Association of vitamin D status with arterial blood pressure and hypertension risk: a mendelian randomisation study
The Lancet Diabetes & Endocrinology, Early Online Publication, 26 June 2014, doi:10.1016/S2213-8587(14)70113-5
study leader Professor Elina Hyppönen from the University of South Australia (Huge list of authors)
Low 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.
In 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.
In 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).
Increased plasma concentrations of 25(OH)D might reduce the risk of hypertension.
This finding warrants further investigation in an independent, similarly powered study.
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- Hypertension and vitamin D
- Hypertention (both systolic and diastolic) reduced with 2,000 IU of vitamin D – RCT June 2014
- Blood pressure in diabetics reduced by 12 weekly doses of 50,000 IU vitamin D – RCT Jan 2014
- Search VitaminDWiki for CYP2R1 197 items as of June 2014
- Search VitaminDWiki for DHCR7 67 items as of June 2014
- Search VitaminDWiki for hypertension (CYP2r1 OR DHCR7) 509 items as of March 2019
Pages listed in BOTH the categories Hypertension and Genetics
- Hypertension 2X more likely if poor CYP24A1 vitamin D gene (China) – Jan 2020
- Hypertension 3.1 X more likely in males with poor CPY24A1 gene (but 2.5 X less likely for females) – May 2019
- Hypertension gene expression reduced by high-dose vitamin D (hypertensive rats) – March 2019
- Hypertension associated with genes which reduce vitamin D – meta-analysis June 2014
- Clinical trials for Hypertension and "Vitamin D" 50 as of June 2014
- Medical Express on the study
They found that for each 10% increase in 25(OH)D concentration there was a drop in
diastolic blood pressure (-0.29 mm Hg) and
systolic blood pressure (-0.37 mm Hg), and an
8.1% decrease in the odds of developing hypertension.
- NHS (UK) has a good overview of the study and its implications - the following are a few sentences from the article
The researchers hypothesised that these genes should have an influence on lifelong vitamin D levels, so they could be used to look for an association with blood pressure and hypertension.
If people were taking antihypertensive drugs, they added 15mmHg to the systolic reading and 10mmHg to the diastolic reading to account for the likely effect of the drugs.
The study's strengths include the large number of participants, although they were all of European descent, so it is not known if the results could be directly applicable to other ethnicities.