Circulating Calcitriol Concentrations and Total Mortality
ABSTRACT 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.
Full-textDOI: · Available from: Armin Zittermann, Jan 06, 2014
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ABSTRACT: Circulating 25-hydroxyvitamin D [25(OH)D] is the hallmark for determining vitamin D status. Serum parathyroid hormone [PTH] increases progressively when 25(OH)D falls below 75 nmol/l. Concentrations of 25(OH)D below 50 nmol/l or even below 25 nmol/l are frequently observed in various population groups throughout the world. This paper highlights the relationship of vitamin D insufficiency with cardiovascular disease and non-insulin dependent diabetes mellitus, two diseases that account for up to 50% of all deaths in western countries. There is evidence from patients with end-stage renal disease that high PTH concentrations are causally related to cardiovascular morbidity and mortality. Activated vitamin D is able to increase survival in this patient group significantly. Moreover, already slightly enhanced PTH concentrations are associated with ventricular hypertrophy and coronary heart disease in the general population. Experimental studies have demonstrated that a lack of vitamin D action leads to hypertension in mice. Some intervention trials have also shown that vitamin D can reduce blood pressure in hypertensive patients. In young and elderly adults, serum 25(OH)D is inversely correlated with blood glucose concentrations and insulin resistance. Sun-deprived lifestyle, resulting in low cutaneous vitamin D synthesis, is the major factor for an insufficient vitamin D status. Unfortunately, vitamin D content of most foods is negligible. Moreover, fortified foods and over-the-counter supplements usually contain inadequate amounts of vitamin D to increase serum 25(OH)D to 75 nmol/l. As a consequence, legislation has to be changed to allow higher amounts of vitamin D in fortified foods and supplements.Progress in Biophysics and Molecular Biology 10/2006; 92(1):39-48. DOI:10.1016/j.pbiomolbio.2006.02.001 · 3.38 Impact Factor
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ABSTRACT: There has been an emphasis over the last several years to identify and treat chronic kidney disease (CKD) and its complications as they evolve rather than waiting until the patient reaches end-stage renal disease (ESRD), also known as CKD stage 5. The number of patients who will be identified and prescribed therapies for complications such as secondary hyperparathyroidism (SHPT) is greater than initially proposed. To review the pathways, complications, management, and estimated treatment costs of CKD-related SHPT. An electronic literature search of MEDLINE (January 1980 through January 2007) was conducted for English-language publications using the base search term secondary hyperparathyroidism. To refine subsequent searches, the authors added Boolean operators to the following secondary and tertiary search terms: parathyroid hormone, chronic kidney disease, renal osteodystrophy, adynamic bone disease, vascular calcification, cardiovascular disease, vitamin D, vitamin D analogs, hypercalcemia, hyperphosphatemia, calcimimetics, costs, prevalence, and economics. The initial MEDLINE search produced 278 relevant articles. After refining the search terms, the authors triaged the results for English-language publications relevant to the discussion of SHPT and its complications in CKD, eliminating 149 publications. The remaining 129 publications were accepted for review. These articles represent a growing body of primarily observational evidence that demonstrates that elevated intact parathyroid hormone (PTH) levels cause deleterious physiological results across a variety of organ systems, including the cardiovascular and skeletal systems. Specific complications associated with SHPT are left ventricular hypertrophy (LVH), renal osteodystrophy (ROD), and extraskeletal calcification. Medical management of the PTH/vitamin D/calcium and phosphorus imbalances in SHPT focus on regulating PTH levels via vitamin D therapy. The class of calcimimetics is a newer treatment modality that has favorable effects on biochemical laboratory values, such as serum calcium and phosphorus levels, but current data do not show differences on hard endpoint patient-oriented outcomes compared with standard generic agents. The direct drug costs in April 2007 U.S. dollars of treating CKD-associated elevations in PTH in predialysis patients range from $8.40 per patient per week ($437 per year) for oral generic calcitriol to $88.90 per patient per week ($4,623 per year) for oral paricalcitol (expressed as 85% of average wholesale price [AWP] for brand drugs or 70% of AWP for generic drugs). The direct drug costs of treating SHPT in hemodialysis patients range from $80.20 per patient per week ($4,170 per year) for generic calcitriol (IV) to $278.46 per patient per week ($14,480 per year) for oral cinacalcet. SHPT causes skeletal and cardiovascular complications in CKD patients. Calcitriol therapy is effective in managing PTH levels, but efforts to reduce the associated hypercalcemia and hyperphosphatemia have led to the development of newer, yet more expensive, vitamin D analogs. With the lack of evidence to support comparative superior outcomes in end-organ disease among SHPT therapy alternatives, future research is still needed to clearly identify which newer agents are most competitive with the historical gold standard of calcitriol therapy.Journal of managed care pharmacy: JMCP 07/2007; 13(5):397-411. · 2.68 Impact Factor
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ABSTRACT: Hyperparathyroidism occurs in most patients during the progression of chronic kidney disease (CKD) and one of its initiating events, reduced serum levels of 1,25-dihydroxyvitamin D, results from a decrease in renal 1alpha hydroxylase activity, which converts 25-hydroxyvitamin D to its activated form. The combination of persistently high parathyroid hormone (PTH) and low 1,25-dihydroxyvitamin D is associated with bone loss, cardiovascular disease, immune suppression and increased mortality in patients with end-stage kidney failure. Recent studies in dialysis patients suggest that paricalcitol, a selective activator of the vitamin D receptor (VDR), is associated with a more favorable efficacy to side effect profile than calcitriol, with less morbidity and better survival. One hypothesis derived from such studies suggests that systemic activation of VDRs may have direct effects on the cardiovascular system to decrease mortality in CKD. Although current guidelines for regulating serum calcium, phosphate and PTH recommend specific interventions at the various stages of CKD to prevent or postpone irreversible parathyroid disease and decrease cardiovascular morbidity and mortality, emerging data suggest that vitamin D therapy may prolong survival in this patient population by mechanisms that are independent of calcium, phosphate and PTH. It is suggested that a re-evaluation of current treatment recommendations is needed and that future research should focus on mechanisms that distinguish potential tissue specific benefits of selective VDR activators in patients with CKD.Kidney International 02/2006; 69(1):33-43. DOI:10.1038/sj.ki.5000045 · 8.52 Impact Factor