Background
The relevance of vitamin D for prevention of cardiovascular disease is uncertain. The BEST‐D (Biochemical Efficacy and Safety Trial of vitamin D) trial previously reported effects of ...vitamin D on plasma markers of vitamin D status, and the present report describes the effects on blood pressure, heart rate, arterial stiffness, and cardiac function.
Methods and Results
This was a randomized, double‐blind, placebo‐controlled trial of 305 older people living in United Kingdom, who were allocated vitamin D 4000 IU (100 μg), vitamin D 2000 IU (50 μg), or placebo daily. Primary outcomes were plasma concentrations of 25‐hydroxy‐vitamin D and secondary outcomes were blood pressure, heart rate, and arterial stiffness in all participants at 6 and 12 months, plasma N‐terminal prohormone of brain natriuretic peptide levels in all participants at 12 months, and echocardiographic measures of cardiac function in a randomly selected subset (n=177) at 12 months. Mean (SE) plasma 25‐hydroxy‐vitamin D concentrations were 50 (SE 2) nmol/L at baseline and increased to 137 (2.4), 102 (2.4), and 53 (2.4) nmol/L after 12 months in those allocated 4000 IU/d, 2000 IU/d of vitamin D, or placebo, respectively. Allocation to vitamin D had no significant effect on mean levels of blood pressure, heart rate, or arterial stiffness at either 6 or 12 months, nor on any echocardiographic measures of cardiac function, or plasma N‐terminal prohormone of brain natriuretic peptide concentration at 12 months.
Conclusions
The absence of any significant effect of vitamin D on blood pressure, arterial stiffness, or cardiac function suggests that any beneficial effects of vitamin D on cardiovascular disease are unlikely to be mediated through these mechanisms.
Clinical Trial Registration
URL: https://www.clinicaltrialsregister.eu/ctr-search/search. Unique identifier: EudraCT number: 2011–005763‐24a
A multicenter, randomized trial involving participants with diabetes and no evident cardiovascular disease at trial entry showed that aspirin led to a lower risk of serious vascular events than ...placebo but also caused a higher risk of major bleeding.
In this trial involving patients with diabetes without evidence of cardiovascular disease, the risk of serious vascular events was similar in those who received n−3 fatty acid supplements and those ...who received placebo.
Clinical trials require cost-effective methods for identifying, randomising, and following large numbers of people in order to generate reliable evidence. ASCEND (A Study of Cardiovascular Events iN ...Diabetes) is a randomised '2 × 2 factorial design' study of aspirin and omega-3 fatty acid supplements for the primary prevention of cardiovascular events in people with diabetes; this study used central disease registers and a mail-based approach to identify, randomise, and follow 15,000 people. In collaboration with UK consultants and general practitioners (GPs), researchers identified potentially eligible people with diabetes from centrally held registers (e.g. for retinopathy screening) and GP-held disease registers. Permission was obtained under section 251 of the National Health Service Act 2006 (previously section 60 of the NHS act 2001) to allow invitation letters to be generated centrally in the name of the holder of the register. In addition, with the collaboration of the National Institutes for Health Research (NIHR) Diabetes and Primary Care Research Networks (DRN and PCRN), general practices sent pre-assembled invitation packs to people with a diagnosis of diabetes. Invitation packs included a cover letter, screening questionnaire (with consent form), information leaflet, and a Freepost envelope. Eligible patients entered a 2-month, pre-randomisation, run-in phase on placebo tablets and were only randomised if they completed a randomisation form and remained willing and eligible at the end of the run-in. Follow-up is ongoing, using mail-based approaches that are being supplemented by central registry data.
Information on approximately 600,000 people listed on 58 centrally held diabetes registers was obtained, and 300,188 potentially eligible patients were invited to join the study. In addition, 785 GP practices mailed invitations to 120,875 patients. A further 2,340 potential study participants were identified via other routes. In total, 423,403 people with diabetes were invited to take part; 26,462 entered the 2-month, pre-randomisation, run-in phase; and 15,480 were randomised.
If sufficient numbers of potentially eligible patients can be identified centrally and the trial treatments do not require participants to attend clinics, the recruitment and follow-up of patients by mail is feasible and cost-effective. Wider use of these methods could allow more, large, randomised trials to be undertaken successfully and cost-effectively.
Current Controlled Trials, ISRCTN60635500 , registered on 14 July 2005.
Highlights • The BEST-D (Biochemical Efficacy and Safety Trial of vitamin D) trial will compare the biochemical and other effects of daily dietary supplementation with 100 μg or 50 μg vitamin D3 or ...placebo, when administered for 12 months, in 305 ambulant community-dwelling older people living in Oxfordshire, England. • The primary analyses will compare 12-month mean plasma concentrations of 25(OH)D as well as the proportion of participants with a 12-month concentration >90 nmol/L between participants allocated 100 μg and participants allocated 50 μg daily. Secondary analyses will compare the two active doses (both separately and when combined) with placebo. • Additional end-points include biochemical assessments of safety, blood pressure, arterial stiffness, falls, fractures, heel and wrist bone density, grip strength and physical performance and echocardiographic assessments of cardiac function in a random sample of participants. • The results of this trial will help determine the optimum dose of vitamin D to test in a larger trial investigating whether vitamin D supplementation can reduce the risk of fractures, cardiovascular disease or cancer.
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