Abstract-Serum creatinine, a surrogate for both renal function and homocysteine generation, is a determinant of fasting plasma total homocysteine levels in coronary artery disease (CAD) patients. We hypothesized that among stable-CAD patients with normal creatinine levels (ie, Յ1.4 mg/dL), serum cystatin C, a more sensitive indicator of glomerular filtration rate, would better predict fasting total homocysteine levels in comparison with serum creatinine. Fasting plasma total homocysteine, folate, vitamin B 12 , and pyridoxal 5Ј-phosphate levels, along with serum cystatin C, creatinine, and albumin levels, were determined in 164 consecutive stable-CAD patients (meanϮSD age, 61Ϯ9 years; 78.7% men) whose serum creatinine level was Յ1.4 mg/dL. All subjects were examined at least 3 to 4 months after the widespread availability of cereal grain flour products fortified with folic acid. General linear modeling with ANCOVA revealed that serum cystatin C (PϽ0.001), B 12 (PϽ0.001), age (Pϭ0.002), albumin (Pϭ0.008), and sex (Pϭ0.024) were independent determinants of fasting total homocysteine levels. Cystatin C alone determined over half of the variability (ie, R 2 ) in total homocysteine levels accounted for by these 5 independent regressors. In contrast, creatinine, folate, and pyridoxal 5Ј-phosphate were not independently predictive of fasting total homocysteine levels (PϾ0.2). Consistent with the impact of folic acid fortification of cereal grain flour in the general population, only 1 of the CAD subjects (0.6%) had a plasma folate level Ͻ3 ng/mL. We conclude that serum cystatin C levels may reflect subtle decreases in renal function that independently predict fasting total homocysteine levels among stable-CAD patients with normal serum creatinine. Key Words: coronary arteriosclerosis Ⅲ renal function Ⅲ homocysteine Ⅲ determinants P ooled observational data strongly suggest that mild hyperhomocysteinemia is an independent risk factor for coronary artery disease (CAD). 1,2 Creatinine, a surrogate for both glomerular filtration rate 3 and homocysteine (Hcy) generation, 4 is a significant determinant of total homocysteine (tHcy) levels in CAD 5,6 and general populations. 7 Systemic arteriosclerosis 8 and clinical 9 as well as subclinical CAD 10 have been associated with nephrosclerosis, specifically, renal arteriolar hyalinization. 8 -10 In cross-sectional analyses, creatinine may be a relatively insensitive marker of the mildly to moderately reduced glomerular filtration rates 11 likely to be encountered among CAD patients with subclinical nephrosclerosis.Cystatin C is a nonglycosylated 13-kDa basic protein produced at a stable rate by all investigated nucleated cells and whose serum concentration is primarily determined by the glomerular filtration rate. 12 Consistent investigations now clearly indicate that serum cystatin C is superior to serum creatinine for the detection of early decreases in glomerular filtration rate. [13][14][15] There is a strong, independent (inverse) association between glomerular filtration ra...

Abstract-Fortification of enriched cereal grain flour products with folic acid has drastically reduced the prevalence of deficient plasma folate status, a major determinant of plasma total homocysteine (tHcy) levels. We hypothesized that even more liberally defined "suboptimal" plasma folate status might no longer contribute importantly to the population attributable risk (PAR) for mild hyperhomocysteinemia, a putative atherothrombotic risk factor. We determined fasting plasma tHcy, folate, vitamin B 12 , and pyridoxal 5Ј-phosphate levels, along with serum creatinine and albumin levels, in 267 consecutive patients (aged 61Ϯ9 [meanϮSD] years, 76.4% men and 26.6% women) with stable coronary artery disease (CAD) who were nonusers of vitamin supplements or had abstained from supplement use for at least 6 weeks before examination. Subjects were evaluated a minimum of 3 months after the implementation of flour fortification was largely completed. Relative risk estimates for the calculation of PAR were derived from a multivariable-adjusted logistic regression model with Ն12 mol/L tHcy as the dependent variable and with age, sex, pyridoxal 5Ј-phosphate (continuous), albumin (continuous), Ͻ5 ng/mL folate, Ͻ250 pg/mL vitamin B 12 , and Ն1.3 mg/dL creatinine as the independent variables. The prevalence of Ն12 mol/L plasma tHcy was 11.2% (30 of 267 patients). PAR estimates (percentage) for Ն12 mol/L tHcy were as follows: Ͻ5 ng/mL folate (Ͻ1%), Ͻ250 pg/mL vitamin B 12 (24.5%), and Ն1.3 mg/dL creatinine (37.5%

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