Multiple facets of HDLs as modifiable risk factors in stroke-the good, the bad, and the ugly

J Lipid Res. 2025 Sep;66(9):100879. doi: 10.1016/j.jlr.2025.100879. Epub 2025 Aug 19.

Abstract

HDL as a component of the lipid profile has been extensively studied for its link to CVDs, particularly its relationship with atherogenesis. It has been observed that plasma levels of HDL-C display an inverse relationship with stroke as well, suggesting that higher levels could potentially reduce the risk of stroke. Nevertheless, recent studies suggest that HDL-C alone may not fully predict stroke risk. The complexity of HDL particles arises from their diverse nature, showing significant heterogeneity in various dimensions. The functional quality of HDL extends beyond its quantity, with factors like lipoprotein subspecies (varying in size, lipid compositions, microRNA, and protein content) influencing HDL functionality under different pathophysiological conditions. This heterogeneity of HDL, particularly in the context of stroke, has received limited attention in reviews. While some studies have suggested that higher levels of HDL-C are linked to a reduced risk of stroke, others have found no such association. While HDL is known for its atheroprotective effects, its antioxidant and anti-inflammatory properties may be as vital as cholesterol efflux in preventing atherosclerosis-related stroke. This review emphasizes the importance of exploring various functionalities of HDL in the context of stroke.By elucidating the multifaceted relationship between HDL and stroke as demonstrated by contemporary literature, we aim to enhance the understanding of HDL's influence on stroke pathophysiology and identify avenues for future research in this field.

Keywords: HDL; HDL functionality; HDL particle concentration; atherosclerosis; cholesterol efflux; stroke.

Publication types

  • Review

MeSH terms

  • Animals
  • Cholesterol, HDL* / blood
  • Humans
  • Lipoproteins, HDL* / blood
  • Lipoproteins, HDL* / metabolism
  • Risk Factors
  • Stroke* / blood
  • Stroke* / metabolism

Substances

  • Lipoproteins, HDL
  • Cholesterol, HDL