Cardiac links, abstracts, articles, etc.
 Click on the title to read more about iron & the heart.

• ABC of diseases of liver, pancreas, and biliary system Other causes of parenchymal liver disease 
  BMJ 2001;322:290-292 ( 3 February ) Haemochromatosis is the commonest inherited liver disease in the United Kingdom. It affects about 1 in 200 of the population and is 10 times more common than cystic fibrosis.

• Acute Coronary Syndromes     Library of National Medical Society

• A history of phlebotomy therapy for hemochromatosis.  Crosby WH. Chapman Cancer Center, Joplin, MO Am J Med Sci 1991 Jan  The earlier the disease is discovered, the less risk of morbidity and mortality. Screening tests (serum iron, total iron-binding capacity, serum ferritin) are recommended for all blood relatives of index cases of this hereditary disease and for all clinics where complications of hemochromatosis may be treated: liver disorder however mild, diabetes mellitus, heart disease, arthropathies, sterility, impotence, premature menopause, and abnormal pigmentation of the skin.

• A middle aged man with diabetes mellitus and a liver mass.   Steven Eliason, M.D., Elizabeth M. Brunt, M.D., Bruce R. Bacon, M.D., Leonard E. Grosso, M.D., Ph.D.  SLUCARE PathLab Case of the Month  

• An aviator with cardiomyopathy and genetic susceptibility to hereditary hemochromatosis
  A case report Aviat Space Environ Med 2001 Oct

• Annals of Internal Medicine SUPPLEMENT DIAGNOSIS AND MANAGEMENT 
  Diagnosis of Hemochromatosis, Annals of Internal Medicine, 1 December 1998. 129:925-931.Lawrie W. Powell, MD; D. Keith George, MD; Sharon M. McDonnell, MD; and Kris V. Kowdley, MD

• Answers to your questions about hereditary hemochromatosis
  from The College of American Pathologists (CAP) Dec 18, 2001

• A prospective study of coronary heart disease and the hemochromatosis gene (HFE) C282Y mutation: the Atherosclerosis Risk in Communities (ARIC) study.  Atherosclerosis 2001 Feb 15 Our prospective findings suggest that individuals carrying the HFE C282Y mutation may be at increased risk of CHD.

• Association of increased ferritin with premature coronary stenosis in men
  Clin Chem 2001 Sep

• A unique rodent model for both the cardiotoxic and hepatotoxic effects of prolonged iron overload.
  Lab Invest. 1993 Aug   This model will allow the detailed study of the mechanism of iron induced, free radical tissue damage, which is though to be the cause of these lesions and will also be useful in the evaluation of iron chelating therapies to determine whether the hepatic and cardiac pathology of iron overload can be modulated over a long period.

• Biochemical and Genetic Markers of Iron Status and the Risk of Coronary Artery Disease: An Angiography-based Study.   Clin Chem 2002 Apr;48(4):622-8   Bozzini C, Girelli D, Tinazzi E, Olivieri O, Stranieri C, Bassi A, Trabetti E, Faccini G, Pignatti PF, Corrocher R.    Department of Clinical and Experimental Medicine, Department of Mother and Child, Biology and Genetics, and. the Institute of Clinical Chemistry, University of Verona, 37134 Verona, Italy.    CONCLUSIONS: Our results do not support a role for biochemical or genetic markers of iron stores as predictors of the risk of CAD or its thrombotic complications.

• Body Iron Stores and the Risk of Carotid Atherosclerosis Circulation 1997 AHA

• C282Y and H63D mutations of the haemochromatosis gene in patients with iron overload
  Rev Esp Enferm Dig 2001 [a pdf file]

• Cardiac alterations in 36 consecutive patients with idiopathic haemochromatosis: polygraphic and echocardiographic evaluation.  Eur Heart J 1991 Feb;12(2):224-30 Early diagnosis and treatment of IH cardiopathy is needed before irreversible cardiac damage occurs

• Cardiac dysfunction because of secondary hemochromatosis caused by congenital non-spherocytic hemolytic anemia. Jpn Circ J. 2001 Feb Cardiac failure accounts for approximately one-third of the deaths associated with hemochromatosis. Liver dysfunction or hormonal disorders such as diabetes generally precede cardiac failure

• Cardiac hemochromatosis: beneficial effects of iron removal therapy. An echocardiographic study. 
   Statistically significant increases in left ventricular (LV) mass, end-diastolic and end-systolic diameters of the left ventricle and in left atrial dimension were observed in patients with IH; significant changes of systolic function indexes (decrease in fractional shortening and ejection fraction and increase in distance of the E point to the septum) were seen as well.  Am J Cardiol 1983 Oct 1

• Cardiac pathology of extracardiac origin (II). The cardiac repercussion of amyloidosis and hemochromatosis   Rev Esp Cardiol 1997 Nov.  Although rare, amyloidosis and hemochromatosis are the infiltrative diseases in which the heart is more frequently involved. The most common clinical presentation is heart failure with hemodynamic features of restrictive heart disease in cardiac amyloidosis.  [Abstract in English, Article in Spanish]

• Cardiac transplantation in a patient with hereditary hemochromatosis:
   role of adjunctive phlebotomy and erythropoietin, J Heart Lung Transplant 2001 Jun

• Cardiomyopathy as the cause of death in genetic hemochromatosis-.
  Z Gastroenterol. 1996 Mar [article in German] The reports of these two cases underline that hemochromatosis-associated cardiomyopathy is often irreversible if severe congestive heart failure is present. In cardiac decompensation heart transplantation has to be considered as early as possible.

• Cardiomyopathy Data Highway Report of the 1995 WHO/ISFC Task Force on the Definition and Classification of Cardiomyopathies, Circulation 1996

• Case 77 -- Hereditary Hemochromatosis  Department of Pathology, University of Utah School of Medicine Sept. 1996 A 38 year old male was admitted to hospital with a two month history of fatigue and a two week history of increasing edema. Congestive heart failure was diagnosed.

• Chapter 11 What is the explanation for heart problems due to iron overload?
  When a lot of iron gets stored in the heart, it may become much larger, and sometimes it beats irregularly. [Problems in Thalassaemia]

• Chronic iron overload and toxicity: clinical chemistry perspective. Clin Lab Sci 2001 Summer; This toxicity involves many organs leading to a variety of serious diseases such as liver disease, heart disease, diabetes mellitus, hormonal abnormalities, dysfunctional immune system, etc. The tissue damage associated with iron overload is believed to result primarily from free radical reactions mediated by iron.

• Clinical and molecular aspects of juvenile hemochromatosis in Saguenay-Lac-Saint-Jean (Quebec, canada)Blood Cells Mol Dis 2000 Feb   Although the mean age at onset of the first symptoms was 21. 5 years, their mean age at diagnosis was 23.8 years; the diagnosis was particularly delayed among women. Seventy-seven percent of the patients had hypogonadotrophic hypogonadism and 69% heart failure and/or cardiac arrhythmias.

• Clinical Consequences of New Insights in the Pathophysiology of Disorders of Iron and Heme Metabolism Hematology 2000  The American Society of Hematology The screening strategy could be based on the assessment of serum transferrin saturation in adults aged 18 or more. Genetic testing testing for C282Y would be confined to individuals with transferrin saturation > 45%. This strategy would then avoid the ethical, logistical, and financial problems raised by systematic genetic testing as well as the societal impact of discovering a genetic mutation in asymptomatic persons without a disease. It is, in fact, essential that major changes occur in the attitudes towards unexpressed or slightly expressed HFE homozygosity, especially by insurers and health care administrators, to avoid any adverse genetic discrimination.

• Clinical management of iron overload. Gastroenterol Clin North Am. 1998 Sep HHC is a common inherited disorder, characterized by iron accumulation in the liver, heart, pancreas, and other organs. The clinical consequences of systemic iron loading are diverse and not always improved with iron reduction therapy.

• Clinical spectrum and management of haemochromatosis 
  Baillieres Clin Haematol 1994 Dec Further strategies have to evaluate the design of screening programmes in order to diagnose more patients in the precirrhotic and asymptomatic stage.

• Clinical Studies of Haemochromatosis  Queensland Institute of Medical  Research, Hepatocellular Cancer Laboratory, Professor Lawrie Powell   Knowledge of haemochromatosis, its prevention, the type and severity of symptoms it causes, the availability and nature of treatment, ability of sufferers to participate in normal activities, and longevity are relevant issues for community education. Members of an informed public can mobilise support for the early diagnosis of haemochromatosis, encourage people to be tested for the disorder and influence the debate about screening.

• Clinico-morphologic characteristics of primary hemochromatosis
   Arkh Patol. 1995 Nov-Dec 12 autopsy cases of primary hemochromatosis were studied

• Combined orthotopic heart and liver transplantation for genetic hemochromatosis.
  J Heart Lung Transplant. 1997 May Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic and Mayo Foundation, Rochester, Minnesota, 55905, USA.  A 47-year-old man with cirrhotic liver disease complicated by encephalopathy and class IV congestive heart failure caused by genetic hemochromatosis underwent combined orthotopic heart and liver transplantation. The patient remains well, working full time, 4 years after operation. Combined heart and liver transplantation is an effective therapy for selected patients with concurrent heart and liver failure caused by systemic iron overload.

• Correlation between the depth of inverted T waves and the serum level of ferritin in a deferoxamine-treated patient with primary hemochromatosis and hyperthyroidism.   Jpn J Med. 1989 Mar-Apr There seemed to be a correlation between the depth of inverted T waves and the serum level of ferritin.

• Current concepts in rational therapy for haemochromatosis.  
  Drugs. 1991 Jun . Venesection should be continued until all excess iron stores are removed as judged by failure of a rise in haemoglobin concentration on cessation of phlebotomy. Screening of first degree relatives should commence from a young age (e.g. 10 years).

• Current diagnosis: hereditary metabolic diseases of the liver
   (primary hemochromatosis, Wilson disease] Schweiz Rundsch Med Prax 1996 Nov [article in German]

• Diagnosis and Management of Decompensated Congestive Heart Failure 
  Library of National Medical Society, Non-Ischemic Causes of CHF include Iron (Hemochromatosis)  

• Diagnosis and management of hemochromatosis by Dr. Anthony Tavill, Director of the Maurice and Sadie Friedman Center For Digestive Diseases and Liver Disorders, Mathile and Morton J. Stone Professor of Digestive Diseases and Liver Disorders at the Mt. Sinai Medical Center, Professor of Medicine and Nutrition at Case Wetern Reserve University. [Excellent & thorough article of diagnosis & treatment.  This is a pdf file] 

• Diagnosis and treatment of genetic hemochromatosis Rev Prat. 2000 May 1 [Article in French]
  Moirand R, Guillygomarc'h A, Brissot P, Deugnier Y. The disease can be lethal due to liver disease, carcinoma or heart disease, but life expectancy goes to normal if patients are treated before the occurrence of cirrhosis. Treatment relies on regular venesections. Familial screening is essential.

• Dietary Iron Supplements - Use or not to use? Nutrition Today James R. Connor John L. Beard 05-06-1997 There is little reason to support a general need for iron supplementation in the diet at any age. Perhaps this article and review of supplementation pros and cons should conclude with a new interpretation of an old saying: "It is better to wear out than to rust out;" don't expose your system to more iron than it needs.

• Disease-Related Conditions in Relatives of Patients with Hemochromatosis
  Zaneta J. Bulaj, M.D., Richard S. Ajioka, Ph.D., John D. Phillips, Ph.D., Bernard A. LaSalle, B.S., Lynn B. Jorde, Ph.D., Linda M. Griffen, B.A., Corwin Q. Edwards, M.D., and James P. Kushner, M.D.  Volume 343:1529-1535  November 23, 2000  Number 21  In conclusion, our data emphasize the importance of screening relatives of persons with hemochromatosis.

• Dr. Rose's Peripheral Brain--HEMOCHROMATOSIS

• Echocardiographic features of idiopathic hemochromatosis. In conclusion, there is a spectrum of cardiac dysfunction in idiopathic hemochromatosis.  Am J Cardiol 1987 Oct

• Endomyocardial biopsy in hemochromatosis: clinicopathologic correlates in six cases 
  Iron staining is recommended for endomyocardial biopsy specimens from patients with idiopathic cardiac dysfunction.  J Am Coll Cardiol 1989 Jan

• Effects of Iron Overload Harvard University website

• Epidemiology, clinical spectrum and prognosis of hemochromatosis, abnormality in liver function tests (75%), weakness and lethargy (74%), skin hyperpigmentation (70%), diabetes mellitus (48%), arthralgia (44%), impotence (45% in males), and ECG abnormalities (31%) were the most frequent findings and symptoms at diagnosis.  Adv Exp Med Biol 1994

• Excess Iron Damages Blood Vessels
  Optimal Wellness Center Issue 179 November 12, 2000 Dr. Joseph Mercola. Although iron is an essential and important nutrient, excessive levels can cause significant harm. A new study has shown that excess iron can cause damage to the endothelium, the inner lining of blood vessels, boosting a person's chances of developing hardening of the arteries (atherosclerosis) and heart attack.

• Excess Iron Intake Increases The Risk Of Coronary Heart Disease 

• Excess Iron Throws Out Welcome Mat to Bacteria  Heart, liver, intestines may suffer from over-fortified diet 11/2/2001 News By Serena Gordon HealthScoutNews Reporter (HealthScoutNews) -- Too much iron in the diet could be making people more susceptible to intestinal infections, claims a new study.  And that puts into question whether U.S. food makers need to fortify foods with iron, says one of the nutritionists who conducted the research.

• Facts about Cardiomyopathy  
  National Institutes of Health, National Heart, Lung, and Blood Institute

• Fatal Listeria meningitis, endocarditis and pericarditis in a patient with haemochromatosis.
  A 65-year-old man with primary haemochromatosis was admitted because of fever and confusion. He was found to have bacteraemia and meningitis due to Listeria monocytogenes Scand J Infect Dis 1997

• Ferritin Physiology Overview of the function of ferritin with a section on hemochromatosis.

• FINAL DIAGNOSES: 
  A case of Hereditary Hemochromatosis with dilated cardiomyopathy, micronodular cirrhosis, history of chronic alcoholism from Department of Pathology, University of Pittsburgh School of Medicine.

• Fried reich's Ataxia Fact Sheet ......the finding of abnormally high levels of iron in the heart tissue of people with Friedreich's ataxia  National Institute of Neurological Disorders and Stroke

• Genetic Haemochromatosis:   A guideline on Diagnosis & Therapy compiled on behalf of the Clinical Task Force of the  British Committee for Standards in Haemotology  2/2000 [a pdf file]

• Genetic Health-What Is Hemochromatosis?
  By Amanda Ewart Toland, PhD  Reviewed by Chris Friedrich, MD, PhD Last updated September 1, 2000

• Genetics helps to define a multifactorial disease Clin Genet, 54(1):1-9 1998 Jul

• Genetics of idiopathic dilated cardiomyopathy
  Herz 2000 May;25, Cardiomyopathies with atrioventricular block are observed in hemochromatosis

• Haemochromatosis and Diabetes– By Paul Steel
  Paul Steel is a diabetes educator with Manningham Community Health Service in Victoria. He has both a personal and professional interest in haemochromatosis, the most common genetic disorder in Australia, occurring in about one in 300 people.

• Haemochromatosis gene mutations in idiopathic dilated cardiomyopathy
  Heart 2000 Nov The frequency of the H63D mutation is significantly increased in patients with idiopathic dilated cardiomyopathy. As H63D has a relatively minor effect on iron status, the mechanism of this association may be unrelated to iron metabolism.

• Haemochromatosis may present as exercise related joint pains without arthropathy, early treatment improving outcome, Case reports including x-ray pictures of hips, hands, knees. CLINICAL REVIEW Lesson of the week: Ian McCurdie and J David Perry BMJ 1999

• Heart transplantation for end-stage heart failure caused by iron overload  
  Br J Haematol, 97(2):293-6 1997 May, case presentations

• Hemochromatosis: A Common, Rarely Diagnosed Disease
  By Vincent J. Felitti, MD, FACP  Commentary by David Baer, MD, FACP.  Hemochromatosis is the most common, life-threatening genetic disorder in North America, yet most physicians have never personally diagnosed a case: all see an unrecognized case in their offices every two weeks.

• Hemochromatosis: a review.  Clin J Oncol Nurs 2001 Nov-Dec;5(6):257-60   Dolbey CH. Fletcher Allen Health Care, UHC Campus, Arnold 2, 1 South Prospect Avenue, Burlington, VT, 05401, USA. This disorder affects the liver, pancreas, heart, and endocrine systems, and if undetected and untreated, organ damage and death can result.

• Hemochromatosis, A simple genetic trait,
  Dr. Richard D. Press, Oregon Health Sciences University With the discovery of the causative gene, the disorder stands revealed as America's single most common mendelian disease. Unlike other genetic diseases, it is already curable. Indeed, genetic screening makes it potentially preventable.

• Hemochromatosis at the intersection of classical medicine and molecular biology  
  C R Acad Sci III 2001 Sep

• Hemochromatosis can now be appropriately defined as the presence of two hemochromatosis alleles with or without organ injury, and with or without the presence of iron overload. [I have not been able to retrieve the url to the website from where this came, so if anyone locates it, please let me know!]

• Hemochromatosis:  Conemaugh Health System   Hemochromatosis is a condition that develops when too much iron builds up in the body. Excess iron is stored in the organs, such as the kidneys, liver, and heart, and in the joint tissues.

• Hemochromatosis, Cooley Dickinson Hospital   Editor: George R Bowers MD CDH Oncology  January 2000 Volume 4: No. 1.   Hemochromatosis is a common, genetically transmitted disease. The diagnosis of hemochromatosis is sometimes difficult and frequently missed. This issue will review the pathogenesis, diagnosis and treatment of this fascinating disease. Ms. Kathy Fleming will review the management of a most troubling complication of therapy---lymphedema. 

• Hemochromatosis, Front Range Gastroenterology Associates, P.C.  
  2030 Mountain View Avenue, Suite 300, Longmont, CO.  Basic statistics on HH.

• Hemochromatosis  Gale Encyclopedia of Medicine The symptoms of hemochromatosis include fatigue, weight loss, weakness, shortness of breath, heart palpitations, chronic abdominal pain, and impaired sexual performance. The patient may also show symptoms commonly connected with heart failure, diabetes or cirrhosis of the liver. Changes in the pigment of the skin may appear, such as grayness in certain areas, or a tanned or yellow (jaundice) appearance.

• Hemochromatosis: Gastrointestinal Health Hemochromatosis, the most common genetic disease in the United States, results in iron overload and, if left untreated, severe organ damage. 

• Hemochromatosis gene HFE Cys282Tyr polymorphism is associated with two-fold increased risk at acute myocardial infarction in men.  Tuomainen T-P, Kontula K, Nyyssonen K, Lakka TA, Salonen JT. Circulation 1998;98 These data suggest that HFE gene Cys282Tyr substitution is an independent risk factor for AMI. This finding supports the assumption that increased body iron contributes to the development of AMI.

• Hemochromatosis: genetics helps to define a multifactorial disease 
  Clin Genet, 54(1):1-9 1998 Jul University of Washington, Seattle 98105 wburke@u.washington.edu  Early detection is desirable, because periodic phlebotomy provides effective treatment for iron overload and may prevent complications of the disorder.

• Hemochromatosis:  Genetics, Pathophysiology, Diagnosis and Treatment, "Introduction to Hemochromatosis"  Part I,  by Barton & Edwards.  Except from their book, [a pdf file] This is a large & excellent book covering all areas of hemochromatosis.  Published in 2000, $215.00

• Hemochromatosis gene variants in patients with cardiomyopathy
  Am J Cardiol 2001 Aug 15, HFE gene was associated with ischemic cardiomyopathy

• Hemochromatosis heart disease:
  an unemphasized cause of potentially reversible restrictive cardiomyopathy Am J Med 1980 Dec

• HEMOCHROMATOSIS; HFE Mercier et al. (1997) urged strongly that the symbol HFE be used for the hemochromatosis gene rather than 'HLA-H' as used by Feder et al. (1996)

• Hemochromatosis in Ireland and HFE, Blood Cells, Molecules, and Diseases 1998

• Hemochromatosis in Ireland and HFE. Blood Cells Mol Dis. 1998  The allele frequency of 14% for the C282Y mutation in our control population is the highest reported and supports the hypothesis of a Celtic origin for the hereditary hemochromatosis gene.[pdf file]

• Hemochromatosis:  Life Extension Foundation website.  Disease, Prevention & Treatment 3rd editon.  Dietary & Vitamin recommendations listed here including calcium for blocking of iron absorption.

• Hemochromatosis Mutation Detection, Cys282Tyr and His63Asp  
  Guide to Clinical Laboratory Testing &  Interpretation of genetic testing. 

• Hemochromatosis Special  American Liver Foundation newsletter,  ALF Progress, Vol. 21 No. 1, Summer 1999 The ALF newsletter created three scenarios based on the real life ethical, economic and medical quandaries posed by hemochromatosis, and asked three experts from divergent fields to respond with their opinions. The experts are: Bruce R. Bacon, MD [Director, Div. of Gastroenterology & Hepatology, Saint Louis University School of Medicine, St. Louis, M0]; medical ethicist Mark A. Rothstein, Esq. [Director, University of Houston Law Center, Health Law & Policy Institute, Houston, TX] and hemachromatosis patient Gayle Hoffman.

• Hepatic injury in chronic iron overload. Role of lipid peroxidation.   Chem Biol Interact. 1989 Bacon BR, Britton RS. Excess deposition of iron in the parenchymal tissues of several organs (e.g. liver, heart, pancreas, joints, endocrine glands) results in cell injury and functional insufficiency.

• Hereditary Hemochromatosis and Cancer risk:  More fuel to the fire?  Gastroenterology Vol. 121, No. 5, November 2001  Pg. 1253 [a pdf file]  These data suggest an involvement of iron in carcinogenesis even in heterozygotes for HFE mutations. 

• Hereditary Haemochromatosis and Iron Metabolism, Carlson J, Olsson S, eJIFCC vol 13 no 2, THE JOURNAL OF THE INTERNATIONAL FEDERATION OF CLINICAL CHEMISTRY

• Hereditary hemochromatosis.  Ann Clin Lab Sci. 1998 Sep-Oct   Patients at risk for genetic hemochromatosis should be screened, identified, and treated as early as age 20 to prevent or minimize the deadly complications of hemochromatosis. Population screening should include measurements of serum iron concentration, total iron binding capacity (TIBC), percent saturation of transferrin, and serum ferritin concentrations.  Early diagnosis and treatment will reduce the population of aging individuals with severe, complicated hemochromatosis and dramatically reduce medical costs (billions of U.S. dollars per annum) associated with the management of this disease.

• Hereditary Hemochromatosis--A Risk Factor for Cardiovascular Disease The HH mutation is a human genetic model of disturbed iron metabolism, which facilitates research to the mechanism of HH and iron involved in cardiovascular disease. We expect that in the near future, the mechanism of disturbed iron metabolism leading to cardiovascular disease in human will be better understood.

• Hereditary Hemochromatosis 
  CME Activity, Release Date: 2/28/2000 Expiration Date: 2/28/2002 From the February 2000 Issue of Physician Assistant  Objectives: After reading the article, the reader should be able to:
  1. describe the pathophysiology of hereditary hemochromatosis;
  2. recognize the clinical symptoms and signs of hereditary hemochromatosis;
  3. outline screening and evaluation testing; and
  4. provide accurate diagnosis, management, and treatment.

• Hereditary hemochromatosis: diagnosis and treatment in primary care Tenn Med 1999 Nov With early detection and treatment this can be a manageable chronic disease. If undetected, it is potentially fatal.

• Hereditary Hemochromatosis FamilyPractice.com  Robert B. Hash, MD, Department of Family Medicine, Mercer University School of Medicine, Macon, Ga. [J Am Board Fam Pract Dec. 2000] Considering the prevalence of the disease, it is important for physicians to consider it in the differential diagnosis when patients complain of the common signs and symptoms. For most patients hereditary hemochromatosis can be successfully treated in the physician's office. Early diagnosis and treatment, before signs of iron toxicity, if possible, can result in improved quality and quantity of life for many patients.

• Hereditary hemochromatosis: impact of molecular and iron-based testing on the diagnosis, treatment, and prevention of a common, chronic disease.  Arch Pathol Lab Med. 1999 Nov Press RD. Department of Pathology, Oregon Health Sciences University, Portland 97201, USA. pressr@ohsu.edu This direct HFE mutation test can now be used not only to confirm the diagnosis of HH in those with symptomatic disease, but also, perhaps more importantly, to detect those with presymptomatic iron overload in whom future disease manifestations may be prevented (with phlebotomy therapy).

• Hereditary hemochromatosis in children, adolescents, and young adults.  Am J Pediatr Hematol Oncol. 1988 Spring  Young individuals who should be screened for iron overload include patients with cardiac myopathies, hypogonadism, amenorrhea, loss of libido, diabetes mellitus, other endocrine disorders, cirrhosis of the liver, and arthritis, as well as the siblings, parents, and children of patients with hereditary hemochromatosis or iron loading of unknown cause.

• Hereditary hemochromatosis. 
  J Fam Pract, 44(3):304-8 1997 Mar  Hereditary hemochromatosis is a genetic disorder of iron metabolism that has an excellent prognosis if diagnosed early.

• Hereditary hemochromatosis: Preventing chronic effects of this underdiagnosed disorder
  Sharon M. McDonnell, MD, MPH; David Witte, MD, PhD VOL 102 / NO 6 / DECEMBER 1997 / POSTGRADUATE MEDICINE.  In this article, Drs McDonnell and Witte discuss the diagnosis and management of this underrecognized problem as well as the various issues involved in screening. An illustrative case of hemochromatosis is also included.

• Hereditary Hemochromatosis Since Discovery of the HFE Gene  Clinical Chemistry 2001 [a pdf file] Includes an algorithm for screening and diagnosis of hemochromatosis. This review provides a comprehensive discussion of known mutations in the HFE gene and their phenotypic expression

• Heterozygosity for a hereditary hemochromatosis gene is associated with cardiovascular death in women Abstract.  For full text article in pdf format, click here. Circulation, 100(12):1268-73 1999 Sep 21

• HFE gene and hereditary hemochromatosis: a HuGE review. Human Genome Epidemiology
   Am J Epidemiol 2001 Aug 1

• HFE gene knockout produces mouse model of hereditary hemochromatosis Proc Natl Acad Sci U S A. 1998 Mar.  Xiao Yan Zhou, Shunji Tomatsu, Robert E. Fleming, Seppo Parkkila, Abdul Waheed, Jinxing Jiang, Ying Fei, Elizabeth M. Brunt, David A. Ruddy, Cynthia E. Prass, Randall C. Schatzman, Rosemary O'Neill, Robert S. Britton, Bruce R. Bacon, and William S. Sly  The knockout mouse model of HH will facilitate investigation into the pathogenesis of increased iron accumulation in HH and provide opportunities to evaluate therapeutic strategies for prevention or correction of iron overload.

• HFE-PROTEIN IN HEREDITARY HEMOCHROMATOSIS
  Hereditary hemochromatosis is the most common known autosomal recessive disorder in Caucasians

• High Body Iron Stores In Men Confirmed As Risk Factor For MI  Circulation 1998, This story is about the hazards of even "normal" iron levels, not just those seen in hemochromatosis

• HIGH DIETARY IRON ASSOCIATED WITH INCREASED HEART ATTACK RISK IN ELDERLY 
  Issue 90 February 28, 1999 Optimal Wellness Health News  "Ideally, the ferritin level should be between 20 and 80."

• Idiopathic hemochromatosis in a young female. A case study and review of the syndrome in young people Gastroenterology 1979 Jan;76(1):178-83  The case presented here describes a 26-yr-old woman with problems presenting heart failure, insulin-dependent diabetes, hepatomegaly, and secondary amenorrhea.

• Illustrations to Hemochromatosis, Radiology CT scan pictures

• Increased risk of acute myocardial infarction in carriers of the hemochromatosis gene Cys282Tyr mutation  Circulation, 100(12):1274-9 1999 Sep 21

• Investigating Anaemia and Iron Storage Disease
  Discussion of the different types of anemia, as well as the effects of iron overload.  

• Iron and the Genetics of Cardiovascular Disease Jerome L. Sullivan, MD, PhD Circulation 1999 AHA
  

• Iron, Atherosclerosis, and Ischemic Heart Disease  
  Arch Intern Med. 1999; Objective  To review the epidemiological and experimental data concerning iron and the development of atherosclerosis and ischemic heart disease.

• Iron catalyzed oxidative damage, in spite of normal ferritin and transferrin saturation levels and its possible role in Werner's syndrome, Parkinson's disease, cancer, gout, rheumatoid arthritis, etc. Med Hypotheses 2000 Sep the disease is often overlooked by physicians, until several organs have been damaged permanently (heart, liver, brain, pancreas, kidneys, spleen, etc.). Moreover, since ferritin, transferrin saturation and hematocrit levels are not directly related to cellular iron levels, and since excess iron can wreak havoc in the cell, we can conclude that there is a need for a better way to evaluate intracellular iron levels and especially the intracellular free iron levels by a non-invasive technique.

• 'Iron' Gene Mutation Increases Heart Attack Risk  
  Full Health Nutrition Canada ArterialHealth e-News^© December 1999 [located about halfway down the page] Those with an abnormal iron gene faced a 52% increased risk of heart attack with each 100 microgram increase in ferritin, while the risk in those with normal iron genes varied little with ferritin concentration. Carriers almost universally don't know that they are at increased risk... They have almost no increase in iron stores, but that small increase is significant and that small increase is probably what caused the increased incidence of heart disease deaths.

• Iron is Hot:  An Update on the Pathophysiology of Hemochromatosis: Blood Journal Sept. 15, 1998  Genetic iron overload disorders are prevalent yet poorly understood. [A pdf file.]

• Iron Loading and Disease Surveillance
  Eugene D. Weinberg   Indiana University, Bloomington, Indiana   Emerging Infectious Diseases Journal, National Center for Infectious Diseases, Centers for Disease Control and Prevention. Excessive iron in specific tissues and cells (iron loading) promotes development of infection, neoplasia, cardiomyopathy, arthropathy, and various endocrine and possibly neurodegenerative disorders.

• Iron-mediated cardiovascular injury   Vasc Med, 4(2):93-9 1999

• Iron overload and heart fibrosis in mice deficient for both beta2-microglobulin and Rag1
   Am J Pathol 2000 Dec, Experimental model of iron-related cardiomyopathy

• Iron overload cardiomyopathies: new insights into an old disease Cardiovasc Drugs Ther 1994 Feb Iron overload cardiomyopathy is an old disease that has evolved from a rare undiagnosable and untreatable condition to a now much more common, diagnosable, and potentially treatable condition.

• Iron-overload cardiomyopathy: evidence for a free radical--mediated mechanism of injury and dysfunction in a murine model.  Biol Res Nurs. 2000 Jul  Iron-overload cardiomyopathy is a restrictive cardiomyopathy that manifests itself as systolic or diastolic dysfunction secondary to increased deposition of iron in the heart and occurs with common genetic disorders such as primary hemochromatosis and beta-thalassemia major.

• Iron Overload Disease due to Hereditary Hemochromatosis  CDC website, National Center for Chronic Disease Prevention and Health Promotion.  Early detection and treatment for this genetic condition can lessen morbidity and mortality, and in some cases prevent the onset of disease. Therefore, early detection of hemochromatosis represents a major chronic disease prevention opportunity.

• Iron Overload Disorder Common and Increases Risk for Heart Attacks
  Full Health Nutrition Canada ArterialHealth e-News^© October 1999 A genetic defect that causes iron overload disease is the most common inherited disorder among whites, affecting one in 188 people of northern European descent.

• Iron Overload Disorder Common and Increases Risk for Heart Attacks Issue 117 September 5, 1999 Optimal Wellness Health News  Excerpt from Dr. Mercola's comments: The simple screening test to check for this problem is the serum ferritin level.  It should be below 80. If it is significantly above 100, there is a high likelihood of hemochromatosis.  I screen all of our heart disease patients for this and I probably see it on nearly ten percent of these patients.

• Iron Overload (Hemosiderosis; Hemochromatosis) The Merck Manual of Diagnosis and Therapy Section 11. Hematology And Oncology Chapter 128. Hemochromatosis is often diagnosed late in the course of disease after significant tissue injury is present because the clinical symptoms are insidious and the extent of organ involvement varies; thus, the full clinical picture evolves slowly

• Iron: 'Too Much Is A Problem'
  by Joseph B. Verrengia [News Science Writer]  High levels of iron, already considered to be a major risk factor in heart attacks, are being implicated in the progression of AIDS, Lou Gehrig's disease and cancer.   "Iron will be the cholesterol of the 1990s," McCord predicts, ". . .most people don't know their iron status."

• Is Too Much Iron in the Blood Related to Heart Attack  
  CardioConsult Reviews, May 1998, Case-control study

• Juvenile idiopathic haemochromatosis: a life-threatening disorder presenting as hypogonadotropic hypogonadism.   Hum Genet 1983  We describe here four cases of idiopathic haemochromatosis having onset of symptoms before or around the age of 20 years.  These subjects may have a history of unexplained abdominal pain, present with hypogonadotropic hypogonadism, and, unless proper treatment is started, die early because of cardiac dysfunction.

• Liver transplantation for hereditary hemochromatosis. This suggests that regardless of the cause, iron overload may be detrimental in patients undergoing OLT. Liver Transpl 2001 Aug

• Long-term survival in patients with hereditary hemochromatosis Gastroenterology, Vol 110, 1107-1119, 1996 by American Gastroenterological Association   Prognosis of hemochromatosis and most of its complications, including liver cancer, depend on the amount and duration of iron excess. Early diagnosis and therapy largely prevent the adverse consequences of iron overload.

• Management of hereditary hemochromatosis. Blood Rev. 1994 Dec Phatak PD, Cappuccio JD. Early diagnosis and institution of phlebotomy treatments will prevent these manifestations and normalize life expectancy. Once organ damage is established many of the manifestations are irreversible. Since the early manifestations of the disease are subtle, a case can be made for routine screening.

• Management of hemochromatosis. Hemochromatosis Management Working Group.
  Ann Intern Med. 1998 Dec 1  Barton JC, McDonnell SM, Adams PC, Brissot P, Powell LW, Edwards CQ, Cook JD, Kowdley KV.  The complications of iron overload in hemochromatosis can be avoided by early diagnosis and appropriate management.

• Molecular basis for the arrhytmogenesis of iron overloaded cardiomyopathy
  MetroHealth Med Ctr, Case Western Reserve Univ, Cleveland, OH

• Molecular genetics of hemochromatosis  Ann Endocrinol (Paris) 1999 Sep Hemochromatosis is a recessive disorder of iron metabolism characterized by progressive iron loading of parenchymal organs, which accounts for clinical complications such as cirrhosis, diabetes mellitus, cardiopathy, endocrine dysfunctions and arthropathy.

• Most People Get Too Much Not Too Little Iron   Optimal Wellness Center Issue 200 March 7, 2001 Dr. Joseph Mercola.  DR. MERCOLA'S COMMENT: I have warned about the dangers of iron many times before in this newsletter. It is a potentially dangerous supplement and it needs to be used very cautiously, especially in those with an increased risk of heart disease.

• Overview on Iron Overload and Hemochromatosis CDC website, National Center for Chronic Disease Prevention and Health Promotion.  Early detection of hemochromatosis is essential because the disease’s potentially serious complications can be prevented by early therapy.

• Pathology Cases for Diagnosis: A 37 year old male is referred to the liver clinic for evaluation of abnormal liver related enzymes.  Includes pictures of biopsy slides. Case 96-19: Liver II Contributed by D. Robert Dufour, M.D., CAPT, MC, USNR-R Date Available: July 22, 1996 - December 31, 1996 

• Physical work capacity studied by measured physical loading in patients with hereditary hemochromatosis  Ter Arkh. 1989 [Article in Russian] A significant decrease of work fitness was revealed in 23 patients with verified diagnosis of hereditary hemochromatosis exposed to graded physical exercise.

• Possible causes of symptoms in suspected coronary heart disease but normal angiograms. 
  Clin Cardiol 2001 Apr   In patients with suspected coronary heart disease and normal angiograms, hypertension, neuromuscular disorders, tachycardiomyopathy, hypothyroidism, and hemochromatosis should be considered as possible causes.

• Population screening in hereditary hemochromatosis   Annu Rev Public Health 2000

• Practice guideline development task force of the College of American Pathologists. Hereditary hemochromatosis. Witte DL, Crosby WH, Edwards CQ, Fairbanks VF, Mitros FA. College of American Pathologists Clin Chim Acta 1996 Feb. In view of the high prevalence in the American population (prevalence varies with ethnic background), the low cost of diagnosis and treatment, the efficacy of treatment if begun early, and, on the other hand, high costs and low success rate of late diagnosis and treatment, systematic screening for hemochromatosis is warranted for all persons over the age of 20 years.

• Primary hemochromatosis: anatomic and physiologic characteristics of the cardiac ventricles and their response to phlebotomy  Am J Cardiol 1984 Jul 1  Primary hemochromatosis can effect LV and RV size and function; clinically occult cardiac involvement can be identified by echocardiography and equilibrium blood pool imaging; therapeutic phlebotomy can ameliorate or reverse the deleterious effects of excess cardiac iron deposition.

• Progressive hemochromatotic cardiomyopathy despite reversal of iron deposition after liver transplantation   Am J Clin Pathol 1993 Jan;99

• PULLING IRON OUT OF THE FIRE by Shelly Morrow.  This article appeared in the Sept/Oct 2000 issue of Arthritis Today, published by the Arthritis Foundation, Inc.

• Quantitative Texture Analysis in Two-Dimensional Echocardiography: Application to the Diagnosis of Myocardial Hemochromatosis.Echocardiography. 1996 Jan Myocardial walls affected by hemochromatosis show ultrasound image texture alterations that may be quantified with digital image analysis techniques and appear mostly unrelated to hematologic and conventional, as well as radiofrequency-based, echocardiographic parameters. These changes in quantitatively evaluated echo reflectivity are present even before the development of clinical and echocardiographic signs of cardiac dysfunction.

• Radial artery wall alterations in genetic hemochromatosis before and after iron depletion therapy Hepatology. 2000 Sep This alteration is reverted by iron depletion, which also can improve the initial and modest radial artery wall stiffening associated with this condition. Thus, functional and structural alterations in midsize muscle arteries may be an early abnormality of hemochromatosis.

• Reduced Left Ventricular Contractile Reserve
  Identified by Low Dose Dobutamine Echocardiography as an Early Marker of Cardiac Involvement in Asymptomatic Patients with Thalassemia Major Echocardiography 1996 Sep

• Refractory heart failure in a 26-year-old woman with idiopathic hemochromatosis 
  Rev Port Cardiol. 1994 Oct  In this paper, we report a case of a young woman with a eight years evolution of amenorrhea, cardiac failure, diabetes mellitus and increased pigmentation of the skin, associated with biochemical markers of iron overload. It is emphasized that hemochromatosis most be excluded in all patients with a unexplained cardiac failure.

• Renal Transplantation and Evolution of Hemochromatosis:  A Clinical Case Report
  Despite being one of the world's most frequent autosomal recessive diseases, there are very few cases in the literature concerning hereditary hemochromatosis and renal transplantation. [a pdf file]

• Refractory heart failure in a 26-year-old woman with idiopathic hemochromatosis 
  Rev Port Cardiol 1994 Oct   It is emphasized that hemochromatosis most be excluded in all patients with a unexplained cardiac failure.
   
• Relating Genomic Research to Patient Care JAMA 11/2000 Educating health care professionals about the complexities of the genetics of adult disease (in addition to congenital illness) is an important goal, and one disease model that is useful for this purpose involves hemochromatosis.

• Research Supports Link Between Iron Levels And Heart Disease    
  News article, 11-11-1997

• Restrictive Cardiomyopathy
  Targeted therapy directed against specific causal entities (such as the use of somatostatin analogues in carcinoid syndrome or iron chelation with desferrioxamine in hemochromatosis) may be more effective than simple symptomatic therapy. Curr Treat Options Cardiovasc Med 2000 Oct

• Reversible severe hereditary hemochromatotic cardiomyopathy Can J Cardiol 1997 Apr

• Risk Factors for Cardiovascular Disease—Too Much Iron  
   A recently identified and intriguing possible risk factor is high blood iron level, medformation.com.

• Role of C282Y mutation in haemochromatosis gene in development of type 2 diabetes in healthy men: prospective cohort study  British Medical Journal BMJ 2000; 320:17061707 (24 June) As the incidence of diabetes in northern Europe is among the highest in the world and rising, screening for C282Y mutation by DNA analysis, monitoring of iron status, and iron depleting treatment could potentially constitute new important measures in the primary prevention of diabetes.

• Safety aspects of iron in food. 
  Ann Nutr Metab 2001;  There is no regulated iron excretion in overload. Excess of pharmaceutical iron may cause toxicity and therapeutic doses may cause gastrointestinal side effects.

• Screening for genetic haemochromatosis in blood samples with raised alanine aminotransferase
  Gut 2000;46:707-710 ( May )

• Screening for Iron Overload due to Hereditary Hemochromatosis 
  CDC website, Reyes, Michele, PhD and Muin J. Khoury, MD, PhD,  National Center for Chronic Disease Prevention and Health Promotion  Identifying people early with evidence of iron overload represents a major chronic disease prevention opportunity.

• Secondary and Infiltrative Cardiomyopathies Curr Treat Options Cardiovasc Med 2000 Oct Rush Heart Failure and Cardiac Transplant Program, Rush-Presbyterian-St. Luke's Medical Center, 1725 West Harrison Street, Suite 439, Chicago, IL Patients with hemochromatosis related cardiomyopathy should be treated with iron chelation therapy and phlebotomy. 

• Serum ferritin and risk of myocardial infarction in the elderly: the Rotterdam Study, American Journal of Clinical Nutrition, Vol. 69, No. 6, 1231-1236, June 1999

• Severe hereditary hemochromatotic cardiomyopathy
  responsive to small-volume venesections combined with deferoxamine, case reports

• Successful pregnancy following gonadotropin therapy in a young female with juvenile idiopathic hemochromatosis and secondary hypogonadotropic hypogonadism 
  Haematologica 1995 Jul-Aug; Heart failure and hypogonadotropic hypogonadism are the most frequent clinical problems encountered in patients with juvenile idiopathic hemochromatosis

• Sullivan, JL HH & MI study

• Sustained ventricular tachycardia in cardiac hemochromatosis treated with amiodarone
  J Electrocardiol, 30(2):147-9 1997 Apr

• The articular damage of hemochromatosis.  A little known aspect Recenti Prog Med 1999 Apr The aim of this report is to underline that the patients with premature osteoarthritis or unexplained chondrocalcinosis must be screened for genetic haemochromatosis in order to formulate the correct diagnosis before the development of severe internal organ involvement

• The Heart In Iron Overload  September/October, 1995: Cardiovascular Medicine, case presentation

• The HFE CYS282Tyr polymorphism is associated with cardiovascular mortality.
  Roest M, Schouw Yvd, B. de Valk BD, Marx JJM, Tempelman M, de Groot P, Sixma J, Banga JD.  Presented at the July 1998 meeting of the European Iron Club. Conclusions: Heterozygosity for HH is associated with increased risk of cerebrovascular and total cardiovascular mortality, in particular in combination with hypertension and smoking. Long term exposure to minimal iron overload may enhance atherosclerosis.

• The morphological changes in the internal organs in hemochromatosis
  Cardiomyopathy and diabetes mellitus at autopsy

• The relationship between iron overload, clinical symptoms, and age in 410 patients with genetic hemochromatosis. Hepatology. 1997 Jan The nonspecific nature of the presenting features in patients and the presence of significant clinical symptoms in patients discovered through family investigations underscore the importance of family and population screening for hemochromatosis.  The prevalence of cirrhosis, diabetes, cardiac disease, pigmentation, and fatigue increased as liver iron concentration increased. The most common presentations at diagnosis were fatigue

• Too fit for a heart attack?
  Well known marathon runner and author Jim Fixx had just had a checkup. His values were normal, including cholesterol, so the doctor declared him fit. Two days later he died of a heart attack.

• Too much iron can hurt joints, body organs 
  The Albuquerque Tribune. By John Crowe The Associated Press 1/11/00

• Too Much Iron in Your Blood? Then donate a pint. Research shows a possible link between higher blood iron levels and risk of heart disease. Some experts say it's another great reason to give blood. By Michael Alvear WebMD Medical News

• Too Much Iron May Lead to Heart Attack  
  Study Finds It Damages Vessel Lining   By Jeff Levine WebMD Washington Bureau Chief   Oct. 25, 2000

• Use of HFE Mutation Analysis for Hereditary Hemochromatosis:  The Need for Physician Education in the Translation of Basic Science to Clinical PracticeManish Kohli, MB, ChB, Steven A. Schichman, MD, PhD, Louis Fink, MD, Clive S. Zent, MB, BCh, Department of Internal Medicine, Division of Hematology/Oncology and the Department of Pathology, John L. McClellan Memorial Veteran's Hospital and University of Arkansas for Medical Sciences, Little Rock.  Southern Medical Journal

• Ventricular tachycardia and cardiac hemochromatosis Rev Esp Cardiol 2001 Nov

• What's new in hemochromatosis.  Curr Opin Hematol 2001 Mar  The high correlation of HFE to HHC has caused it to be considered as a candidate gene for population-based genetic testing for diagnosis and detection of predisposition to HHC. 

• Why concentration of serum ferritin does not in all circumstances reflect storage iron but is still of value in its estimation.  Rajantie J, Siimes MA. We describe a 10-year-old girl with familial haemochromatosis which is associated with a normal concentration of S-ferritin, myocardial disease and diabetes mellitus. We speculate that iron is accumulated primarily in the heart and pancreas as such isoferritins are not detected by the routine assay of serum ferritin based on antispleen or placenta ferritin.

Click on this link to read about HH. Discussion of a liver biopsy is also here: 

Back to the "Munnsters" main Hemochromatosis page