INCLUSION CRITERIA:
HH Patients
Group A patients (untreated HH patients)
Adults 21 years or older
New York Heart Association Functional Classification Class I
Documented positive phenotyping for homozygote Cys282Tyr of Hfe gene with documented serum ferritin level above 400 ng/ml or documented % iron saturation more than 60%.
Patient has not received standard chronic phlebotomy or deferoxamine treatment. Individuals are allowed to have up to 3 emergency phlebotomies for alleviation of severe iron accumulation before enrollment.
Group B patients (treated HH patients)
Adults 21 years or older
New York Heart Association Functional Classification Class I
Documented positive phenotyping for homozygote Cys282Tyr of Hfe gene with documented serum ferritin level above 400 ng/ml or documented % iron saturation more than 60%.
Patient has been compliant with standard phlebotomy and/or deferoxamine treatment for 6 months or longer and in stable phase with iron saturation 50% or less.
Healthy Volunteers
Group C Patients (Age-Gender Matched Healthy Control Subjects)
Adults 21 years or older.
No symptoms suggestive of heart disease or any other medical conditions, negative Hfe genotyping for Cys282Tyr or His63Asp with normal ferritin and iron saturation.
EXCLUSION CRITERIA:
HH patients
Group A patients (untreated HH patients)
Pregnant or lactating women
History or present evidence of coronary artery disease, heart failure, peripheral vascular disease, coagulopathy, or uncontrolled hypertension (systolic blood pressure over 170 mmHg and/or diastolic pressure over 100 mmHg).
History of significant end-organ damage secondary to HH.
Serum creatinine greater than 2.0 mg/ml
LFT's more than 2.5 times above upper limit of normal
History of structural cardiac disease except mitral valve prolapse with mild mitral regurgitation
Uncontrolled glucose levels with hemoglobin A(1c) above 8 mg/dl or the use of more than one oral hyperglycemic agents or insulin therapy to control diabetes.
Current use of antioxidant treatment such as vitamin E and C. However, the cessation of this treatment 4 weeks prior to the study will allow for inclusion.
Evidence of impaired immunity including HIV
Chronic systemic inflammatory disease such as SLE, rheumatoid arthritis, collagen vascular disease.
Participation in unrelated research involving investigational pharmacological agent in past 30 days.
Current alcohol use (more than 26 grams averaged ethanol intake per day) or drug abuse.
Inability to provide informed consent
Smoking in past 3 months.
Use of beta-adrenergic blocking agents and calcium channel blockers with negative chronotropic effect within 1 week.
Inability to perform treadmill or bicycle exercise testing.
Inability to undergo MRI such as ferromagnetic implant.
Group B patients (treated HH patients)
Pregnant or lactating women
History or present evidence of coronary artery disease, heart failure, peripheral vascular disease, coagulopathy, or uncontrolled hypertension (systolic blood pressure over 170 mmHg and/or diastolic pressure over 100 mmHg).
History of significant end-organ damage secondary to HH.
Serum creatinine greater than 2.0 mg/ml
LFT's more than 2.5 times above upper limit of normal
History of structural cardiac disease except mitral valve prolapse with mild mitral regurgitation
Uncontrolled glucose levels with hemoglobin A(1c) above 8 mg/dl or the use of more than one oral hyperglycemic agents or insulin therapy to control diabetes.
Current use of antioxidant treatment such as vitamin E and C. However, the cessation of this treatment 4 weeks prior to the study will allow for inclusion.
Evidence of impaired immunity including HIV
Chronic systemic inflammatory disease such as SLE, rheumatoid arthritis, collagen vascular disease.
Participation in unrelated research involving investigational pharmacological agent in past 30 days.
Current alcohol use (more than 26 grams averaged ethanol intake per day) or drug abuse.
Inability to provide informed consent
Smoking in past 3 months.
Use of beta-adrenergic blocking agents and calcium channel blockers with negative chronotropic effect within 1 week.
Inability to perform treadmill or bicycle exercise testing.
Inability to undergo MRI such as ferromagnetic implant.
Healthy volunteers
Group C Patients (Age-Gender Matched Healthy Control Subjects)
Pregnant or lactating women.
History or present evidence of any structural cardiac disease except mitral valve prolapse with mild mitral regurgitation, heart failure, peripheral vascular disease, coagulopathy, and uncontrolled hypertension (systolic blood pressure over 170 mmHg and/or diastolic pressure over 100 mmHg).
Serum creatinine greater than 2.0 mg/ml.
LFT's more than 2.5 times above upper limit of normal.
Current use of antioxidant treatment such as vitamin E and C. However, the cessation of this treatment 4 weeks prior to the study will be included.
Uncontrolled glucose levels with hemoglobin A(1C) above 8 mg/dl or the use of oral hyperglycemic agents or insulin therapy to control diabetes.
Evidence of impaired immunity including HIV.
Chronic systemic inflammatory disease such as SLE, rheumatoid arthritis, collagen vascular disease.
Participation in unrelated research involving investigational pharmacological agent in past 30 days.
Current alcohol use (more than 26 grams averaged ethanol intake per day) or drug abuse.
Inability to provide informed consent.
Smoking in past 3 months.
Subjects with any chronic medical problems*
Inability to undergo MRI such as ferromagnetic implant.
*For the purpose of this protocol "chronic medical problems' is defined as any current condition not amenable to curative therapy and which requires long-term medical treatment and/or clinical monitoring.