From the Guidelines
Elevated homocysteine levels are associated with a 2- to 3-fold increased risk for atherosclerotic vascular disease, including stroke, and can cause blood vessel constriction and reduced diameter. Homocysteine damages the endothelium (inner lining of blood vessels) by promoting oxidative stress, reducing nitric oxide production, and increasing inflammation, as noted in the guidelines for the primary prevention of stroke 1. This endothelial dysfunction impairs vasodilation and promotes vasoconstriction, leading to narrower blood vessels. Additionally, homocysteine enhances smooth muscle cell proliferation in vessel walls, causing thickening and further narrowing of the vessel lumen. These mechanisms contribute to reduced blood flow and increased blood pressure. Homocysteine also promotes platelet aggregation and coagulation, which can further compromise vessel diameter through thrombus formation.
Some key points to consider:
- Elevated plasma homocysteine levels are associated with increased carotid IMT and carotid artery stenosis, as found in the Study of Health Assessment and Risk in Ethnic groups (SHARE) 1.
- The relationship between homocysteine levels and carotid IMT may be eliminated after adjustment for other cardiovascular risk factors or renal function, as noted in several recent investigations 1.
- B-complex vitamins, including pyridoxine (B6), cobalamin (B12), and folic acid, can lower homocysteine levels, but their effect on clinical cardiovascular end points is still unclear, as seen in the Vitamin Intervention for Stroke Prevention (VISP) trial and the Women’s Antioxidant and Folic Acid Cardiovascular Study (WAFACS) 1.
- Maintaining normal homocysteine levels through adequate B vitamin intake can help preserve normal vascular function and blood vessel diameter, but the evidence is insufficient to justify a recommendation for or against routine therapeutic use of vitamin supplements in patients with extracranial carotid and vertebral artery disease, as stated in the 2011 ASA/ACCF/AHA/AANN/AANS/ACR/ASNR/CNS/SAIP/SCAI/SIR/SNIS/SVM/SVS guideline 1.
Overall, managing homocysteine levels is crucial to preventing blood vessel constriction and reduced diameter, and maintaining normal vascular function, but more research is needed to fully understand the relationship between homocysteine and cardiovascular disease.
From the Research
Effect of Homocysteine on Blood Vessel Diameter
- Homocysteine has been shown to impair vascular endothelial and smooth muscle cell function, leading to endothelial dysfunction and alterations in endothelium-dependent vasomotor regulation 2.
- Elevated homocysteinemia can diminish vasodilation by nitric oxide, increase oxidative stress, stimulate the proliferation of vascular smooth muscle cells, and alter the elastic properties of the vascular wall, ultimately contributing to elevated blood pressure 2.
- The mechanism of homocysteine-induced endothelial dysfunction involves the reduction of nitric oxide bioavailability, which can be caused by various factors including disruptive uncoupling of nitric oxide synthase activity, quenching of nitric oxide by oxidative stress, and enzymatic inhibition by asymmetric dimethylarginine 3.
- Homocysteine-induced endothelial dysfunction can lead to impaired endothelial-dependent dilatation, which can be monitored by flow-mediated dilation method using ultrasound 3.
- Studies have shown that supplementation of folic acid and vitamin B12 can lower mildly elevated plasma homocysteine levels and reverse homocysteine-induced impairment of endothelium-dependent vasoreactivity 4.
- The interaction of hyperhomocysteinemia with hypertension and smoking is strong, and the combined effect is more than multiplicative, suggesting that homocysteine can exacerbate the effects of other cardiovascular risk factors 5.
- Homocysteine produces atherosclerosis, thromboembolism, and vascular endothelial cell injury, which can lead to vascular dysfunction and increased risk of cardiovascular disease 5, 6.