In familial hypercholesterolaemia, remnant cholesterol above 1 mmol/L is associated with 50% higher risk of coronary artery disease

AIMS: Familial hypercholesterolaemia (FH) leads to lifelong elevated low-density lipoprotein (LDL) cholesterol and increased risk of coronary artery disease. We tested the hypothesis that elevated remnant cholesterol additionally increases cardiovascular risk in FH. METHODS: In the Copenhagen General Population Study (CGPS) and UK Biobank, 108,751 and 428,625 individuals were classified as with or without FH according to clinical scores and genetic mutations. In the two cohorts, 7,708 and 50,997 experienced coronary artery disease, respectively. RESULTS: In CGPS and UK Biobank, remnant cholesterol ≥1 mmol/L (39 mg/dL) was observed in 12% and 11% of individuals without FH (N = 104,226 and 403,172), in 33% and 40% with Simon Broome FH (N = 3,923 and 23,860), in 44% and 78% with MEDPED FH (N = 1,005 and 2,465), in 33% and 34% with DLCN FH (N = 744 and 1,207), and in 12% and 21% of individuals with genetic FH (N = 188 and 875). Likewise in the CGPS and UK Biobank, the multivariable adjusted hazard ratios for coronary artery disease by remnant cholesterol ≥1 vs. < 1 mmol/L (39 mg/dL) were 1.49 (95% CI: 1.39-1.59) and 1.47 (1.43-1.52) in individuals without FH, 1.59 (1.31-1.93) and 1.18 (1.10-1.27) in Simon Broome FH, 1.50 (1.08-2.08) and 1.14 (0.89-1.45) in MEDPED FH, 1.60 (1.17-2.21) and 1.59 (1.20-2.09) in DLCN FH, and 1.48 (0.59-3.69) and 1.39 (0.88-2.19) in genetic FH. CONCLUSION: In familial hypercholesterolaemia, remnant cholesterol ≥1 mmol/L (39 mg/dL) vs below is associated with ≈50% higher risk of coronary artery disease, that is, above the already high risk due to lifelong genetically elevated LDL cholesterol.