Serum Bioavailable and Free 25-Hydroxyvitamin D Levels, but Not Its Total Level, Are Associated With the Risk of Mortality in Patients With Coronary Artery Disease

Yu, Chao; Xue, Hongliang; Wang, Liqing; Chen, Qian; Chen, Xuechen; Yuan, Zuyi; Hu, Gang; Liu, Wenhua

doi:10.1161/circresaha.118.313558

Cited by 71 publications

(59 citation statements)

References 38 publications

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“…(33) In addition, bioavailable 25OHD has been suggested to be a more informative measure of vitamin D status for the prognosis of coronary artery disease than total 25OHD. (34) The nonsignificant association of free 25OHD levels with survival is unexpected in the current study. However, considering that only tiny amounts (<0.03%) of total 25OHD are free and unbound in serum, (15) bioavailable 25OHD levels are approximately equal to albumin-bound 25OHD levels.…”

Section: Discussionmentioning

confidence: 40%

“…Findings from epidemiological studies support this notion that bioavailable 25OHD levels were better linked to biological outcomes than the free fraction alone. (34,35) Our results highlight that bioavailable measures of 25OHD are potentially useful for predicting the risk of liver cancer mortality. With the recent availability of a commercial direct free 25OHD measurement ELISA kit, the determination of bioavailable 25OHD is much easier and more precise than the calculation based on the DBP and total 25OHD levels.…”

Section: Discussionmentioning

confidence: 78%

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Serum Bioavailable, Rather Than Total, 25‐hydroxyvitamin D Levels Are Associated With Hepatocellular Carcinoma Survival

Fang

Long²,

Zhang

et al. 2020

Hepatology

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BaCKgRoUND aND aIMS:Free and bioavailable 25-hydroxyvitamin D (25OHD) are emerging measurements of vitamin D status. It remains unclear whether circulating free or bioavailable 25OHD are relevant to hepatocellular carcinoma (HCC) prognosis. Our aim was to test the hypothesis that bioavailable 25OHD may be a better serum biomarker of vitamin D status than total 25OHD on the association with HCC survival. appRoaCH aND ReSUltS: We included 1,031 newly diagnosed, previously untreated patients with HCC from the Guangdong Liver Cancer Cohort enrolled between September 2013 and April 2017. Serum total 25OHD levels were measured using an electrochemiluminescence immunoassay. Serum-free 25OHD levels were measured using a two-step enzyme-linked immunosorbent assay. Bioavailable 25OHD levels were calculated from measured free 25OHD and albumin using a previously validated equation. Primary outcomes were liver cancer-specific (LCSS) and overall survival (OS). Cox proportional hazards models were performed to calculate the multivariable hazard ratios (HRs) and 95% confidence intervals (CIs). During a median follow-up of 726 days, 430 patients had deceased, including 393 deaths from HCC. In multivariable analyses, higher bioavailable 25OHD levels were significantly associated with better survival, independent of nonclinical and clinical prognostic factors including serum C-reactive protein, Barcelona Clinic Liver Cancer stage, and cancer treatment. The multivariable-adjusted HRs in the highest versus lowest quartile of bioavailable 25OHD levels were 0.69 (95% CI: 0.51, 0.93; P for trend = 0.014) for LCSS and 0.71 (95% CI: 0.53, 0.94; P for trend = 0.013) for OS. In contrast, neither total nor free 25OHD levels were associated with LCSS or OS. CoNClUSIoNS:Higher bioavailable, rather than total, 25OHD levels were independently associated with improved survival in a population-based HCC cohort, suggesting a potential utility of bioavailable 25OHD in HCC prognosis. (Hepatology 2020;0:1-14).

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Section: Discussionmentioning

confidence: 40%

Section: Discussionmentioning

confidence: 78%

Serum Bioavailable, Rather Than Total, 25‐hydroxyvitamin D Levels Are Associated With Hepatocellular Carcinoma Survival

Fang

Long²,

Zhang

et al. 2020

Hepatology

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“…In normal subjects, the use of serum T25D which is widely available is the optimal screening test for assessment of vitamin D insufficiency and deficiency. There may be a role for the use of F25D, based on a recent study that showed F25D was more closely associated with cardiovascular mortality than with T25D; however, this result needs confirmation in other clinical outcomes studies.…”

Section: Discussionmentioning

confidence: 99%

“…In a short 12-week study of weekly 50 000 IU D2 or D3, the decrease in serum PTH at 4 weeks was more highly correlated with F25D than T25D but after 8-12 weeks of treatment this was no longer true [17]. A recent paper in 1387 Chinese patients with proven coronary disease showed that F25D, but not T25D was highly correlated with coronary disease and mortality during a 6.7-year follow-up suggesting that F25D may have an important clinical role in cardiovascular disease [18]. In a comparison of baseline physical tests of grip strength and gait speed, there were significant correlations with F25D but not T25D [19].…”

Section: Discussionmentioning

confidence: 99%

Effect of vitamin D supplementation on total and free 25 hydroxyvitamin D and parathyroid hormone. An analysis of two randomized controlled trials

Smith

Gallagher

2019

J Intern Med

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Background It is questionable as to whether total serum 25 hydroxyvitamin D (T25D) levels are lower in African Americans. We measured serum T25D, free 25hydroxyvitamin D (F25D) and serum parathyroid hormone (PTH) in African American and Caucasian women and studied the effect of vitamin D dosing to determine if differences by race or age occur. Methods Healthy young and older Caucasian and African American women who were vitamin D insufficient were randomized in two clinical trials to escalating daily doses of vitamin D from 400 to 4800 IU and placebo for 12 months. Results Baseline F25D and T25D were significantly lower in young but not older African American compared to Caucasian women. At baseline, the rate of change, or slope, in F25D with T25D was significantly greater in younger women than in older women, but difference in the rate of change in F25D with T25D is similar in African American and Caucasian women. After vitamin D supplementation, there was an increase in F25D, and the dose response was not significantly different by age or race. The ratio of F25D/T25D decreased in all groups once T25D exceeded ~60 nmol L−1. There was a progressive decrease in serum PTH with increasing vitamin D doses and the per cent change was similar for F25D and T25D. Conclusion Serum F25D and T25D are lower in younger African American women, and since dietary vitamin D is similar in the groups, it is likely that the cause of low serum 25OHD in African American women is due to reduced UV exposure and reduced skin production of vitamin D.

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“…However, several studies reported that bioavailable 25(OH)vitD may be a better biomarker for vitD status. For example, free and bioavailable 25(OH)vitD levels may be useful predictors for the prognosis of patients with coronary artery disease [20]. By contrast, other studies refuted this view [21,22].…”

Section: Introductionmentioning

confidence: 99%

Total, Bioavailable, and Free Vitamin D Levels and Their Prognostic Value in Pulmonary Arterial Hypertension

Callejo

Mondéjar-Parreño

Esquivel-Ruiz

et al. 2020

JCM

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Introduction: Epidemiological studies suggest a relationship between vitamin D deficiency and cardiovascular and respiratory diseases. However, whether total, bioavailable, and/or free vitamin D levels have a prognostic role in pulmonary arterial hypertension (PAH) is unknown. We aimed to determine total, bioavailable, and free 25-hydroxy-vitamin D (25(OH)vitD) plasma levels and their prognostic value in PAH patients. Methods: In total, 67 samples of plasma from Spanish patients with idiopathic, heritable, or drug-induced PAH were obtained from the Spanish PH Biobank and compared to a cohort of 100 healthy subjects. Clinical parameters were obtained from the Spanish Registry of PAH (REHAP). Results: Seventy percent of PAH patients had severe vitamin D deficiency (total 25(OH)vitD < 10 ng/mL) and secondary hyperparathyroidism. PAH patients with total 25(OH)vitD plasma above the median of this cohort (7.17 ng/mL) had better functional class and higher 6-min walking distance and TAPSE (tricuspid annular plane systolic excursion). The main outcome measure of survival was significantly increased in these patients (age-adjusted hazard ratio: 5.40 (95% confidence interval: 2.88 to 10.12)). Vitamin D-binding protein (DBP) and albumin plasma levels were downregulated in PAH. Bioavailable 25(OH)vitD was decreased in PAH patients compared to the control cohort. Lower levels of bioavailable 25(OH)vitD (<0.91 ng/mL) were associated with more advanced functional class, lower exercise capacity, and higher risk of mortality. Free 25(OH)vitD did not change in PAH; however, lower free 25(OH)vitD (<1.53 pg/mL) values were also associated with high risk of mortality. Conclusions: Vitamin D deficiency is highly prevalent in PAH, and low levels of total 25(OH)vitD were associated with poor prognosis.

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Serum Bioavailable and Free 25-Hydroxyvitamin D Levels, but Not Its Total Level, Are Associated With the Risk of Mortality in Patients With Coronary Artery Disease

Cited by 71 publications

References 38 publications

Serum Bioavailable, Rather Than Total, 25‐hydroxyvitamin D Levels Are Associated With Hepatocellular Carcinoma Survival

Serum Bioavailable, Rather Than Total, 25‐hydroxyvitamin D Levels Are Associated With Hepatocellular Carcinoma Survival

Effect of vitamin D supplementation on total and free 25 hydroxyvitamin D and parathyroid hormone. An analysis of two randomized controlled trials

Total, Bioavailable, and Free Vitamin D Levels and Their Prognostic Value in Pulmonary Arterial Hypertension

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