleukin 6 (IL-6) cascade with infarct size and cardiac function after ST-elevation myocardial infarction (STEMI). Methods In 369 STEMI patients IL-6, soluble IL-6 receptor (sIL-6R), and soluble glycoprotein (sgp) 130 were measured at baseline (hospital admission), 24 h, 2 weeks, 7 weeks, 4 months, and 1 year post-PCI and sIL-6R/IL-6 ratio was calculated. At 4 months, infarct size and left ventricular ejection fraction (LVEF) were assessed by magnetic resonance imaging. Diastolic function ( E / e ′) was determined by echocardiography. Results Hospital admission levels for IL-6, sIL-6R, sgp 130 were 3.7 pg/ml (IQR 2.1–6.7 pg/ml), 51.6 ng/ml (IQR 37.3–69.0 ng/ml), and 332 ng/ml (IQR 280–399 ng/ml), respectively. 24 h after admission, IL-6 had increased threefold compared to baseline ( p < 0.001) and returned below baseline ( p < 0.001) 2 weeks after STEMI. sIL-6R and sgp130 levels at 24 h remained similar to baseline but were increased at 2 weeks ( p < 0.001; p < 0.001, respectively). IL-6 and sIL-6R/IL-6 ratio at 24 h were independently associated with infarct size [ β 5.4 (95% CI 3.3–7.5); p < 0.001, β − 4.0 (95% CI − 6.1 to − 1.9); p < 0.001, respectively]. Higher levels of IL-6 at 24 h were associated with lower LVEF [ β − 4.2 (95% CI -6.7 to − 1.8); p = 0.001]. Conclusions Higher IL-6 and lower sIL-6R/IL-6 ratio early after presentation with STEMI are indicative for larger infarct size and decreased cardiac function at 4 months. Electronic supplementary material The online version of this article (10.1007/s00392-018-1387-z) contains supplementary material, which is available to authorized users.

Background: The Genetics of Subsequent Coronary Heart Disease (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD. Methods: The consortium currently includes 57 studies from 18 countries, recruiting 185 614 participants with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. All studies collected biological samples and followed-up study participants prospectively for subsequent events. Results: Enrollment into the individual studies took place between 1985 to present day with a duration of follow-up ranging from 9 months to 15 years. Within each study, participants with CHD are predominantly of self-reported European descent (38%–100%), mostly male (44%–91%) with mean ages at recruitment ranging from 40 to 75 years. Initial feasibility analyses, using a federated analysis approach, yielded expected associations between age (hazard ratio, 1.15; 95% CI, 1.14–1.16) per 5-year increase, male sex (hazard ratio, 1.17; 95% CI, 1.13–1.21) and smoking (hazard ratio, 1.43; 95% CI, 1.35–1.51) with risk of subsequent CHD death or myocardial infarction and differing associations with other individual and composite cardiovascular endpoints. Conclusions: GENIUS-CHD is a global collaboration seeking to elucidate genetic and nongenetic determinants of subsequent event risk in individuals with established CHD, to improve residual risk prediction and identify novel drug targets for secondary prevention. Initial analyses demonstrate the feasibility and reliability of a federated analysis approach. The consortium now plans to initiate and test novel hypotheses as well as supporting replication and validation analyses for other investigators.

IntroductionDiastolic dysfunction is an important predictor of poor outcome after myocardial infarction. Metformin treatment improved diastolic function in animal models and patients with diabetes. Whether metformin improves diastolic function in patients presenting with ST-segment elevation myocardial infarction (STEMI) is unknown.MethodsThe GIPS-III trial randomized STEMI patients, without known diabetes, to metformin or placebo initiated directly after PCI. The previously reported primary endpoint was left ventricular ejection fraction at 4 months, which was unaffected by metformin treatment. This is a predefined substudy to determine an effect of metformin on diastolic function. For this substudy trans-thoracic echocardiography was performed during hospitalization and after 4 months. Diastolic dysfunction was defined as having the combination of a functional alteration (i.e. decreased tissue velocity: mean of septal e’ and lateral e’) and a structural alteration (i.e. increased left atrial volume index (LAVI)). In addition, left ventricular mass index and transmitral flow velocity (E) to mean e' ratio (E/e’) were measured to determine an effect of metformin on individual echocardiographic markers of diastolic function.ResultsIn 237 (63%) patients included in the GIPS-III trial diastolic function was measured during hospitalization as well as at 4 months. Diastolic dysfunction was present in 11 (9%) of patients on metformin and 11 (9%) patients on placebo treatment (P = 0.98) during hospitalization. After 4 months 22 (19%) of patients with metformin and 18 (15%) patients with placebo (P = 0.47) had diastolic dysfunction. In addition, metformin did not improve any of the individual echocardiographic markers of diastolic function.ConclusionsIn contrast to experimental and observational data, our randomized placebo controlled trial did not suggest a beneficial effect of short-term metformin treatment on diastolic function in STEMI patients.