Effect of follow-up time on the relation between prediagnostic serum 25-hydroxyvitamin D and all-cause mortality rate

Evidence continues to mount that vitamin D reduces the risk and mortality rates of many types of disease. However, evidence from prospective cohort studies is sometimes weaker than that from case-control and ecological studies. A suggested reason for this discrepancy is that, because serum levels of 25-hydroxyvitamin D [25(OH)D] change over time, a single 25(OH)D concentration measurement taken at study enrollment does not reliably indicate 25(OH)D concentration related to the health outcome. To evaluate this suggestion further, this paper plots results from 12 prospective cohort studies of all-cause mortality rate vs. follow-up time. The regression fit to the hazard ratio per 20-nmol/l increase in serum 25(OH)D concentration vs. time increased from 0.82 (95% CI, 0.67-1.02) for 6 y to 0.96 (95% CI, 0.90-1.01) for 14 y. The value extrapolated for zero follow-up time was 0.72 (95% CI, 0.50-1.03), giving a hazard ratio reduction 3.5 times higher than the standard result from the meta-analysis [0.92 (95% CI, 0.89-0.95)]. Using the example of the Vitamin D Pooling Project of Rarer Cancers, this paper also discusses follow-up time's effect in interpreting prospective cohort studies of cancer outcome. This paper recommends that meta-analyses of prospective cohort studies account for follow-up time and, if possible, that studies measure serum 25(OH)D concentration every 2-4 y.