1{alpha}-Hydroxy vitamin D3 and cardiovascular mortality

Sir,

The observations from Japan [1] on the effect of vitamin D on cardiovascular mortality are very encouraging but also difficult to assess. Hence, a number of issues could perhaps be clarified.

As stated, treatment with vitamin D was not assigned at random, and comparison between the groups taking or not taking the drug shows a number of important differences. It would be interesting to know how the authors believe patients or doctors determined who had and who had not vitamin D administered. Could it be that the patients on drugs were better off and more ‘advanced’ also in other respects, be it statin treatment, ACE-inhibitors, general compliance, so the vitamin D treatment was kind of proxy for a more healthy status altogether?

In judging the results, it might be helpful to know the overall crude mortality rate of the two groups, and also the distribution of observation time between people on and not on vitamin D. This is even more important as the authors admit the possibility of a huge misclassification as far as sudden death being categorized as cardiovascular is concerned. Other misclassification problems might also abound.

Even though the authors were unable to assess exactly the medication of the patients, it seems they had data on at least the approximate dosing of vitamin D. If the effect of the drug on cardiovascular mortality had a biological background, a dose–response relationship might be surface and should be searched for.

Most puzzling, the effect of 1HD on the ensuing cardiovascular mortality by univariate Cox analysis is only borderline significant (P = 0.077). By multivariate analysis, most common predictors of cardiovascular mortality suffer the loss of significance, and their forced entrance into the model do not remove the effect of vitamin D. Which biological model could accommodate such features is difficult to grasp. Simply put, the observations are unlikely and possibly the result of statistical mishaps in applying too demanding techniques on a small sample under ill-defined baseline circumstances.

The study was performed in Japan, and compared with Caucasian populations a number of differences might be important with regard to prevalence of diseases and distribution of causes of mortality, diet, dialysis intensity, etc.

A controlled clinical trial with hard, clinical endpoints of the management of renal osteodystrophy is very long overdue. This important paper from Japan certainly adds further to the importance of such a study.

Conflict of interest statement. None declared.

Troels Ring

Department of Nephrology Aalborg Hospital Denmark Email: tring{at}gvdnet.dk

References

  1. Shoji T, Shinohara K, Kimoto E et al. Lower risk for cardiovascular mortality in oral 1{alpha}-hydroxy vitamin D3 users in a haemodialysis population. Nephrol Dial Transplant 2004; 19: 179–184[Abstract/Free Full Text]




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