Introduction to HCY
Homocysteine in plasma exists in two forms: oxidized homocysteine and reduced homocysteine.
Reduced homocysteine contains a free sulfhydryl group that is highly reactive and easily oxidized, forming disulfides.
Oxidized homocysteine is the main form present in plasma, existing as disulfides or covalently bound to proteins.
Pathogenic Mechanism
HCY can cause endothelial cell damage by promoting the massive production of oxidative free radicals, leading to lipid peroxidation and increased oxidized low-density lipoprotein, thereby causing injury and damage to blood vessels.
Under the influence of HCY, plaques form on damaged vessel walls, promoting atherosclerosis.
Main Clinical Applications
1. Cardiovascular Disease Prevention and Management
(1) Relationship between elevated HCY and atherosclerosis (AS):
As early as 1969, autopsies of two patients with plasma HCY concentrations dozens of times higher than normal revealed extensive atherosclerosis and arterial thrombosis. Clinically, patients with homocystinuria often die prematurely from cerebral infarction and myocardial infarction due to systemic atherosclerosis and thrombosis, which is related to elevated blood HCY levels.
(2) Relationship between HCY levels and cardiovascular disease risk:
Observation of AS plaques using intravascular ultrasound showed that when plasma HCY concentration was <8 μmol/L, plaques were smaller (0.17-0.76 mm). When >8 μmol/L, plaques were significantly larger (0.27-1.04 mm, p<0.001), indicating a positive correlation with the severity of coronary artery lesions. Mild to moderate elevation of HCY levels can increase the risk of death from cardiovascular disease by 4 to 6 times. For every 5 μmol/L increase in plasma total HCY, the risk of CHD increases by 60% in men and 80% in women.
2. HCY and Nervous System Diseases
Cerebrovascular disease is a major threat to human health. In recent years, with the advancement of molecular biology, the role of HCY in stroke has gained increasing attention. It is generally accepted that plasma HCY >15 μmol/L defines hyperhomocysteinemia. Elevated plasma Hey levels are found in less than 5% of the general population but in 30-40% of stroke patients.
Elevated HCY is a significant risk factor associated with stroke. The latest US data show that the incidence of stroke in late middle-aged men (55-64 age group) is three times that of the 45-54 age group.
High HCY is an important factor contributing to Alzheimer's disease and Parkinson's disease.
3. Diabetes and Complication Prevention/Management
Numerous studies domestically and internationally have shown that plasma HCY level can serve as an independent risk factor for macrovascular disease in patients with type 2 diabetes.
Monitoring HCY levels in diabetic patients is beneficial for prognosis assessment. Elevated HCY is more severe in diabetic patients with renal, retinal, and vascular complications.
Hyperhomocysteinemia can also promote the occurrence and development of diabetic microvascular complications.
4. Chronic Renal Failure Complication Prevention/Management
Patients with chronic renal failure (CRF) commonly have hyperhomocysteinemia, with an incidence 33 times higher than in normal individuals.
In uremia, on one hand, the activity of hepatic methionine adenosyltransferase increases, leading to elevated S-adenosylmethionine levels. On the other hand, decreased renal function reduces the synthesis of serine, an essential co-substrate for HCY metabolism, inhibiting HCY metabolism and causing HCY accumulation.
5. Pulmonary Thromboembolism Prevention/Management
Studies show that hyperhomocysteinemia (>20 μmol/L) significantly increases the risk of deep vein thrombosis, increasing the incidence of deep vein thrombosis by 4 times.
High HCY is an independent risk factor for pulmonary thromboembolism (PTE) in the Chinese Han population. Lowering HCY can reduce the risk of venous thromboembolism (VTE) in Chinese individuals.
Who Should Undergo HCY Testing?
① Individuals with established CHD, cerebrovascular disease, or peripheral arterial disease.
② Individuals with hypertension, diabetes, obesity, or smokers.
③ Individuals with a family history of CHD or atherosclerosis, especially those with premature disease or death in first-degree relatives.
④ Individuals with xanthomas or xanthelasmas.
⑤ Individuals with familial hyperlipidemia.
⑥ Men over 40 years old and postmenopausal women.
Reference Range
Normal fasting plasma total HCY: 5-15 μmol/L
Ideal value: <10 μmol/L
Hyperhomocysteinemia: >15 μmol/L
Mild: 15-30 μmol/L
Moderate: 31-100 μmol/L
Severe: >100 μmol/L
Prevention and Treatment of Hyperhomocysteinemia
Dietary Control:
Limit alcohol consumption.
Consume a diet low in animal protein and high in plant protein.
Medications that can prevent and treat hyperhomocysteinemia:
Folic Acid
Vitamin B6
Vitamin B12
Betaine (trimethylglycine)
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