Author + information
- Panagiota Veloudi, MRes,
- C. Leigh Blizzard, PhD,
- Changhai H. Ding, PhD,
- Flavia M. Cicuttini, PhD,
- Xingzhong Jin, MMed,
- Anita E. Wluka, PhD,
- Tania Winzenberg, PhD,
- Graeme Jones, PhD and
- James E. Sharman, PhD∗ ()
- ↵∗Menzies Institute for Medical Research, University of Tasmania, Medical Science 1 Building, Liverpool Street, Hobart, 7000, Australia
Increased aortic stiffness (aPWV), peripheral blood pressure (pBP), and central hemodynamic parameters independently predict cardiovascular events and all-cause mortality (1,2). Moreover, BP variability (BPV) has been shown to be an independent predictor of cardiovascular risk (3). Data from intervention studies assessing the effects of vitamin D on aPWV and BP indices are sparse and inconclusive. There are no vitamin D intervention studies targeting visit-to-visit (VVV) BPV.
People with osteoarthritis (OA) represent a population enriched with vascular risk factors that may be amenable to benefit with treatment from vitamin D supplementation. Here, we present findings from a substudy of a clinical trial investigating the effect of vitamin D supplementation on musculoskeletal outcomes among older people with vitamin D deficiency and OA (principal trial study design previously published) (4). The aim of this substudy was to determine the effects of vitamin D supplementation on aPWV, pBP, central blood pressure (cBP), and VVV indices.
Participants were randomized to receive intervention (monthly capsule of 50,000 IU [1.25 mg] cholecalciferol) or identical inert placebo. Duplicate measures of supine aPWV (carotid-to-femoral tonometry), pBP (automatic oscillometry), and cBP (radial arterial tonometry) were recorded at baseline, and 6 and 12 months. VVV was quantified using the coefficient of variation ([standard deviation/mean BP]×100). Between-group differences in the change in outcomes were assessed across the 3 time points using mixed-effect model analysis (verified with generalized estimating equations) with maximum likelihood estimations for missing data. Changes in aPWV were also estimated after adjusting for changes in mean arterial pressure (MAP). The sample size allowed for a clinically significant difference of at least 0.5 m/s for aPWV and 4.5 mm Hg for peripheral and central systolic BP.
Participants (age 63 ± 7 years, 49% female) with vitamin D deficiency (43.12 ± 12.24 nmol/l) and knee OA were randomly assigned to intervention (n = 118) or placebo (n = 123). Baseline vitamin D, age, sex, BP indices, and aPWV were similar between groups. Fifty-one percent of intervention participants and 48% of placebo participants self-reported hypertension. Vitamin D increased with intervention compared with placebo (45.10 [95% confidence interval (CI): 40.20 to 49.93] nmol/l vs. 7.99 [95% CI: 4.32 to 11.66] nmol/l; p < 0.001).
There was no significant between-group difference in the change in aPWV (Table 1). The difference attenuated after adjustment for changes in MAP (−0.10 [95% CI: −0.47 to 0.26] m/s vs. 0.05 [95% CI: −0.33 to 0.42] m/s; p = 0.56). Post-hoc analysis among participants with high baseline aPWV (>10 m/s; intervention n = 34 vs. placebo n = 33) showed a near significant intervention effect (intervention: −1.77 m/s [95% CI: −2.57 to −0.97] vs. placebo: −0.72 m/s [95% CI: −1.50 to 0.07]; p = 0.065). However, this attenuated after adjustment for changes in MAP (p = 0.14). There were no significant between-group differences for changes in any of the pBP, cBP, or VVV indices (Table 1).
This is the longest vitamin D intervention trial, to our knowledge, assessing the effect on aPWV, and the results are concordant with previous studies of considerably shorter duration. Importantly, when accounting for the BP effect on aPWV by adjusting for changes in MAP, the treatment effect decreased from −0.26 to −0.10 m/s. It is also the longest trial to test the effects on cBP indices, and the results confirm negative effects in smaller studies of select patient populations. Our findings also add novel information on VVV and confirm recent work showing no effect of vitamin D on pBP.
Despite being the longest study to date, limitations include a relatively short follow-up and lack of data on cardiovascular events, as well as mineral metabolism markers that could have affected results (i.e., calcium). Lastly, findings may not be generalizable to people with severe vitamin D deficiency.
In conclusion, we found no effect of vitamin D supplementation on aPWV, BP, or VVV among older people with vitamin D deficiency and OA. Despite a plethora of observational data supporting a relationship between vitamin D and cardiovascular health via pathways involving BP and large artery stiffness, evidence from our high-quality clinical trial and other existing trials do not support the use of vitamin D supplementation as an intervention to improve these endpoints. Previously documented associations between vitamin D, aPWV, and BP are likely to be epiphenomena rather than causative, and vitamin D supplementation for these aspects of cardiovascular health cannot be recommended.
Please note: This study was supported by the National Health & Medical Research Council (NHMRC ID 605501). The sponsors had no role in study design, conduct, data analysis, or interpretation. Drs. Wluka, Winzenberg, and Sharman are recipients of NHMRC Career Development Fellowships (references 409940, 1063574, and 1045373, respectively). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. (Vitamin D Effect on Osteoarthritis Study [VIDEO]; NCT01176344).
- 2015 American College of Cardiology Foundation