Objective 7-Ketocholesterol (7-KC), a major oxidation product of cholesterol, is found in human atherosclerotic plaque and more atherogenic than cholesterol in animal models. This study was designed to investigate the association of plasma 7-KC level with the incident cardiovascular disease (CVD) events in general population.

Methods We measured plasma 7-KC concentrations at baseline in 1944 participants free from CVD in a community-based cohort study. The primary endpoint was incident of a major adverse cardiovascular event. A Cox proportional hazards model was used to calculate the HRs with 95% CI.

Results A total of 101 incident CVD events were recorded during the 5.2 year median follow-up. The baseline plasma 7-KC levels were associated with a higher risk of incident CVD events; compared with quartile 1, participants in quartile 4 had an unadjusted HR of 2.38 (2.03–2.85, p<0.001) and an adjusted HR of 1.70 (1.45–1.91, p=0.004) after adjusting for traditional risk factors. Plasma 7-KC levels improved all of the metrics of discrimination and reclassification when added to the intima–media thickness (C-statistic: p=0.002; net reclassification improvement (NRI): p<0.001; integrated discrimination improvement (IDI): p<0.001), family history of myocardial infarction (C-statistic: p=0.011; NRI: p=0.004; IDI: p=0.003) and elevated high-sensitivity C reactive protein (C-statistic: p=0.008; NRI: p=0.015; IDI: p=0.009).

Conclusions Elevated plasma 7-KC levels are associated with the incident CVD events in a population-based cohort. Further studies are needed to confirm this observation.