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 health risks.

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 saturation.

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 2005).

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