Hyperhomocyst(e)inaemia: an independent risk factor for intermittent claudication
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J Mölgaard1, M R Malinow, C Lassvik
1Department of Internal Medicine, Faculty of Health Sciences, University Hospital, Linköping, Sweden.
Insights
High homocysteine levels are a risk factor for intermittent claudication (IC) independent of other factors. Folic acid supplementation may benefit IC patients with hyperhomocysteinemia.
Area of Science:
- Cardiovascular Epidemiology
- Metabolic Syndrome
- Vascular Disease
Background:
- Intermittent claudication (IC) is a manifestation of peripheral atherosclerotic disease.
- Established risk factors for IC include smoking, hypertension, diabetes, and dyslipidemia.
- The role of hyperhomocysteinemia as an independent risk factor for IC requires further investigation.
Purpose of the Study:
- To determine if hyperhomocysteinemia is an independent risk factor for intermittent claudication (IC).
- To assess the relationship between plasma homocysteine levels and other known risk factors for peripheral atherosclerotic disease.
- To explore the influence of folate levels on hyperhomocysteinemia in IC patients.
Main Methods:
- A population-based study in Sweden screened 15,253 middle-aged men for IC.
- Seventy-eight IC patients and 98 healthy controls were randomly selected for analysis.
- Plasma homocysteine levels were measured, and logistic regression was used to control for confounding factors.
Main Results:
- Plasma homocysteine levels were significantly higher in IC subjects compared to controls (P = 0.0002).
- Elevated homocysteine was an independent risk factor for IC, even after adjusting for traditional risk factors.
- The association between high homocysteine and IC was more pronounced in individuals with low serum folate levels.
Conclusions:
- Hyperhomocysteinemia is an independent risk factor for intermittent claudication.
- Folic acid supplementation should be considered for IC patients with elevated homocysteine levels.
- Further research into the role of homocysteine metabolism in vascular disease is warranted.
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 (HLD) cholesterol and age. The study population was recruited from an epidemiological study in Linköping County, Sweden, where all middle-aged men (n = 15,253, 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 mumol l-1, mean value +/- SD, P = 0.0002) in IC subjects than in controls (13.80 +/- 3.21 mumol 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 less than or equal to 11.0 nmol l-1. The results suggest that folic acid supplementation should be tried in IC subjects with hyperhomocyst(e)inaemia.