BackgroundThe relationship between cumulative non-high-density lipoprotein cholesterol (non-HDL-C) burden and atherosclerotic cardiovascular disease (ASCVD) remains unclearObjectiveTo prospectively examine the association between cumulative non-HDL-C burden and ASCVD risk in the Kailuan cohort of China.MethodsA total of 49,679 subjects who were free of ASCVD participated in three consecutive examinations in 2006, 2008 and 2010 were enrolled. Duration and concentration of cumulative exposure to non-HDL-C (cumNon-HDL-C) were respectively used to estimate the extent of cumulative non-HDL-C burden. The participants were divided into four groups according to durations of cumNon-HDL-C (0, 2, 4 and 6 years) and five groups according to the quintiles of cumNon-HDL-C concentration (<10.93, 10.93–12.68, 12.69–14.32, 14.33–16.72 and ≥16.73 mmol/L). Cox regression models were used to analyze the influence of cumulative non-HDL-C burden on ASCVD risk.ResultsWe identified 1,134 incident ASCVD cases during a mean of 4.89 years of follow-up. Multivariable adjusted analysis revealed that compared with no exposure, cumNon-HDL-C duration 2, 4 and 6 years increased ASCVD risk by 26% (HR: 1.26, 95% CI: 1.07–1.47), 56% (HR: 1.56, 95% CI: 1.31–1.86) and 91% (HR: 1.91, 95% CI: 1.59–2.31) respectively; The hazard ratios (HRs) for the fourth and fifth versus lowest quintile of cumNon-HDL-C concentration were 1.25 and 1.72 for ASCVD. Each standard deviation increment in cumNon-HDL-C concentration was associated with a 10% increased risk of ASCVD.ConclusionLong-term and higher cumNon-HDL-C were all significantly associated with an increased risk of ASCVD independent of single non-HDL-C level.