Reduction of body iron stores and cardiovascular outcomes

February 13, 2007

The reduction of body iron stores through phlebotomy (blood removal) in patients with peripheral artery disease (PAD) does not appear to decrease the risk of death plus nonfatal cardiovascular events, according to a study published in the February 14 issue of JAMA.

PAD is a partial or total blockage of an artery, usually one leading to a leg or an arm. According to background information in the article, "accumulation of iron in excess of physiologic requirements has been implicated in the risk of several chronic diseases through increased iron-catalyzed free radical-mediated oxidative stress. Common diseases of aging that have been attributed to this mechanism include cardiovascular disease and cancer." The authors cite the "iron-heart" hypothesis of atherosclerotic cardiovascular disease to explain the age-related increase in myocardial infarction (MI) [heart attack] in women following menopause. Men have increasing levels of iron from childhood to late teens and their rates of MI increase earlier as compared to women.

Leo R. Zacharski, M.D., from the VA Medical Center, White River Junction, VT, and colleagues conducted a multicenter, randomized controlled clinical trial from May 1, 1999 and April 30, 2005 based on the Iron (Fe) and Atherosclerosis Study (FeAST), a pilot study that demonstrated the accuracy of a formula for calculating the amount of blood required to be removed to achieve the desired iron (ferritin) reduction safely and without causing iron deficiency. Patients with symptomatic PAD were assigned to a control group (n = 641) or to a group undergoing reduction of iron stores by phlebotomy with removal of defined volumes of blood at six-month intervals (n=636).

"There were no significant differences between treatment groups for the primary (all-cause death) or secondary (death plus nonfatal MI and stroke) study end points," the authors report. "All-cause deaths occurred in 148 patients (23 percent) in the control group and in 125 (20 percent) in the iron-reduction group. Death plus nonfatal myocardial infarction and stroke occurred in 205 patients (32 percent) in the control group and in 180 (28 percent) in the iron-reduction group." The researchers also examined whether effects of iron reduction differed across subgroups. They found apparent improvement with iron reduction among younger patients, those without diabetes and in smokers.

In conclusion the authors write, "The FeAST data show that it should be possible to test definitively whether controlling iron levels may reduce disease risk. Additional research is needed to further define ferrotoxic diseases, stratify risk reduction with intervention, and clarify mechanisms, particularly in younger patients."
(JAMA. 2007;297: 603-610. Available pre-embargo to the media at Editor's Note: This study was funded by the Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development Clinical Science Research & Development Service. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Editorial: The Iron-Heart Hypothesis

In an accompanying editorial Frank B. Hu, M.D., Ph.D., from the Harvard School of Public Health, Boston, writes that results from this first randomized controlled clinical trial assessing iron-store reduction have been eagerly awaited to test the hypothesis that iron depletion through phlebotomy or other means can lower the risk for coronary heart disease (CHD).

"The results from this well-designed and executed trial generate more questions than answers." Dr. Hu questions whether the study was adequately powered, whether the study patients were a suitable population and whether the findings can be generalized to healthy individuals.

"Like any other theory in cardiovascular medicine, the iron-heart hypothesis will undergo many 'trials and tribulations' before it is proven or refuted. Fortunately, it is not necessary to wait for additional data to implement effective strategies that can prevent coronary arteries from getting 'rusty.' Even though the question of whether reduced iron stores and CHD risk are causally linked remains unanswered, there is solid evidence that regular exercise and maintaining a healthy weight can reduce both iron stores and risk of CHD." (JAMA. 2007;297:639-641. Available pre-embargo to the media at Editor's Note: No financial disclosures reported.

The JAMA Network Journals

Related Myocardial Infarction Articles from Brightsurf:

Treatment shows reduction in heart failure after myocardial infarction
Researchers at Baylor College of Medicine identified potential preventative therapies for heart failure after a significant heart attack.

The challenges of treating acute myocardial infarction due to variant angina
In a new publication from Cardiovascular Innovations and Applications; DOI, Wen-Yuan Ding, Jia-Min Li, Fei Zheng, Li-Li Wang, Xin-Yi Wei and Guo-Hua Li from Shandong Provincial Qianfoshan Hospital, Ji'nan, China, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Ji'nan, China and Shandong First Medical University, Tai'an, China consider the challenges of treating acute myocardial infarction due to variant angina.

WeChat group of chest pain center for patients with acute ST-segment elevation myocardial infarction
In a new publication from Cardiovascular Innovations and Applications; DOI, Liu Yue, Qin Zhu-Yun, Yang Xin, Tang Rong and Gao Ling-Yun from the The First Affiliated Hospital of Chongqing Medical University, Chongqing, China consider the use of a social media platform (WeChat) to provide faster treatment and improve prognoses for a group of patients with acute ST-segment Elevation Myocardial Infarction.

Improved survival after obesity operation in patients with previous myocardial infarction
Researchers at Karolinska Institutet and Danderyd Hospital in Sweden have studied the risk of additional myocardial infarctions and early death in severely obese patients who undergo metabolic surgery following a myocardial event.

Researchers discover a cell type responsible for cardiac repair after infarction
The researcher of the Faculty of Science of the UMA Adrián Ruiz-Villalba, who is also member of the Andalusian Center for Nanomedicine and Biotechnology (BIONAND) and the Biomedical Research Institute of Malaga (IBIMA), is the first author of an international study that has identified the heart cells in charge of repairing the damage caused to this organ after infarction.

Discovery of cells that heal cardiac damage after infarction
Researchers at Cima and the Clinica Universidad de Navarra (Spain) have led an international study identifying the cardiac cells responsible for repairing the damage to this organ after infarction.

CHOP researchers find MIS-C associated with myocardial injury
Using sensitive parameters to assess cardiac function, researchers at Children's Hospital of Philadelphia (CHOP) have found that cardiac involvement in multisystem inflammatory syndrome in children (MIS-C) differs from Kawasaki disease (KD) and is associated with myocardial injury.

Heart attack modeled with human stem cells
A model of ischemic heart disease was developed using human induced pluripotent stem cells (hiPSC).

The relationship between lifetime drinking and non-fatal acute myocardial infarction
New research from the Prevention Research Center of the Pacific Institute for Research and Evaluation suggests that the impact of alcohol consumption on coronary heart disease may be underestimated.

The relationship between mean platelet volume and in-hospital mortality in geriatric patients with ST segment elevation myocardial infarction who underwent primary percutaneous coronary intervention
In the current issue of Cardiovascular Innovations and Applications volume 4, issue 2, pp.

Read More: Myocardial Infarction News and Myocardial Infarction Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to