Remnant cholesterol, not LDL cholesterol, explains peripheral artery disease risk conferred by apolipoprotein B: a cohort study

Abstract

Abstract Background Elevated apolipoprotein B (apoB)-containing lipoproteins (=remnants + low-density lipoproteins [LDL]) are a major risk factor for atherosclerotic cardiovascular disease, including peripheral artery disease (PAD) and myocardial infarction. We tested the hypothesis that remnants and LDL both explain part of the increased risk of PAD conferred by elevated apoB-containing lipoproteins. For comparison, we also studied risk of chronic limb-threatening ischemia and myocardial infarction. Methods ApoB, remnant cholesterol, and LDL cholesterol were measured in 93,461 individuals without statin use at baseline from the Copenhagen General Population Study (2003-2015). During up to 15 years of follow-up, 1,207 had PAD, 552 had chronic limb threatening ischemia, and 2,022 had myocardial infarction in the national Danish Patient Registry. Remnant and LDL cholesterol were calculated from a standard-lipid profile. Remnant and LDL particle counts were additionally measured with nuclear magnetic resonance spectroscopy in 25,347 of the individuals. Results were replicated in 302,167 individuals without statin use from the UK Biobank (2004-2010). Results In the Copenhagen General Population Study, multivariable adjusted hazard ratios for risk of PAD per 1 mmol/L (39 mg/dL) increment in remnant and LDL cholesterol were 1.9 (95% confidence interval: 1.5-2.4) and 1.1 (1.0-1.2), respectively; corresponding results in the UK Biobank were 1.7 (1.4-2.1) and 0.9 (0.9-1.0), respectively. In the association from elevated apoB to increased risk of PAD, remnant and LDL cholesterol explained 73% (32-100%) and 8% (0-46%), respectively; corresponding results were 63% (30-100%) and 0% (0-33%) for risk of chronic limb-threatening ischemia, and 41% (27-55%) and 54% (38-70%) for risk of myocardial infarction; results for remnant and LDL particle counts corroborated these findings. Conclusions PAD risk conferred by elevated apoB-containing lipoproteins was explained mainly by elevated remnants, while myocardial infarction risk was explained by both elevated remnants and LDL.