Giacconi, RobertinaPiacenza, FrancescoMaggi, FabrizioBürkle, AlexanderMoreno-Villanueva, MaríaMancinelli, LuciaSpezia, Pietro GiorgioNovazzi, FedericaDrago Ferrante, FrancescaMinosse, ClaudiaGrossi, Paolo AntonioMancini, NicasioCecati, MoniaDollé, Martijn E TJansen, EugèneGrune, TilmanGonos, Efstathios SFranceschi, ClaudioCapri, MiriamWeinberger, BirgitSikora, EwaDebacq-Chainiaux, FlorenceStuetz, WolfgangHurme, MikkoSlagboom, P ElineBernhardt, JürgenGentilini, DavideCalzari, LucianoDi Rosa, MirkoBonfigli, Anna RitaGaleazzi, RobertaCherubini, AntonioLattanzio, FabriziaProvinciali, MauroMalavolta, Marco2025-01-032025-01-032024-11-013944652610.1093/gerona/glae228https://rivm.openrepository.com/handle/10029/628102The implication of Torquetenovirus (TTV) in ischemic heart disease (IHD) has not been thoroughly explored. This study investigated the association between TTV viremia, pro-inflammatory cytokines, and IHD risk in an aging population. This cross-sectional study included 900 non-IHD subjects and 86 individuals with IHD (aged 55-75 years) selected from the MARK-AGE project. Results were verified in another independent Report-Age cohort, including 94 inpatients with chronic IHD and 111 inpatients with non-IHD (aged 65-96 years). Multivariable logistic regression in the MARK-AGE cohort revealed that male sex, TTV viremia ≥4log, Cu/Zn ratio, diabetes, hypertension, and smoking were significant IHD predictors. Notably, TTV viremia ≥4log independently increased the IHD risk (odds ratio [OR]: 2.51, 95% confidence interval [CI]: 1.42-4.43), confirmed in the Report-Age cohort (OR: 4.90, 95% CI: 2.32-10.39). In a RASIG subgroup, individuals with TTV viremia ≥4 log, both with and without IHD, exhibited increased plasma pro-inflammatory cytokine levels (IFN-γ, IL-1β, IL-6, IL-10, IL-12p70, TNF-α) compared to those with TTV viremia <4 log. No significant difference in cytokine production was observed between IHD patients and non-IHD with TTV viremia ≥4 log. A positive correlation between TTV viremia and DNA methylation estimator of leukocyte telomere length was observed in Report-Age patients. Additionally, IHD Report-Age patients with TTV viremia ≥4 log displayed higher NLR and SIRI index than those with TTV viremia <4 log. In conclusion, a high TTV viremia is associated with an elevated IHD risk in the older population, potentially arising from an augmented pro-inflammatory response and immunosenescence.en© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America.AgingInflammationIschemic heart diseaseTorquetenovirusArticleJ Gerontol A Biol Sci Med Sci 2024; 79(11):glae2287835914