两项不同人群基础研究中他汀类药物摄入与炎症参数之间的多效效应。

IF 5.4 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Communications medicine Pub Date : 2025-09-11 DOI:10.1038/s43856-025-01124-x

Dennis Freuer, Jakob Linseisen, Timo Schmitz, Barbara Thorand, Annette Peters, Agnese Petrera, Margit Heier, Christa Meisinger

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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 ( <math> <msub><mrow><mi>β</mi></mrow> <mrow><mi>F</mi> <mi>i</mi> <mi>t</mi></mrow> </msub> </math> = 0.21; 95% CI = [0.08; 0.33]; <math> <msub><mrow><mi>P</mi></mrow> <mrow><mi>F</mi> <mi>D</mi> <mi>R</mi></mrow> </msub> </math> = 0.035, <math> <msub><mrow><mi>β</mi></mrow> <mrow><mi>A</mi> <mi>g</mi> <mi>e</mi> <mn>1</mn></mrow> </msub> </math> = 0.13; 95% CI = [0.05; 0.21]; <math> <msub><mrow><mi>P</mi></mrow> <mrow><mi>F</mi> <mi>D</mi> <mi>R</mi></mrow> </msub> </math> = 0.019) and TRAIL ( <math> <msub><mrow><mi>β</mi></mrow> <mrow><mi>F</mi> <mi>i</mi> <mi>t</mi></mrow> </msub> </math> = 0.09; 95% CI = [0.03; 0.15]; <math> <msub><mrow><mi>P</mi></mrow> <mrow><mi>F</mi> <mi>D</mi> <mi>R</mi></mrow> </msub> </math> = 0.045, <math> <msub><mrow><mi>β</mi></mrow> <mrow><mi>A</mi> <mi>g</mi> <mi>e</mi> <mn>1</mn></mrow> </msub> </math> = 0.09; 95% CI = [0.05; 0.13]; <math> <msub><mrow><mi>P</mi></mrow> <mrow><mi>F</mi> <mi>D</mi> <mi>R</mi></mrow> </msub> </math> = <math><mn>5</mn> <mo>⋅</mo> <msup><mrow><mn>10</mn></mrow> <mrow><mo>-</mo> <mn>4</mn></mrow> </msup> </math> ) and the negative association with SCF ( <math> <msub><mrow><mi>β</mi></mrow> <mrow><mi>F</mi> <mi>i</mi> <mi>t</mi></mrow> </msub> </math> = _0.11; 95% CI = [-0.19; -0.03]; <math> <msub><mrow><mi>P</mi></mrow> <mrow><mi>F</mi> <mi>D</mi> <mi>R</mi></mrow> </msub> </math> = 0.121, <math> <msub><mrow><mi>β</mi></mrow> <mrow><mi>A</mi> <mi>g</mi> <mi>e</mi> <mn>1</mn></mrow> </msub> </math> = -0.11; 95% CI = [-0.17; -0.06]; <math> <msub><mrow><mi>P</mi></mrow> <mrow><mi>F</mi> <mi>D</mi> <mi>R</mi></mrow> </msub> </math> = 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. 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引用次数: 0

摘要

背景：除了降脂作用外，他汀类药物还表现出许多有益和不利的作用（即所谓的多效效应）。他汀类药物的主要多效性是其抗炎特性，但对参与特定代谢途径的广泛炎症相关蛋白的影响仍不确定。因此，在这项研究中，我们使用两项独立的基于人群的研究数据，研究了他汀类药物使用与许多炎症相关蛋白循环水平之间的关系。方法：分别在KORA-Fit和KORA-Age1研究的803名和1008名参与者（总年龄范围：53-93岁，52%为女性）中调查了他汀类药物摄入量与多达90种炎症相关蛋白（Olink蛋白质组学）之间的关系。采用特定于关联的多变量参数和非参数回归模型来获得稳健估计。使用有向无环图选择混杂因素，并评估未测量混杂的潜在影响。结果：经多次检验调整后，在KORA-Fit和KORA-Age1研究中分别保留了3个和8个关联。最有力的证据(效果而言,复制,和健壮性)是积极联系发现炎症相关蛋白反式(βF t = 0.21; 95%可信区间= [0.08,0.33];P F D R = 0.035,β1 g e = 0.13; 95%置信区间CI = [0.05, 0.21]; P F D R = 0.019)和小道(βF t = 0.09; 95%可信区间= [0.03,0.15];P F D R = 0.045,β1 g e = 0.09; 95%置信区间CI = [0.05, 0.13];P F D R = 5⋅10 - 4)，与SCF呈负相关（β F it = 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）。其中一项研究中发现的与NT-3、MMP-10、uPA和CD244的进一步关联与另一项研究的点估计一致。结论：本研究确定了他汀类药物摄入与炎症相关蛋白指向某些代谢途径之间的关联。该结果有助于更好地理解他汀类药物多效作用的机制。

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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 ( $β_{F i t}$ = 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]; $P_{F D R}$ = $5 \cdot 10^{- 4}$ ) 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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Communications medicine

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