High Remnant Cholesterol Linked to 5-Fold Increased Risk for PAD

Individuals with elevated remnant cholesterol had a 5-fold higher risk for peripheral artery disease (PAD) than the general population, according to results of a study published in the European Heart Journal.

Researchers sourced data from the Copenhagen General Population Study and Copenhagen City Heart Study. Individuals were assessed for lipid profiles and cardiovascular outcomes at a follow-up of up to 15 years (General Population) or 43 years (City).

Among the General Population and City cohorts, a total of 1586 and 1033 individuals were diagnosed with PAD, 2570 and 2236 with myocardial infarction, and 2762 and 1976 with ischemic stroke, respectively.

Stratified by remnant cholesterol levels, 35% had levels lower than 0.5 mmol/L; 45% 0.5-0.99 mmol/L; 15% 1.0-1.49 mmol/L; and 5% greater than or equal to 1.5 mmol/L. Individuals with higher remnant cholesterol tended to be male, former smokers, and had higher total cholesterol, low-density lipoprotein cholesterol, and systolic blood pressure.

Among the General Population, the cumulative instance for PAD at age 80 years was 2.9%, 4.7%, 6.3%, and 9.1% for the increasing quartiles of remnant cholesterol. This trend was similar to data from the City cohort (4.2%, 6.2%, 8.3%, 11.1%), respectively.

These values translated to risk for PAD among the lowest General Population (hazard ratio [HR], 1.9; 95% CI, 1.4-2.6) and City (HR, 2.1; 95% CI, 1.4-3.0) remnant cholesterol subgroups as substantially lower than the highest General Population (HR, 4.8; 95% CI, 3.1-7.5) and City (HR, 4.9; 95% CI, 2.9-8.5) remnant cholesterol subgroups.

After correction for measurement error, every 1 mmol/L increase in remnant cholesterol corresponded with an increased risk for PAD (HR, 1.8; 95% CI, 1.5-2.1) among the General Population and (HR, 1.7; 95% CI, 1.4-2.0) City cohorts.

Among the highest remnant cholesterol cohort for the General Population group, the HR for myocardial infarction was 4.2 (95% CI, 2.9-6.1) and for City was 2.6 (95% CI, 1.8-3.8) and risk for ischemic stroke was 1.8 (95% CI, 1.4-2.5) and 2.1 (95% CI, 1.5-3.1), respectively.

This study may have been limited by not including other PAD risk confounders.

The study authors concluded that trends observed in a real-world dataset indicated there was a 5-fold increased risk for PAD among individuals with elevated remnant cholesterol. These individuals were also, to a lesser extent, at increased risk for myocardial infarction and ischemic stroke.

“In the future, large randomized trials of triglyceride and remnant cholesterol-lowering

treatment, such as the ongoing PROMINENT trial, should investigate if lowering of remnant cholesterol can also reduce the risk of PAD,” the researchers said.

Disclosure: An author declared affiliations with industry. Please refer to the original article for a full list of disclosures.

Reference

Wadström BN, Wulff AB, Pedersen KM, Jensen GB, Nordestgaard BG. Elevated remnant cholesterol increases the risk of peripheral artery disease, myocardial infarction, and ischaemic stroke: a cohort-based study. Eur Heart J. 2021;ehab705. doi:10.1093/eurheartj/ehab705