Page 139 - Vitamin D and Cancer

126 R. Scragg

CV disease and infectious disease, compared to those who did not receive vitamin
D [125]. Other publications from cohort studies of patients with chronic kidney
disease have reported relative reductions in all-cause mortality of about 20% for
those who received activated vitamin D, regardless of whether patients are on dialy-
sis [126–129] or not [130].
Vitamin D supplementation can remove the association between vitamin D
status and mortality in dialysis patients. A cohort study of incident hemodialysis
patients, using the nested case–control design, observed increased CV mortality
after 90 days follow-up in those with low baseline 25OHD levels in patients not on
vitamin D therapy; while no association with baseline 25OHD was observed in
those on vitamin D [131]. Recently, activated vitamin D has been associated with
racial differences in survival in US hemodialysis patients, with all-cause mortality
being 16% lower in treated-black versus treated-white patients, and 35% higher in
untreated-black versus untreated-white patients [132]. The consistent findings from
cohort studies of vitamin D treatment and mortality are compelling, but we need
results from randomized trials before we can be certain that activated vitamin D
improves survival in hemodialysis patients [133, 134].

6.4.2 Studies in Healthy Populations

6.4.2.1 Cardiovascular Disease

In 2008, a tipping point was reached with the publication of results from four large
cohort studies showing that low baseline blood levels of 25OHD predict subsequent
increased risk of CV disease and all-cause mortality. The first study was from the
Framingham Study Offspring cohort (n = 1,739) which found that participants with
baseline serum 25OHD levels <10 ng/mL (25 nmol/L) had an adjusted hazard ratio
of 1.80 (95% CI: 1.05, 3.08) for CV disease during the 5-year follow-up period,
compared with those >15 ng/mL (37.4 nmol/L) [135]. The effect was evident in
participants with hypertension (blood pressure ³ 140/90 mmHg), but not in those
with normal blood pressure, suggesting that hypertension could magnify the benefi-
cial effects of vitamin D on the CV system. The second report was from the US
Health Professionals Follow-up Study (n = 18,225) which found in a nested case–
control comparison that men with baseline plasma 25OHD levels £ 15 ng/mL
(37.4 nmol/L) had a relative risk of 2.09 (95% CI: 1.24, 3.54) for myocardial infarc-
tion (fatal plus nonfatal) over 10-year follow-up compared to those with
25OHD < 30 ng/mL (74.9 nmol/L) adjusting for covariates [136]. The third was
from the follow-up cohort (n = 13,331) of the Third National Health and Nutrition
examination Survey (NHANES III), a representative sample of the US population
surveyed during 1988–1994, which found that participants in the lowest quartile of
baseline serum 25OHD < 17.8 ng/mL (44.4 nmol/L) had a 26% (95% CI: 8, 46)
increased risk of all-cause mortality during a median 8.7-year follow-up, compared
with those in the highest 25OHD quartile [137].