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Vitamin D Status and Risk of All-Cause and Cause-Specific Mortality in a Large Cohort: Results From the UK Biobank.
J Clin Endocrinol Metab. 2020 10 01; 105(10)JC

Abstract

CONTEXT

Although an inverse association between vitamin D status and mortality has been reported in observational studies, the precise association shape and optimal vitamin D status remain undetermined.

OBJECTIVE

To investigate the association between vitamin D status and risk of all-cause and cause-specific mortality and estimate optimal serum 25-hydroxyvitamin D [25(OH)D] concentrations.

DESIGN

Prospective cohort study.

SETTING

UK Biobank.

PARTICIPANTS

365 530 participants who had serum 25(OH)D measurements and no history of cardiovascular disease (CVD), cancer, or diabetes at baseline (2006-2010).

MAIN OUTCOME MEASURES

All-cause and cause-specific mortality.

RESULTS

During a median follow-up of 8.9 (interquartile range: 8.3-9.5) years, 10 175 deaths occurred, including 1841 (18.1%) due to CVD and 5737 (56.4%) due to cancer. The multivariate analyses revealed nonlinear inverse associations, with a decrease in mortality risk appearing to level off at 60 nmol/L of 25(OH)D for all-cause and CVD deaths and at 45 nmol/L for cancer deaths. Compared to participants with 25(OH)D concentrations below the cutoffs, those with higher concentrations had a 17% lower risk for all-cause mortality (hazard ratio [HR]: 0.83, 95% confidence interval [CI]: 0.79-0.86), 23% lower risk for CVD mortality (HR: 0.77, 95% CI: 0.68-0.86), and 11% lower risk for cancer mortality (HR: 0.89, 95% CI: 0.84-0.95).

CONCLUSIONS

Higher 25(OH)D concentrations are nonlinearly associated with lower risk of all-cause, CVD, and cancer mortality. The thresholds of 45 to 60 nmol/L might represent an intervention target to reduce the overall risk of premature death, which needs further confirmation in large clinical trials.

Authors+Show Affiliations

Department of Epidemiology and Biostatistics, International Joint Research Center on Environment and Human Health, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.Department of Epidemiology and Biostatistics, International Joint Research Center on Environment and Human Health, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA, US. Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, US. Clinical and Translational Epidemiology Unit and Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, US.Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA, US. Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, US. Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, US.Department of Epidemiology and Biostatistics, International Joint Research Center on Environment and Human Health, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China. State Key Laboratory of Reproductive Medicine, Center for Global Health, Nanjing Medical University, Nanjing, China. Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing, China.Department of Epidemiology and Biostatistics, International Joint Research Center on Environment and Human Health, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China. State Key Laboratory of Reproductive Medicine, Center for Global Health, Nanjing Medical University, Nanjing, China. Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing, China.Department of Epidemiology and Biostatistics, International Joint Research Center on Environment and Human Health, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China. State Key Laboratory of Reproductive Medicine, Center for Global Health, Nanjing Medical University, Nanjing, China. Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing, China.Department of Epidemiology and Biostatistics, International Joint Research Center on Environment and Human Health, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China. Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing, China.Department of Epidemiology and Biostatistics, International Joint Research Center on Environment and Human Health, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China. Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing, China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32620963

Citation

Fan, Xikang, et al. "Vitamin D Status and Risk of All-Cause and Cause-Specific Mortality in a Large Cohort: Results From the UK Biobank." The Journal of Clinical Endocrinology and Metabolism, vol. 105, no. 10, 2020.
Fan X, Wang J, Song M, et al. Vitamin D Status and Risk of All-Cause and Cause-Specific Mortality in a Large Cohort: Results From the UK Biobank. J Clin Endocrinol Metab. 2020;105(10).
Fan, X., Wang, J., Song, M., Giovannucci, E. L., Ma, H., Jin, G., Hu, Z., Shen, H., & Hang, D. (2020). Vitamin D Status and Risk of All-Cause and Cause-Specific Mortality in a Large Cohort: Results From the UK Biobank. The Journal of Clinical Endocrinology and Metabolism, 105(10). https://doi.org/10.1210/clinem/dgaa432
Fan X, et al. Vitamin D Status and Risk of All-Cause and Cause-Specific Mortality in a Large Cohort: Results From the UK Biobank. J Clin Endocrinol Metab. 2020 10 1;105(10) PubMed PMID: 32620963.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Vitamin D Status and Risk of All-Cause and Cause-Specific Mortality in a Large Cohort: Results From the UK Biobank. AU - Fan,Xikang, AU - Wang,Jiayu, AU - Song,Mingyang, AU - Giovannucci,Edward L, AU - Ma,Hongxia, AU - Jin,Guangfu, AU - Hu,Zhibin, AU - Shen,Hongbing, AU - Hang,Dong, PY - 2020/03/06/received PY - 2020/06/29/accepted PY - 2020/7/6/pubmed PY - 2021/2/20/medline PY - 2020/7/5/entrez KW - vitamin D KW - 25-hydroxyvitamin D KW - cancer KW - cardiovascular disease KW - mortality JF - The Journal of clinical endocrinology and metabolism JO - J Clin Endocrinol Metab VL - 105 IS - 10 N2 - CONTEXT: Although an inverse association between vitamin D status and mortality has been reported in observational studies, the precise association shape and optimal vitamin D status remain undetermined. OBJECTIVE: To investigate the association between vitamin D status and risk of all-cause and cause-specific mortality and estimate optimal serum 25-hydroxyvitamin D [25(OH)D] concentrations. DESIGN: Prospective cohort study. SETTING: UK Biobank. PARTICIPANTS: 365 530 participants who had serum 25(OH)D measurements and no history of cardiovascular disease (CVD), cancer, or diabetes at baseline (2006-2010). MAIN OUTCOME MEASURES: All-cause and cause-specific mortality. RESULTS: During a median follow-up of 8.9 (interquartile range: 8.3-9.5) years, 10 175 deaths occurred, including 1841 (18.1%) due to CVD and 5737 (56.4%) due to cancer. The multivariate analyses revealed nonlinear inverse associations, with a decrease in mortality risk appearing to level off at 60 nmol/L of 25(OH)D for all-cause and CVD deaths and at 45 nmol/L for cancer deaths. Compared to participants with 25(OH)D concentrations below the cutoffs, those with higher concentrations had a 17% lower risk for all-cause mortality (hazard ratio [HR]: 0.83, 95% confidence interval [CI]: 0.79-0.86), 23% lower risk for CVD mortality (HR: 0.77, 95% CI: 0.68-0.86), and 11% lower risk for cancer mortality (HR: 0.89, 95% CI: 0.84-0.95). CONCLUSIONS: Higher 25(OH)D concentrations are nonlinearly associated with lower risk of all-cause, CVD, and cancer mortality. The thresholds of 45 to 60 nmol/L might represent an intervention target to reduce the overall risk of premature death, which needs further confirmation in large clinical trials. SN - 1945-7197 UR - https://www.unboundmedicine.com/medline/citation/32620963/Vitamin_D_Status_and_Risk_of_All_Cause_and_Cause_Specific_Mortality_in_a_Large_Cohort:_Results_From_the_UK_Biobank_ L2 - https://academic.oup.com/jcem/article-lookup/doi/10.1210/clinem/dgaa432 DB - PRIME DP - Unbound Medicine ER -