Interleukin 33, left ventricular geometry and diastolic filling in hypertension and obesity

Abstract

Background. Interleukin 33 is a novel member of IL-1 family of cytokines that performs a wide range of functions under physiologic and pathologic conditions. While its role in the pathogenesis of allergic and rheumatoid diseases is known, pathogenetic actions of IL-33 in cardiovascular pathology remains unclear. Objective. To investigate interrelations between interleukin 33 (IL-33) and 1β (IL-1β) serum levels, left ventricular (LV) remodeling and diastolic dysfunction (DD) in hypertensive patients with obesity. Method. 80 hypertensive patients (34 male, 46 female), aged 59,2±8,2 years, with preserved LV systolic function had been observed, including 51 obese patients. An ultrasound examination of heart (including estimation of transmitral blood flow and mitral valve annulus motion parameters) was performed. LV geometric pattern by A.Ganau, E/A and E/E’ ratios, PWP by S.Nagueh were calculated. The statistical analysis was conducted using Mann-Whitney and Pearson χ2 methods, cluster analysis by K-means. IL-33 and IL-1β serum levels were estimated using ELISA. Results. Both levels of IL-33 and IL-1β were significantly higher in all groups of hypertensive patients (p<0,001), independently of body mass index. Prominent increase of both cytokines (IL-33>73 pg/ml, IL-1β>25 pg/ml) was associated with the highest LV myocardial mass index (MMI) (160,5 (142,8; 185,8) g/m2, p<0,05 vs other groups), highest prevalence of LV hypertrophy (LVH) (100,0%, 90,0% of concentric LVH), moderate decrease in E’ velocity (9,95 (8,32; 10,60) cm/sec), relatively low pulmonary wedge pressure (PWP) (9,23 (8,83; 13,03) mm Hg) and 70,0% prevalence of LV DD (60,0% of type I). Prevalent increase in IL-1β (>20 pg/ml with IL-33<71 pg/ml) was characterized by relatively low LV MMI (116,9 (104,4; 163,1) g/m2), 55,0% prevalence of LVH plus 30,0% of concentric remodeling, lowest E’ (7,68 (6,50; 9,67) cm/sec, p<0,01 vs other groups), highest PWP (12,26 (10,72; 13,12) mm Hg, p<0,05 vs other groups) and highest rate of DD (85,0%, 70,0% of type I). Prevalent increase in IL-33 (>71 pg/ml with IL-1β<25 pg/ml) was associated with MMI of 121,4 (111,7; 140,5) g/m2, 66,7% rate of LVH (equal for concentric and eccentric variants), highest values of E’ (11,04 (9,49; 12,00) cm/sec), lowest PWP (9,07 (7,04; 11,51) mm Hg) and lowest prevalence of LV DD (66,7%, 50,0% of type I). Absence of increase of both cytokines vs control group (IL-33<71 pg/ml, IL-1β<20 pg/ml) had intermediate characteristics: LV MMI of 137,4 (121,3; 157,8) g/m2, 78,9% prevalence of LVH (50,0% of concentric variant), E’ of 9,95 (8,30; 12,20) cm/sec, PWP of 11,20 (9,55; 12,33) mm Hg, and 71,1% rate of DD (50,0% of type 1). Conclusion. IL-33 and IL-1β serum levels in patients with essential hypertension and obesity have been investigated. Significant increase in IL-33 and IL-1β serum levels in patients with hypertension compared to healthy persons has been revealed independently of presence of obesity. A pronounced increase in both cytokines’ levels was associated with the highest rates of LVH and DD. Prevalent increase in IL-1β was connected to the worst state of diastolic function despite low rates of hypertrophy. Prevalent increase in IL-33 had the most favorable influence on the severity of LVH as well as diastolic filling.