NDT Advance Access originally published online on April 10, 2008
Nephrology Dialysis Transplantation 2008 23(7):2428-2429; doi:10.1093/ndt/gfn066
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Hopeful for a second HOPE-2 post hoc analysis
Correspondence and offprint requests to: E-mail: righettim{at}hotmail.comSir,
I think that the post hoc analysis of the HOPE-2 study by Mann et al. [1], though interesting, does not answer the question of whether folic acid therapy reduces cardiovascular morbidity and mortality in patients with chronic kidney disease. I am doubtful of whether in their final opinion that vitamin B therapy does not reduce cardiovascular disease in hyperhomocysteinaemic patients for many reasons:
- baseline homocysteine values were not an inclusion criteria and, as a result, a large part of the enrolled patients did not have hyperhomocysteinaemia;
- baseline folate levels were not an inclusion criteria and, consequently, all patients had high folate levels because they originated from fortification areas, all patients having taken vitamin B therapy before starting the trial;
- a large part of enrolled patients showed other cardiovascular risk factors and, in particular,
45% were diabetics and 70% of patients were submitted to lipid-lowering drugs;
- homocysteine levels were not adjusted for nutritional and inflammatory indexes which have, respectively, a direct and inverse relationship;
- a small net decrease of homocysteine levels might be inadequate to observe any sort of effect on cardiovascular disease;
- a few determinations of homocysteine levels might be misleading of lifetime exposure.
I think that diabetic and nondiabetic patients’ data concerning the cardiovascular effects of homocysteine-lowering vitamin B therapy should be shown separately because diabetics have a higher cardiovascular morbidity rate, but lower homocysteine levels than nondiabetic ones [2]. It might be intriguing to perform a post hoc analysis excluding diabetic patients and comparing the subgroup of patients responsive to vitamin B therapy, defined by normal homocysteine values and high cobalamin levels, with the remaining patients, characterized by high homocysteine levels and low cobalamin levels. This opinion is strengthened by the interesting post hoc analysis of the VISP trial by Spence et al. [3] who have shown a significant risk reduction for composite cardiovascular events in patients treated with high doses of vitamin B and high serum cobalamin levels.
I think that, attending well-designed prospective trials in nondiabetic hyperhomocysteinaemic patients, the most impressive data have been recently published by Yang et al. [4] who, after a food fortification program with folic acid in the US and Canada populations, showed a highly significant decrease of fatal stroke when compared with both a similar population before the beginning of the program and the contemporary populations of England and Wales not submitted to a food fortification with folate. Nowadays, we can say that vitamin B therapy might be useful to lower cerebrovascular morbidity in patients with moderate–severe hyperhomocysteinaemia [5], and also that vitamin D therapy might be useful to reduce cardiovascular morbidity in patients with moderate–severe hyperparathyroidism. So, it is important to check not only parathyroid hormone, but also homocysteine in patients with stage 3–5 renal failure.
Conflict of interest statement. None declared.
Nephrology and Dialysis Unit Vimercate Hospital, Vimercate Italy
References
- Mann JFE, Sheridan P, McQueen MJ. on behalf of the HOPE-2 investigators. Homocysteine lowering with folic acid and B vitamins in people with chronic kidney disease-results of the renal Hope-2 study. Nephrol Dial Transplant (2008) 23:645–653.
[Abstract/Free Full Text] - Righetti M, Serbelloni P, Milani S, et al. Homocysteine-lowering vitamin B treatment decreases cardiovascular events in hemodialysis patients. Blood Purif (2006) 24:379–386.[CrossRef][Web of Science][Medline]
- Spence JD, Bang H, Chambless LE, et al. Vitamin intervention for stroke prevention trial: an efficacy analysis. Stroke (2005) 36:2404–2409.
[Abstract/Free Full Text] - Yang Q, Botto LD, Erickson JD, et al. Improvement in stroke mortality in Canada and the United States, 1990 to 2002. Circulation (2006) 13:1335–1343.
- Righetti M. Review: homocysteine-lowering vitamin B treatment decreases cardiovascular events in hemodialysis patients. Clin Chem Lab Med (2007) 45:1586–1589.[CrossRef][Web of Science][Medline]
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