Original article
Clinical
Relationship of Cardiovascular Risk Factors and Serum Ferritin with C-reactive Protein

https://doi.org/10.1016/j.arcmed.2006.08.008Get rights and content

Background

Serum iron plays an important role in the oxidation of low-density lipoprotein (LDL) cholesterol, it induces inflammatory reactions and it is positively related to coronary heart disease. An increase of the inflammatory marker, C-reactive protein (CRP), is a risk factor for future cardiac events. Hence, we examined the association of the cardiovascular disease risk factors and serum ferritin with CRP.

Methods

This study was performed on 808 subjects (465 males and 343 females). CRP levels >3.0 mg/L, serum ferritin levels >200 ng/mL, total cholesterol levels >200 mg/dL and LDL-cholesterol levels >160 mg/dL were all considered as elevated. High-density lipoprotein cholesterol levels <40 mg/dL were considered as low.

Results

In the group with low LDL-cholesterol, no correlation was detected between serum ferritin and hsCRP [odds ratio (OR) = 1.68, 95% confidence interval (CI) = 0.81–3.48, p = 0.144]. However, a correlation was detected in the group with elevated LDL-cholesterol (OR = 11.21, 95% CI = 1.14–110.27, p = 0.032). In addition, when the interaction term was added to the assessment of the correlation between the elevated hsCRP and LDL-cholesterol, the strong correlation of hsCRP and serum ferritin was confirmed (p = 0.002).

Conclusions

Oxidation of LDL-cholesterol by serum ferritin may play a role in the inflammatory reaction and for the increased hsCRP. Future prospective studies may be required to assess whether reducing the serum ferritin and CRP levels via medical intervention and life style modification would be helpful for preventing cardiovascular disease.

Introduction

Many studies have suggested a link between abnormal iron storage and the development of atherosclerotic CAD 1, 2, 3, 4, 5. A study on Finnish subjects reported that 2.2 times greater levels of cardiovascular disease were observed in the group with high serum iron compared to the group with low serum iron (6) and serum ferritin was reported to be associated with cardiovascular disease and cardiovascular mortality (7). This link has been referred to as the “iron hypothesis” (3). The rationale for the hypothesis is that iron donates electrons to promote the formation of reactive oxygen species (ROS) such as the hydroxyl radical (OH) from hydrogen peroxide (H2O2) via the Fenton reaction. Excessive iron in tissues may catalyze the formation of highly reactive forms of oxygen free radicals. Unstable free radicals such as the hydroxyl radical, singlet oxygen or H2O2 can cause oxidation of low-density lipoprotein (LDL), which is a trigger for the development of atherosclerotic CAD (8). Recently a study has reported an association between ferritin and C-reactive protein (CRP) (9). It has been reported that chronic inflammatory reactions promote the progression of atherosclerosis and induce cardiovascular disease. The increase of one inflammatory reaction marker, CRP, is a risk factor for future cardiac events even in healthy individuals 10, 11. CRP has also been shown to be related to various cardiovascular risk factors such as age, total cholesterol levels, triglyceride, blood glucose levels, systolic blood pressure and insulin resistance 12, 13. However, there have been insufficient data (and especially about apparently healthy Asians), to suggest a correlation between CRP and oxidative stress and serum ferritin 6, 14, 15. Therefore, this study investigated the effects of serum ferritin and the cardiovascular risk factors on the CRP levels in Korean subjects.

Section snippets

Study Population

The study population was selected from among subjects who underwent health screening at Kangbuk Samsung Hospital from September to December 2003. We selected a total of 808 subjects (465 males and 343 females) who had their serum ferritin levels measured.

We excluded those subjects who were taking statins, antihypertensive agents or antidiabetic agents, and who had acute or chronic inflammatory diseases, thyroid diseases or any suspicion of malignancies. All subjects gave written informed

Clinical Characteristics of the Study Population

The mean age of the total study population was 47.7 ± 11.1 years, with 43% of the subjects being >50 years old. The male:female ratio was 1.36:1. Of the subjects, 2.6% had a body mass index >30, 6.3% had diabetes, and 28.1% were smokers. The mean body mass index was 24.2 ± 2.9 kg/m2 and 10.0% of the subjects had hypertension. Subjects' mean serum total cholesterol was 209.6 ± 38.4 mg/dL, mean HDL-cholesterol was 55.4 ± 13.1 mg/dL, mean LDL-cholesterol was 118.1 ± 30.9 mg/dL, mean hsCRP was 1.22

Discussion

Inflammatory reactions are well known to induce and accelerate atherosclerosis. Several studies have reported the correlation of the inflammatory reaction marker CRP and the risk of cardiovascular disease 10, 11, 12, 13, 18. CRP and serum ferritin are acute phase reactants that are elevated during inflammation or infection. Salonen (6) reported that increases in serum ferritin accelerate the oxidation of LDL-cholesterol. This oxidized LDL-cholesterol induced inflammation in blood vessels,

References (21)

There are more references available in the full text version of this article.

Cited by (14)

  • Decreased iron stores are associated with cardiovascular disease in patients with type 2 diabetes both cross-sectionally and longitudinally

    2018, Atherosclerosis
    Citation Excerpt :

    CRP, haemoglobin and fibrinogen levels were measured at the original baseline of ET2DS, one year before ferritin was measured. However, CRP and haemoglobin levels were related to ferritin quintiles in a dose-response manner, which is in line with the positive associations between these markers observed in diverse populations [22,23], although with variable and modest strength in the case of CRP [24–26]. There were slight differences in definitions of CHD and CEVD in the ET2DS and SIDIAP studies due to predetermined ways of establishing variables of disease in each study.

  • The role of iron in type 2 diabetes in humans

    2009, Biochimica et Biophysica Acta - General Subjects
  • Association of γ-Glutamyltransferase with Cardiovascular Risk: A Prognostic Outlook

    2009, Archives of Medical Research
    Citation Excerpt :

    It is also a key component of numerous pathways implicated in inflammation (16). Considerable association of high-sensitivity C-reactive protein, a major inflammatory marker for cardiovascular risk, with GGT and other cardiovascular risk factors has been described implying that elevation of serum GGT (conceivably acting as a marker of oxidative stress) is correlated with subclinical microinflammatory response involved in the pathogenesis of atherosclerosis (17,18). Then, baseline GGT testing can plausibly have an adjunctive merit in estimating cardiovascular risk.

View all citing articles on Scopus
1

These authors contributed equally to this manuscript.

View full text