doi: 10.1161/CIRCULATIONAHA.106.634691
(Circulation. 2006;114:e547.)
© 2006 American Heart Association, Inc.
Correspondence |
Letter by Undas and Jakubowski Regarding Article, "Relationship Between Homocysteine and Mortality in Chronic Kidney Disease"
Institute of Cardiology, Jagiellonian University School of Medicine, Kraków, Poland
Department of Microbiology and Molecular Genetics, UMDNJ-New Jersey Medical School, International Center for Public Health, Newark, NJ, jakubows{at}umdnj.edu
We read with keen interest the article by Menon et al,1 which concluded that plasma total homocysteine (tHcy) is not a risk factor for all-cause or cardiovascular disease (CVD) mortality in patients with stage 3 and 4 chronic kidney disease (CKD). The conflicting results of other studies are explained by Menon et al by the failure to adjust for the kidney function.
However, a major limitation of this type of study is that it relies on a composite marker, tHcy, that comprises at least 5 different homocysteine species, each of which can exert a distinct biological effect.2 Moreover, tHcy does not encompass other homocysteine metabolites present in human blood.2 Thus, a contribution of specific Hcy-related mechanisms to cardiovascular risk or mortality is likely to be overlooked by using tHcy as a marker. For example, a highly reactive metabolite, Hcy-thiolactone, reacts avidly with proteins to form N-Hcy-protein adducts, which induce an autoimmune response in humans.2 N-Hcy-protein adducts occur in human blood2 and are elevated in patients undergoing hemodialysis.3 Elevated levels of anti–N-Hcy-protein autoantibodies, observed in patients with stroke4 and CVD,5 are a common feature of atherosclerosis.2 Moreover, anti–N-Hcy-protein autoantibodies also are associated with C-reactive protein levels.5 Given a high prevalence of elevated tHcy levels in patients with CKD, it might be hypothesized that an autoimmune response against N-Hcy-protein may also play an important role in the pathogenesis of CVD in these subjects.
Accumulating evidence suggests that specific homocysteine-mediated mechanisms, including protein modification by Hcy-thiolactone, are implicated in the progression of CVD in subjects with moderate hyperhomocystinemia. If so, tHcy levels may not be the best marker of homocysteine toxicity, at least in some patient groups, such as patients with CKD. It would be more informative to investigate specific markers of homocysteine metabolism both in patients with CKD and in those with normal renal function to elucidate an intricate relation between homocysteine and CVD.
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Acknowledgments |
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Disclosures
None.
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References |
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 Top References |
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- Menon V, Sarnak MJ, Greene T, Wang X, Pereira AA, Beck GJ, Kusek JW, Selhub J, Collins AJ, Levey AS, Shlipak MG. Relationship between homocysteine and mortality in chronic kidney disease. Circulation. 2006; 113: 1572–1577.
[Abstract/Free Full Text] - Jakubowski H. Anti-N-homocysteinylated protein autoantibodies and cardiovascular disease. Clin Chem Lab Med. 2005; 43: 1011–1014.[CrossRef][Medline]
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- Perna AF, Satta E, Acanfora F, Lombardi C, Ingrosso D, De Santo NG. Increased plasma protein homocysteinylation in hemodialysis patients. Kidney Int. 2006; 69: 869–876.[CrossRef][Medline]
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- Undas A, Perla J, Laci
ski M, Trzeciak W, Ka
mierski R, Jakubowski H. Autoantibodies against N-homocysteinylated proteins in humans: implications for atherosclerosis. Stroke. 2004; 35: 1299–1304.[Abstract/Free Full Text] - Undas A, Jankowski M, Twardowska M, Padjas A, Jakubowski H, Szczeklik A. Autoantibodies to N-homocysteinylated albumin as a marker for early-onset coronary artery disease in men. Thromb Haemost. 2005; 93: 346–350.[Medline]
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