WHAT CAUSE HEART PROBLEMS?
The cardiomyopathy of idiopathic or acquired haemochromatosis
suggests that the heart may be especially sensitive to toxic
effects of excess iron (Sullivan 1990). The features of inherited
iron overload include cardiac problems (arrhythmias and heart
failure), and/or cirrhosis of the liver, diabetes, arthritis and
skin pigmentation. Since haemochromatosis can be easily treated by
phlebotomy once diagnosed, this condition is considered a
preventable form of heart disease amongst other equally important
Not only homozygosity for the HFE C282Y mutation, but also the
heterozygous state is associated with increased serum iron
parameters (Rossi et al. 2001). Individuals with serum transferrin
saturation levels above 55% carry an increased all-cause mortality
risk especially when combined with high red meat intake (Mainous et
al. 2004a,b). Coronary heart disease rates rise sharply from age 20
onwards in males, who begin accumulating excess iron from late
adolescence. Healthy women, on the other hand, do not accumulate
excess iron in their tissues until after the menopause, when they
rapidly develop the same risk of CVD as men of the same age.
Detection of an association between heterozygosity for mutation
C282Y and increased risk of acute myocardial infarction in men
(Tuomainen et al. 1999), as well as with cardiovascular death in
postmenopausal women (Roest et al. 1999), support the iron-heart
link. The risk of cardiovascular death in postmenopausal women with
at least one copy of the C282Y mutation appeared to be stronger in
women who were hypertensive or current smokers, with a nearly
20-fold increased risk when both risk factors were present,
compared with nonsmokers, nonhypertensives, and noncarriers. This
finding again emphasised the importance of multiple risk factor
assessment when low-expression mutations are analysed.
The potential combined effects of elevated body iron stores and
hypercholesterolaemia is of particular concern, as two independent
studies demonstrated worse clinical outcomes under such
circumstances (Salonen et al. 1992; Wells et al. 2004). Persons
with both elevated transferrin saturation and elevated LDL showed a
significantly greater risk for CVD mortality than persons when both
parameters normal or elevated LDL without elevated transferrin
Recent studies performed in the South African population
demonstrated the significance of LDL particle size as a risk factor
for CVD in patients with non-alcoholic liver disease (NAFLD), while
the presence of HFE mutations may be associated with disease
severity in some families (FC Kruger 2008, PhD study). Due to the
findings relating to dyslipidaemia, obesity and insulin resistance
in the South African study cohort, a diagnosis of NAFLD or
metabolic syndrome is regarded an important indication for referral
of chronic disease risk management, including the assessment of
multiple genetic risk factors for CVD performed in conjunction with
a medical and lifestyle/nutrition assessment (Kotze and Badenhorst
Kotze MJ, Badenhorst H. Chronic disease risk management: Combining
genetic testing with medical and nutrition therapy. SA Fam Pract
2005; 47 (4): 40-42.
Mainous AG III, Gill JM, Pearson WS, Carek PJ.
Elevated serum transferrin saturation and mortality. Ann Fam Med
2004a; 2: 133-138.
Mainous AG III, Wells BJ, Carek PJ, et al. The
mortality risk of elevated serum transferrin saturation and
consumption of dietary iron. Ann Fam Med 2004b, 2: 139-144.
Milani MY, Kotze MJ. Molecular diagnosis of hereditary
haemochromatosis: identify an affected person and save a family.
S Afr Med J 1999; 89: 263-264.
Roest M, van der Schouw YT, de Valk B, et al.
Heterozygosity for a hereditary hemochromatosis gene is associated
with cardiovascular death in women.
Circulation 1999; 100: 1268-1273.
Rossi E, Bulsara MK, Olynyk JK, et al.
Effect of hemochromatosis genotype and lifestyle factors on iron and
red cell indices in a community population.
Clin Chem 2001; 47: 202-208.
Salonen JT, Nyyssonen K, Korpela H, et al.
High stored iron levels are associated with excess risk of myocardial
infarction in Eastern Finnish men. Circulation 1992; 86:
JL. Heterozygous haemochromatosis as a risk factor for premature
myocardial infarction. Medical Hypotheses 1990; 31: 1-5.
Tuomainen T-P, Kontula K, Nyyssonen K, et al. Increased risk of
acute myocardial infarction in carriers of the hemochromatosis gene
Cys282Tyr mutation. A prospective cohort study in men in Eastern
Circulation 1999; 100: 1274-1279.
Wells BJ, Mainous AG III, King DE, et al. The combined effect of
transferrin saturation and low density lipoprotein on mortality.
Fam Med 2004; 36: 324-329.
genetic testing service is combined with an ethically approved research
project to enable us to
monitor the success of a wellness initiative in collaboration with the
referring clinician. Patients will be assisted to sign the
research informed consent form that may be be provided together with a
sample collection kit. EDTA blood (purple top tube) can also be
provided for DNA testing when the informed consent form is downloaded
from this website.
Patients are encouraged to contact
Professor Maritha Kotze (firstname.lastname@example.org / email@example.com; tel. 27 21 9389324 / 0828799108) with any questions they may have about the research or test-related payment.
A quote for the amount due will be emailed to you once the service
request has been entered online. Please provide the contact
details of the consulting healthcare practitioner for participation.