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Hyperhomocysteinaemia: a risk factor for extracranial carotid artery atherosclerosis
R Clarke1, D Fitzgerald, C O'Brien
1Department of Cardiology, Adelaide Hospital, Dublin, Ireland.
Insights
Elevated homocysteine levels, a marker of hyperhomocysteinemia, are a weak risk factor for asymptomatic carotid artery atherosclerosis in healthy individuals. This genetic trait poses a lesser risk compared to symptomatic vascular disease patients.
Area of Science:
- Cardiovascular Medicine
- Genetics
- Metabolic Disorders
Background:
- Hyperhomocysteinemia, resulting from impaired methionine metabolism often due to cystathionine beta-synthase deficiency, is a known risk factor for symptomatic vascular disease.
- The association between hyperhomocysteinemia and atherosclerosis in asymptomatic individuals, independent of conventional risk factors, remains unclear.
Purpose of the Study:
- To investigate the prevalence of asymptomatic extracranial carotid artery atherosclerosis in individuals with a genetic predisposition to hyperhomocysteinemia.
- To determine if hyperhomocysteinemia is an independent risk factor for subclinical atherosclerosis in a healthy population.
Main Methods:
- Duplex ultrasound was used to assess carotid artery atherosclerosis in 25 obligate heterozygotes for cystathionine beta-synthase deficiency and 21 controls.
- Hyperhomocysteinemia was diagnosed via a methionine-loading test, and conventional cardiovascular risk factors were recorded.
Main Results:
- Extracranial carotid artery atherosclerosis was observed in 12 of 25 heterozygotes and 8 of 21 controls.
- While the genetic trait of hyperhomocysteinemia was not a significant marker, elevated homocysteine levels were associated with increased carotid disease risk (OR 1.038 per unit increase, P=0.03) after adjusting for other factors.
Conclusions:
- Hyperhomocysteinemia is a weak risk factor for asymptomatic extracranial carotid atherosclerosis.
- The relative risk associated with this genetic trait is lower than that seen in patients with symptomatic vascular disease.
Abstract:
Hyperhomocysteinemia arising from impaired methionine metabolism, and usually due to a deficiency of cystathionine beta-synthase is a significant and independent risk factor for symptomatic vascular disease. It is not known if hyperhomocysteinemia in apparently healthy asymptomatic subjects is associated with atherosclerosis and whether such a relationship is independent of conventional risk factors. The prevalence of asymptomatic extracranial carotid artery atherosclerosis was determined by duplex ultrasound examination in 25 obligate heterozygotes with respect for cystathionine beta-synthase deficiency (whose children were known to be homozygous for this genetic defect) and in 21 controls. Hyperhomocysteinemia was determined by a standard methionine-loading test and conventional risk factors were also recorded. Twelve of 25 obligate heterozygotes and 8 of 21 normal controls had evidence of extracranial carotid artery atherosclerosis. Hyperhomocysteinemia as a genetic trait was not a significant risk marker, but the actual homocysteine level was associated with an increased risk of carotid disease. After adjustment for the effects of other significant risk factors, the odds ratio of hyperhomocysteinemia for carotid disease was 1.038 per unit increase in homocysteine level (P = 0.03). Hyperhomocysteinemia is a weak risk factor for asymptomatic extracranial carotid atherosclerosis and the relative risk associated with this genetic trait is less than that observed in a study of patients presenting with clinical manifestations of vascular disease.