Il-1 Alpha And Il-6 Predict Vascular Events Or Death In Patients With Cerebral Small Vessel Disease-Data From The Shef-Csvd Study

Purpose: The natural clinical course of cerebral small vessel disease (CSVD) was not thoroughly described. The aim of this single center cohort study was to establish biochemical predictors of vascular events and death in CSVD patients during a 24-month follow-up.Patients and methods: A total of 130 functionally independent patients with marked MRI features of CSVD and recent lacunar stroke (n = 52,LS), vascular Parkinsonism (n = 28,VaP) or dementia (n = 50,VaD) were prospectively recruited. Serum markers of endothelial dysfunction, inflammation and hemostasis were determined at baseline. The primary outcome was defined as occurrence of death or any vascular events during the observation.Results: The mean age was 72 +/- 8.1 years, and 37.6% of the patients were women. The mean follow-up time was 22.3 +/- 4.3 months, and 84.6% of patients had extensive white matter lesions on baseline MRI. The overall mortality rate was 6.9%, and vascular events or death occurred in 27% of the patients. Kaplan-Meier survival curves revealed no significant differences between CSVD groups (log rank p = 0.49). Cox regression analysis revealed that IL-1 alpha (HR 1.4; 95%CI 1.09-1.8), IL-6 (1.4;1.1-2.2), hs-CRP (1.1;1.06-1.9), homocysteine (1.4;1.1-1.8), fibrinogen (1.4;1.05-2), and D-dimer (2.7;1.6-4.5) were significantly associated with the primary outcome. IL-1 alpha (1.3;1.07-1.8), IL-6 (1.4;1.02-2.2), D-dimer (2.8;1.6-5) and homocysteine (1.4;1.1-1.8) remained significant after adjusting for age, sex and CSVD radiological markers.Conclusions: Our study demonstrated the important prognostic role of various circulation markers of inflammation in individuals with different clinical signs and radiological markers of CSVD. The strongest association occurred between IL-1 alpha, IL-6 and recurrent stroke, other vascular events and death.