Association of vitamin D status with arterial blood pressure and hypertension risk: a mendelian randomisation study

Publication type

Journal Article

Authors

Publication date

September 15, 2014

Summary:

BackgroundLow
plasma 25-hydroxyvitamin D (25[OH]D) concentration is associated with
high arterial blood pressure and hypertension risk, but whether this
association is causal is unknown. We used a mendelian randomisation
approach to test whether 25(OH)D concentration is causally associated
with blood pressure and hypertension risk.MethodsIn
this mendelian randomisation study, we generated an allele score
(25[OH]D synthesis score) based on variants of genes that affect 25(OH)D
synthesis or substrate availability (CYP2R1 and DHCR7),
which we used as a proxy for 25(OH)D concentration. We meta-analysed
data for up to 108 173 individuals from 35 studies in the D-CarDia
collaboration to investigate associations between the allele score and
blood pressure measurements. We complemented these analyses with
previously published summary statistics from the International
Consortium on Blood Pressure (ICBP), the Cohorts for Heart and Aging
Research in Genomic Epidemiology (CHARGE) consortium, and the Global
Blood Pressure Genetics (Global BPGen) consortium.FindingsIn
phenotypic analyses (up to n=49 363), increased 25(OH)D concentration
was associated with decreased systolic blood pressure (β per 10%
increase, −0·12 mm Hg, 95% CI −0·20 to −0·04; p=0·003) and reduced odds
of hypertension (odds ratio [OR] 0·98, 95% CI 0·97–0·99; p=0·0003), but
not with decreased diastolic blood pressure (β per 10% increase, −0·02
mm Hg, −0·08 to 0·03; p=0·37). In meta-analyses in which we combined
data from D-CarDia and the ICBP (n=146 581, after exclusion of
overlapping studies), each 25(OH)D-increasing allele of the synthesis
score was associated with a change of −0·10 mm Hg in systolic blood
pressure (−0·21 to −0·0001; p=0·0498) and a change of −0·08 mm Hg in
diastolic blood pressure (−0·15 to −0·02; p=0·01). When D-CarDia and
consortia data for hypertension were meta-analysed together (n=142 255),
the synthesis score was associated with a reduced odds of hypertension
(OR per allele, 0·98, 0·96–0·99; p=0·001). In instrumental variable
analysis, each 10% increase in genetically instrumented 25(OH)D
concentration was associated with a change of −0·29 mm Hg in diastolic
blood pressure (−0·52 to −0·07; p=0·01), a change of −0·37 mm Hg in
systolic blood pressure (−0·73 to 0·003; p=0·052), and an 8·1% decreased
odds of hypertension (OR 0·92, 0·87–0·97; p=0·002).InterpretationIncreased
plasma concentrations of 25(OH)D might reduce the risk of hypertension.
This finding warrants further investigation in an independent,
similarly powered study.

Published in

The Lancet Diabetes and Endocrinology

Volume and page numbers

Volume: 2 , p.719 -729

DOI

http://dx.doi.org/10.1016/S2213-8587(14)70113-5

ISSN

22138587

Subjects

Notes

Open Access article

#522615