The association between small dense low-density lipoprotein cholesterol and peripheral artery disease: a large-scale cohort study and meta-analysis

AIMS: 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.

METHODS: 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.

RESULTS: 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.

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