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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1999;19:2241-2244.)
© 1999 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Cystatin C as a Determinant of Fasting Plasma Total Homocysteine Levels in Coronary Artery Disease Patients With Normal Serum Creatinine

Andrew G. Bostom; Linda Bausserman; Paul F. Jacques; Gintaras Liaugaudas; Jacob Selhub; Irwin H. Rosenberg

From the Divisions of General Internal Medicine and Cardiology, Memorial Hospital of Rhode Island, Providence, RI (A.G.B., G.L.); the Tufts–Jean Mayer USDA Human Nutrition Research Center on Aging, Boston, Mass (A.G.B., P.F.J., J.S., I.H.R.); and the Lipid Research Laboratory, The Miriam Hospital, Providence, RI (L.B.).

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, 1.4 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 B₁₂, and pyridoxal 5'-phosphate levels, along with serum cystatin C, creatinine, and albumin levels, were determined in 164 consecutive stable-CAD patients (mean±SD age, 61±9 years; 78.7% men) whose serum creatinine level was 1.4 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 (P<0.001), B₁₂ (P<0.001), age (P=0.002), albumin (P=0.008), and sex (P=0.024) were independent determinants of fasting total homocysteine levels. Cystatin C alone determined over half of the variability (ie, R²) in total homocysteine levels accounted for by these 5 independent regressors. In contrast, creatinine, folate, and pyridoxal 5'-phosphate were not independently predictive of fasting total homocysteine levels (P>0.2). 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 <3 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 • renal function • homocysteine • determinants

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