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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #203721
Title: Total plasma homocysteine and arteriosclerotic outcomes in type 2 diabetes with nephropathy

Author
item FRIEDMAN, ALLON - INDIANA UNIV SCH MED
item HUNSICKER, LAWRENCE - UNIV IOWA COLLEGE MEDICIN
item Selhub, Jacob
item BOSTOM, ANDREW - RHODE ISLAND HOSPITAL

Submitted to: Journal of the American Society of Nephrology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/1/2005
Publication Date: 9/14/2005
Citation: Friedman, A.N., Hunsicker, L.G., Selhub, J., Bostom, A.G. 2005. Total plasma homocysteine and arteriosclerotic outcomes in type 2 diabetes with nephropathy. Journal of the American Society of Nephrology. 16:3397-3402.

Interpretive Summary: Homocysteine is an amino acid which has important functions in the body but it is thought to be harmful when its concentration in blood becomes high. In this study we examined the possibility that high homocysteine in the blood can predict heart disease in diabetic patients. Our data showed that patients with diabetic are at higher risk of cardiovascular disease if they already have one and if they are hypertensive. But homocysteine did not predict a higher risk for cardiovascular disease.

Technical Abstract: Total serum homocysteine (tHcy) has been shown to predict de novo and recurrent cardiovascular events in many studies. However, results in diabetic populations with minimal nephropathy are mixed. The independent relationship between tHcy and arteriosclerotic outcomes and congestive heart failure (CHF) events in a population with high cardiovascular risk and diabetic nephropathy was examined. A total of 1575 individuals were enrolled in the international Irbesartan Diabetic Nephropathy Trial (IDNT) and followed for 2.6 yr. All participants had baseline diabetic nephropathy, overt proteinuria, and hypertension and were recruited between 1996 and 1999. A total of 492 total arteriosclerotic outcomes (primary outcome) and 317 CHF events (secondary outcome) were tallied. Established cardiovascular risk factors were highly prevalent, as were high tHcy levels (quintiles [uM]: first 4.5 to 11; second >11 to 13; third >13 to 15; fourth >15 to 19; fifth >19). No association between tHcy and arteriosclerotic outcomes was observed in a univariate model or after adjustment for study randomization and established cardiovascular risk factors. The strongest outcome predictor was the presence of baseline cardiovascular disease, followed by an inverse relationship to diastolic BP. The significant univariate association between tHcy and CHF events disappeared when serum creatinine alone was added to the model. These findings question the utility of tHcy in predicting de novo or recurrent cardiovascular events in individuals with diabetic nephropathy. Further studies are needed to confirm whether these negative results apply to other populations with heavy cardiovascular risk burdens. Previous positive findings can potentially be explained through tHcy’s role as a sensitive surrogate marker for kidney disease, itself a recognized cardiovascular risk factor.