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

Freuer, Dennis ; Linseisen, Jakob; Schmitz, Timo; Thorand, Barbara ; Peters, Annette ; Petrera, Agnese; Heier, Margit und Meisinger, Christa (2025): Pleiotropic effects between statin intake and inflammation parameters in two distinct population-based studies. In: Communications Medicine, Bd. 5, 387

Abstract

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 ( βFit = 0.21; 95% CI = [0.08; 0.33]; PFDR = 0.035, βAge1 = 0.13; 95% CI = [0.05; 0.21]; PFDR = 0.019) and TRAIL ( βFit = 0.09; 95% CI = [0.03; 0.15]; PFDR = 0.045, βAge1 = 0.09; 95% CI = [0.05; 0.13]; PFDR = 5⋅10−4 ) and the negative association with SCF ( βFit = _0.11; 95% CI = [-0.19; -0.03]; PFDR = 0.121, βAge1 = -0.11; 95% CI = [-0.17; -0.06]; PFDR = 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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin > Institut für Medizinische Informationsverarbeitung, Biometrie und Epidemiologie
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 2730-664X
• Sprache: Englisch