Hypovitaminosis D and Organ Damage In Patients With Arterial Hypertension: A Multicenter Double Blind Randomised Controlled Trial of Cholecalciferol Supplementation (HYPODD)

Rendina, Domenico; Ippolito, R.; D’Elia, Lanfranco; Giacchetti, Gilberta; Lonati, Chiara; Gianfrancesco, Fernando; Fallo, Francesco; Rebellato, Andrea; Ruggiero, Carmelinda; Rubattu, Speranza; Volpe, Massimo; Gennari, Luigi; Merlotti, Daniela; Isaia, G.C.; Spertino, Elena; Fabris, Bruno; Sechi, Leonardo A.; Catena, Cristiana; Maresca, Andrea Maria; Gessi, V.; Dalbeni, Andrea; Strazzullo, Pasquale

doi:10.1007/s40292-015-0080-9

Cited by 4 publications

(7 citation statements)

References 23 publications

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“…Another mechanism potentially involved in this association is the regulatory effect of vitamin D on the activity of the RAAS [27], which interferes with insulin signaling in various tissues, reducing endothelial responsiveness [28]. In fact, at the molecular level, the activation of the PI3K/Akt/e-NOS axis is significantly reduced, while the MAPK signal, which induces proliferative and proinflammatory stimulation and endothelinmediated vasoconstrictors that predispose to endothelial dysfunction and atherosclerosis, is enhanced [29].…”

Section: Discussionmentioning

confidence: 99%

“…However, the beneficial effect of vitamin D supplementation on arterial stiffness and LVM is currently controversial, as demonstrated by multiple reviews and meta-analysis studies carried out to obtain evidence on the effect of vitamin D supplementation on cardiometabolic factors. The HYPODD study, a double-blind, multicenter, randomized trial to evaluate the effects of cholecalciferol supplementation on blood pressure control and progression of organ damage in patients with essential hypertension and hypovitaminosis D, did not lead to achievement of these cardiovascular endpoints [29]. However, recruited patients were already treated and well controlled; therefore, pharmacological treatment may have influenced the study results.…”

Section: Discussionmentioning

confidence: 99%

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Vitamin D and Subclinical Cardiovascular Damage in Essential Hypertension

Magurno¹,

Crescibene²,

Spinali³

et al. 2021

Endocrines

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Vitamin D deficiency is linked to cardiac dysfunction, vascular remodeling, metabolic syndrome and insulin resistance (IR). The aim of the present study was to evaluate the association between vitamin D levels and cardiovascular (CV) organ damage in a large cohort of newly diagnosed treatment-naïve hypertensive patients, and the role of IR in this context. We enrolled 500 Caucasian individuals, without CV or renal complications. Subjects underwent a complete evaluation and measurements of vitamin D, standard laboratory determinations and instrumental examination, including echocardiography and applanation tonometry. Linear regression analyses were performed to assess the correlation between pulse wave velocity (PWV) and left ventricular mass index (LVMI) with different covariates. PWV was significantly correlated with age (p < 0.0001), LDL cholesterol (p < 0.0001), BMI (p = 0.001), pulse pressure (PP) (p = 0.005) and high sensitivity C-reactive protein (hs-CRP) (p = 0.006), while an inverse correlation was observed with vitamin D levels (p < 0.0001), Matsuda index (p < 0.0001) and estimated glomerular filtration ratio (e-GFR) (p = 0.006). LVMI significantly correlated with PP (p < 0.0001), hs-CRP (p < 0, 0001) and age (p = 0.001), while an inverse relationship was observed with vitamin D levels (p < 0.0001), Matsuda’s insulin sensitivity index (ISI) (p < 0.0001) and e-GFR (p < 0.0001). Vitamin D was the strongest predictor of PWV and LVMI, explaining, respectively, 28.3% and 19.1% of their variation. Our study suggests that low vitamin D might be a biomarker of end-organ damage.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Vitamin D and Subclinical Cardiovascular Damage in Essential Hypertension

Magurno¹,

Crescibene²,

Spinali³

et al. 2021

Endocrines

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“…The HYPODD study was conceived by the Working Group on Vitamin D and Cardiorenal Disorders, established jointly by the Italian Society of Hypertension (SIIA) and the Forum in Bone and Mineral Research (FBMR) and coordinated by the Federico II University of Naples European Society of Hypertension Excellence Center [27]. Initially, twelve SIIA and FBMR Centers joined HYPODD, but nine of them found it difficult to enroll the participants according to the trial protocol and dropped out of the project.…”

Section: The Hypodd Studymentioning

confidence: 99%

“…Taking these data into account altogether, it is reasonable to study the relationship of vitamin D to miR-21 in patients with hypertension. The HYPODD (HYPOvitaminosis D and organ Damage) study was conceived against this background: As previously described, it was a no-profit multicenter parallel-group double-blind placebo-controlled randomized trial aiming to assess the effects of cholecalciferol supplementation on the cardiovascular risk profiles of patients with essential hypertension and vitamin D deficiency [27]. To assess miR expression, RNA samples were obtained from participating patients.…”

Section: Introductionmentioning

confidence: 99%

Vitamin D Status, Cardiovascular Risk Profile, and miRNA-21 Levels in Hypertensive Patients: Results of the HYPODD Study

et al. 2022

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The vitamin D and microRNA (miR) systems may play a role in the pathogenesis of cardiometabolic disorders, including hypertension. The HYPODD study was a double-blind placebo-controlled trial aiming to assess the effects of cholecalciferol treatment in patients with well-controlled hypertension and hypovitaminosis D (25OHD levels < 50 nmol/L). In addition to this clinical trial, we also evaluated the effects of cholecalciferol and calcitriol treatment on miR-21 expression in vivo and in vitro, respectively. Changes in the cardiovascular risk profiles were evaluated in HYPODD patients treated with cholecalciferol (C-cohort) or with placebo (P-cohort). The miR-21circulating levels were measured in four C-cohort patients and five P-cohort patients. In vitro, the miR-21 levels were measured in HEK-293 cells treated with calcitriol or with ethanol vehicle control. Cholecalciferol treatment increased 25OHD levels and reduced parathormone, total cholesterol, and low-density lipoprotein cholesterol levels in C-cohort patients, whereas no significant changes in these parameters were observed in P-cohort patients. The miR-21 circulating levels did not change in the C- or the P-cohort patients upon treatment. Calcitriol treatment did not affect miR-21 levels in HEK-293 cells. In conclusion, hypovitaminosis D correction ameliorated the cardiovascular risk profiles in hypertensive patients treated with cholecalciferol but did not influence the miR-21 expression.

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“…In Mendelian analysis it was concluded that increased Vitamin D levels could reduce hypertension risk, but further replication of study is necessary [ 90 ]. Vitamin D supplementation for hypertensive, low Vitamin serum levels subjects did not improve their blood pressure when given either 2800 IU of Vitamin D3 per day as oily drops ( n = 100) or placebo ( n = 100) for 8 weeks [ 91 ]; further controlled trial is on the way to assess the link [ 92 ]. In a review conducted on Vitamin D supplementation trials, the result was inconclusive, since randomized trials with higher Vitamin D dose are potentially required to realize specific outcome [ 93 ].…”

Section: Vitamin D and Cvdmentioning

confidence: 99%

The Role of Vitamin D in Diabetes and Cardiovascular Disease: An Updated Review of the Literature

Papandreou

Hamid

2015

Disease Markers

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The dietary reference values for Vitamin D were set primarily considering its role in bone health, but with the discovery of Vitamin D receptors throughout body tissues, new links with other health conditions are now studied, such as for diabetes and cardiovascular diseases (CVD). This paper shall analyze and examine all new research studies carried out, especially in 2013–2015 regarding diabetes mellitus (DM) and cardiovascular diseases (CVD). Vast research has been carried out to establish strong relationship between Vitamin D serum levels, supplementation, diabetes, and CVD. However, the results from researches identified in this paper are disputable. Benefits of Vitamin D adequate levels were recognized from gestational period until later in disease development such as diabetes and/or CVD, but since not all studies are in agreement further investigation is suggested. Researches conducting large randomized controlled trials, exploring range of supplement doses, with variable baseline serum Vitamin D levels, and inclusion of array of associated parameters, are still required to conduct large-scale analysis and draw conclusion as a risk factor. Until then it is possible to conclude that maintenance of serum Vitamin D levels holds advantageous aspects in diabetic and cardiovascular conditions, and people should strive to attain them.

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Hypovitaminosis D and Organ Damage In Patients With Arterial Hypertension: A Multicenter Double Blind Randomised Controlled Trial of Cholecalciferol Supplementation (HYPODD)

Cited by 4 publications

References 23 publications

Vitamin D and Subclinical Cardiovascular Damage in Essential Hypertension

Vitamin D and Subclinical Cardiovascular Damage in Essential Hypertension

Vitamin D Status, Cardiovascular Risk Profile, and miRNA-21 Levels in Hypertensive Patients: Results of the HYPODD Study

The Role of Vitamin D in Diabetes and Cardiovascular Disease: An Updated Review of the Literature

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