TY - JOUR
T1 - Associations between levels of oxidative nucleoside damage and cardiovascular risk in patients newly diagnosed with bipolar disorder and their unaffected relatives
AU - Bøgh, Helena Lykke
AU - Stanislaus, Sharleny
AU - Kjærstad, Hanne Lie
AU - Sletved, Kimie Stefanie Ormstrup
AU - Forman, Julie Lyng
AU - Poulsen, Henrik Enghusen
AU - Vinberg, Maj
AU - Kessing, Lars Vedel
AU - Coello, Klara
N1 - © 2022. The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - Enhanced oxidative stress-generated nucleoside damage may contribute to the increased cardiovascular disease mortality in patients with bipolar disorder (BD) but the association has never been investigated. We investigated the associations between oxidative stress-generated damage to DNA (8-oxodG) and RNA (8-oxoGuo), respectively, and three measures reflecting cardiovascular risk; namely, the Framingham 30-year risk score of cardiovascular diseases, the metabolic syndrome, and the insulin resistance index in 360 patients newly diagnosed with BD, 102 of their unaffected relatives (UR) and 197 healthy control individuals (HC). In sex- and age-adjusted models, the 30-year cardiovascular risk score increased by 20.8% (CI = 7.4-35.9%, p = 0.002) for every one nM/mM creatinine increase in 8-oxoGuo and by 15.6% (95% CI = 5.8-26.4%, p = 0.001) for every one nM/mM creatinine increase in 8-oxodG, respectively. Further, insulin resistance index increased by 24.1% (95% CI = 6.7-43%, p = 0.005) when 8-oxoGuo increased one nM/mM creatinine. The associations between cardiovascular measures and oxidative nucleoside damage were more pronounced in patients with BD compared with UR, and HC. Metabolic syndrome was not associated with nucleoside damage. Overall, higher oxidative stress-generated nucleoside damage was associated with a higher cardiovascular risk score and a higher degree of insulin resistance index, and having BD impacted the associations. Further, within patients, treatment with psychotropics seemed to enhance the associations between 30-year CVD risk score and insulin resistance index, respectively, and oxidatively stress-generated nucleoside damage. Our findings support enhanced oxidative stress-generated nucleoside damage as a putative pathophysiological mechanism that may mediate the higher cardiovascular risk observed in patients with BD already at the time of diagnosis.
AB - Enhanced oxidative stress-generated nucleoside damage may contribute to the increased cardiovascular disease mortality in patients with bipolar disorder (BD) but the association has never been investigated. We investigated the associations between oxidative stress-generated damage to DNA (8-oxodG) and RNA (8-oxoGuo), respectively, and three measures reflecting cardiovascular risk; namely, the Framingham 30-year risk score of cardiovascular diseases, the metabolic syndrome, and the insulin resistance index in 360 patients newly diagnosed with BD, 102 of their unaffected relatives (UR) and 197 healthy control individuals (HC). In sex- and age-adjusted models, the 30-year cardiovascular risk score increased by 20.8% (CI = 7.4-35.9%, p = 0.002) for every one nM/mM creatinine increase in 8-oxoGuo and by 15.6% (95% CI = 5.8-26.4%, p = 0.001) for every one nM/mM creatinine increase in 8-oxodG, respectively. Further, insulin resistance index increased by 24.1% (95% CI = 6.7-43%, p = 0.005) when 8-oxoGuo increased one nM/mM creatinine. The associations between cardiovascular measures and oxidative nucleoside damage were more pronounced in patients with BD compared with UR, and HC. Metabolic syndrome was not associated with nucleoside damage. Overall, higher oxidative stress-generated nucleoside damage was associated with a higher cardiovascular risk score and a higher degree of insulin resistance index, and having BD impacted the associations. Further, within patients, treatment with psychotropics seemed to enhance the associations between 30-year CVD risk score and insulin resistance index, respectively, and oxidatively stress-generated nucleoside damage. Our findings support enhanced oxidative stress-generated nucleoside damage as a putative pathophysiological mechanism that may mediate the higher cardiovascular risk observed in patients with BD already at the time of diagnosis.
KW - 8-Hydroxy-2'-Deoxyguanosine
KW - Bipolar Disorder/genetics
KW - Cardiovascular Diseases
KW - Case-Control Studies
KW - Creatinine
KW - Heart Disease Risk Factors
KW - Humans
KW - Insulin Resistance
KW - Nucleosides
KW - Oxidative Stress/genetics
KW - Risk Factors
UR - http://www.scopus.com/inward/record.url?scp=85135789571&partnerID=8YFLogxK
U2 - 10.1038/s41398-022-02095-6
DO - 10.1038/s41398-022-02095-6
M3 - Journal article
C2 - 35948543
SN - 2158-3188
VL - 12
SP - 327
JO - Translational psychiatry
JF - Translational psychiatry
IS - 1
M1 - 327
ER -