Expression of Interleukin 6 signaling receptors in carotid atherosclerosis

Interleukin (IL) 6 contributes to atherosclerotic plaque development through IL6 membrane-bound (IL6R and gp130) and soluble (sIL6R and sgp130) receptors. We investigated IL6 receptor expression in carotid plaques and its correlation with circulating IL6 and soluble receptor levels. Plasma samples and carotid plaques were obtained from 78 patients in the Biobank of Karolinska Endarterectomies study. IL6, sIL6R, and sgp130 were measured in plasma and IL6, IL6R, sIL6R, GP130, and s GP130-RAPS (s GP130) gene expression assessed in carotid plaques. Correlations between plaque IL6 signaling gene expression and plasma levels were determined by Spearman’s correlation. Differences in plasma and gene expression levels between patients with ( n = 53) and without ( n = 25) a history of a cerebral event and statin-treated ( n = 65) and non-treated ( n = 11), were estimated by Kruskal–Wallis. IL6 and its receptors were all expressed in carotid plaques. There was a positive, borderline significant, moderate correlation between plasma IL6 and sIL6R and the respective gene expression levels (rho 0.23 and 0.22, both p = 0.05). IL6R expression was higher in patients with a history of a cerebrovascular event compared to those without ( p = 0.007). Statin-treated had higher IL6R, sIL6R, and s GP130 expression levels and plasma sIL6R compared to non-treated patients (all p < 0.05). In conclusion, all components of the IL6 signaling pathways are expressed in carotid artery plaques and IL6 and sIL6R plasma levels correlate moderately with IL6 and sIL6R. Our data suggest that IL6 signaling in the circulation might mirror the system activity in the plaque, thus adding novel perspectives to the role of IL6 signaling in atherosclerosis.

High Triglyceride-Glucose Index is Associated with Poor Cardiovascular Outcomes in Non-Diabetic ACS Patients with LDL-C Below 1.8mmol/L

Background: To evaluate the prognostic value of triglyceride glucose (TyG) index in non-diabetic acute coronary syndrome (ACS) patients with low-density lipoprotein cholesterol (LDL-C) below 1.8mmol/L.Methods: A total of 1655 non-diabetic ACS patients with LDL-C below 1.8mmol/L were included in the analysis. Patients were stratified into 2 groups. Incidence of acute myocardial infarction (AMI), infarct size in patients with AMI, and major adverse cardiac and cerebral event (MACCE) during a median of 35.6-month follow-up were determined and compared between the 2 groups. The TyG index was calculated using the following formula: ln [fasting triglycerides (mg/dL) ×fasting plasma glucose (mg/dL)/2].Results: Compared with the TyG index <8.33 group, the TyG index ≥8.33 group had significantly higher incidence of AMI (21.2% vs. 15.2%, p =0.014) and larger infarct size in patients with AMI (pTNI: 10.4 vs. 4.8 ng/ml, p =0.003; pCKMB: 52.8 vs. 22.0 ng/ml, p =0.006; pMyo: 73.7 vs. 46.0 ng/ml, p =0.038). Although there was no significant difference in mortality between the 2 groups, the incidence of revascularization of TyG index ≥8.33 group was significantly higher than that of TyG index <8.33 group (8.9% vs. 5.0%, p =0.035). Multivariable Cox regression revealed that the TyG index was positively associated with revascularization [HR (95% CI): 1.67 (1.02,2.75), p=0.043].Conclusion: In non-diabetic ACS patients with LDL-C below 1.8mmol/L, the high TyG index level was associated with higher incidence of AMI, larger infarct size, and higher incidence of revascularization. The high TyG index level might be a valid predictor of subsequent revascularization.Trial registration: retrospectively registered.

Prefibrotic Myelofibrosis Presenting with Multiple Cerebral Embolic Infarcts and the Rare MPL W515S Mutation

Acquired, activating mutations of MPL W515 are recognised driver mutations of the myeloproliferative neoplasms (MPN), namely, essential thrombocythemia and primary myelofibrosis. The most common mutation at this codon is W515L with several other mutations also described at a lower frequency. Of these less common mutations, MPL W515S has only been reported sporadically with limited information on clinicopathological associations. We describe the case of an elderly man with persistent thrombocytosis presenting with an ischemic cerebral event. Bone marrow biopsy showed evidence of prefibrotic myelofibrosis with targeted sequencing demonstrating the presence of the rare MPL W515S mutation. Thrombolytic and cytoreductive therapies resulted in a favorable outcome and follow-up. This case provides additional, necessary, and phenotypic data for the rare MPN-associated MPL W515S mutation.

P1373 Cardiac source of embolism diagnosed by transeophageal echocardiography - what to expect in nowadays clinical practice

Background Transeophageal echocardiography (TEE) is an essential tool to diagnose cardiac source of embolism (CSE) and to define treatment approach. Purpose: To review the identified CSE in 25 years experience in TEE at a tertiary centre. Methods: Retrospective study of consecutive patients (pts) who underwent TEE to search for CSE, from 1994 to 2019. Results: 2936 pts (55% males, mean age 53 ± 13 years). Ischemic cerebral event (96%) was the main location of embolism. TEE identified potential CSE in 41.5% and 7% had more than one diagnostic. The most frequent CSE were patnt foramen ovale (PFO) (16.3%) and atrial septal aneurysm (ASA), among these 65% had concomitant PFO or atrial septal defect (ASD) (14.1%). Aortic plaques ≥ 4mm were noted in 9.6%, followed by valve disease or prosthesis (5.4%), intracavitary thrombi (3.9%), vegetations (1.6%), ASD (1.5%), dilated cardiomyopathy (1.4%) and tumors (0.7%). In the last 15 years, the diagnostic effectiveness increased (35.6% vs 45.95%) and there was a shift in etiologies with an increased in the diagnose of PFO/ASD (26.8% vs 38.5%) and valve disease or prosthesis became less frequent (29.9% vs 3.7%). Overall, in elderly pts there was a preponderance of atherosclerotic plaques in the aorta, contrasting with younger pts who presented a predominance of PFO (Table1). The prevalence of spontaneous echo contrast increased with age. Pts with ischemic cerebral event were younger, mostly male and PFO was the main source of embolism (17%), while in pts with peripheral embolism the most frequent etiologies were intracavitary trombi (16%) and aortic plaques ≥ 4mm (14%). Conclusion: The main cause to perform a TEE to search for CSE was cerebral embolism, with a diagnostic effectiveness overall of 41.5%, that increased in the last 15years. Table 1 Characteristics &lt;50 years (n = 1191) 50-75 years (n = 1569) ≥75 years (n = 171) Male (%) 601 (50%) 931 (59%) 80 (47%) Atrial septal defect (%) 23 (2%) 20 (1%) 0 Patent foramen ovale (%) 239 (20%) 226 (14%) 12 (7%) Atrial septal aneurysm (%) 70 (6%) 130 (8%) 13 (8%) Vegetations (%) 8 (0.7%) 29 (2%) 9 (5%) Tumors (%) 10 (0.8%) 8 (0.5%) 4 (2%) Intracavitary trombi (%) 28 (2%) 74 (5%) 14 (8%) Aortic plaque ≥4mm (%) 31 (3%) 203 (13%) 48 (28%) Valve disease or prothesis (%) 54 (4.5%) 109 (6%) 11 (6%) Spontaneous echo contrast (%) 36 (3%) 155 (10%) 32 (19%) Distribution of cardiac source embolism by age