Association between serum vitamin D and All-Cause and Cause-Specific death in a general Japanese population ― the hisayama study ―

Background: Few studies have investigated the association between serum vitamin D levels and mortality in general Asian populations. Methods and Results: We examined the association of serum 1,25-dihydroxyvitamin D (1,25(OH)₂D) levels with the risk of all-cause and cause-specific death in an average 9.5-year follow-up study of 3,292 community-dwelling Japanese subjects aged ≥40 years (2002-2012). The multivariable-adjusted hazard ratio (HR) for all-cause death increased significantly with lower serum 1,25(OH)₂D levels (HR 1.54 [95% confidence interval, 1.18-2.01] for the lowest quartile, 1.31 [0.99-1.73] for the 2nd quartile, 0.94 [0.70-1.25] for the 3rd quartile, 1.00 [Ref.] for highest quartile; P for trend <0.001). A similar association was observed for cardiovascular and respiratory infection death (both P for trend <0.01), but not for cancer death or death from other causes. In the stratified analysis, the association between lower serum 1,25(OH)₂D levels and the risk of respiratory infection death was stronger in subjects with an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m² than in those with eGFR ≥60 mL/min/1.73 m²; there was a significant heterogeneity in the association between eGFR levels (P for heterogeneity=0.04). Conclusions: The findings suggested that a lower serum 1,25(OH)₂D level is a potential risk factor for all-cause death, especially cardiovascular and respiratory infection death, in the general Japanese population, and that lower serum 1,25(OH)²D levels greatly increase the risk of respiratory infection death in subjects with kidney dysfunction.