From the Guidelines
Hereditary Hemochromatosis and Vascular Disease
Hereditary hemochromatosis (HH) contributes to vascular disease by promoting oxidative stress, inflammation, and atherosclerosis, ultimately leading to cardiovascular events 1. The iron overload associated with HH can impair endothelial function, as seen in patients with hereditary hemochromatosis, and directly favor atherosclerosis 1. Key factors involved in this process include:
- Elevated hepcidin levels, which may act as a physiologic defense mechanism against iron overload but are also related to fatal and nonfatal cardiovascular events 1
- Increased oxidative stress, usually encountered in end-stage renal disease (ESRD) and provoked by IV iron infusions and iron overload 1
- Arterial and cardiac structural changes, potentially resulting from the pleiotropic effects of hepcidin-25 and the induction of fibroblast growth factor 23 (FGF 23) by iron infusions 1
Mechanisms and Risks
The mechanisms by which HH contributes to vascular disease are multifaceted and involve:
- Oxidative stress: IV iron infusions and iron overload can release labile, non-transferrin-bound iron, leading to oxidative stress and adverse effects on the vascular bed 1
- Inflammation: Iron overload can promote inflammation, which is a key factor in the development of atherosclerosis and cardiovascular events 1
- Atherosclerosis: Excess iron can directly favor atherosclerosis, increasing the risk of cardiovascular complications 1
- Cardiac toxicity: FGF 23, induced by iron infusions, can exert cardiac toxicity, further contributing to the risk of cardiovascular events 1
Clinical Implications
In clinical practice, it is essential to consider the potential risks of vascular disease in patients with hereditary hemochromatosis. Phlebotomy and iron chelation therapy may be used to reduce iron stores and mitigate vascular risk 1. However, the specific treatment approach should be individualized based on the patient's condition, iron overload severity, and other factors.
From the Research
Hereditary Hemochromatosis and Vascular Disease
- Hereditary hemochromatosis (HH) is a genetic disorder characterized by excessive absorption and accumulation of iron in the body, which can lead to damage to various organs, including the cardiovascular system 2.
- The excess iron deposition in HH can cause cardiovascular manifestations, such as dilated cardiomyopathy, conduction abnormalities, heart failure, cardiac fibrosis, myocardial infarction, and valvular heart disease 2.
- Iron overload in HH can also lead to increased risk of cardiac and liver damage, which can be reversed with iron chelation therapy 3.
- The relationship between HH and vascular disease is complex, and the excess iron can lead to tissue damage and increased risk of morbidity and mortality 4, 5.
Mechanisms of Iron-Overload Cardiomyopathy
- Iron-overload cardiomyopathy is a primary determinant of survival in patients with secondary iron overload and a leading cause of morbidity and mortality in patients with primary hemochromatosis 6.
- The mainstay therapies for iron overload associated with primary hemochromatosis and secondary iron overload are phlebotomy and iron chelation therapy, respectively 6.
- Early diagnosis of iron-overload cardiomyopathy is critical, as the cardiac dysfunction is reversible if effective therapy is introduced before the onset of overt heart failure 6.
Clinical Implications
- Hereditary hemochromatosis is a common genetic disease, but screening of the general population is not routinely recommended 4.
- Genotypic check of the frequent mutations of the HFE gene is vital to prevent the development of HH and to initiate treatment before the development of clinical symptoms 5.
- Therapeutic phlebotomy is the primary form of treatment for HH, combined with the use of chelating agents, and orthotopic liver transplantation (OTL) is performed in patients with advanced cirrhosis 5.