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Non-linear associations of 25-hydroxyvitamin D concentrations with risk of cardiovascular disease and all-cause mortality: Results from The Health Improvement Network (THIN) database.
J Steroid Biochem Mol Biol. 2019 12; 195:105480.JS

Abstract

BACKGROUND

There is increasing evidence that vitamin D supplementation may only be beneficial in people with vitamin D deficiency, and the lack of sufficient people with very low vitamin D levels could explain the lack of protection against cardiovascular disease (CVD) reported in recent clinical trials of vitamin D supplementation. The aim of this study was to assess associations of low to moderate circulating concentrations of 25-hydroxyvitamin D (25(OH)D with risk of incident CVD and all-cause mortality, as well as the risk of ischaemic heart disease (IHD), cerebrovascular disease, and heart failure separately.

METHODS AND RESULTS

Longitudinal analysis of electronic health records in The Health Improvement Network (THIN), a UK primary care database. The analysis included 180,263 patients age 18 years and older without a history of CVD and with circulating concentrations of 25(OH)D. After a mean follow-up of 2.2 (SD 1.7) years, there were 3747 patients diagnosed with CVD and 3912 patients died. Compared to patients in the highest quintile of 25(OHD) (≥ 67.5 nmol/L), those in the lowest 25(OH)D quintile (<23.1 nmol/L) had a hazard ratio (HR) of 1.24 (95% CI 1.12-1.38, P < 0.001) for CVD and 1.71 (1.55-1.88, P < 0.001) for mortality. The HR for both outcomes associated with 25(OH)D concentration was non-linear, being significantly increased in patients with 25(OH)D <35 nmol/L, and highest in those with 25(OH)D <25 nmol/L, although increased for mortality at 25(OH)D ≥100 nmol/L. The increased CVD HR in the lowest 25(OH)D quintile was more from IHD (1.35, 95% CI 1.13-1.60) and heart failure (1.38, 95% CI 1.08-1.77), than from cerebrovascular disease (1.13, 95% CI 0.97-1.31).

CONCLUSION

Low 25(OH)D are associated with highest risk of CVD and mortality, and are consistent with accumulating evidence that increased risk of these diseases occurs primarily in people with vitamin D deficiency.

Authors+Show Affiliations

Institute of Applied Health Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.Institute of Applied Health Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK; Centre for Endocrinology, Diabetes and Metabolism, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.Institute of Applied Health Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.School of Population Health, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand. Electronic address: r.scragg@auckland.ac.nz.Institute of Applied Health Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK. Electronic address: K.Nirantharan@bham.ac.uk.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31541727

Citation

Crowe, Francesca L., et al. "Non-linear Associations of 25-hydroxyvitamin D Concentrations With Risk of Cardiovascular Disease and All-cause Mortality: Results From the Health Improvement Network (THIN) Database." The Journal of Steroid Biochemistry and Molecular Biology, vol. 195, 2019, p. 105480.
Crowe FL, Thayakaran R, Gittoes N, et al. Non-linear associations of 25-hydroxyvitamin D concentrations with risk of cardiovascular disease and all-cause mortality: Results from The Health Improvement Network (THIN) database. J Steroid Biochem Mol Biol. 2019;195:105480.
Crowe, F. L., Thayakaran, R., Gittoes, N., Hewison, M., Thomas, G. N., Scragg, R., & Nirantharakumar, K. (2019). Non-linear associations of 25-hydroxyvitamin D concentrations with risk of cardiovascular disease and all-cause mortality: Results from The Health Improvement Network (THIN) database. The Journal of Steroid Biochemistry and Molecular Biology, 195, 105480. https://doi.org/10.1016/j.jsbmb.2019.105480
Crowe FL, et al. Non-linear Associations of 25-hydroxyvitamin D Concentrations With Risk of Cardiovascular Disease and All-cause Mortality: Results From the Health Improvement Network (THIN) Database. J Steroid Biochem Mol Biol. 2019;195:105480. PubMed PMID: 31541727.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Non-linear associations of 25-hydroxyvitamin D concentrations with risk of cardiovascular disease and all-cause mortality: Results from The Health Improvement Network (THIN) database. AU - Crowe,Francesca L, AU - Thayakaran,Rasiah, AU - Gittoes,Neil, AU - Hewison,Martin, AU - Thomas,G Neil, AU - Scragg,Robert, AU - Nirantharakumar,Krishnarajah, Y1 - 2019/09/18/ PY - 2019/06/17/received PY - 2019/08/18/revised PY - 2019/09/18/accepted PY - 2019/9/22/pubmed PY - 2020/1/15/medline PY - 2019/9/22/entrez KW - 25-Hydroxyvitamin D KW - Cardiovascular disease KW - Electronic health records KW - Mortality KW - Vitamin D SP - 105480 EP - 105480 JF - The Journal of steroid biochemistry and molecular biology JO - J Steroid Biochem Mol Biol VL - 195 N2 - BACKGROUND: There is increasing evidence that vitamin D supplementation may only be beneficial in people with vitamin D deficiency, and the lack of sufficient people with very low vitamin D levels could explain the lack of protection against cardiovascular disease (CVD) reported in recent clinical trials of vitamin D supplementation. The aim of this study was to assess associations of low to moderate circulating concentrations of 25-hydroxyvitamin D (25(OH)D with risk of incident CVD and all-cause mortality, as well as the risk of ischaemic heart disease (IHD), cerebrovascular disease, and heart failure separately. METHODS AND RESULTS: Longitudinal analysis of electronic health records in The Health Improvement Network (THIN), a UK primary care database. The analysis included 180,263 patients age 18 years and older without a history of CVD and with circulating concentrations of 25(OH)D. After a mean follow-up of 2.2 (SD 1.7) years, there were 3747 patients diagnosed with CVD and 3912 patients died. Compared to patients in the highest quintile of 25(OHD) (≥ 67.5 nmol/L), those in the lowest 25(OH)D quintile (<23.1 nmol/L) had a hazard ratio (HR) of 1.24 (95% CI 1.12-1.38, P < 0.001) for CVD and 1.71 (1.55-1.88, P < 0.001) for mortality. The HR for both outcomes associated with 25(OH)D concentration was non-linear, being significantly increased in patients with 25(OH)D <35 nmol/L, and highest in those with 25(OH)D <25 nmol/L, although increased for mortality at 25(OH)D ≥100 nmol/L. The increased CVD HR in the lowest 25(OH)D quintile was more from IHD (1.35, 95% CI 1.13-1.60) and heart failure (1.38, 95% CI 1.08-1.77), than from cerebrovascular disease (1.13, 95% CI 0.97-1.31). CONCLUSION: Low 25(OH)D are associated with highest risk of CVD and mortality, and are consistent with accumulating evidence that increased risk of these diseases occurs primarily in people with vitamin D deficiency. SN - 1879-1220 UR - https://www.unboundmedicine.com/medline/citation/31541727/Non_linear_associations_of_25_hydroxyvitamin_D_concentrations_with_risk_of_cardiovascular_disease_and_all_cause_mortality:_Results_from_The_Health_Improvement_Network__THIN__database_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0960-0760(19)30363-2 DB - PRIME DP - Unbound Medicine ER -