Open AccessCMV seropositivity and T‐cell senescence predict increased cardiovascular mortality in octogenarians: results from the Newcastle 85+ study
Author(s) -
Spyridopoulos Ioakim,
MartinRuiz Carmen,
Hilkens Catharien,
Yadegarfar Mohammad E.,
Isaacs John,
Jagger Carol,
Kirkwood Tom,
Zglinicki Thomas
Publication year - 2016
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12430
Subject(s) - immunosenescence , senescence , cd8 , medicine , stroke (engine) , biology , immunology , myocardial infarction , proportional hazards model , immune system , mechanical engineering , engineering
Summary Although chronic infection with cytomegalovirus ( CMV ) is known to drive T lymphocytes toward a senescent phenotype, it remains controversial whether and how CMV can cause coronary heart disease ( CHD ). To explore whether CMV seropositivity or T‐cell populations associated with immunosenescence were informative for adverse cardiovascular outcome in the very old, we prospectively analyzed peripheral blood samples from 751 octogenarians (38% males) from the Newcastle 85+ study for their power to predict survival during a 65‐month follow‐up (47.3% survival rate). CMV ‐seropositive participants showed a higher prevalence of CHD (37.7% vs. 26.7%, P = 0.030) compared to CMV ‐seronegative participants together with lower CD 4/ CD 8 ratio (1.7 vs. 4.1, P < 0.0001) and higher frequencies of senescence‐like CD 4 memory cells (41.1% vs. 4.5%, P < 0.001) and senescence‐like CD 8 memory cells ( TEMRA , 28.1% vs. 6.7%, P < 0.001). CMV seropositivity was also associated with increased six‐year cardiovascular mortality ( HR 1.75 [1.09–2.82], P = 0.021) or death from myocardial infarction and stroke ( HR 1.89 [107–3.36], P = 0.029). Gender‐adjusted multivariate Cox regression analysis revealed that low percentages of senescence‐like CD 4 T cells ( HR 0.48 [0.32–0.72], P < 0.001) and near‐senescent ( CD 27 negative) CD 8 T cells ( HR 0.60 [0.41–0.88], P = 0.029) reduced the risk of cardiovascular death. For senescence‐like CD 4, but not near‐senescent CD 8 T cells, these associations remained robust after additional adjustment for CMV status, comorbidities, and inflammation markers. We conclude that CMV seropositivity is linked to a higher incidence of CHD in octogenarians and that senescence in both the CD 4 and CD 8 T‐cell compartments is a predictor of overall cardiovascular mortality as well as death from myocardial infarction and stroke.