Civieri, GiovanniGiovanniCivieriAbohashem, ShadyShadyAbohashemGrewal, Simran SSimran SGrewalAldosoky, WesamWesamAldosokyQamar, IqraIqraQamarHanlon, ErinErinHanlonChoi, Karmel WKarmel WChoiShin, Lisa MLisa MShinRosovsky, Rachel PRachel PRosovskyBollepalli, Sandeep ChandraSandeep ChandraBollepalliLau, Hui ChongHui ChongLauArmoundas, AntonisAntonisArmoundasSeligowski, Antonia VAntonia VSeligowskiTurgeon, Sarah MSarah MTurgeonPitman, Roger KRoger KPitmanTona, FrancescoFrancescoTonaWasfy, Jason HJason HWasfySmoller, Jordan WJordan WSmollerIliceto, SabinoSabinoIlicetoGoldstein, JillJillGoldsteinGebhard, Cathérine SimoneCathérine SimoneGebhardOsborne, Michael TMichael TOsborneTawakol, AhmedAhmedTawakol2024-10-212024-10-212024-09https://boris-portal.unibe.ch/handle/20.500.12422/47891Background Prior studies have incompletely assessed whether the development of cardiometabolic risk factors (CVDRF) (hypertension, hyperlipidemia, and diabetes mellitus) mediates the association between anxiety and depression (anxiety/depression) and cardiovascular disease (CVD).Objectives The authors aimed to evaluate the following: 1) the association between anxiety/depression and incident CVDRFs and whether this association mediates the increased CVD risk; and 2) whether neuro-immune mechanisms and age and sex effects may be involved.Methods Using a retrospective cohort design, Mass General Brigham Biobank subjects were followed for 10 years. Presence and timing of anxiety/depression, CVDRFs, and CVD were determined using ICD codes. Stress-related neural activity, chronic inflammation, and autonomic function were measured by the assessment of amygdalar-to-cortical activity ratio, high-sensitivity CRP, and heart rate variability. Multivariable regression and mediation analyses were employed.Results Among 71,214 subjects (median age 49.6 years; 55.3% female), 27,048 (38.0%) developed CVDRFs during follow-up. Pre-existing anxiety/depression associated with increased risk of incident CVDRF (OR: 1.71 [95% CI: 1.59-1.83],  < 0.001) and with a shorter time to their development (β = -0.486 [95% CI: -0.62 to -0.35],  < 0.001). The development of CVDRFs mediated the association between anxiety/depression and CVD events (log-odds: 0.044 [95% CI: 0.034-0.055],  < 0.05). Neuro-immune pathways contributed to the development of CVDRFs ( < 0.05 each) and significant age and sex effects were noted: younger women experienced the greatest acceleration in the development of CVDRFs after anxiety/depression.Conclusions Anxiety/depression accelerate the development of CVDRFs. This association appears to be most notable among younger women and may be mediated by stress-related neuro-immune pathways. Evaluations of tailored preventive measures for individuals with anxiety/depression are needed to reduce CVD risk.enamygdalacardiometabolicmental healthneuro immunepreventionsex differences600 - Technology::610 - Medicine & healtharticle10.48620/364103923885010.1016/j.jacadv.2024.101208