The statin-iron nexus: anti-inflammatory intervention for arterial disease prevention

Am J Public Health. 2013 Apr;103(4):e105-12. doi: 10.2105/AJPH.2012.301163. Epub 2013 Feb 14.


Objectives: We postulated the existence of a statin-iron nexus by which statins improve cardiovascular disease outcomes at least partially by countering proinflammatory effects of excess iron stores.

Methods: Using data from a clinical trial of iron (ferritin) reduction in advanced peripheral arterial disease, the Iron and Atherosclerosis Study, we compared effects of ferritin levels versus high-density lipoprotein to low-density lipoprotein ratios (both were randomization variables) on clinical outcomes in participants receiving and not receiving statins.

Results: Statins increased high-density lipoprotein to low-density lipoprotein ratios and reduced ferritin levels by noninteracting mechanisms. Improved clinical outcomes were associated with lower ferritin levels but not with improved lipid status.

Conclusions: There are commonalities between the clinical benefits of statins and the maintenance of physiologic iron levels. Iron reduction may be a safe and low-cost alternative to statins.

Publication types

  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Atherosclerosis / prevention & control*
  • Chi-Square Distribution
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Inflammation / drug therapy
  • Iron / metabolism*
  • Iron Overload / complications*
  • Linear Models
  • Lipoproteins, HDL / blood
  • Lipoproteins, LDL / blood
  • Male
  • Peripheral Arterial Disease / prevention & control*
  • Proportional Hazards Models
  • Prospective Studies
  • United States
  • United States Department of Veterans Affairs


  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Lipoproteins, HDL
  • Lipoproteins, LDL
  • Iron