Biobank Study Of Severe Deficiency Of Vitamin D In Pulmonary Arterial Hypertension Patients

Pixabay License | Source: Pete Linforth, added background.

Vitamin D is produced in the skin by photochemical transformation of 7-dehydrocholesterol (7DHC) into pre-vitamin D and can also be absorbed from dietary intake. In blood 25 hydroxyvitamin D (25(OH)D) is the most abundant and studied form of vitamin D and provides a basis for assessing vitamin D status.

Normally, roughly 0.03% of 25(OH)D is free, 85% is bound to vitamin D binding protein (DBP), and 15% is bound to albumin. Most tissues absorb vitamin D only in the free form, leading to the suggestion that bioavailable 25(OH)D is more clinically relevant than total 25(OH)D. That said albumin bound vitamin D is bioavailable through ready dissociation, and the kidney can also absorb DBP bound 25(OH)D, where it is further metabolized to the most active form, known as calcitriol.

Vitamin D plays an important role in regulation of calcium and phosphorous metabolism and deficiency of the vitamin can lead to bone diseases. It also has other functions in cellular growth, metabolism, and the innate and adaptive immune responses. Vitamin D supplements have shown some efficacy in reducing asthma and COPD exacerbations.

Observational studies have shown association between low vitamin D and increased risk of cardiovascular disease, respiratory disease, and all-cause mortality. Vitamin D deficiency may be common in pulmonary arterial hypertension (PAH) and the authors of a new study led by Francisco Perez-Vizcaino of Universidad Complutense de Madrid, published in the Journal of Clinical Medicine, aimed to more clearly define the relationship of 25(OH)D levels with mortality in PAH patient samples from the Spanish PH Biobank (n=67) and the Biobanco Vasco (n=98).


Even in control subjects severe total 25(OH)D deficiency (<10ng/ml) was widespread; 35% and 70% of the control subjects and PAH patients, respectively. Free 25(OH)D was similar between groups, however DBP and albumin were significantly lower in PAH patients. Vitamin D deficient PAH patients had hyperparathyroidism. Six-minute walking distance and right-ventricular systolic function were significantly reduced in severely 25(OH)D deficient patients compared to other PAH patients. Kaplan–Meier mortality analysis revealed a significant reduction in survival (p = 0.015) in patients with 25(OH)D levels below median.

Limitations of the study include that no time-course analysis of vitamin D status or PAH progression was performed. Although age was statistically adjusted for, vitamin D levels do decrease with age, which could have influenced the functional tests such as walking speed and the mortality rate.

“The present study demonstrates that total 25(OH)D, rather than bioavailable or free 25(OH)D, is a potential predictor of adverse outcomes in PAH patients. Given the high prevalence of vitamin D deficiency in PAH population, it seems reasonable that serum total vitamin D levels should be regularly assessed. Further studies are required to clarify whether our findings have potential clinical implications,” concluded the authors.