Plasma total homocysteine is associated with abdominal aortic aneurysm and aortic diameter in older men
Yuen Y E Wong1, Jonathan Golledge, Leon Flicker
1Western Australian Centre for Health and Ageing, Centre for Medical Research, Western Australian Institute for Medical Research, Perth, Western Australia, Australia. ewong@meddent.uwa.edu.au
Insights
High plasma total homocysteine (tHcy) is linked to abdominal aortic aneurysm (AAA) and larger aortic diameter in older men. Lowering tHcy may be a future therapeutic target for AAA.
Area of Science:
- Cardiovascular research
- Genetics and epidemiology
- Vascular disease
Background:
- Abdominal aortic aneurysm (AAA) is a significant vascular disease.
- The role of plasma total homocysteine (tHcy) and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism in AAA pathogenesis requires further investigation.
Purpose of the Study:
- To investigate the association between plasma tHcy levels and the MTHFR C677T polymorphism with abdominal aortic aneurysm (AAA) and aortic diameter.
Main Methods:
- Cross-sectional study of 4248 men aged 70-88 years in Western Australia.
- Infrarenal aortic diameter measured by ultrasound.
- Plasma tHcy measured by immunoassay; MTHFR C677T polymorphism detected by polymerase chain reaction.
Main Results:
- Elevated tHcy (≥ 15 μmol/L) was associated with increased odds of AAA (OR, 1.45; 95% CI, 1.10-1.91).
- Each 5-μmol/L increase in tHcy correlated with a 0.15-mm increase in mean aortic diameter.
- MTHFR C677T polymorphism showed no significant association with AAA or aortic diameter.
Conclusions:
- Elevated plasma tHcy is associated with AAA presence and abdominal aortic diameter in older men.
- A dose-response relationship exists between tHcy and aortic diameter.
- Further longitudinal studies and clinical trials are needed to confirm causality and evaluate tHcy-lowering interventions.
Objective:
This study was conducted to determine whether plasma total homocysteine (tHcy) and the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism are associated with abdominal aortic aneurysm (AAA) and aortic diameter.
Methods:
This was a cross-sectional study set in Western Australia of 4248 community-dwelling men aged 70 to 88 years. Infrarenal aortic diameter was measured using ultrasound scan, tHcy was measured by immunoassay, and MTHFR 677T polymorphism was detected by polymerase chain reaction.
Results:
Adjusted multinomial logistic regression analysis showed the odds of having an AAA (aortic diameter ≥ 30 mm) for men with high tHcy (≥ 15 μmol/L) compared with those with normal tHcy (<15 μmol/L) was 1.45 (95% confidence interval [CI], 1.10-1.91). Every 5-μmol/L increment in tHcy was associated with 0.15-mm (95% CI, 0.01-0.28 mm) increase in mean aortic diameter. The tHcy concentration was higher in MTHFR TT homozygote individuals than in wild-type CC individuals. There was, however, no apparent association between MTHFR C677T polymorphism with AAA (TT vs CC genotype: odds ratio, 0.97; 95% CI, 0.72-1.31) or aortic diameter (TT vs CC genotype: mean increment of 0.01 mm; 95% CI, -0.63 to 0.65 mm).
Conclusions:
Elevated tHcy is associated with the presence of AAA in older men. There is also a positive dose-response relationship between tHcy and abdominal aortic diameter. Longitudinal studies and clinical trials of lowering tHcy are required to assess whether these relationships are causal.
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