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Randomized Controlled Trial
. 2013 Apr;103(4):e105-12.
doi: 10.2105/AJPH.2012.301163. Epub 2013 Feb 14.

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

Leo R Zacharski  1 , Ralph G DePalma, Galina Shamayeva, Bruce K Chow
Affiliations
Randomized Controlled Trial

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

Leo R Zacharski et al. Am J Public Health. 2013 Apr.

Erratum in

  • Am J Public Health. 2013 May;103(5):e9

Abstract

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.

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Figures

FIGURE 1—
FIGURE 1—
Linear regression analysis for the overall cohort (n = 1277): the Iron and Atherosclerosis Study (FeAST), Multiple US Veterans Administration Centers, 1999–2005. Note. HDL = high-density lipoprotein; LDL = low-density lipoprotein. There was no association between mean follow-up ferritin levels and mean follow-up HDL/LDL ratios (P = .89).
FIGURE 2—
FIGURE 2—
Mean follow-up HDL/LDL ratio and log-relative hazard for all-cause mortality for the overall cohort (n = 1277): the Iron and Atherosclerosis Study (FeAST), Multiple US Veterans Administration Centers, 1999–2005. Note. CI = confidence interval; HDL = high-density lipoprotein; HR = hazard ratio; LDL = low-density lipoprotein. HR = 1.01 (95% CI = 0.89, 1.16; P = .84).
FIGURE 3—
FIGURE 3—
Kaplan–Meier analysis for all-cause mortality in the overall cohort (n = 1277): the Iron and Atherosclerosis Study (FeAST), Multiple US Veterans Administration Centers, 1999–2005. Note. HDL = high-density lipoprotein; LDL = low-density lipoprotein. There was no difference between patients having mean follow-up HDL/LDL ratios above vs below the median of the means for the cohort (hazard ratio = 0.97; 95% confidence interval = 0.66, 1.41; P = .857).
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