PreprintReviewVersion 2This version is not peer-reviewed
How Follow-Up Period in Prospective Cohort Studies Affects the Relationship Between Baseline Serum 25(OH)D Concentration and Risk of Stroke and Major Cardiovascular Events
Version 1
: Received: 7 October 2024 / Approved: 7 October 2024 / Online: 8 October 2024 (03:18:53 CEST)
Version 2
: Received: 8 October 2024 / Approved: 9 October 2024 / Online: 9 October 2024 (12:20:49 CEST)
How to cite:
Grant, W. B.; Boucher, B. J. How Follow-Up Period in Prospective Cohort Studies Affects the Relationship Between Baseline Serum 25(OH)D Concentration and Risk of Stroke and Major Cardiovascular Events. Preprints2024, 2024100486. https://doi.org/10.20944/preprints202410.0486.v2
Grant, W. B.; Boucher, B. J. How Follow-Up Period in Prospective Cohort Studies Affects the Relationship Between Baseline Serum 25(OH)D Concentration and Risk of Stroke and Major Cardiovascular Events. Preprints 2024, 2024100486. https://doi.org/10.20944/preprints202410.0486.v2
Grant, W. B.; Boucher, B. J. How Follow-Up Period in Prospective Cohort Studies Affects the Relationship Between Baseline Serum 25(OH)D Concentration and Risk of Stroke and Major Cardiovascular Events. Preprints2024, 2024100486. https://doi.org/10.20944/preprints202410.0486.v2
APA Style
Grant, W. B., & Boucher, B. J. (2024). How Follow-Up Period in Prospective Cohort Studies Affects the Relationship Between Baseline Serum 25(OH)D Concentration and Risk of Stroke and Major Cardiovascular Events. Preprints. https://doi.org/10.20944/preprints202410.0486.v2
Chicago/Turabian Style
Grant, W. B. and Barbara J. Boucher. 2024 "How Follow-Up Period in Prospective Cohort Studies Affects the Relationship Between Baseline Serum 25(OH)D Concentration and Risk of Stroke and Major Cardiovascular Events" Preprints. https://doi.org/10.20944/preprints202410.0486.v2
Abstract
Abstract: Background/Objectives: Prospective cohort studies are useful for studying how biomolecular status affects risk of adverse health outcomes. Less well known is that the longer the follow-up time, the lower the apparent effect due to “regression dilution.” Here we evaluate how follow-up time affects the relationship between serum 25-hydroxyvitamin D [25(OH)D] concen-tration and incidence of stroke and major cardiovascular events (MCEs). Methods: Findings re-garding the relative risk (RR) of stroke and MCEs with respect to serum 25(OH)D concentrations at baseline from prospective cohort studies were plotted against mean follow-up time. Fifteen studies from mainly European countries and the United States were used for stroke, with nine studies for MCEs. Linear regression analyses were performed for follow-up periods of up to 10 years. Results: For stroke, the linear regression fit for 1–10 years is RR = 0.34 + (0.065 × follow-up [years]), r = 0.84, adjusted r2 = 0.67, p <0.001. No significant change was evident for studies with follow-up periods of 10–20 years. For MCEs, the linear fir for 1–8.1 years is RR = 1.61 ‒ (0.074 × follow-up [years]), r = 0.75, adjusted r2 = 0.49, p = 0.03. Discussion: The shorter the follow-up period, the greater the apparent effect of vitamin D in reducing risk of stroke and MCEs. In addition, the apparent effect of higher 25(OH)D concentration found for the shortest follow-up time is more than twice as high as the estimate based on averaging the results for all studies without considering follow-up time. Mechanisms have been found to explain how higher serum 25(OH)D concentrations could reduce risk of stroke and MCEs. Randomized controlled trials have not shown that vitamin D supplementation significantly reduces risk of either stroke or MCE, probably because risk of both outcomes increases rapidly below 15 ng/mL (38 nmol/L) and it is difficult in Western developed countries to enroll enough participants with concentrations that low. Nonetheless, vitamin D’s role in reducing risk of stroke and MCE can be considered causal on the basis of an evaluation of the evidence with respect to Hill’s criteria for causality in a biological system. Conclusions: Serum 25(OH)D concentrations above 20 ng/mL are associated with significantly reduced risk of stroke and MCEs in an apparent causal manner. Raising serum 25(OH)D concentrations to >20 ng/mL should be recommended for everyone likely to be at risk for stroke or MCE and indeed in the general population.
Public Health and Healthcare, Public Health and Health Services
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
