Circulating Calcitriol Concentrations and Total Mortality

Department of Cardio-Thoracic Surgery, Heart Center North Rhine-Westfalia, Ruhr University Bochum, Bad Oeynhausen, Germany.
Clinical Chemistry (Impact Factor: 7.91). 05/2009; 55(6):1163-70. DOI: 10.1373/clinchem.2008.120006
Source: PubMed


Evidence is accumulating that vitamin D supplementation of patients with low 25-hydroxyvitamin D concentrations is associated with lower cardiovascular morbidity and total mortality during long-term follow-up. Little is known, however, about the effect of low concentrations of the vitamin D hormone calcitriol on total mortality. We therefore evaluated the predictive value of circulating calcitriol for midterm mortality in patients of a specialized heart center.
This prospective cohort study included 510 patients, 67.7% with heart failure (two-thirds in end stage), 64.3% hypertension, 33.7% coronary heart disease, 20.2% diabetes, and 17.3% renal failure. We followed the patients for up to 1 year after blood collection. For data analysis, the study cohort was stratified into quintiles of circulating calcitriol concentrations.
Patients in the lowest calcitriol quintile were more likely to have coronary heart disease, heart failure, hypertension, diabetes, and renal failure compared to other patients. They also had low 25-hydroxyvitamin D concentrations and high concentrations of creatinine, C-reactive protein, and tumor necrosis factor alpha. Eighty-two patients (16.0%) died during follow-up. Probability of 1-year survival was 66.7% in the lowest calcitriol quintile, 82.2% in the second quintile, 86.7% in the intermediate quintile, 88.8% in the fourth quintile, and 96.1% in the highest quintile (P < 0.001). Discrimination between survivors and nonsurvivors was best when a cutoff value of 25 ng/L was applied (area under the ROC curve 0.72; 95% CI 0.66-0.78).
Decreased calcitriol levels are linked to excess midterm mortality in patients of a specialized heart center.

Download full-text


Available from: Armin Zittermann, Jan 06, 2014
21 Reads
  • Source
    • "Similar data were also obtained for low 1,25(OH)2D (wolf et al. 2007). considering that 1,25(OH)2D is usually not measured in clinical routine , there are only few data available on 1,25(OH)D and adverse outcomes, but accumulating evidence suggests that circulating 1,25(OH)2D might also be related to cardiovascular risk and mortality, even in the absence of significant cKD (Zittermann et al. 2009; Pilz et al. 2008). Future research should therefore put more emphasis on the relationship between circulating 1,25(OH)2D and cardiovascular risk (Zittermann et al. 2012a "
    [Show abstract] [Hide abstract]
    ABSTRACT: The high worldwide prevalence of vitamin D deficiency is largely the result of low sunlight exposure with subsequently limited cutaneous vitamin D production. Classic manifestations of vitamin D deficiency are linked to disturbances in bone and mineral metabolism, but the identification of the vitamin D receptor in almost every human cell suggests a broader role of vitamin D for overall and cardiovascular health. The various cardiovascular protective actions of vitamin D such as anti-diabetic and anti-hypertensive effects including renin suppression as well as protection against atherosclerosis and heart diseases are well defined in previous experimental studies. In line with this, large epidemiological studies have highlighted vitamin D deficiency as a marker of cardiovascular risk. However, randomized controlled trials (RCTs) on vitamin D have largely failed to show its beneficial effects on cardiovascular diseases and its conventional risk factors. While most prior vitamin D RCTs were not designed to assess cardiovascular outcomes, some large RCTs have been initiated to evaluate the efficacy of vitamin D supplementation on cardiovascular events in the general population. When considering the history of previous disappointing vitamin RCTs in general populations, more emphasis should be placed on RCTs among severely vitamin D-deficient populations who would most likely benefit from vitamin D treatment. At present, vitamin D deficiency can only be considered a cardiovascular risk marker, as vitamin D supplementation with doses recommended for osteoporosis treatment is neither proven to be beneficial nor harmful in cardiovascular diseases.
    Archives of Toxicology 10/2013; 87(12). DOI:10.1007/s00204-013-1152-z · 5.98 Impact Factor
  • Source
    • "Third, no data on circulating levels of the biologically active form of vitamin D, 1,25(OH)2D, were presented. Circulating 1,25(OH)2D is probably a better predictor of total mortality compared with circulating 25OHD, at least if mid-term mortality is assessed [14]. Circulating 1,25(OH)2D declines significantly (and parathyroid hormone levels increase substantially) at 25OHD levels below 10 ng/ml, whereas levels of both hormones seem to plateau at 25OHD levels of 20 ng/ml [15]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Like vitamin D deficit, magnesium deficit is considered to be a risk factor for cardiovascular disease. Several steps in the vitamin D metabolism, such as vitamin D binding to its transport protein and the conversion of vitamin D into the hormonal form 1,25-dihydroxyvitamin D by hepatic and renal hydroxylation, depend on magnesium as a cofactor. A new analysis of two National Health and Nutrition Examination Surveys data sets, published in BMC Medicine, investigated potential interactions between magnesium intake, circulating 25-hydroxyvitamin D, which is the generally accepted indicator of vitamin D status, and mortality. Data indicate a reduced risk of insufficient/deficient vitamin D status at high magnesium intake and an inverse association between circulating 25-hydroxyvitamin D and mortality, particularly cardiovascular mortality, among those with magnesium intake above the median. The study provides important findings concerning potential metabolic interactions between magnesium and vitamin D and its clinical relevance. However, results should be considered preliminary since biochemical data on individual magnesium status were lacking, confounding cannot be excluded and questions on the dose?response relationship still remain to be answered. Please see related research article:
    BMC Medicine 10/2013; 11(1):229. DOI:10.1186/1741-7015-11-229 · 7.25 Impact Factor
  • Source
    • "It is difficult to extrapolate from this study to the likely effects of VitD deficiency on the level of transdifferentiation of muscle precursor cells to adipocytes that occur in muscle in vivo. Our findings suggest that low (deficient) levels (Zittermann et al. 2009) of 1,25(OH)2D3 (i.e. 10−13 M) may actually enhance adipogenic transdifferentiation, whereas high (sufficient) levels (i.e. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Fat infiltration within muscle is one of a number of features of vitamin D deficiency which leads to a decline in muscle functionality. The origin of this fat is unclear but one possibility is that it forms from myogenic precursor cells present in the muscle, which transdifferentiate into mature adipocytes. The current study examined the effect of the active form of vitamin D3, 1,25 dihydroxyvitamin D3 (1,25(OH)2D3), on the capacity of the C2C12 muscle cell line to differentiate towards the myogenic and adipogenic lineages. Cells were cultured in myogenic or adipogenic differentiation media containing increasing concentrations (0, 10-13, 10-11, 10-9, 10-7 or 10-5M) of 1,25(OH)2D3 for up to 6 days and markers of muscle and fat development measured.Mature myofibres were formed in both adipogenic and myogenic media, but fat droplets were only observed in adipogenic media. Relative to controls, low physiological concentrations (10-13 and 10-11M) of 1,25(OH)2D3 increased fat droplet accumulation, whereas high physiological (10-9M) and supraphysiological concentrations (≥10-7M) inhibited fat accumulation. This increased accumulation of fat with low physiological concentrations (10-13 and 10-11M) was associated with a sequential up-regulation of PPARγ2 and FABP4 mRNA, indicating formation of adipocytes, whereas higher concentrations (≥10-9M) reduced all these effects, and the highest concentration (10-5M) appeared to have toxic effects.This is the first study to demonstrate dose-dependent effects of 1,25(OH)2D3 on the transdifferentiation of muscle cells into adipose cells. Low physiological concentrations (possibly mimicking a deficient state) induced adipogenesis, whereas higher (physiological and supraphysiological) concentrations attenuated this effect.
    Journal of Endocrinology 01/2013; 217(1). DOI:10.1530/JOE-12-0234 · 3.72 Impact Factor
Show more