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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:1158.)
© 2008 American Heart Association, Inc.

Clinical and Population Studies

Homocysteine or Renal Impairment

Which Is the Real Cardiovascular Risk Factor?

Kathleen Potter; Graeme J. Hankey; Daniel J. Green; John W. Eikelboom; Leonard F. Arnolda

From the School of Medicine and Pharmacology (K.P., G.J.H., L.F.A.), University of Western Australia, Perth, Australia; the Department of Neurology (G.J.H.), Royal Perth Hospital, Perth, Australia; Research Institute for Sport and Exercise Science (D.J.G.), Liverpool John Moores University, Liverpool, UK; School of Sport Science, Exercise, and Health (D.J.G.), The University of Western Australia, Perth, Western Australia; the Department of Medicine (J.W.E.), McMaster University, Hamilton, Canada; and the Department of Cardiology (L.F.A.), Royal Perth Hospital, Perth, Australia.

Correspondence to Dr Kathleen Potter, Department of Cardiology, Level 4, A Block, Royal Perth Hospital, Perth WA6847, Australia. E-mail pottek04{at}cyllene.uwa.edu.au

Objective— The purpose of this study was to determine whether adjustment for renal function eliminates the relationship between total plasma homocysteine (tHcy) and vascular risk, assessed by carotid intima medial thickness (CIMT) and flow-mediated dilation (FMD) of the brachial artery.

Methods and Results— We used cross-sectional data from 173 stroke patients treated with B-vitamins (folic acid 2 mg, vitamin B₆ 25 mg, and vitamin B₁₂ 0.5 mg) or placebo in a randomized double-blinded trial to test the relationships between posttreatment tHcy, cystatin C (a marker of glomerular filtration rate), estimated glomerular filtration rate (eGFR, Modification of Diet in Renal Disease equation) creatinine, CIMT, and FMD in stepwise and multivariable regression models. The strong linear relationship between tHcy and cystatin C was not altered by long-term B-vitamin treatment. tHcy lost significance as a predictor of the vascular measurements after adjustment for any single marker of renal function. Cystatin C, but not tHcy, was a significant independent predictor of FMD after adjustment for age, sex, smoking, systolic blood pressure, high-density lipoprotein cholesterol, and treatment group.

Conclusions— Adjusting for renal function eliminates the relationship between tHcy and CIMT and FMD, supporting the hypothesis that elevated tHcy is a marker for renal impairment rather than an independent cardiovascular risk factor.

We tested the effect of adjusting for renal function on the relationship between plasma homocysteine concentrations (tHcy) and carotid intima medial thickness (CIMT) and flow-mediated dilation (FMD) with regression analysis of randomized data from 173 stroke patients. Adjusting for renal function eliminated the association between tHcy and CIMT and FMD.

Key Words: homocysteine • cystatin c • stroke • flow-mediated dilation • carotid intima-medial thickness

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