Combined effects of vitamin D deficiency and systemic inflammation on all-cause mortality and cause-specific mortality in older adults

Background Vitamin D deficiency and systemic inflammation share common pathological mechanisms in muscle loss, cardio-pulmonary function decline, and abnormal metabolism, which are linked to chronic conditions, senescence, and early mortality. However, their combined effect on mortality in older adults has not been well established. This study longitudinal aimed to explore the independent and combined associations of serum 25-hydroxyvitamin D [25(OH)D] and high sensitivity C-reactive protein (hs-CRP) with mortality risk in Chinese community-based older people. Methods 3072 older adults (86.07 +/- 11.87 years, 54.52% female) from the Chinese Longitudinal Healthy Longevity Survey (2012-2018) were enrolled. Baseline 25(OH)D and hs-CRP levels were collected, and survival information was recorded in the 2014 and 2018 follow-up waves. Cox proportional hazard regressions were conducted to explore the associations between 25(OH)D, hs-CRP, and mortality. Demographic characteristics, health behaviors, and chronic disease biomarkers were adjusted. Results During 10,622.3 person-years of follow-up (median: 3.51 years), 1321 older adults died, including 448 deaths due to cardiovascular disease (CVD). Increased mortality risk was associated with lower 25(OH)D and higher hs-CRP quantiles, even after adjusting for each other and multiple covariates (all P-trend < 0.05). In combined analyses, the highest all-cause mortality (HR: 2.18, 95% CI: 1.73 similar to 2.56), CVD mortality (HR: 2.30, 95% CI: 1.64 similar to 3.21), and non-CVD mortality (HR: 2.19, 95% CI: 1.79 similar to 2.49) were obtained in participants with both 25(OH)D deficiency (< 50 nmol/L) and high hs-CRP (>= 3.0 mg/L), respectively. We observed significant additive interactions of 25(OH)D and hs-CRP on all-cause mortality and non-CVD mortality (RERIS > 0). Conclusions Low 25(OH)D and high hs-CRP, both independently and jointly, increase mortality risk in Chinese community-dwelling older adults. Thus, priority should be given to early detection and appropriate intervention in older individuals with combined vitamin D deficiency and systemic inflammation. Molecular mechanisms of related adverse health effect are worthy of further investigation.