Hyperhomocyst(e)inaemia: an independent risk factor for intermittent claudication

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Abstract
The aim of this study was to test the question of hyperhomocyst(e)inaemia as a risk factor for intermittent claudication (IC) independent of other important risk factors for peripheral atherosclerotic disease, such as smoking, hypertension, diabetes mellitus, hypercholesterolaemia, hypertriglyceridaemia, low levels of high-density-lipoprotein (HDL) cholesterol and age. The study population was recruited from an epidemiological study in LinkÖping County, Sweden, where all middle-aged men (n = 15253, 45–69 years of age) were screened for IC. Seventy-eight subjects with verified IC and 98 healthy sex- and age-matched controls were randomly selected. Plasma levels of homocyst(e)ine (including the sum of free and bound forms of homocysteine and their disulphide oxidation products, homocystine, and homocysteine-cysteine mixed disulphide) were significantly higher (16.74 ± 5.45 μmol l−1, mean value ± SD, P = 0.0002) in IC subjects than in controls (13.80 ± 3.21 μmol l−1), with 23% of the claudicants above the 95th percentile for controls. Stepwise logistic regression analysis revealed that the difference in plasma homocyst(e)ine was independent of the other above-mentioned risk factors. Moreover, the elevation of plasma homocyst(e)ine in claudicants was mainly confined to subjects with serum folate levels of < 11.0 nmol l−1. The results suggest that folic acid supplementation should be tried in IC subjects with hyperhomocyst(e)inaemia.