
One in five atherosclerotic cardiovascular disease (ASCVD) events in people with diabetes can be attributed to elevated remnant cholesterol, according to an analysis of 3,806 individuals with diabetes identified among 107,243 people from the Copenhagen General Population Study (CGPS).1
Elevated remnant cholesterol was defined as levels higher than those in individuals with non-HDL-C <2.6 mmol/L (100 mg/dL), ie. the European guideline goal.
During 15 years follow-up, 498 patients in CGPS were diagnosed with ASCVD, 172 with peripheral artery disease (PAD), 185 with myocardial infarction (MI) and 195 with ischaemic stroke.
In individuals with non-HDL cholesterol <2.6 mmol/L (100 mg/dL) and in all those 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 PAD, 24% (10%–37%) for MI and 17% (1%–31%) for ischaemic stroke.
The analysis was replicated using UK Biobank data, and corresponding values were 16% (9%–22%), 25% (12%–36%), 17% (8%–25%) and 7% (0%–19%), respectively.
In a second study using CGPS data, 15-year follow-up results were analysed on 10,427/107,925 individuals with impaired renal function (estimated glomerular filtration rate, <60 mL/min per 1.73 m2).2
In this group, 597 were diagnosed with MI, 618 with ischaemic stroke, and 1182 with ASCVD. Every 1 mmol/L (39 mg/dL) higher remnant cholesterol level was associated with multivariable-adjusted hazard ratios of 1.22 (95% CI, 1.05-1.42) for MI, 1.16 (95% CI, 0.97-1.38) for ischaemic stroke, and 1.21 (95% CI, 1.08-1.36) for ASCVD. Corresponding hazard ratios for ASCVD were 1.40 (95% CI, 1.07-1.83) in statin users and 1.16 (95% CI, 1.01-1.34) in non-users.
Of the 1.36-fold excess risk of ASCVD in impaired versus normal renal function, elevated remnant cholesterol and elevated LDL-C explained 25% (95% CI, 2.5%-47%) and 0% in statin users and 8.3% (95% CI, 2.4%-14%) and 14% (95% CI, 6.4%-22%) in non-users, respectively.
Professor Børge G Nordestgaard, University of Copenhagen, Denmark, and colleagues concluded that clinical trials are still needed to find out if lowering remnant cholesterol may prevent ASCVD and that higher remnant cholesterol (but maybe not higher LDL-C) is a good marker of increased ASCVD risk in individuals with impaired renal function.
References
- Wadström BN, Pedersen KM, Wulff AB, Nordestgaard BG. One in Five Atherosclerotic Cardiovascular Disease Events in Individuals With Diabetes Attributed to Elevated Remnant Cholesterol. Diabetes Metab Res Rev. 2024 Nov;40(8):e70005. doi: 10.1002/dmrr.70005. PMID: 39550770.
- Elías-López D, Vedel-Krogh S, Kobylecki CJ, Wadström BN, Nordestgaard BG. Impaired Renal Function With Higher Remnant Cholesterol Related to Risk of Atherosclerotic Cardiovascular Disease: A Cohort Study. Arterioscler Thromb Vasc Biol. 2024 Dec;44(12):2647-2658. doi: 10.1161/ATVBAHA.124.321387.