Objectives Lipoprotein-associated phospholipase A2 (Lp-PLA₂) has been shown to be associated with an increased risk of clinical cardiovascular events. We aimed to investigate whether Lp-PLA₂ is also associated with the progression of subclinical atherosclerosis in a general population free of clinical cardiovascular disease.

Methods In a prospective cohort study in Beijing, carotid plaque and maximal intima-media thickness (IMT) were measured twice over a 5-year interval in 913 participants aged 45 to 74 years at baseline. Association of plasma Lp-PLA₂ activity and the progression of carotid plaque and IMT was assessed in men and women after adjusting for traditional Framingham risk factors (including age, smoking, diabetes, hypertension, LDL-C, and HDL-C) and high-sensitivity C-reactive protein (hsCRP).

Results During 5 years of follow-up, carotid plaque progression was found in 58.5% of men and 48.3% of women, and the median level of carotid IMT increased by 0.62 mm in men and 0.46 mm in women. Progression increased with quartiles of Lp-PLA₂ in men (P <0.05 for trend) but not in women. After adjustment for traditional risk factors and hsCRP, the odds ratio for plaque progression associated with increase in Lp-PLA₂ by one unit was 1.03 (95% CI = 1.00-1.06, P = 0.026) in men and 0.99 (95% CI = 0.96-1.01, P = 0.273) in women, and the regression coefficient for IMT progression was 0.016 (P = 0.008) in men and -0.007 (P = 0.143) in women, when baseline IMT was further adjusted. The risk of atherosclerosis progression was the highest in men with a higher level of Lp-PLA₂ activity combined with either higher LDL-C or lower HDL-C, the lowest in men with a lower Lp-PLA₂ activity coupled with either lower LDL-C level or higher HDL-C, with the rest in the middle.

Conclusions Lp-PLA₂ is associated with the progression of subclinical atheroslcerosis in men. It may play an important role in the pathogenesis of atherosclerosis and may be a potential target for early prevention of CVD.