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

Robertina Giacconi, Francesco Piacenza, Fabrizio Maggi, Alexander Bürkle, María Moreno-Villanueva, Lucia Mancinelli, Pietro Giorgio Spezia, Federica Novazzi, Francesca Drago Ferrante, Claudia Minosse, Paolo Antonio Grossi, Nicasio Mancini, Monia Cecati, Martijn E.T. Dollé, Eugène Jansen, Tilman Grune, Efstathios S. Gonos, Claudio Franceschi, Miriam Capri, Birgit WeinbergerEwa Sikora, Florence Debacq-Chainiaux, Wolfgang Stuetz, Mikko Hurme, P. Eline Slagboom, Jürgen Bernhardt, Davide Gentilini, Luciano Calzari, Mirko Di Rosa, Anna Rita Bonfigli, Roberta Galeazzi, Antonio Cherubini, Fabrizia Lattanzio, Mauro Provinciali, Marco Malavolta

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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.

Original languageEnglish
Article numberglae228
Number of pages9
JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
Volume79
Issue number11
DOIs
Publication statusPublished - Nov 2024
Publication typeA1 Journal article-refereed

Keywords

  • Aging
  • Inflammation
  • Ischemic heart disease
  • Torquetenovirus

Publication forum classification

  • Publication forum level 3

ASJC Scopus subject areas

  • General Medicine

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