Aims Cyclooxygenase-2 (COX-2)-mediated prostaglandin production by activated macrophages is associated with inflammation and atherosclerosis. We investigated the relationship between COX-2-mediated prostaglandin-E₂ (PGE₂) release, cardiovascular risk factors, and carotid atherosclerosis in apparently healthy subjects.

Methods and results PGE₂ release by lipopolysaccharide-stimulated blood monocytes was measured by ELISA in 291 subjects (76.5% men, mean age 58) who underwent global vascular risk assessment and carotid ultrasonography. COX-2 expression (real-time RT–PCR) was analysed in a subgroup of 100 subjects (76% men, mean age 59). Inducible PGE₂ production was associated with smoking and diabetes (P<0.05), but not with arterial hypertension, dyslipidaemia, or obesity. Subjects in the highest tertile of PGE₂ (>8.1 ng/mL) had significantly higher mean carotid intima–media thickness (IMT) than those in the lowest tertile (P<0.01). No significant differences among tertiles were observed in the levels of inflammatory markers (C-reactive protein, fibrinogen, and von Willebrand factor). The association between PGE₂ and carotid IMT remained statistically significant (P=0.012) after adjustment for a number of cardiovascular and inflammatory risk factors. A correlation between COX-2 expression and PGE₂ production was observed (P<0.005).

Conclusions COX-2-mediated PGE₂ overproduction by stimulated monocytes might provide a new marker of subclinical atherosclerosis in asymptomatic subjects exposed to cardiovascular risk factors.