Causal role proposed for vitamin D in blood pressure

By Eleanor McDermid, Senior medwireNews Reporter

The results of a mendelian randomisation analysis suggest a causal link between low levels of vitamin D and increased blood pressure (BP).

“[T]he potential to prevent or reduce blood pressure and therefore the risk of hypertension with vitamin D is very attractive”, said study author Elina Hyppönen (University of South Australia, Adelaide) in a press statement.

However, randomised trials of vitamin D supplementation have so far yielded disappointing results, despite the strong associations seen between vitamin D and hypertension in observational studies.

In a comment accompanying the current study, in The Lancet Diabetes and Endocrinology, Shoaib Afzal and Børge Nordestgaard, from Copenhagen University Hospital in Denmark, describe the findings as “timely”.

A mendelian randomisation analysis assesses genetic determinants of a variable of interest. In this case, the researchers created a vitamin D synthesis score based on possession of four single nucleotide polymorphisms known to affect vitamin D synthesis or the availability of its substrates.

The team used data from 35 studies in the D-CarDia collaboration, totalling 99,582 adults and 8591 adolescents. About half of these participants had plasma vitamin D measurements, which were strongly associated with their vitamin D synthesis scores, with no evidence of heterogeneity. In turn, higher vitamin D levels were associated with lower systolic BP and a reduced risk of hypertension.

Among all D-CarDia participants, the genetic synthesis score was not significantly associated with BP. However, significant associations emerged after adding data from the International Consortium for Blood Pressure, to give a total 146,581 participants. Each additional allele in the genetic synthesis score was then associated with a significant 0.10 mmHg reduction in systolic BP and 0.08 mmHg reduction in diastolic BP, and a significant 2% reduction in the risk of hypertension.

In their commentary, Afzal and Nordestgaard sound a note of caution, saying that the associations were not very strongly significant, and pointing out that an association with stroke, which was not assessed, would give greater clinical relevance to the findings.

However, they also note that the study may provide the clearest picture when it comes to determining causality, because of its ability to assess the lifelong effect of vitamin D levels, rather than just a short exposure to supplementation as occurs in clinical trials.

“Thus, estimates from randomised intervention trials might be somewhat attenuated compared with estimates from mendelian randomisation studies”, they say.

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