The association between small dense low-density lipoprotein cholesterol and peripheral artery disease: a large-scale...

High levels of small dense low-density lipoprotein (sdLDL) cholesterol is associated with increased risk of ischemic heart disease and stroke; however, data on peripheral artery disease is sparse and results inconclusive. We tested the hypothesis that higher levels of sdLDL cholesterol are associated with increased risk of peripheral artery disease.

We studied 31,036 individuals free of lipid-lowering therapy, ischemic heart disease, and ischemic stroke with measurements of sdLDL cholesterol at study entry in 2013-2017. During a median follow-up of 6.2 years, 155 were diagnosed with peripheral artery disease. The association was confirmed using ankle-brachial index (ABI) ≤0.9 as an endpoint. Furthermore, a meta-analysis of current and previous studies was conducted in 46,748 individuals including 660 peripheral artery disease cases. Lastly, as a comparison across different vascular beds, risk estimates for myocardial infarction and ischemic stroke were calculated.

In multivariable adjusted models per 1 mmol/L(37 mg/dL) higher sdLDL cholesterol, the hazard ratio for peripheral artery disease was 2.06(95%CI: 1.45-2.92) while the odds ratio for ABI ≤0.9 was 1.53(1.08-2.15). Fixed and random effect meta-analysis risk estimates for peripheral artery disease did not differ and was 1.62(1.27-2.06) for the highest versus the lowest quartile of sdLDL cholesterol. For the 91st-100th versus the 1st-50th percentiles of sdLDL cholesterol, we found hazard ratios of 2.59(1.55-4.33) for peripheral artery disease, 2.18(1.58-3.02) for myocardial infarction, and 1.84(1.37-2.48) for ischemic stroke.

Higher levels of sdLDL cholesterol were robustly associated with increased risk of peripheral artery disease in the present study and in a meta-analysis.