Cardiovascular disease outcomes in relation to 25-hydroxyvitamin D and its seasonal variation: Results from the BiomarCaRE consortium

It has been hypothesized but seldom tested that the winter excess in cardiovascular disease (CVD) is related to hypovitaminosis D. The present study examined the association between CVD and (i) seasonality of 25-hydroxyvitamin D (25[OH]D) and (ii) individual 25(OH)D concentrations. Harmonized 25(OH)...

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Published in:PloS one Vol. 20; no. 4; p. e0319607
Main Authors: Oskarsson, Viktor, Salomaa, Veikko, Jousilahti, Pekka, Palmieri, Luigi, Donfrancesco, Chiara, Sans, Susana, Iacoviello, Licia, Costanzo, Simona, Ferrario, Marco M., Cesana, Giancarlo, Thorand, Barbara, Peters, Annette, Tunstall-Pedoe, Hugh, Woodward, Mark, Zeller, Tanja, Blankenberg, Stefan, Kuulasmaa, Kari, Söderberg, Stefan
Format: Journal Article
Language:English
Published: United States Public Library of Science 24.04.2025
Public Library of Science (PLoS)
Subjects:
25-Hydroxyvitamin D
Age
Aged
Alfacalcidol
Analysis
Biology and Life Sciences
Biomarkers
Calcifediol
Cardiac arrhythmia
Cardiovascular disease
Cardiovascular diseases
Cardiovascular Diseases - blood
Cardiovascular Diseases - epidemiology
Cardiovascular Diseases - mortality
Coronary artery disease
Cross-sectional studies
Diabetes
Dosage and administration
Earth Sciences
Epidemiology
Ethics
Europe - epidemiology
Failure analysis
Female
Health hazards
Health risks
Heart diseases
Heart failure
Humans
Incidence
Male
Medicine and Health Sciences
Middle Aged
Mortality
Observational studies
Prevention
Risk assessment
Risk factors
Seasonal variations
Seasonal variations (Diseases)
Seasons
Stroke
Stroke (Disease)
Vitamin D
Vitamin D - analogs & derivatives
Vitamin D - blood
Vitamin D Deficiency - blood
Vitamin deficiency
Winter
Europe
Germany
Italy
Sweden
United States > US
ISSN:1932-6203, 1932-6203
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Summary:It has been hypothesized but seldom tested that the winter excess in cardiovascular disease (CVD) is related to hypovitaminosis D. The present study examined the association between CVD and (i) seasonality of 25-hydroxyvitamin D (25[OH]D) and (ii) individual 25(OH)D concentrations. Harmonized 25(OH)D data were obtained from the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) project, including 79,570 participants examined between 1984 and 2010. One 25(OH)D measurement was available per participant. Primary endpoints were CVD incidence (coronary heart disease or stroke; n = 6006) and CVD mortality (n = 2985). To study (i), Poisson regression-derived rate ratios were compared according to two-month categories, ordered by baseline 25(OH)D concentrations. To study (ii), Cox regression-derived hazard ratios were compared according to quarters of baseline 25(OH)D concentrations. With respect to (i), despite a median 25(OH)D concentration ratio of 1:1.79, the trough months of 25(OH)D in March and April had a similar CVD incidence as the peak months of 25(OH)D in August and September (rate ratio: 1.07, 95% CI: 0.98-1.17). CVD mortality was slightly higher in the trough months compared to the peak months (rate ratio: 1.27, 95% CI: 1.12-1.44) but not compared to the other months (despite median 25[OH]D concentration ratios up to 1:1.62; p ≥ 0.077). The CVD mortality peak in January preceded the 25(OH)D trough, not adhering to the temporality criterion of Bradford Hill. With respect to (ii), compared to the lowest quarter, the highest quarter of 25(OH)D was associated with lower CVD incidence (hazard ratio: 0.82, 95% CI: 0.76-0.89) and CVD mortality (hazard ratio: 0.64, 95% CI: 0.57-0.72). The present study does not support the hypothesis that seasonal increases in CVD are driven by short-term reductions in 25(OH)D. As in most observational studies, higher 25(OH)D concentrations were inversely associated with CVD.
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Competing Interests: Abbott Diagnostics provided test reagents for the 25(OH)D measurements within the frame of the BiomarCaRE project. Abbott Diagnostics had no role in the study design, data collection, blood sample and data analysis, decision to publish, or preparation of the manuscript. Veikko Salomaa has received an honorarium from Sanofi for consulting and has ongoing research collaboration with Bayer Ltd (both outside of the submitted work). Mark Woodward has done consultancy work for Amgen and Freeline (outside of the submitted work). Stefan Blankenberg has recieved research funding from Abbott Diagnostics, Bayer, SIEMENS, Singulex, and Thermo Fisher; speaker fees from Abbott, Abbott Diagnostics, Astra Zeneca, Bayer, AMGEN, Medtronic, Pfizer, Roche, SIEMENS Diagnostics, SIEMENS, and Thermo Fisher; and honoraria as a member of advisory boards and for consulting for Bayer, Novartis, and Thermo Fisher (all outside of the submitted work). Stefan Söderberg has recieved speaker fees and done consultancy work for Merck Sharp & Dohme and Actelion Pharmaceuticals Ltd, a Johnson & Johnson company (both outside of the submitted work). This does not alter our adherence to PLOS ONE policies on sharing data and materials.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0319607