Abstract P173: Serum 25-hydroxyvitamin D and Mortality in Middle-aged Men and Women: Results from the MONICA/KORA Augsburg Study
Authors: Thorand Barbara , Zierer Astrid , Schneider Andrea , Huth Cornelia , Autenrieth Christine S , Linseisen Jakob , Roden Michael , Peters Annette , Koenig Wolfgang , Herder Christian 
Published: July 2021

Background:
Recent studies found an inverse association between vitamin D status and both morbidity and mortality from major chronic diseases such as cardiovascular diseases (CVD) and cancer. In contrast, some studies have suggested adverse health effects such as increased all-cause mortality at the high end of vitamin D levels. Therefore, the aim of the present study was to further elucidate the relationship between 25-hydroxyvitamin D (25[OH]D) and all-cause as well as CVD and non-CVD mortality.

Methods:
Our study population comprised 851 men and 774 women aged 35-74 years at baseline selected randomly, stratifying by sex and survey out of 9,531 subjects with available blood samples. All had participated in at least one of the three population-based MONICA/KORA Augsburg surveys between 1984-1995. Participants were followed-up for a mean of 16.8 ± 5.4 years. During this period 197 persons died from CVD (ICD9 390-459, 798) and 226 from non-cardiovascular causes. For three participants the cause of death was missing. 25[OH]D was measured in serum samples collected at baseline using an enzyme immunoassay from IDS, Frankfurt.

Results:
After adjustment for age, sex, survey, and season of blood sampling we observed a significant inverse association between serum 25[OH]D and all-cause mortality. The hazard ratio (HR) and 95% confidence interval (CI) comparing subjects with levels >75 nmol/l to those with levels ≤25 nmol/l was 0.59 (0.38-0.93); P
trend
=0.007 across the following four categories: ≤25 nmol/l; >25-≤50 nmol/l; >50-≤75 nmol/l; >75 nmol/l, assigning the median value within each category to the respective category. Further adjustment for BMI, education and lifestyle factors attenuated the association and it became non-significant (HR [95% CI]: 0.78 [0.48-1.27]; P
trend
=0.205). For CVD mortality, we also observed an inverse association which persisted after adjustment for the above mentioned confounders (HR [95% CI]: 0.49 [0.21-1.11]; P
trend
=0.012). After further multivariable adjustment including potential intermediate risk factors such as systolic blood pressure, total cholesterol/HDL-cholesterol, diabetes and markers of inflammation the association became non-significant (HR [95% CI]: 0.63 [0.26-1.51]; P
trend
=0.122). We did not observe any significant association between 25[OH]D and non-CVD mortality regardless of the degree of adjustment. However, there was a trend towards increased non-CVD mortality in women with 25[OH]D >75 nmol/l compared to those with concentrations ≤25 nmol/l (HR [95% CI]: 2.87 [0.99-8.33]; P
trend
=0.111 for the fully adjusted model).

Conclusions:
Our data indicate that vitamin D status is inversely related to CVD mortality. However, before large scale measures to improve vitamin D status should be initiated, further studies should evaluate potentially harmful effects of very high levels of 25[OH]D on other outcomes especially among women.