Physicians' Academy for Cardiovascular Education

Low levels of vitamin D associated with increased vascular mortality

Literature - Tomson J, Emberson J, Hill M, et al. - Eur Heart J. 2013 May;34(18):1365-74

Vitamin D and risk of death from vascular and non-vascular causes in the Whitehall study and meta-analyses of 12 000 deaths.

Tomson J, Emberson J, Hill M, et al.
Eur Heart J. 2013 May;34(18):1365-74. doi: 10.1093/eurheartj/ehs426


Low circulating levels of 25-hydroxyvitamin D [25(OH)D] have been associated with higher cardiovascular (CV) risk in observational studies [1-7]. Because 25(OH)D is also correlated to other vascular risk factors, is it not know whether these observations are confounded by these risk factors. Furthermore, the association between low 25(OH)D and CV disease may reflect reverse causation, as CV patients may be exposed less to sunlight because they stay indoors more and therefore have low plasma 25(OH)D concentrations.
Little information is available of the relevance of measuring 25(OH)D in the general population, or of the effect of vitamin D treatment on vascular outcomes. This study therefore aimed to examine cross-sectional associations of 25(OH)D with other vascular risk factors, in a prospective study of 5409 older men, with a mean follow-up of 13 year (Whitehall study)[8,9]. Furthermore, the shape and strength of the associations between 25(OH)D and vascular and non-vascular causes of death were studied. These results were compared with meta-analyses of similar prospective studies.

Main results

  • Plasma concentrations of 25(OH)D varied substantially by month of blood collection.
    At any age, men with higher 25(OH)D concentrations were less likely to have a history of vascular disease, cancer or diabetes, or to have been diagnosed with or treated for hypertension than men with lower concentrations.
    Higher plasma 25(OH)D was associated with higher mean LDL-C, HDL-C, ApoA1 and albumin concentrations, but with lower mean CRP and fibrinogen concentrations.
  • 3215 men died during over 50000 person years of follow up, of which 1358 deaths from vascular causes.  
    After classification based on season-adjusted 25(OH)D concentration, higher concentrations were inversely correlated to the risk of vascular mortality, and to non-vascular mortality in the range of 40-90 nmol/L, independent of prior history of vascular disease, cancer or diabetes.
  • A doubling in 25(OH)D concentration was associated with a mean 34% lower risk of vascular mortality (RR 0.66, 95%CI: 0.58-0.75) and a 36% lower risk of non-vascular mortality (RR 0.64, 95%CI: 0.58-0.72). Adjustment for prior disease, established vascular risk factors, markers of inflammation and renal function, decreased the risk reduction to 20% for vascular mortality (RR: 0.80, 95%CI: 0.70-0.91) and 23% for non-vascular mortality (RR 0.77, 95%CI: 0.69-0.86).
  • A meta-analysis of 12 prospective studies including the current one, showed that 25(OH)D concentration in the top versus bottom quartile had on average 25% (95%CI: 13-28) lower vascular mortality and 28% (95%: 24-32) lower total mortality.


25(OH)D concentrations are inversely associated with risk of vascular mortality. This is relevant for public health, since low 25(OH)D are common in the general population and may easily be reversed. However, the specific nature of the associations remains unclear. Large trials investigating the effect of high doses of vitamin D supplements will need to shed light on whether these associations are causal and reversible.


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