Statin treatment, oxidative stress and inflammation in a Danish population

TY - JOUR

T1 - Statin treatment, oxidative stress and inflammation in a Danish population

AU - Sørensen, Anders L

AU - Hasselbalch, Hans C

AU - Nielsen, Claus H

AU - Poulsen, Henrik E

AU - Ellervik, Christina

N1 - Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

PY - 2019/2

Y1 - 2019/2

N2 - Background: While statins may have anti-inflammatory effects, anti-oxidative effects are controversial. We investigated if statin treatment is associated with differences in oxidatively generated nucleotide damage and chronic inflammation, and the relationship between nucleotide damage and chronic inflammation. Methods: We included 19,795 participants from the Danish General Suburban Population Study. In 3420 participants, we measured urinary 8-oxodG and 8-oxoGuo by liquid chromatography-tandem mass spectrometry as markers of oxidatively generated damage to DNA and RNA, respectively. We used a composite score for chronic inflammation (INFLA score) of hsCRP, WBC, platelet count, and neutrophil granulocyte to lymphocyte ratio. Associations were assessed using multivariate linear regression models. Results: Compared with non-users, statin users had 4.3–6.0% lower 8-oxodG in three separate models (p < 0.05); there were no differences in 8-oxoGuo. Among participants aged > 60 y, statin users had 11.4% lower 8-oxodG (95%CI: 6.7–15.9%, p interaction <0.001) and 3.9% lower 8-oxoGuo (95%CI: 0.1–7.5%, p interaction = 0.002), compared with non-users. Compared with non-users, statin users had 11.1% (95%CI: 5.4–16.5%, p interaction <0.001) lower 8-oxodG in participants treated for hypertension, and 18.6% (95%CI: 6.8–28.9%, p interaction <0.001) lower 8-oxodG in participants with decreased renal function. Compared with non-users, statin users had significantly lower INFLA score (p < 0.001). 8-oxodG and 8-oxoGuo associated positively with markers of chronic inflammation. Conclusions: Oxidatively generated DNA damage and inflammatory burden are lower in statin users compared with non-users. Together, anti-oxidative and anti-inflammatory effects may contribute to the beneficial effects of statins.

AB - Background: While statins may have anti-inflammatory effects, anti-oxidative effects are controversial. We investigated if statin treatment is associated with differences in oxidatively generated nucleotide damage and chronic inflammation, and the relationship between nucleotide damage and chronic inflammation. Methods: We included 19,795 participants from the Danish General Suburban Population Study. In 3420 participants, we measured urinary 8-oxodG and 8-oxoGuo by liquid chromatography-tandem mass spectrometry as markers of oxidatively generated damage to DNA and RNA, respectively. We used a composite score for chronic inflammation (INFLA score) of hsCRP, WBC, platelet count, and neutrophil granulocyte to lymphocyte ratio. Associations were assessed using multivariate linear regression models. Results: Compared with non-users, statin users had 4.3–6.0% lower 8-oxodG in three separate models (p < 0.05); there were no differences in 8-oxoGuo. Among participants aged > 60 y, statin users had 11.4% lower 8-oxodG (95%CI: 6.7–15.9%, p interaction <0.001) and 3.9% lower 8-oxoGuo (95%CI: 0.1–7.5%, p interaction = 0.002), compared with non-users. Compared with non-users, statin users had 11.1% (95%CI: 5.4–16.5%, p interaction <0.001) lower 8-oxodG in participants treated for hypertension, and 18.6% (95%CI: 6.8–28.9%, p interaction <0.001) lower 8-oxodG in participants with decreased renal function. Compared with non-users, statin users had significantly lower INFLA score (p < 0.001). 8-oxodG and 8-oxoGuo associated positively with markers of chronic inflammation. Conclusions: Oxidatively generated DNA damage and inflammatory burden are lower in statin users compared with non-users. Together, anti-oxidative and anti-inflammatory effects may contribute to the beneficial effects of statins.

KW - Adult

KW - Aged

KW - Biomarkers

KW - Cross-Sectional Studies

KW - Denmark/epidemiology

KW - Female

KW - Humans

KW - Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects

KW - Inflammation/epidemiology

KW - Male

KW - Middle Aged

KW - Oxidation-Reduction

KW - Oxidative Stress

KW - Population Surveillance

KW - Suburban Population

U2 - 10.1016/j.redox.2018.101088

DO - 10.1016/j.redox.2018.101088

M3 - Journal article

C2 - 30594900

SN - 2213-2317

VL - 21

JO - Redox Biology

JF - Redox Biology

M1 - 101088

ER -