title: Inflammation underlying cardiovascular mortality is a late consequence of evolutionary programming.
abstract: 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)-alpha and interleukin (IL)-10 was determined in lipopolysaccharide-stimulated whole blood samples and studied prospectively in association with cardiovascular mortality. High TNF-alpha 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-alpha (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.
authors.affiliation: Department of General Internal Medicine, Section Gerontology and Geriatrics, Leiden University Medical Center, C2-R, Albinusdreef 2, P.O. Box 9600, 2300 RC Leiden, The Netherlands. Biggelaar@lumc.nl
authors.forename: Anita H J
authors.initials: AH
authors.lastname: Van Den Biggelaar
authors.forename: Anton J M
authors.initials: AJ
authors.lastname: De Craen
authors.forename: Jacobijn
authors.initials: J
authors.lastname: Gussekloo
authors.forename: Tom W J
authors.initials: TW
authors.lastname: Huizinga
authors.forename: Bastiaan T
authors.initials: BT
authors.lastname: Heijmans
authors.forename: Marijke
authors.initials: M
authors.lastname: Frölich
authors.forename: Tom B L
authors.initials: TB
authors.lastname: Kirkwood
authors.forename: Rudi G J
authors.initials: RG
authors.lastname: Westendorp
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005075:Biological Evolution; D002318:Cardiovascular Diseases / Q000097:blood / Q000150:complications* / Q000235:genetics / Q000401:mortality*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000150:complications* / Q000235:genetics / Q000401:mortality; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008393:Marriage; D008875:Middle Aged; D009426:Netherlands; D010298:Parity; D011401:Promoter Regions, Genetic / Q000235:genetics; D012098:Reproduction / Q000502:physiology; D012307:Risk Factors; D016019:Survival Analysis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10