Among participants with atherosclerotic vascular disease, the addition of extended-release niacin-laropiprant to statin-based LDL cholesterol-lowering therapy did not significantly reduce the risk of major vascular events but did increase the risk of serious adverse events. (Funded by Merck and others; HPS2-THRIVE ClinicalTrials.gov number, NCT00461630.).

SummaryThis trial compared the effects of daily treatment with vitamin D or placebo for 1 year on blood tests of vitamin D status. The results demonstrated that daily 4000 IU vitamin D3 is required to achieve blood levels associated with lowest disease risks, and this dose should be tested in future trials for fracture prevention.IntroductionThe aim of this trial was to assess the effects of daily supplementation with vitamin D3 4000 IU (100 μg), 2000 IU (50 μg) or placebo for 1 year on biochemical markers of vitamin D status in preparation for a large trial for prevention of fractures and other outcomes.MethodsThis is a randomized placebo-controlled trial in 305 community-dwelling people aged 65 years or older in Oxfordshire, UK. Outcomes included biochemical markers of vitamin D status (plasma 25-hydroxy-vitamin D [25[OH]D], parathyroid hormone [PTH], calcium and alkaline phosphatase), cardiovascular risk factors and tests of physical function.ResultsMean (SD) plasma 25(OH)D levels were 50 (18) nmol/L at baseline and increased to 137 (39), 102 (25) and 53 (16) nmol/L after 12 months in those allocated 4000 IU, 2000 IU or placebo, respectively (with 88%, 70% and 1% of these groups achieving the pre-specified level of >90 nmol/L). Neither dose of vitamin D3 was associated with significant deviation outside the normal range of PTH or albumin-corrected calcium. The additional effect on 25(OH)D levels of 4000 versus 2000 IU was similar in all subgroups except for body mass index, for which the further increase was smaller in overweight and obese participants compared with normal-weight participants. Supplementation with vitamin D had no significant effects on cardiovascular risk factors or on measures of physical function.ConclusionsAfter accounting for average 70% compliance in long-term trials, doses of 4000 IU vitamin D3 daily may be required to achieve plasma 25(OH)D levels associated with lowest disease risk in observational studies.Electronic supplementary materialThe online version of this article (doi:10.1007/s00198-016-3833-y) contains supplementary material, which is available to authorized users.

Despite strong inverse and apparently independent associations of 25(OH)D with vascular and non-vascular mortality, causality remains uncertain. Large-scale randomized trials, using high doses of vitamin D, are required to assess the clinical relevance of these associations.

Diabetes mellitus is a disease, which is at the epitome of cardiovascular risk factors causing considerable morbidity and mortality. In addition to microvascular complications, there is two- to six-fold increased risk of macrovascular diseases, such as coronary artery disease, peripheral artery disease and stroke. While the mortality from coronary artery disease in patients without diabetes has declined over the past 20 years, the mortality in men with type 2 diabetes mellitus has not changed. Furthermore, the prevalence of diabetes in the UK has increased by 30% since 1991 and the same among the world population in 2010 is expected to be twice in 1990. This dramatic increase has serious implications from a cardiovascular perspective and thus the aggressive management of blood pressure, dyslipidaemia and blood glucose in diabetes is of vital importance. The aim of this review is to evaluate the current evidence and to discuss the implications of type 2 diabetes and its relevance to clinical practice in cardiology. We address this broad subject in discussing (i) the pathophysiology of cardiovascular disease in the setting of type 2 diabetes and (ii) the prevalence of cardiovascular risk, complications and prognostic implications in type 2 diabetes, with a discussion of current therapeutic interventions for the prevention or delay of these consequences where relevant.