Haemochromatosis is an inherited disease in which too much iron is absorbed by the liver, heart, and pancreas. Overt symptoms occur only in people who are homozygous for a Cys282Tyr mutation in the protein coded for by HFE (HLA-H). This week, two independent groups report that people heterozygous for the mutation may be at increased risk of cardiovascular disease.

Mark Roest and colleagues (Utrecht University Medical Center, Netherlands) followed 12 239 women aged 51­69 years for a period of 16­18 years; 4% were heterozygous for the Cys282Tyr allele. Cardiovascular death rates were 1·6 times higher in heterozygotes than in women with two wild-type alleles (95% CI 1·1­2·4). The death rate from myocardial infarction was 1·5 times higher (0·9­2·5), and for stroke 2·4 times higher (1·3­4·4). Women who smoked, had hypertension, and were heterozygous for the Cys282Tyr mutation had a 19-fold increased risk of death from a heart attack or stroke compared with women without these three risk factors (Circulation 1999; 100: 1268­73).

Hold back on the iron

In the second study, 1150 men aged 42­60 years were followed up as part of the population-based Kuopio Ischemic Heart Disease Risk Factor Study. Jukka Salonen's group (University of Kuopio, Finland) found that the incidence of acute myocardial infarction in men who were heterozygous for the Cys282Tyr allele was 2·3 times higher (1·1­4·8) than in men with two wild-type alleles ( Circulation 1999; 100: 1274­79).

The prevalence of the Cys282Tyr allele in the European population is about 5%, but "in our study of Finnish men, we found a prevalence of 6·7%", says Salonen. He speculates that this finding might explain the higher rate of cardiovascular disease in Finland than in other European countries.

"The new data are highly supportive of the hypothesis that iron is an important risk factor for ischemic heart disease in men and women", writes editorialist Jerome Sullivan (University of Florida, Gainsville, FL, USA). He adds that "a strong case could now be made for recommending blood donation as a way to lower iron levels, thus lowering heart attack risk", and suggests that a consensus on specific public- health recommendations is now a priority.

Yvonne van der Schouw, co-author of the Dutch study, agrees with Sullivan and suggests that "the significant association between the Cys282Tyr allele and heart-disease risk might in part explain why many women are protected from coronary heart disease until the menopause". The authors add that testing for this allele might help predict a postmenopausal woman's risk of cardiovascular death.

Kathryn Senior