A Reverse J-Shaped Association Between Serum 25-Hydroxyvitamin D and Cardiovascular Disease Mortality: The CopD Study

Durup, Darshana; Jørgensen, Henrik L.; Christensen, Jane; Tjønneland, Anne; Olsen, Anja; Halkjær, Jytte; Lind, Bent; Heegaard, Anne‐Marie; Schwarz, Peter

doi:10.1210/jc.2014-4551

Cited by 155 publications

(110 citation statements)

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“…Extension of these studies to 52 weeks of ERC treatment [14] demonstrated no increased risks related to these parameters. One observational study has suggested a J-shaped association between serum 25-hydroxyvitamin D levels and all-cause mortality [39], while another study has shown an increased hazard ratio only at low levels of serum 25-hydroyvitamin D [40]. In the present studies, a positive correlation was observed between serum total 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D, but no correlation was observed between serum total 25-hydroxyvitamin D and serum calcium or phosphorus.…”

Section: Discussion/conclusioncontrasting

confidence: 51%

Rationale for Raising Current Clinical Practice Guideline Target for Serum 25-Hydroxyvitamin D in Chronic Kidney Disease

et al. 2019

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Background: Vitamin D repletion is recommended for secondary hyperparathyroidism (SHPT) and associated vitamin D insufficiency (VDI) in chronic kidney disease (CKD), but optimal levels of serum total 25-hydroxyvitamin D remain undefined. Clinical practice guidelines target sufficiency, whereas recent data indicate that higher levels are required to control the elevation of intact parathyroid hormone (iPTH) as CKD advances. This secondary analysis of 2 randomized controlled trials seeks to identify the minimum level of mean serum 25-hydroxyvitamin D required to control SHPT arising from VDI in stage 3 or 4 CKD. Methods: Adult subjects (n = 429) with SHPT, VDI, and stage 3 or 4 CKD were stratified by stage and treated daily with either extended-release calcifediol (ERC) or placebo in 2 identical, parallel, randomized, double-blind studies. After treatment for 26 weeks, all subjects were ranked by the level of serum total 25-hydroxyvitamin D and divided into quintiles in order to examine the relationships between the degree of vitamin D repletion and the associated changes in plasma iPTH, serum bone turnover markers, calcium, phosphorus, intact fibroblast growth factor 23 (FGF23) and vitamin D metabolites, estimated glomerular filtration rate (eGFR), and urine calcium:creatinine (Ca:Cr) ratio. Results: Progressive increases in serum 1,25-dihydroxyvitamin D and reductions in plasma iPTH and serum bone turnover markers were observed as mean posttreatment serum 25-hydroxyvitamin D rose from 13.9 ng/mL (in Quintile 1) to 92.5 ng/mL (in Quintile 5), irrespective of CKD stage. Mean serum calcium, phosphorus and FGF23, eGFR, and urine Ca:Cr ratio (collectively “safety parameters”) did not significantly change from Quintile 1. Suppression of iPTH and bone turnover markers was not observed until serum 25-hydroxyvitamin D rose to at least 50.8 ng/mL (Quintile 3). Conclusion: ERC therapy produced exposure-dependent reductions in plasma iPTH and bone turnover markers only when mean serum total 25-hydroxyvitamin D reached at least 50.8 ng/mL, indicating that current targets for vitamin D repletion therapy in CKD are too low. Gradual elevation of mean serum 25-hydroxyvitamin D to 92.5 ng/mL was not associated with significant adverse changes in safety parameters.

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Section: Discussion/conclusioncontrasting

confidence: 51%

Rationale for Raising Current Clinical Practice Guideline Target for Serum 25-Hydroxyvitamin D in Chronic Kidney Disease

et al. 2019

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“…Vitamin D deficiency has also been implicated in bone abnormalities in various diseases including infections, diseases cardiovasculares 27-29, endothelial dysfunction 30, some types of neoplasms 31, insulin resistance 32,33, diabetic nephropathy 34, autoimmune diseases, depressives states 35 and decrease in mass muscular 36. Was also associated with high cardiovascular and all causes mortality 37,38.…”

Section: Discussionmentioning

confidence: 99%

Vitamin D (25 ( OH) D ) in patients with chronic kidney disease stages 2-5

Valencia

Arango

2019

Colomb Med

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This corrects the article "Vitamin D (25 ( OH) D ) in patients with chronic kidney disease stages 2-5" in volume 47(3) on page 163, Table 3. The September 30, 2016, article by Restrepo and Aguirre (Colomb Med (Cali). 2016;47(3): 160-6, was published with errors in Table 3. In body of Table 3, the sixth line of the first column entitled PH (pg/mL), this should read: PTHi (pg/mL). The sixth line of the eight column reads: 11.65, this should read: 116.5. That date appears well in the English XML version, but in both the PDF ingles and the Spanish version appears the value 11.65, must be changed to the real value: 116.5.

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“…We found the mutagenesis of key bass pairs in heterodimeric or coactivator binding sites in VDR gene leads to a significant impairment of liganded VDR functions [6,7]. With changed lifestyles in the modern society, people have a low amount of sunlight exposure resulting in reduced vitamin D synthesis in the skin, which largely contributes to current high prevalence of vitamin D deficiency [8,9] that is associated with increased cardiovascular disease mortality among adults, especially with EH [10][11][12].…”

Section: Is Vitamin D Deficiency Causally Linked To Eh?mentioning

confidence: 98%

Effect of Vitamin D on the Treatment and Prevention of Essential Hypertension

Chen¹

2017

Drug Des

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The vast majority of epidemiological studies have consistently shown that vitamin D levels are inversely related to blood pressure (BP) and the incidence of hypertension (HTN). Animal studies from diet-induced or genetic models of vitamin D deficiency suggest that vitamin D deficiency directly causes HTN. Based on basic and clinical studies, modestly increased renin expression in genetic mouse models of vitamin D deficiency is associated with, but not causally linked to vitamin D deficiency-induced HTN. Our mechanistic studies indicate that overexpression of a novel target gene seems to play a critical role in vitamin D-deficient HTN, and that vitamin D signaling defect in vascular smooth muscle cells and CD4+ T lymphocytes seems predominantly be responsible for vitamin D deficiencymediated HTN. The data from many clinical trials have consistently demonstrated a minimal or no effect of shortterm vitamin D supplementation on BP in normotensive healthy individuals, but long-term vitamin D supplementation should prevent the development of essential HTN (EH) at high-risk susceptible people. More than 13 randomized controlled trials have shown that vitamin D repletion significantly reduces BP in vitamin D-deficient EH patients, which appears to be more effective in those with type 2 diabetes or impaired glucose tolerance. Short-term administration of active vitamin D or its analogue has a better antihypertensive role than natural vitamin D in the treatment of vitamin D-deficient EH. While these promising data from relatively small trials have displayed potential beneficial vitamin D effect on EH, it is urgently needed to comprehensively elucidate molecular mechanisms of vitamin D deficiency-induced HTN, which will provide a solid theoretical basis to well design large randomized controlled trials to further address the antihypertensive role of vitamin D in vitamin D-deficient EH patients. Currently, EH is lacking an etiology-specific therapy. Identification of vitamin D deficiency as an environmental stressor that triggers the development of EH at vulnerable individuals will make a great advance in the field of EH research.Keywords: Vitamin D; Deficiency; Blood pressure; Essential hypertension; Molecular mechanisms; Clinical trials Etiology-Specific Treatment for EH is a Knowledge GapMore than 95% hypertensive patients suffer from EH, a chronic disease that displays an elevated BP phenotype with unknown etiology. EH can lead to stroke, coronary artery disease, peripheral artery disease, heart failure, renal failure and increased mortality if it is not well controlled [1]. Although there are several classes of antihypertensive medications available, in America, 50% of hypertensive patients do not have their BP well-controlled and about 5 million patients are resistant to antihypertensive treatment with a combination of at least three antihypertensive medications [2]. One of critical problems is lacking an etiology-specific effective therapy for EH. Currently, treatment of EH is largely empiric, and the lesseff...

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A Reverse J-Shaped Association Between Serum 25-Hydroxyvitamin D and Cardiovascular Disease Mortality: The CopD Study

Cited by 155 publications

References 39 publications

Rationale for Raising Current Clinical Practice Guideline Target for Serum 25-Hydroxyvitamin D in Chronic Kidney Disease

Rationale for Raising Current Clinical Practice Guideline Target for Serum 25-Hydroxyvitamin D in Chronic Kidney Disease

Vitamin D (25 ( OH) D ) in patients with chronic kidney disease stages 2-5

Effect of Vitamin D on the Treatment and Prevention of Essential Hypertension

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