Lack of Association between Vitamin D Insufficiency and Cardiovascular or Fracture Risk: A UK Biobank Study

Abstract

Background: Vitamin D deficiency has been linked to increased risks of fractures and cardiovascular (CV) events, but the clinical relevance of the &apos;insufficiency&apos; range remains unclear. We investigated CV and fracture risks across vitamin D levels, with a focus on the insufficiency range. Methods: Using UK Biobank data, we analyzed 375,044 participants aged 40 to 69 years. Vitamin D status was categorized as deficient (<50 nmol/L), insufficient (>= 50 to <75 nmol/L), or sufficient (>= 75 nmol/L). Outcomes included three-point major adverse cardiovascular events (3P-MACE; myocardial infarction, stroke, and CV mortality) and major osteoporotic fractures, assessed via hospital records, registries, and death certificates. Results: The vitamin D-deficient group had an increased risk of CV events (adjusted hazard ratio [aHR], 1.17; 95% confidence interval [CI], 1.11 to 1.24) and fractures (aHR, 1.09; 95% CI, 1.01 to 1.18) compared to the vitamin D-sufficient group. Within the deficient group, the severely deficient group (<30 nmol/L) exhibited a markedly higher risk (aHR, 1.29; 95% CI, 1.21 to 1.37 for 3PMACE; and aHR, 1.20; 95% CI, 1.10 to 1.32 for fractures). In contrast, the vitamin D-insufficient group (50 to 75 nmol/L) showed no significant increase in the risk of either outcome, with no clear benefit or harm observed. Spline curve analysis revealed a negative correlation between vitamin D levels and risk, which was observed only within the deficient range and not within the insufficient range. Conclusion: Vitamin D deficiency is strongly associated with increased CV disease and fracture risks, whereas the insufficiency range shows no significant risk or benefit, raising questions about its clinical relevance.