Directly measured vs. calculated remnant cholesterol identifies additional overlooked individuals in the general population at higher risk of myocardial infarction

Aims: We tested the hypothesis that high directly measured remnant cholesterol is associated with increased risk of ischaemic heart disease (IHD) and myocardial infarction (MI) in the general population. We also explored whether directly measured vs. calculated remnant cholesterol is superior in identifying individuals at increased risk.

Methods and results: Overall, 16 207 individuals from the Copenhagen General Population Study with both directly measured and calculated remnant cholesterol, both representing cholesterol content in triglyceride-rich lipoproteins, were followed up for 14 years to analyse the risk for IHD and MI. For directly measured and calculated remnant cholesterol, hazard ratios for individuals with concentrations ≥95th percentile vs. <40th percentile were 1.75 (95% confidence interval 1.42-2.15) and 1.76 (1.42-2.17) for IHD and 2.05 (1.50-2.80) and 1.93 (1.40-2.66) for MI. Compared to individuals with both directly measured and calculated remnant cholesterol <80th percentile (75% of the whole population), those with only directly measured remnant cholesterol ≥80th percentile (5%) had hazard ratios of 1.42 (1.15-1.75) for IHD and 1.83 (1.35-2.47) for MI. Corresponding hazard ratios for individuals with only calculated remnant cholesterol ≥80th percentile (5%) were 1.14 (0.91-1.44) and 1.14 (0.80-1.62), respectively, and corresponding hazard ratios for individuals with both directly measured and calculated remnant cholesterol ≥80th percentiles (15%) were 1.48 (1.30-1.68) and 1.67 (1.38-2.01), respectively. In individuals with high directly measured or high calculated remnant cholesterol, the median directly measured remnant cholesterol was 1.9 and 1.5 mmol/L, the median plasma triglycerides were 2.0 and 2.7 mmol/L, and the median plasma apolipoprotein B was 132 and 142 mg/dL, respectively.

Conclusions: Directly measured vs. calculated remnant cholesterol identifies 5% overlooked individuals in the general population with cholesterol-rich, triglyceride-poor remnants and 1.8-fold increased risk of MI.