One in Five Atherosclerotic Cardiovascular Disease Events in Individuals With Diabetes Attributed to Elevated Remnant Cholesterol

ABSTRACT Aims Elevated remnant cholesterol (= the cholesterol carried in triglyceride‐rich lipoproteins) is a causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and is common in individuals with diabetes. We tested the hypothesis that ASCVD in individuals with diabetes can be partly attributed to elevated remnant cholesterol. Materials and Methods We included 3806 individuals with diabetes identified among 107,243 individuals from the Copenhagen General Population Study and used multivariable adjusted Poisson regression to estimate the fraction of ASCVD attributable to elevated remnant cholesterol. Elevated remnant cholesterol was defined as levels higher than those observed in individuals with non‐high‐density lipoprotein (non‐HDL) cholesterol < 2.6 mmol/L (100 mg/dL), the European guideline goal. Results were replicated in the UK Biobank. Results During 15 years of follow‐up, 498 patients were diagnosed with ASCVD, 172 with peripheral artery disease, 185 with myocardial infarction and 195 with ischaemic stroke. In individuals with non‐HDL cholesterol < 2.6 mmol/L (100 mg/dL) and in all individuals with diabetes, median remnant cholesterol levels were 0.5 mmol/L (20 mg/dL) and 0.8 mmol/L (31 mg/dL). The fraction of events attributable to elevated remnant cholesterol was 19% (95% confidence interval: 10%–28%) for ASCVD, 21% (5%–37%) for peripheral artery disease, 24% (10%–37%) for myocardial infarction and 17% (1%–31%) for ischaemic stroke; in the UK Biobank, corresponding values were 16% (9%–22%), 25% (12%–36%), 17% (8%–25%) and 7% (0%–19%), respectively. Conclusions One in five ASCVD events in individuals with diabetes can be attributed to elevated remnant cholesterol. It remains to be determined in clinical trials if remnant cholesterol‐lowering therapy may prevent ASCVD.