Estimating mean annual 25-hydroxyvitamin D concentrations from single measurements: the Multi-Ethnic Study of Atherosclerosis

Abstract

Single measurements may misclassify annual exposure, which may lead to bias in research and complicate clinical decision making. Objective: We aimed to develop and validate a model for adjusting a single measurement of a serum 25(OH)D concentration to the time of year it was measured. Design: We measured serum 25(OH)D concentrations by using mass spectrometry in 6476 participants from the Multi-Ethnic Study of Atherosclerosis at baseline and again in a subset of 368 participants at a median of 17 mo later. We estimated a cosinor model to describe the seasonal variability in 25(OH)D concentrations and evaluated this model by using follow-up 25(OH)D measurements. Results: The mean age of subjects was 62.1 y, 61.2% of participants were nonwhite, and 53.3% of participants were women. The cosinor model predicted follow-up 25(OH)D concentrations better than a single measurement [difference in root mean squared error (RMSE): 1.3 ng/mL; P, 0.001]. The cosinor model also better predicted the measured annual mean 25(OH)D concentration (difference in RMSE: 1.0 ng/mL; P, 0.001). Annual mean 25(OH)D concentrations estimated from the cosinor model reclassified 7.1% of participants with regard to 25(OH)D deficiency, which was defined as ,20 ng/mL. An estimated annual mean 25(OH)D concentration ,20 ng/mL was significantly associated with lower bone mineral density, whereas an untransformed 25(OH)D concentration ,20 ng/mL was not. Conclusions: Cross-sectional data can be used to estimate subjectspecific mean annual 25(OH)D concentrations from single values by using a cosinor model. The tool we developed by using this approach may assist research and clinical care of adults in North America by reducing the misclassification of 25(OH)D deficiency.

Plasma 1,25-Dihydroxyvitamin D and the Risk of Developing Hypertension

“…[4][5][6] Our study confirms previous work that mainly found modest inverse associations between 18 whereas the seasonal variation of circulating 1,25-dihydroxyvitamin D has scarcely been studied. 21 We observed seasonal variation in 1,25-dihydroxyvitamin D over the full range of 1,25-dihydroxyvitamin D concentrations, including participants in the highest quartile (>172 pmol/L).…”

“…The first model was adjusted for age, sex, and a cosinor model to adjust for the time of the year of blood sampling. 18 The second model was additionally adjusted for BMI (6 categories), smoking (5 categories), education (3 categories), alcohol intake (5 categories), and parental history of hypertension (yes/no). In addition, we examined the associations by adding eGFR and 24-hour urinary albumin excretion to the final model.…”

Plasma Vitamin D Level and Change in Albuminuria and eGFR According to Sodium Intake

“…The multivariable-adjusted model included baseline age, sex, type II diabetes, history of cardiovascular disease, current smoking, use of lipid-lowering drugs, use of BPlowering drugs, body mass index, systolic BP, day of blood sampling, total HDL cholesterol ratio, triglycerides, baseline eGFR, and baseline albuminuria as potential confounders. To adjust for day of blood sampling, the time variable t (day) was transformed as sine [(2p/365)3t] and cosine [(2p/365)3t], which were then fitted as two variables in multivariable-adjusted models (19). As an alternative approach to account for seasonal variation, we performed additional analyses using month-specific quartiles of 25(OH)D (20).…”

Associations between Vitamin D and Cardiovascular Disease Risk Factors in African Americans Are Partly Explained by Circulating Adipokines and C-Reactive Protein: The Jackson Heart Study

“…Because vitamin D is known to be affected by seasonal variation, we also performed sensitivity analysis accounting for the effects of seasonal variation of 25(OH)D. We estimated the annual mean 25(OH)D by fitting a parametric seasonal cosinor model to the observed 25(OH)D data, which follows a sinusoidal pattern (29). A detailed description of the cosinor model is presented in Supplemental Methods 4.…”