Published: Jun 12, 2013 | Updated: Jun 13, 2013
By Kathleen Struck , Senior Editor, MedPage Today
Action Points
- Note that this large genetic analysis demonstrated that individuals with genes linked to lower vitamin D levels are more likely to have hypertension mediated by low vitamin D, strengthening the argument for a causal link.
- Be aware that the absolute effect of vitamin D levels on blood pressure was negligible, even though statistically significant.
A genetic study of more than 150,000 individuals internationally has confirmed a causal association between low levels of vitamin D and hypertension, researchers reported.
Every 10% increase in serum 25-hydroxyvitamin D concentrations was associated with a 0.24 mmHg decrease in diastolic blood pressure (95% CI, -0.43 to -0.05, P=0.02) and an 8.1% decrease in the risk of developing hypertension (95% CI, 2.4% to 11.1%, P=0.003), according to Vimal Karani Santhanakrishnan, PhD, of the Institute of Children Health at the University College London, and colleagues.
For their Mendelian randomization analysis, the researchers used genetic variants called single nucleotide polymorphisms (SNPs) as proxy markers to reflect vitamin D levels, they reported at the European Society of Human Genetics in Paris.
The examination of 35 earlier studies and 158,846 individuals confirmed earlier observational studies that showed a causal association between vitamin D levels and blood pressure, Santhanakrishnan and colleagues stated.
“There’s been an incredible number of confounding variables that have entered into many of the [vitamin D] studies, leading to very inconclusive findings or observations,” Domenic Sica, MD, of Virginia Commonwealth University, said in an interview with MedPage Today.
“Using a genetic analysis model employed here, one can eliminate many of the confounding variables and in essence take away … reverse causality for the associations. And one gets a rich data set showing a relationship between a specific genetic polymorphism — termed a SNP — and blood pressure with the intermediate being the 25 hydroxy D3 level,” he said.
Santhanakrishnan and colleagues examined associations of four vitamin D-related SNPs with 25 hydroxyvitamin D for validation, and with blood pressure for causal inference. All four SNPs were strongly associated with 25 hydroxyvitamin D (P
Sica commented that the limitations included the study’s observational methodology.
“It’s not showing the other variables, which may independently influence blood pressure,” he said.
Another limitation, Sica said, is not one that the authors intended: “But there’s considerable controversy and debate as to what represents a low level and what’s the best measurement tool for determining what vitamin D levels are,” he commented.
“What creates hypertension in a person is never something as simple as a low vitamin D level. It’s in the context of body weight, salt and water retention, sodium intake, potassium intake, things of a similar ilk, but this is one area now that we have more assuredness that there is a relationship,” he said. “So now you have to fit it like putting a piece into the end of a puzzle as to its contribution to all the other factors that play out in the genesis and/or the progression of hypertension.”
The study was funded by the British Heart Foundation.
The authors said they had no conflicts to report.
Primary source: European Society of Human Genetics
Source reference: Santhanakrishnan VK, et al “A causal association between vitamin D status and blood pressure: a Mendelian randomization study in up to 150,846 individuals” ESHG 2013; Abstract #C18.2.