Remnant cholesterol reduction for ASCVD prevention: modelling in the Copenhagen General Population Study

Aims Elevated remnant cholesterol is a causal factor for atherosclerotic cardiovascular disease (ASCVD); however, whether aggressive lowering will reduce ASCVD is unclear. In women and men, we tested the hypothesis that aggressive lowering of remnant cholesterol has the potential for substantial ASCVD reduction. This was tested using modelling of cohort data. Methods and results From the Copenhagen General Population Study, 56 422 women and 43 952 men without a history of ASCVD were recruited from 2003 through 2015. They were subsequently followed in national Danish health registries until December 2021 for incident ASCVD. During a median follow-up of 12 years, 4946 women and 6043 men developed ASCVD. In women at very-high cardiovascular risk, 2 mmol/L (77 mg/dL) lower levels of remnant cholesterol from 3 mmol/L (116 mg/dL) likely reduces absolute 10-year risk of ASCVD by 17 and 13% in statin users and non-users; corresponding values in men were 20 and 15%, respectively. Corresponding values by 1 mmol/L (39 mg/dL) lower remnant cholesterol were 10 and 7% in women and 11 and 9% in men, respectively. Similar values are also provided for lower starting remnant cholesterol levels, different lowering of remnant cholesterol, and lower baseline cardiovascular risk. Conclusion In women and men, aggressive lowering of remnant cholesterol has the potential for substantial ASCVD reduction. Estimated absolute risk reduction was larger in statin users vs. non-users and in men vs. women, likely because statin users vs. non-user and men vs. women are at higher baseline absolute risk.