Vitamin D and cardiac autonomic tone: Cardiovascular implications in humans with and without chronic kidney disease

Vitamin D deficiency (<50nmol/L 25-hydroxy vitamin D) affects more than 1 billion people worldwide. Furthermore, cardiovascular disease (CVD) is a common cause of mortality globally. Observational studies have shown that vitamin D deficiency and CVD are associated, specifically in the chronic kidney disease (CKD) population whom are burdened with both increased risk of CVD-related death and vitamin D deficiency, though whether this relationship is causal in nature is not clear. Electrocardiogram recordings are used to quantify sympathetic and parasympathetic (vagal) control over the heart (cardiac autonomic tone, CAT), which has been shown to predict CVD-related outcomes. A series of studies was conducted across a range of populations with varying kidney function to assess the impact of vitamin D deficiency and supplementation on CAT. In healthy humans undergoing an angiotensin II (AngII) vascular stress test prior to vitamin D supplementation, subjects with low 1,25(OH)2 vitamin D experienced withdrawal of cardioprotective vagal tone and an upwards shift in overall cardiosympathovagal activity [(∆HF from baseline = -6.98±3, p=0.05; ∆LF:HF from baseline = 0.34±0.1, p=0.043 vs. above 25th percentile]. Following 4 weeks of oral vitamin D3 supplementation, vagal activity during the same AngII stressor was restored (∆HF from baseline 9.5±5 vs. -2.8±3, p=0.07 vs. pre-supplementation). The same study with vitamin D deficient IgA nephropathy (IgAN) subjects yielded similar results. The VITAH Trial then aimed to assess whether a causal relationship existed between activated vitamin D supplementation and CAT in end-stage kidney disease (ESKD) patients requiring hemodialysis. In contrast to healthy and IgAN subjects, six weeks of oral 1,25(OH)2 D supplementation (0.25mcg alfacalcidol 3x per week) or combined activated and nutritional supplementation (additional 50,000IU ergocalciferol 1x per week) enhanced cardiosympathovagal balance during hemodialysis in vitamin D deficient subjects (activated: n=13, ∆LF:HF: 0.20 ± 0.06, p<0.001 vs. ∆LF:HF in non-deficient; combined: n=8, deficient: ∆LF:HF: 0.15 ± 0.06, p<0.001 vs. ∆LF:HF in non-deficient). These novel findings indicate that vitamin D deficiency impairs the regulatory capabilities of the autonomic nervous system during vascular stress, and that vitamin D supplementation may mitigate the risk of CVD-related mortality in humans specifically in the setting of advanced CKD.

Name thesis:degree_name

Doctor of Philosophy (PhD)

Discipline thesis:degree_discipline

Medical Science

Grantor dc:publisher.institution

Graduate Studies

Year dc:date.issued

2015

Author dc:creator

• Mann, Michelle Catherine

Advisor dc:contributor.advisor

• Ahmed, Sofia

• Physiology

Statement dc:rights

• University of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.

Language dc:language.iso

eng

DOI

http://dx.doi.org/10.11575/PRISM/28657

OAI identifier oai:identifier

oai:ucalgary.scholaris.ca:11023/2264