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.
Serum cardiometabolic biomarkers in relation to all-cause and cause-specific mortality
Despite substantial epidemiologic evidence supports the association between cardiometabolic biomarkers and risk of cardiovascular, metabolic disease and cancer, how these biomarkers may influence all-cause and cause-specific mortality remain to be established. Previous studies were limited by the relatively small sample size, inclusion of men or women only, short duration of follow up, examination of CVD or cancer mortality only, or inadequate control for confounding. Therefore, a systematic investigation of cardiometabolic biomarkers with mortality in a large-scale cohort is needed to better understand the role of metabolic disturbances in death risk. We will utilize data from UK biobank to prospectively investigate associations of 14 serum biomarkers, including lipid profiles (i.e., Cholesterol, Direct Low Density Lipoprotein, HDL-Cholesterol, Triglyceride, Apolipoprotein A, and Lipoprotein (a)), inflammatory marker (C-reactive Protein), IGF1, HbA1c, glucose, and sex hormones (i.e., testosterone, oestradiol, sex hormone binding globulin), with the risk of all-cause and cause-specific mortality (i.e., death from CVD, cancer, and other causes).
|Lead investigator:||Dr Dong Hang|
|Lead institution:||Nanjing Medical University|