Association Between TTV Viremia, Chronic Inflammation, and Ischemic Heart Disease Risk: Insights From MARK-AGE and Report-Age Projects

Abstract

The 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.