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Inflammation underlying cardiovascular mortality is a late consequence of evolutionary programming
Author(s) -
Biggelaar Anita H. J.,
Craen Anton J. M.,
Gussekloo Jacobijn,
Huizinga Tom W. J.,
Heijmans Bastiaan T.,
Frölich Marijke,
Kirkwood Tom B. L.,
Westendorp Rudi G. J.
Publication year - 2004
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.03-1162fje
Subject(s) - relative risk , medicine , disease , life expectancy , inflammation , tumor necrosis factor alpha , confidence interval , risk factor , interleukin 10 , mortality rate , immunology , cytokine , population , environmental health
With the increase in life expectancy, death from cardiovascular disease has risen greatly. There is increasing evidence that inflammation plays an important role in cardiovascular disease. We postulate that the development of cardiovascular disease in old age is a late consequence of evolutionary programming for a pro‐inflammatory response to resist infections in early age. In 311 women, aged 85 yr old, the production of the pro‐ and anti‐inflammatory cytokines tumor necrosis factor (TNF)‐α and interleukin (IL)‐10 was determined in lipopolysaccharide‐stimulated whole blood samples and studied prospectively in association with cardiovascular mortality. High TNF‐α was a risk factor for death from cardiovascular disease (relative risk [RR] = 1.56; 95% confidence interval [CI]: 1–2.40), whereas high IL‐10 was protective (RR = 0.58; 95% CI: 0.40–0.85). A genetic variant of the IL‐10 gene promoter, which is associated with lower IL‐10 production, was found to predispose to a 2.8‐fold higher cardiovascular mortality risk (95% CI: 1.17–6.60). Reproductive success, which was studied as a measure of evolutionary programming because it trades off with early survival by pro‐inflammatory resistance genes, was negatively associated with an increasing production of TNF‐α (RR = 0.77; 95% CI: 0.68–0.88), while a positive association with IL‐10 was found (RR = 1.22; 95% CI: 1.05–1.41). We suggest that cardiovascular mortality is a late consequence of evolutionary programming for a pro‐inflammatory response.