Conventional and Novel Lipid Measures and Risk of Peripheral Artery Disease

Arterioscler Thromb Vasc Biol. 2021 Mar;41(3):1229-1238. doi: 10.1161/ATVBAHA.120.315828. Epub 2021 Jan 28.


Objective: The aim of this study was to comprehensively assess the association of multiple lipid measures with incident peripheral artery disease (PAD). Approach and Results: We used Cox proportional hazards models to characterize the associations of each of the fasting lipid measures (total cholesterol, LDL-C [low-density lipoprotein cholesterol], HDL-C [high-density lipoprotein cholesterol], triglycerides, RLP-C [remnant lipoprotein cholesterol], LDL-TG [LDL-triglycerides], sdLDL-C [small dense LDL-C], and Apo-E-HDL [Apo-E-containing HDL-C]) with incident PAD identified by pertinent International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) hospital discharge codes (eg, 440.2) among 8330 Black and White ARIC (Atherosclerosis Risk in Communities) participants (mean age 62.8 [SD 5.6] years) free of PAD at baseline (1996-1998) through 2015. Since lipid traits are biologically correlated to each other, we also conducted principal component analysis to identify underlying components for PAD risk. There were 246 incident PAD cases with a median follow-up of 17 years. After accounting for potential confounders, the following lipid measures were significantly associated with PAD (hazard ratio per 1-SD increment [decrement for HDL-C and Apo-E-HDL]): triglycerides, 1.21 (95% CI, 1.08-1.36); RLP-C, 1.18 (1.08-1.29); LDL-TG, 1.18 (1.05-1.33); HDL-C, 1.39 (1.16-1.67); and Apo-E-HDL, 1.27 (1.07-1.51). The principal component analysis identified 3 components (1: mainly loaded by triglycerides, RLP-C, LDL-TG, and sdLDL-C; 2: by HDL-C and Apo-E-HDL; and 3: by LDL-C and RLP-C). Components 1 and 2 showed independent associations with incident PAD.

Conclusions: Triglyceride-related and HDL-related lipids were independently associated with incident PAD, which has implications on preventive strategies for PAD. However, none of the novel lipid measures outperformed conventional ones. Graphic Abstract: A graphic abstract is available for this article.

Keywords: cholesterol; lipids; lipoproteins; peripheral artery disease; triglycerides.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Apolipoproteins E / blood
  • Cholesterol / blood
  • Cholesterol, HDL / blood
  • Cholesterol, LDL / blood
  • Cohort Studies
  • Dyslipidemias / blood
  • Dyslipidemias / complications
  • Female
  • Humans
  • Lipids / blood*
  • Lipoproteins / blood
  • Lipoproteins, HDL / blood
  • Lipoproteins, LDL / blood
  • Male
  • Peripheral Arterial Disease / blood*
  • Peripheral Arterial Disease / etiology
  • Proportional Hazards Models
  • Prospective Studies
  • Risk Factors
  • Triglycerides / blood


  • Apolipoproteins E
  • Cholesterol, HDL
  • Cholesterol, LDL
  • Lipids
  • Lipoproteins
  • Lipoproteins, HDL
  • Lipoproteins, LDL
  • Triglycerides
  • apolipoprotein E-rich HDL
  • lipoprotein cholesterol
  • low density lipoprotein triglyceride
  • remnant-like particle cholesterol
  • Cholesterol