Haemochromatosis genotype and iron overload: association with hypertension and left ventricular hypertrophy

Ellervik C, Tybjaerg-Hansen A, Appleyard M, Ibsen H, Nordestgaard BG (Herlev Hospital, Copenhagen University Hospital, University of Copenhagen, Herlev; Naestved Hospital, University of Copenhagen, Naestved; Copenhagen University Hospital, University of Copenhagen, Copenhagen East; Bispebjerg Hospital, Copenhagen University Hospital, University of Copenhagen, Bispebjerg; and Holbaek Hospital, Holbaek; Denmark). Haemochromatosis genotype and iron overload: association with hypertension and left ventricular hypertrophy. J Intern Med 2010; 268: 252-264. Objective. We hypothesized that there is an association between haemochromatosis genotype C282Y/C282Y and/or iron overload and risk of hypertension and/or left ventricular hypertrophy (LVH). Methods. We analysed data from a cross-sectional study of the general population including 8992 individuals from the Copenhagen City Heart Study (CCHS), a follow-up study of 36 480 individuals from the Copenhagen General Population Study (CGPS), and a case-only study of 3815 Scandinavians from the Losartan Intervention For End-point Reduction in Hypertension Genetic Substudy (LIFEGEN) with LVH and hypertension. Results. In the CCHS, individuals with C282Y/C282Y versus wild type/wild type had an odds ratio for antihypertensive medication use of 4.8 (1.8-13; P = 0.003). In the CGPS, the corresponding hazard ratio was 1.7 (1.0-2.3; P = 0.003). Also, hazard ratios for antihypertensive medication use in the CGPS were 1.6 (1.0-2.6; P = 0.05) for transferrin saturation >= 80% vs. < 50%, and 2.3 (1.3-4.2; P = 0.005) for C282Y/C282Y + transferrin saturation >= 80% vs. wild type/wild type + transferrin saturation < 50%. These results were most pronounced in men above 55 years of age. We did not find any association between C282Y/C282Y or iron overload and LVH or hypertension (measured as blood pressure at a single occasion or continuous blood pressure), or LVH with hypertension in the CCHS or with severity of LVH in LIFEGEN. Conclusions. We found that haemochromatosis genotype C282Y/C282Y and extremely elevated transferrin saturation either separately or combined were associated with increased risk of antihypertensive medication use. Therefore, testing for haemochromatosis genotype C282Y/C282Y and extreme transferrin saturation could be considered in patients with essential hypertension.