Prostaglandin F2α formation is associated with mortality in a Swedish community-based cohort of older males.

ABSTRACT

AIMS: An increasing number of clinical studies highlight the importance of the inflammatory mediator prostaglandin F2 α (PGF(2α)). Prostaglandin F2 α activity has been suggested to play pivotal roles in the development of cardiovascular diseases and cancer. However, whether systemic PGF(2α) concentrations may signal mortality is unknown. The aim was to evaluate in vivo PGF(2α) formation, by measuring urinary 15-keto-dihydro-PGF(2α), and mortality risk in a community setting. METHODS AND RESULTS: Urinary 15-keto-dihydro-PGF(2α) was measured in a Swedish population of 670 men (aged 77-78 years) and the participants were followed up for a median of 9.7 years (383 died, among them 156 of cardiovascular causes and 102 of cancer). In Cox regression models, urinary 15-keto-dihydro-PGF(2α) was significantly associated with cardiovascular mortality [multivariate hazard ratio (HR) for 1 SD increase of urinary 15-keto-dihydro-PGF(2α) 1.18; 95% CI1.04-1.34; P = 0.01) independent of established cardiovascular risk factors including C-reactive protein. Urinary 15-keto-dihydro-PGF(2α) was also independently associated with total mortality (multivariate HR for 1 SD increase of urinary 15-keto-dihydro-PGF(2α) 1.11; 95% CI 1.01-1.21; P = 0.03). The combination of 15-keto-dihydro-PGF(2α) concentrations above the median and high serum high-sensitive C-reactive protein (>3 mg/L) was independently associated with a two-fold increased risk of cancer and total mortality (P = 0.02 and P < 0.001, respectively). CONCLUSION: This is the first study to show that the inflammatory mediator PGF(2α) was independently associated with mortality and specifically cardiovascular mortality 10 years later. The results are in line with the emerging evidence of the importance of the inflammatory mediator PGF(2α) in fatal cardiovascular disease.