The potential role of inflammation in cryptogenic stroke

Abstract

Purpose: The study aimed to identify biomarkers predictive of cryptogenic stroke in patients aged <65.

Materials and methods: We investigated 520 patients with ischemic stroke. Out of them we assigned 65 patients to the cryptogenic stroke group (age 54 (47-58), 42% male) and 36 without stroke to the control group (age 53 (47-58), 61% male). In all patients we assessed carotid intima-media thickness (cIMT) and the levels of biomarkers which might be involved in the underlying biological mechanism of ischemic stroke.

Results: There were no differences between stroke and control groups in the levels of syndecan 4, resistin, leptin, low-density lipoprotein cholesterol, triglycerides, prothrombin time, or activated partial thromboplastin time. There was no statistically significant difference in cIMT between groups. The level of high-density lipoprotein cholesterol was statistically significantly lower in the cryptogenic stroke group than in the controls (1.1 mmol/L (0.95-1.46) vs 1.37 (1.19-1.6) p = 0.02). Patients in the stroke group had higher levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) (391 pg/ml (107-1249) vs 109 (46-236); p = 0.003), interleukin 6 (2.6 pg/ml (0.8-8.1) vs 0.7 (0.4-1.2) p = 0.002) and asymmetric dimethylarginine (ADMA) (0.44 μmol/L (0.39-0.55) vs 0.36 (0.32-0.4); p = 0.0002) than the control group. In the multivariate analysis Il-6 was the only biomarker statistically significant associated with the occurrence of cryptogenic stroke (odds ratio 1.918, 95% confidence interval 1.029-3.575; p = 0.04).

Conclusions: Endothelial dysfunction assessed by increased level of ADMA affects the inflammatory state in patients with cryptogenic stroke. Increase in the inflammatory cytokine IL-6 by 1 pg/ml almost doubles the risk of stroke.

Keywords: Biomarkers; Cryptogenic stroke; Inflammatory cytokine; Interleukin-6.