Stabilization of Homocysteine in Unseparated Blood over Several Days: A Solution for Epidemiological Studies

Increased blood homocysteine is a potentially modifiable risk factor for cardiovascular disease. In a recent metaanalysis of individual participant data from prospective epidemiologic studies, a 25% lower homocysteine concentration was associated with an 11% lower risk for ischemic heart disease and a 19% lower risk for stroke (1). Blood homocysteine is easily lowered by folic acid supplementation, and several large-scale randomized trials are currently underway to assess the effects of homocysteine-lowering vitamin supplements on the risk of vascular disease. If such trials demonstrate benefit, there will be increasing interest in homocysteine determinations to assess vascular disease risk. In addition, further large-scale epidemiologic studies may be required to investigate the association between homocysteine and cardiovascular disease in a wider range of populations. These would be facilitated by simple and cost-effective methods for blood collection and analysis.One of the chief constraints in homocysteine measurements is the continuing production and release of homocysteine by red blood cells after venipuncture, which causes an artificial increase in plasma concentration of ∼10% per hour (2)(3). It has been recommended, therefore, that blood samples for homocysteine measurements be drawn into tubes containing EDTA, chilled, or placed on ice immediately after collection and that the plasma be separated from the red cells within 1 h. Such procedures can be difficult to implement in large-scale epidemiologic studies or other situations in which samples have to be collected remotely (e.g., in multiple clinics or in people’s homes) and transported to a central laboratory. Use of NaF or acidic citrate has been advocated for stabilization of homocysteine in whole blood at ambient temperature …