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Freuer, D.* ; Linseisen, J.* ; Schmitz, T.* ; Thorand, B. ; Peters, A. ; Petrera, A. ; Heier, M. ; Meisinger, C.*

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

Commun. Med. 5:387 (2025)

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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 ( β F i t = 0.21; 95% CI = [0.08; 0.33]; P F D R = 0.035, β A g e 1 = 0.13; 95% CI = [0.05; 0.21]; P F D R = 0.019) and TRAIL ( β F i t = 0.09; 95% CI = [0.03; 0.15]; P F D R = 0.045, β A g e 1 = 0.09; 95% CI = [0.05; 0.13]; P F D R = 5 ⋅ 10 - 4 ) and the negative association with SCF ( β F i t = ^_0.11; 95% CI = [-0.19; -0.03]; P F D R = 0.121, β A g e 1 = -0.11; 95% CI = [-0.17; -0.06]; 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.

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