Plasma total homocysteine and cysteine levels as cardiovascular risk factors in coronary heart disease

Abstract

Objectives: As an important risk factor for coronary atherosclerosis, elevated plasma total homocysteine (t-hcy) concentration has recently received greater attention than have conventional risk factors. Though less reactive than homocysteine, cysteine (cys) is the most abundant plasma thiol and may function as an extracellular regulating factor of thiol/disulfide exchange in order to maintain an adequate redox status. An increase in the total amount of this compound may be noxious depending on environmental conditions. In the present study, the aim was to investigate changes of plasma total cysteine, homocysteine and other determinants in different types of coronary heart disease. Design and methods: Plasma total homocysteine (t-hcy), cysteine (t-cys), cysteinylglycine (t-cysgly), folic acid, vitamin B 12, lipid parameters, total protein, albumin and creatinine levels were studied in plasma from 68 patients with coronary heart disease and 42 healthy controls. After reduction of disulfide bonds with tri- n-buthylphosphine, plasma total thiols were assayed using high performance liquid chromatography (HPLC) and fluorescence detection following derivatization of sulfhydryl groups with 7-fluoro-benzo-2-oxa-1,3-diazole-4-sulfonate (SBD-F). Other parameters were determined by using commercial kits. Results: Plasma t-hcy and t-cys levels were higher in patients ( P<0.0001) than in controls, but t-cysgly was unchanged. Hcy and cys levels were correlated with age in the whole study population ( r=0.49, r=0.46, P<0.01). Plasma t-hcy positively correlated with plasma t-cys ( r=0.53, P<0.01) and t-cysgly ( r=0.49, P<0.01) in patients, and with plasma t-cys ( r=0.57, P<0.01) in controls. Postmenopausal women had higher t-cys and t-hcy levels than premenopausal women among the controls ( P<0.01). Folate and vitamin B 12 levels were similar in both patients and controls. Patients with vitamin B 12 levels below normal had higher plasma t-cys and t-cysgly levels ( P<0.05). Interestingly, control subjects with lower vitamin B 12 levels had lower plasma t-hcy levels ( P<0.05). Plasma total cholesterol, HDL-cholesterol, LDL-cholesterol, total protein, albumin and creatinine levels in patients and controls were within the normal range, but only HDL-cholesterol levels in patients were lower than in controls ( P<0.0001). Triglyceride and VLDL levels of patients were also higher than those of controls ( P<0.0001). Conclusions: Higher plasma total cysteine levels are as important as higher plasma total homocysteine levels. Both parameters are intercorrelated and may act synergistically. To discern their respective roles in atherosclerotic disease, these aminothiol levels have to be considered together.