Homocysteine, endothelial dysfunction, and coronary artery disease: emerging strategy for secondary prevention.
Atherosclerosis is an important medical problem of the 21st century, but traditional risk factors could only account for 50% of the problem. Hyperhomocysteinemia is emerging as an independent atherosclerosis risk factor, associated with folate deficiency, renal failure, and relative deficiency of MTHFR (C677T polymorphism) or other enzymes depending on gender, age, and smoking status. Hyperhomocysteinemia has been reported to occur in 11-22% of western people, in 3-5% of normal asymptomatic Chinese subjects aged 18-70 years in Hong Kong, Macau, Sydney, and San Francisco, 23-36% of Chinese in Hong Kong with premature coronary artery disease, and 29% of a nonselective series of coronary subjects in Hong Kong. Evidence is accumulating that documents its associations with atherosclerosis disease in both case-control observations and prospective cohort studies, in vitro experiments, and in vivo experimental models in both animals and human subjects, as well as the successful improvement by homocysteine-lowering of endothelial function as surrogate atherosclerosis endpoints in asymptomatic human and coronary patients (secondary prevention). A number of large scale homocysteine-lowering trials are currently underway for stroke and heart attacks prevention. Collectively these trials will include more than 65,000 patients at high-risk for cardiovascular and stroke events, and should provide a reliable evidence-base for prevention.
Woo
Kam Sang
KS
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China. kamsangwoo@cuhk.edu.hk
Qiao
Mu
M
Chook
Ping
P
Poon
Peter Y K
PY
Chan
Anna K Y
AK
Lau
Joseph T F
JT
Fung
Kwok Pui
KP
Woo
Jean L F
JL
D000293:Adolescent; D000328:Adult; D000368:Aged; D003324:Coronary Artery Disease / Q000209:etiology / Q000517:prevention & control*; D003541:Cystathionine beta-Synthase / Q000172:deficiency; D019587:Dietary Supplements; D004730:Endothelium, Vascular / Q000503:physiopathology; D005492:Folic Acid / Q000187:drug effects / Q000627:therapeutic use; D006801:Humans; D020138:Hyperhomocysteinemia / Q000150:complications / Q000235:genetics / Q000517:prevention & control*; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008875:Middle Aged; D009203:Myocardial Infarction / Q000517:prevention & control; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000172:deficiency / Q000235:genetics; D011110:Polymorphism, Genetic; D012307:Risk Factors; D020521:Stroke / Q000517:prevention & control
D005492:Folic Acid; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D003541:Cystathionine beta-Synthase