Pleiotropic effects between statin intake and inflammation parameters in two distinct population-based studies

Background:

Besides their lipid lowering effects, statins exhibit numerous beneficial and adverse effects (so called pleiotropic effects). A major pleiotropic effect of statins is their anti-inflammatory properties, but the impact on a wide range of inflammation-related proteins involved in specific metabolic pathways remains inconclusive. Therefore, in this study we examined the association between statin use and numerous circulating levels of inflammation-related proteins using data from two independent population-based studies.

Methods:

The association between statin intake and up to 90 inflammation-related proteins (Olink Proteomics) were investigated in 803 and 1008 participants of the KORA-Fit and KORA-Age1 studies, respectively (overall age range: 53-93 years, 52% women). Association-specific multivariable parametric as well as non-parametric regression models were performed to obtain robust estimates. Confounding factors were selected using directed acyclic graphs and the potential effect of unmeasured confounding was assessed.

Results:

After adjustment for multiple testing, 3 and 8 associations remain in the KORA-Fit and KORA-Age1 studies, respectively. The strongest evidence (in terms of effect size, replication, and robustness) is found for the positive associations with the inflammation-related proteins TRANS ( $${beta }_{{Fit}}$$ β F i t  = 0.21; 95% CI = [0.08; 0.33]; $${P}_{{FDR}}$$ P F D R  = 0.035, $${beta }_{{Age}1}$$ β A g e 1  = 0.13; 95% CI = [0.05; 0.21]; $${P}_{{FDR}}$$ P F D R  = 0.019) and TRAIL ( $${beta }_{{Fit}}$$ β F i t  = 0.09; 95% CI = [0.03; 0.15]; $${P}_{{FDR}}$$ P F D R  = 0.045, $${beta }_{{Age}1}$$ β A g e 1  = 0.09; 95% CI = [0.05; 0.13]; $${P}_{{FDR}}$$ P F D R  =  $$5cdot {10}^{-4}$$ 5 ⋅ 10 − 4 ) and the negative association with SCF ( $${beta }_{{Fit}}$$ β F i t  = ^_0.11; 95% CI = [−0.19; −0.03]; $${P}_{{FDR}}$$ P F D R  = 0.121, $${beta }_{{Age}1}$$ β A g e 1  = −0.11; 95% CI = [−0.17; −0.06]; $${P}_{{FDR}}$$ P F D R  = 0.003). Further associations with NT-3, MMP-10, uPA, and CD244 found in one of the studies are consistent with the point estimates of the other study.

Conclusions:

The present study identifies associations between statin intake and inflammation-related proteins pointing to certain metabolic pathways. The results could contribute to a better understanding of the mechanisms underlying the pleiotropic effect of statins.