Effect of 9 Months of Vitamin D Supplementation on Arterial Stiffness and Blood Pressure in Graves' Disease: a Randomized Clinical Trial

Purpose: Risk of cardiovascular disease (CVD) is increased in Graves' disease (GD). CVD is predicted by increased pulse wave velocity (PWV) and blood pressure (BP). GD and these risk factors are all associated with lower levels of vitamin D. We aimed to assess the effect of supplemental vitamin D on PWV and BP in GD.

Methods: In a double-blinded trial, newly diagnosed GD patients were randomized to vitamin D3 70 µg/day (n = 44) or placebo (n = 42) as add-on to anti-thyroid medication. At baseline, 3 and 9 months PWV, BP and wave analysis were performed in office and 24 h setting. Between-group differences in change at 9 months were analyzed using linear mixed modelling. In subanalysis, effect of intervention in regard to baseline vitamin D insufficiency (25(OH)D < 50 nmol/L) was investigated. (The DAGMAR study, clinicaltrials.gov ID NCT02384668).

Results: PWV was unaffected by intervention in main analysis. However in the subanalysis, comparing the response to intervention in the vitamin D insufficient (n = 28) and the vitamin D replete patients, supplemental vitamin D induced a significant decrease in office PWV of 1.2 (95% CI: -2.3; -0.1) m/s compared to placebo. Of notice, baseline PWV was non-significantly higher among the vitamin D insufficient as compared to the replete participants. In response to vitamin D, office central systolic BP (-3.9 (95% CI: -7.5; -0.3) and brachial mean BP (-3.3 (95% CI: -6.5; -0.3) declined whereas 24 h measurements were unaffected.

Conclusions: High-dose vitamin D supplementation did not affect PWV. We observed significant reduction in office but not 24 h BP. Subanalysis showed a clinically relevant PWV reduction among vitamin D insufficient participants, although regression towards the mean might contribute to findings. Further studies on supplemental vitamin D in GD should focus on patients with vitamin D insufficiency.