VLDL cholesterol and ASCVD risk: A population-based study

BACKGROUND: Observational and genetic evidence show associations of high remnant cholesterol levels with atherosclerotic cardiovascular disease (ASCVD). New drugs have been developed that substantially lower remnant cholesterol; however, the corresponding absolute risk reduction of ASCVD remains unclear. Remnant cholesterol can be measured directly or calculated, but few studies have analyzed the effects of directly measured remnant cholesterol. OBJECTIVE: To estimate the 10-year absolute risk reductions of ASCVD according to proportional reduction of individual very low-density lipoprotein (VLDL) cholesterol levels among individuals with levels above 1 mmol/L (39 mg/dL). METHODS: We used VLDL cholesterol measured by nuclear magnetic resonance spectroscopy to quantify directly measured remnant cholesterol. We estimated the reduction in the average 10-year ASCVD risk associated with an intervention targeting the 2021 individuals in the Copenhagen General Population Study with VLDL cholesterol levels above 1 mmol/L (39 mg/dL), assuming a proportional reduction in their individual VLDL cholesterol levels. RESULTS: We found that a 50% or 80% proportional reduction in VLDL cholesterol was associated with a 10-year absolute risk reduction of ASCVD of 3.0% (95% CI: 2.6%-3.4%) and 4.5% (3.9%-5.1%), respectively. CONCLUSION: This suggests a clinically meaningful benefit from lowering of VLDL cholesterol in primary prevention.