Von Willebrand factor, its cleaving protease (ADAMTS13), and inflammation in young adults: The African-PREDICT study

Abstract

BackgroundThe role of inflammation in the early development of vascular dysfunction remains complex. Interleukin-6 (IL-6) and C-reactive protein (CRP) can cause an acute imbalance in the von Willebrand factor (vWF)-ADAMTS13 interaction, indicating a possible link between markers of haemostasis and low-grade inflammation. To better understand these inter-relationships in the early phases of disease development, we investigated whether vWF and ADAMTS13 associate with the pro-inflammatory markers, IL-6 and CRP in healthy young adults. We considered the role of blood types, sex and race on these relationships. MethodsIn healthy black and white men and women (n = 1113; 24 ± 5 years; no previous diagnosis or medication use for chronic diseases) we analysed von Willebrand factor antigen (vWFag), ADAMTS13, IL-6 and CRP, and grouped blood types as non-O (A, B and AB) and O. Covariates included socioeconomic status, age, estimated glomerular filtration rate, 24-hour systolic blood pressure, waist circumference, glucose, total cholesterol, platelet count, γ-glutamyl transferase and total energy expenditure. ResultsIn the total group, vWFag was highest in the third tertile of both IL-6 and CRP (p ≤ 0.014), while ADAMTS13 was lowest in the third compared to the first IL-6 tertile (p = 0.006). In multivariate regression, vWFag associated positively with IL-6 (Adj R2 = 0.169; β = 0.123; p = 0.001) and CRP (Adj R2 = 0.163; β=0.094; p = 0.019) in the total group, in the O blood group (all p ≤ 0.051) and white men (all p ≤ 0.035). ADAMTS13 associated negatively with IL-6 (Adj R2 = 0.053; β = −0.154; p = 0.015) and CRP (Adj R2 = 0.055; β = −0.177; p = 0.009), only in the O blood group. ConclusionsMarkers of haemostasis associated independently with low-grade inflammation in the O type blood group and white men. An interplay between the haemostatic and inflammatory systems may already exist in young healthy adults and is dependent on blood groups, sex and race. This extends our understanding on the role of inflammation in the early development of vascular dysfunction prior to cardiovascular compromise.