Homocystine as an Etiologic Factor in Occlusive Vascular Diseases
Homocystine (d) is the etiologic factor in occlusive vascular diseases among the listed options. 1
Evidence for Homocystine's Role in Vascular Occlusion
Hyperhomocysteinemia (elevated levels of homocysteine in the blood) has been established as an independent risk factor for premature vascular occlusion across multiple vascular territories:
- The American Society of Human Genetics and American College of Medical Genetics have established that total plasma homocysteine (tHcy) levels >15 μM constitute hyperhomocysteinemia, with even levels between 10-15 μM potentially increasing risk 1
- Hyperhomocysteinemia is associated with:
- Cerebral arterial and venous thrombosis in both children and adults
- Coronary artery disease
- Peripheral arterial occlusive disease
- Retinal vein occlusions 1
Studies have demonstrated that homocysteine plays a critical role in vascular occlusion, with hyperhomocysteinemia present in:
- 42% of patients with cerebrovascular disease
- 28% with peripheral vascular disease
- 30% with coronary artery disease 2
Mechanism of Vascular Damage
Homocysteine contributes to vascular occlusion through several mechanisms:
- Endothelial dysfunction
- Alterations in blood platelet aggregation
- Changes in coagulation factors
- Oxidative stress 2
Risk Quantification
The relationship between homocysteine and vascular disease is dose-dependent:
- The Physician's Health Study found that an increase in homocysteine concentration of just 1.7 μmol/L above normal values was associated with a threefold higher risk for myocardial infarction 2
- Odds ratios for vascular disease due to hyperhomocysteinemia range from 3.17-4.15 3
- For retinal vascular occlusive disease specifically, hyperhomocysteinemia was present in 66.1% of patients versus only 3.4% of controls (OR 47.5) 4
Clinical Implications
Identifying hyperhomocysteinemia is important in patients with:
- Premature vascular disease
- Retinal vascular occlusions
- Unexplained arterial or venous thrombosis
- Family history of early cardiovascular events 1
Important Considerations
- Homocysteine measurement requires precise handling, including immediate separation and freezing of plasma 1
- Hyperhomocysteinemia can have both genetic causes (e.g., cystathionine synthase deficiency) and non-genetic causes (e.g., deficiencies in B12, folate, or B6) 2
- Treatment approaches typically involve supplementation with B vitamins (folate, B6, B12) which serve as cofactors in homocysteine metabolism 1
Answer to Question
Among the amino acids listed in the question (arginine, glutamine, methionine, homocystine, xanthine), homocystine is the only one that has been established as an etiologic factor in occlusive vascular diseases, supported by extensive clinical evidence and recognized by major medical organizations.