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Vitamin D and vitamin D receptor activators in treatment of hypertension and cardiovascular disease.

Cardiovascular & hematological disorders drug targets
January 1, 2014
Agata Franczyk et al. (4 authors)
Journal ArticleResearch Support, Non-U.S. Gov'tReviewHuman StudyAnimal StudyMolecular Study
Study Details

Study Goal

The researchers aimed to review the role of vitamin D and vitamin D receptor activators in cardiovascular diseases, particularly hypertension and its treatment.

Results Summary

The study found that vitamin D receptor activators improve cardiovascular function and reduce mortality and morbidity in hypertensive patients, though hypercalcemia is a noted side effect of calcitriol. Mice lacking vitamin D signaling pathways exhibited hypertension and cardiac hypertrophy, suggesting a protective role of vitamin D in cardiovascular health.

Population

Patients with vitamin D deficiency and high cardiovascular risk, including those with hypertension.

Effective Dosage

Not specified

Duration

Not specified

Interactions

None mentioned

Extracted Claims (14)
InterventionDirectionEndpointPopulationDosageImpactClaim #
Vitamin D
neutral
calcium homeostasis and bone metabolism
-
-
plays an essential role
#1
Vitamin D
increase
cell proliferation, immunomodulation, and control of other hormonal systems
-
-
induction
#2
1,25-(OH)2D
increase
cell-specific function and gene regulation
cardiomyocytes, vascular endothelial cells, vascular smooth muscle cells, phagocytes, and cells of the nephron
-
respond to
#3
VDR activators (calcitriol and paricalcitol)
neutral
vitamin D deficiency
-
-
available for the treatment
#4
-
increase
cardiovascular disease
Vitamin-D deficient patients
-
present a higher risk
#5
VDR activator therapy
increase
survival
-
-
provides survival benefit
#6
VDR activator therapy
increase
cardiovascular function
-
-
has a positive impact
#7
-
increase
hypertension and cardiac hypertrophy
mice lacking VDR or CYP27B1
-
development
#8
-
increase
renin and atrial natriuretic peptide
these mice
-
presented with overexpression
#9
VDR
neutral
smooth-muscle-cell (SMC) proliferation, thrombosis, fibrinolysis and vessel relaxation
-
-
may play a role in regulating
#10
VDR activators
decrease
mortality, organ damage, and cardiovascular morbidity
VDR-activator-treated patients with hypertension
-
may reduce
#11
calcitriol
decrease
clinical use
-
-
limited
#12
calcitriol
increase
hypercalcemia
-
-
side effect
#13
vitamin D supplementation therapy
neutral
-
patients with high cardiovascular risk
-
may be warranted
#14
Abstract

Vitamin D plays an essential role in calcium homeostasis and bone metabolism, but recent research has exposed a larger spectrum of biological actions that also includes induction of cell proliferation, immunomodulation, and control of other hormonal systems. Many cells that play an important role in the cardiovascular system express the Vitamin D receptor (VDR) and respond to 1,25-(OH)2D (the active product of vitamin D conversion by hydroxylase) with cell-specific function and gene regulation. These cells include cardiomyocytes, vascular endothelial cells, vascular smooth muscle cells, phagocytes, and cells of the nephron, which produce renin. VDR activators (calcitriol and paricalcitol) are available for the treatment of vitamin D deficiency, which can result from inadequate cutaneous production and/or low dietary intake. Vitamin-D deficient patients present a higher risk of cardiovascular disease than the general population. Recent clinical observations have shown that VDR activator therapy provides survival benefit and also has a positive impact on cardiovascular function. Compelling results have arisen from previous studies of mice with disrupted genes of the vitamin D signaling pathways. In mice lacking VDR or CYP27B1 (1α-hydroxylase - an enzyme, which converts vitamin D to its active form), in addition to the expected phenotype (hypocalcaemia, secondary hyperparathyroidism and osteomalacia), development of hypertension and cardiac hypertrophy were also observed. Moreover, these mice presented with overexpression of renin and atrial natriuretic peptide. VDR may play a role in regulating smooth-muscle-cell (SMC) proliferation, thrombosis, fibrinolysis and vessel relaxation. The influence of VDR activators on the modulation of renin expression and vascular function may reduce mortality, organ damage, and cardiovascular morbidity in VDR-activator-treated patients with hypertension. Since clinical use of calcitriol is largely limited, because of the side effect of hypercalcemia, calcitriol analogues have been synthesized to obtain compounds with better therapeutic profiles. The main purpose of this article is to review the role of vitamin D and vitamin D receptor activators in cardiovascular diseases, especially hypertension and its treatment. Due to the high prevalence of hypovitaminosis D among patients with high cardiovascular risk, vitamin D supplementation therapy may be warranted in this population.

Medical Subject Headings (MeSH)
AnimalsCardiovascular DiseasesHumansHypertensionReceptors, CalcitriolVitamin D
Study Links
Quality Scores
Safety70
Efficacy85/10
Quality80/10
Citation Metrics
Total Citations28
Citations/Year2.5
Relative Citation Ratio1.16
NIH Percentile55.9%
Research Impact Scores
APT Score0.50
Weight Score0.83
Normalized Score0.78
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