Determinants of circulating calcitriol in cardiovascular disease.

Circulating calcitriol may contribute to the risk of cardiovascular disease (CVD), but its regulation in patients with CVD is poorly characterized. We therefore aimed to assess determinants of circulating calcitriol in these patients. We analyzed 2183 independent samples from a large cohort of patients scheduled for coronary angiography and 1727 independent samples from different other cohorts from patients with a wide range of CVDs, including heart transplant candidates, to quantify the association of different parameters with circulating calcitriol. We performed univariable and multivariable linear regression analyses using the mathematical function that fitted best with circulating calcitriol. In the multivariable analysis of the large single cohort, nine parameters remained significant, explaining 30.0 % (32.4 % after exclusion of 22 potential outliers) of the variation in circulating calcitriol (r=0.548). Log-transformed 25-hydroxyvitamin D [25(OH)D] and log-transformed glomerular filtration rate were the strongest predictors, explaining 17.6 % and 6.6 %, respectively, of the variation in calcitriol. In the analysis of the combined other cohorts, including heart transplant candidates, the multivariable model explained a total of 42.6 % (46.1 % after exclusion of 21 potential outliers) of the variation in calcitriol (r=0.653) with log-transformed fibroblast growth factor-23 and log-transformed 25(OH)D explaining 29.0 % and 6.2 %, respectively. Circulating 25(OH)D was positively and FGF-23 inversely associated with circulating calcitriol. Although significant, PTH was only a weak predictor of calcitriol in both analyses (<2.5 %). In patients with CVD, FGF-23 and 25(OH)D are important independent determinants of circulating calcitriol. The relative importance of these two parameters may vary according to CVD severity. Future studies should focus on the clinical importance of regulating circulating calcitriol by different parameters.

An Intervention Trial for Strengthening Medical Adherence after Heart Transplantation.

INTRODUCTION: In heart transplant recipients, nonadherence is associated with higher risk of morbidity and mortality. RESEARCH QUESTION: Can a psychoeducational intervention enhance adherence to medical recommendations? DESIGN: We randomized 200 patients awaiting heart transplantation on the high urgency wait list to a manualized psychoeducational intervention or standard care. Follow-up continued to three years after transplantation. Primary endpoint was adherence to immunosuppressive medication, assessed at 3, 6, 12, 24, and 36 months posttransplant. Secondary endpoints were barriers to adherence during follow-up and clinical outcomes, including cardiac rejection within the first postoperative year and postoperative 3-year mortality. RESULTS: Fifty patients died before or within the first 3 months of transplantation. The primary endpoint was analyzed in 66 patients in the intervention group and 66 in the control group. Both study groups showed almost maximal adherence to immunosuppressive medication throughout follow-up, with no significant time x treatment interaction (P>0.99). Likewise, there was no significant time x treatment interaction (P=0.41) on barriers to adherence. The percentage of patients with International Society for Heart and Lung Transplantation standard grade 1 and 2 rejection was in the intervention and control groups 82.5% and 78.7%, respectively, and 8.8% and 13.1%, respectively, without significant differences between study groups (P=0.75). Considering all randomized and transplanted patients in the intervention group (N=85) and control group (N=87), postoperative 3-year mortality was 29.4% and 27.6%, respectively (P=0.82). CONCLUSIONS: Adherence to immunosuppressive medication was high, even without a complex, manualized psychoeducational intervention. The intervention had no significant positive impact on cardiac rejection and mortality.

Vitamin D supplementation of 4000 IU daily and cardiac function in patients with advanced heart failure: The EVITA trial.

BACKGROUND: Data regarding the effects of vitamin D on cardiac function are inconclusive. METHODS: In a post-hoc analysis of the EVITA (Effect of vitamin D on mortality in heart failure) trial, we investigated whether a daily vitamin D3 supplement of 4000 IU for three years affects echocardiography parameters like left ventricular end-diastolic diameter (LVEDD), LV end-systolic diameter (LVESD), and LV ejection fraction (LVEF) in patients with advanced heart failure (HF) and 25­hydroxyvitamin D levels <75 nmol/L. Of 400 patients enrolled, 199 were assigned to vitamin D and 201 to placebo. We assessed time × treatment interaction effects using linear mixed models and analyzed in subgroups vitamin D effects at 12 and 36 months post-randomization using analysis of covariance with adjustments for baseline values. RESULTS: At baseline, values of LVEDD, LVESD, and LVEF were 67.5 ±â€¯10.5 mm, 58.9 ±â€¯12.0 mm, and 30.47 ±â€¯10.2%, respectively. There were no time × treatment interaction effects on LV echocardiographic parameters in the entire study cohort, neither at 12 months nor at 36 months post-randomization (P-values > 0.05). However, in the subgroup of patients aged ≥50 years, vitamin D treatment was associated with an increase in LVEF of 2.73% (95%CI: 0.14 to 5.31%) at 12 months post-randomization (n = 311). The increase was slightly attenuated to 2.60% (95%CI: -2.47 to 7.67%) at 36 months post-randomization (n = 242). CONCLUSION: Our data indicate that vitamin D supplementation does not significantly improve cardiac function in all patients with advanced HF. However, vitamin D probably improves LV function in HF patients aged ≥50 years.

Vitamin D supplementation and bone turnover in advanced heart failure: the EVITA trial.

Low vitamin D status is common in patients with heart failure and may influence bone health. A daily vitamin D dose of 4000 IU (moderately high dose) for 3 years had however no effect on parameters of bone metabolism, even in patients with very low vitamin D status. INTRODUCTION: Low vitamin D status is common in patients with heart failure (HF) and has been related to disturbed bone turnover. The present study investigated the effect of a daily vitamin D3 dose of 4000 IU on bone turnover markers (BTMs) in patients with advanced HF and 25-hydroxyvitamin D (25OHD) concentrations < 75 nmol/L. METHODS: In this pre-specified secondary analysis of a randomized controlled trial, we assessed in 158 male HF patients (vitamin D group: n = 80; placebo group: n = 78) between-group differences in calciotropic hormones (25OHD, 1,25-dihydroxyvitamin D [1,25(OH)2D], intact parathyroid hormone [iPTH]), and BTMs (cross-linked C-telopeptide of type I collagen, bone-specific alkaline phosphatase, undercarboxylated osteocalcin). Comparisons were performed at the end of a 3-year vitamin D supplementation period with adjustments for baseline values. RESULTS: Compared with placebo, vitamin D increased 25OHD on average by 54.3 nmol/L. At study termination, 25OHD and 1,25(OH)2D were significantly higher (P < 0.001 and P = 0.007, respectively), whereas iPTH tended to be lower in the vitamin D group than in the placebo group (P = 0.083). BTMs were initially within their reference ranges and did not differ significantly between groups at study termination, neither in the entire study cohort nor when data analysis was restricted to the subgroup of patients with initial 25OHD concentrations < 30 nmol/L (n = 54) or to patients with initial hyperparathyroidism (n = 65) (all P values > 0.05). CONCLUSIONS: A daily vitamin D3 dose of 4000 IU did not influence BTMs. Data indicate that vitamin D supplementation will not lower bone turnover in male patients with heart failure.

Randomized supplementation of 4000 IU vitamin D3 daily vs placebo on the prevalence of anemia in advanced heart failure: the EVITA trial.

BACKGROUND: Low 25-hydroxyvitamin D (25OHD) levels (< 75 nmol/l) are inversely associated with anemia prevalence. Since anemia and low 25OHD levels are common in patients with heart failure (HF), we aimed to investigate whether vitamin D supplementation can reduce anemia prevalence in advanced HF. METHODS: EVITA (Effect of Vitamin D on Mortality in Heart Failure) is a randomized, placebo-controlled clinical trial in patients with initial 25OHD levels < 75 nmol/l. Participants received either 4000 IU vitamin D3 daily or a matching placebo for 36 months. A total of 172 patients (vitamin D group: n = 85; placebo group: n = 87) were investigated in this pre-specified secondary data analysis. Hemoglobin (Hb) and other hematological parameters were measured at baseline and study termination. Assessment of between-group differences in anemia prevalence and Hb concentrations was performed at study termination, while adjusting for baseline differences. RESULTS: In the vitamin D and placebo group, baseline proportions of patients with anemia (Hb < 12.0 g/dL in females and < 13.0 g/dL in males) were 17.2% and 10.6%, respectively (P = 0.19). At study termination, the proportion of patients with anemia in the vitamin D and placebo groups was 32.2% and 31.8%, respectively (P > 0.99). There was no between-group difference in change in the Hb concentrations (- 0.04 g/dL [95%CI:-0.53 to 0.45 g/dL]; P = 0.87). Results regarding anemia risk and Hb concentrations were similar in the subgroup of patients with chronic kidney disease (vitamin D group: n = 26; placebo group: n = 23). Moreover, results did not differ substantially when data analysis was restricted to patients with deficient baseline 25OHD levels. CONCLUSIONS: A daily vitamin D supplement of 4000 IU did not reduce anemia prevalence in patients with advanced HF. Data challenge the clinical relevance of vitamin D supplementation to increase Hb levels. TRIAL REGISTRATION: The study was registered at EudraCT (No. 2010-020793-42) and clinicaltrials.gov ( NCT01326650 ).

Adherence of Heart Transplant Recipients to Prescribed Medication and Recommended Lifestyle Habits.

INTRODUCTION: Nonadherence may cause severe health problems in heart transplant (HTx) recipients. RESEARCH QUESTIONS: The present study aimed to investigate adherence to prescribed medication and recommended lifestyle habits in post-HTx patients and to assess associations between adherence, quality of life (QOL), and psychological well-being. DESIGN: A questionnaire package was sent to all HTx patients from our clinic (n = 858) to answer questions anonymously on medication adherence, dietary recommendations (avoidance of raw animal products and ice cream), pet keeping (risk of zoonosis), anxiety and depression, QOL, and posttraumatic stress disorders. RESULTS: Of the contacted patients, 524 (61%) responded and 505 fulfilled the inclusion criteria (age ≥18 years and ability to understand German). Of the study participants, 72.4% reported taking their medications very correctly, 72.2% stated consuming alcohol less often than once a week, 58.3% performed physical exercise at least once a week, one-third reported eating nonrecommended foods, 22.1% stated pet keeping, and 4.3% reported smoking. Adherence to prescribed medication was positively associated with age ( P < .001) and mental QOL ( P = .015) but was unrelated to eating nonrecommended foods ( P > .05). Depressiveness correlated inversely with physical QOL ( r = -0.232; P < .01) and mental QOL ( r = -0.411; P < .01). Stress disorders and minor stressful events were reported by 7.8% and 46.6%, respectively. Stress disorders correlated inversely with mental QOL ( r = -0.282; P < .01) and physical QOL ( r = -0.422; P < .01). DISCUSSION: Many HTx patients adhere to prescribed medications and health advice. Nevertheless, nonadherence is a problem, especially in younger HTx patients, indicating the need for a nonadherence crisis intervention program for long-term HTx patients.

Independent associations of vitamin D metabolites with anemia in patients referred to coronary angiography: the LURIC study.

PURPOSE: Anemia and vitamin D deficiency are both frequent in adult patients. Whether low vitamin D metabolite levels are an independent risk factor for different subtypes of anemia remains to be studied in detail. METHODS: In 3299 patients referred for coronary angiography, we investigated the association of 25-hydroxyvitamin D (25OHD) and 1,25-dihydroxyvitamin D [1,25(OH)2D] with anemia [hemoglobin (Hb) <12.5 g/dl] of specific subtypes. RESULTS: Compared with patients with 25OHD levels in the adequate range (50-125 nmol/l), patients with deficient 25OHD concentrations (<30 nmol/l; 33.6 % of patients) had 0.6 g/dl lower Hb levels. Hb values were 1.3 g/dl lower in patients with 1,25(OH)2D levels <40 pmol/l (5.4 % of patients), compared with patients in the highest 1,25(OH)2D category (>70 pmol/l). Of the participants, 16.7 % met the criteria for anemia. In multivariate-adjusted regression analyses, the odds ratios for anemia in the lowest 25OHD and 1,25(OH)2D categories were 1.52 (95 % CI 1.15-2.02) and 3.59 (95 % CI 2.33-5.52), compared with patients with 25OHD levels in the adequate range and patients with 1,25(OH)2D levels >70 pmol/l. The probability of anemia was highest in patients with combined 25OHD and 1,25(OH)2D deficiency [multivariable-adjusted odds ratio 5.11 (95 % CI 2.66-9.81)]. Patients with anemia of chronic kidney disease had the highest prevalence of 25OHD deficiency and 1,25(OH)2D concentrations of <40 pmol/l. CONCLUSIONS: Low 25OHD and 1,25(OH)2D concentrations are independently associated with anemia. Patients with poor kidney function are most affected. Interventional trials are warranted to prove whether administration of plain or activated vitamin D can prevent anemia.

Calciotropic and phosphaturic hormones in heart failure.

AIMS: Despite adherence to evidence-based guidelines, heart failure [HF] still results in 5-year mortality rates of 50%, indicating a need to implement additional preventive/intervention strategies. This review summarizes data on alterations in the calciotropic and phosphaturic hormones 1,25-dihydroxyvitamin D [1,25(OH)2D] and fibroblast growth factors-23 [FGF-23] in HF and discusses non-pharmacological measures for targeting these hormones. DATA SYNTHESIS: The role of 1,25(OH)2D in the regulation of calcium and phosphate homeostasis is central. 1,25(OH)2D also plays a pivotal role in cardiac function, but is downregulated by FGF-23. There is accumulating evidence from epidemiological data that HF is associated with decreased circulating 1,25(OH)2D and elevated FGF-23 levels. In patients with failing hearts, very low 1,25(OH)2D and extremely high FGF-23 levels have been reported. Experimental data support the assumption that vitamin D deficiency and high serum phosphate/FGF-23 levels increase the risk of HF. This review provides a hypothesis of how vitamin D deficiency, high calcium/phosphorus intake, physical inactivity, and age-related renal impairment may all contribute to HF by adversely affecting calcium- and phosphate-regulating hormones. Several case series in infants and a meta-analysis of randomized controlled trials in adults have already reported successful treatment of or a significant risk reduction in HF by vitamin D supplements. The association of calcium/phosphorus intake, physical activity, or renal function with calciotropic/phosphaturic hormones and HF is however less well documented. CONCLUSIONS: More attention should be paid in future to the association of circulating 1,25(OH)2D and FGF-23 levels with HF and to (non-pharmacological) measures for targeting these calciotropic/phosphaturic hormones.

Vitamin D metabolites and fibroblast growth factor-23 in patients with left ventricular assist device implants: association with stroke and mortality risk.

PURPOSE: Stroke and mortality risk in patients with left ventricular assist device (LVAD) implants continue to be high. Whether nonclassical cardiovascular risk markers such as vitamin D metabolites and fibroblast growth factor (FGF)-23 contribute to this risk remains to be studied, and this was the objective of our work. METHODS: In 154 LVAD patients (91 HeartWare and 63 HeartMate II implants), we measured circulating 25-hydroxyvitamin D (25OHD), 1,25-dihydroxyvitamin D3 (1,25[OH]2D3), parathyroid hormone (PTH) and FGF-23 shortly before LVAD implantation and investigated their association with stroke and mortality risk during 1-year follow-up. RESULTS: Of the study cohort, 34.4 and 92.2%, respectively, had deficient 25OHD (<25 nmol/l) and 1,25(OH)2D3 (<41 pmol/l) values, whereas 42.6 and 98.7%, respectively, had elevated PTH levels (>6.7 pmol/l) and FGF-23 values above the reference range (100 RU/ml). One-year freedom from stroke was 80.9 %, and 1-year survival was 64.3%. The multivariable-adjusted hazard ratio of stroke was 2.44 (95% CI: 1.09-5.45; P = 0.03) for the subgroup of 25OHD levels <25 nmol/l (reference group: 25OHD levels ≥25 nmol/l). The multivariable-adjusted hazard ratio of 1-year mortality was 2.78 (95% CI: 1.52-5.09; P = 0.001) for patients with 25OHD levels <25 nmol/l compared with patients with 25OHD levels ≥25 nmol/l. PTH, FGF-23 and 1,25(OH)2D3 were not associated with stroke or mortality risk. CONCLUSIONS: In LVAD patients, deficient 25OHD levels are independently associated with high stroke and mortality risk. If confirmed in randomized controlled trials, preoperative correction of deficient vitamin D status could be a promising measure to reduce stroke and mortality risk in LVAD patients.

Donor-Derived Cell-Free DNA Is a Novel Universal Biomarker for Allograft Rejection in Solid Organ Transplantation.

BACKGROUND: In solid organ transplantation, sensitive real-time biomarkers to assess the graft health are desirable to enable early intervention, for example, to avoid full-blown rejections. During rejection, high amounts of graft-derived cell-free DNA (GcfDNA) are shed into the blood stream. The quantification of this GcfDNA in allotransplantation is considered to fulfill this need, because it can be measured with great precision and at reasonable cost. PATIENTS AND METHODS: Patients from 2 ongoing studies in kidney (KTx) and heart (HTx) transplantation were monitored blinded on a scheduled basis, by means of a published universal droplet digital polymerase chain reaction to quantify the GcfDNA. RESULTS: Immediately after engraftment, GcfDNA reaches high values (>5% of total cfDNA), with a rapid decrease to values of <0.5% within 1 week. Living-related KTx recipients show lower initial values, reflecting the absence of preservation injury. Episodes of rejection in KTx and HTx are accompanied by a significant increase of GcfDNA (>5-fold) above values in patients without complications, occurring earlier than clinical or biochemical hints to rejection. One case of rejection, which became clinically suspect after 1 year and was proven with biopsy, showed a significant 10-fold increase 3 months earlier. CONCLUSIONS: The quantification of GcfDNA has the potential to detect rejection episodes at early stages, when other means of diagnosis are not effective. The method's noninvasiveness enables the monitoring recipients at intervals that are desired to catch rejections at early actionable stages to prevent full-blown rejection. This biomarker will be particularly valuable in regimens to minimize immunosuppression.

Association between circulating 25-hydroxyvitamin D levels and medication use in patients scheduled for cardiac surgery.

BACKGROUND AND AIM: Low vitamin D status, i.e. circulating 25-hydroxyvitamin D (25OHD) levels <50 nmol/l, is independently associated with increased CVD risk. Medication use may influence 25OHD levels. We therefore investigated the association of circulating 25OHD with medication use in patients scheduled for cardiac surgery. METHODS AND RESULTS: A total of 11,256 patients were included in this cross-sectional study. We compared 25OHD levels of medication users (18 groups of continuously used and 5 groups of intermittently used medications) with levels of non-users. Moreover, we assessed variables (medications, demographic and clinical parameters) that were independently associated with 25OHD levels <50 nmol/l. The prevalence of 25OHD levels <50 nmol/l was 65.7%. The use of statins and immunosuppressive agents was significantly associated with higher 25OHD levels and lower odds ratios of 25OHD levels <50 nmol/l. The use of ACE-inhibitors, catecholamines and antibiotics was associated with lower 25OHD levels and higher odds ratios of 25OHD levels <50 nmol/l. However, only use of antibiotics, immunosuppressive agents and catecholamines showed clinically relevant differences in 25OHD levels, i.e. differences of more than +4 nmol/l or -4 nmol/l, compared with respective non-users. These medications were prescribed either intermittently (antibiotics, catecholamines) and/or infrequently (<2%; immunosuppressive agents, catecholamines) and/or its causal relationship with circulating 25OHD is questionable (antibiotics). Female sex and blood drawing during wintertime were associated with the highest odds ratios of 25OHD levels <50 nmol/l. CONCLUSION: Data indicate that in patients with high cardiovascular risk profile medication use does not substantially contribute to 25OHD levels <50 nmol/l.

Body mass index, cardiac surgery and clinical outcome. A single-center experience with 9125 patients.

BACKGROUND AND AIM: There is evidence for a J-shaped association between Body Mass Index (BMI) and all-cause mortality in general populations. In cardiac surgical patients, the effect of BMI on mortality and major adverse cardiac and cerebrovascular events (MACCE) is not completely clear. METHODS AND RESULTS: We investigated the effect of BMI on MACCE (primary endpoint), as well as intensive care unit (ICU)-related outcomes and mid-term mortality in 9125 consecutive patients who were operated on at our institution between July 2009 and July 2012. Of the study cohort, 3.0% were underweight (BMI < 20 kg/m(2)), 28.0% had a normal BMI (20-24.99 kg/m(2)), 43.1% were overweight (BMI 25-29.99 kg/m(2)), 19.3% were obese (BMI 30-34.99 kg/m(2)), and 6.6% were severely obese (BMI ≥ 35 kg/m(2)). Compared with overweight patients (lowest incidence of MACCE), the multivariable-adjusted odds ratio of MACCE in severely obese patients was 1.39 (95% CI: 1.03-1.87). Underweight and severely obese patients had the longest risk-adjusted duration of mechanical ventilator support and ICU stay (P-values 0.004-0.001). The red blood cell concentrates requirement was highest in underweight patients (P < 0.001). Compared with normal and overweight patients, the multivariable-adjusted hazard ratio of 2-year mortality was higher in underweight patients (1.72 [95% CI: 1.26-2.36] and =2.07 [95% CI: 1.51-2.83], respectively), but did not differ significantly in severely obese patients. CONCLUSION: Data demonstrate that both severe obesity and underweight are independent risk factors for operative complications in cardiac surgical patients. With respect to mid-term survival, special attention should be paid to underweight patients scheduled for cardiac surgery.

Clinical outcome in cardiac transplant recipients receiving tacrolimus retard.

Tacrolimus (TAC) retard is a new oral formulation of TAC that is given once instead of twice daily. We investigated the efficacy and safety of TAC retard in heart transplant recipients during a 36-month follow-up period. We included 11 patients receiving TAC retard (once-daily [OD] group) and 11 age- and sex-matched patients receiving TAC (twice-daily [TD] group). The primary endpoint was a composite of death, graft loss, and drug discontinuation (treatment failure). Secondary endpoints were biopsy-proven rejection, malignancy, infection, and safety parameters determined on the basis of laboratory evaluations. In the OD and TD groups, the primary endpoint was reached by 18.2% and 45.54% of patients, respectively (P = .277). In detail, 3-year survivals were 90.0% and 70.0% (P = .291) and freedom from drug discontinuation 90.9% and 77.9% (P = .533), respectively. Freedom from biopsy-proven rejection, malignancy, and infection were similar between the groups. Moreover, biochemical parameters of kidney and liver function, hematologic parameters, and C-reactive protein levels were similar. Despite a remarkably higher prescribed dose, blood trough levels of TAC were below the lower target value in several patients of the OD group at the end of the follow-up period, but in none of the patients in the TD group. In conclusion, this small 3-year follow-up study suggests efficacy and safety in patients receiving TAC retard similar to those in patients receiving TAC. Nevertheless, the required dose of TAC retard for achieving acceptable blood trough levels should be investigated in more detail.

[Postoperative assessment of daily energy expenditure. Comparison of two methods]. / Postoperative bestimmung des täglichen energiebedarfs. Vergleich von zwei methoden.

BACKGROUND: The reference method for determining resting energy expenditure (REE) in clinical nutrition practice is measurement by indirect calorimetry; however, indirect calorimetry has some limitations, is expensive and not widely available. Therefore, the most used methods to estimate the caloric requirements in intensive care patients are predictive equations. The Harris-Benedict equations (HBE) are the most common formulae in the clinical setting. The SenseWear(®) armlet (SWA) is a noninvasive device that monitors skin temperature, heat flux, galvanic skin response and movement. These data as well as anthropometric characteristics are used to calculate REE. The aim of this study was to evaluate the levels of agreement and interchangeability of REE estimated by HBE (EEHBE) and measured by SWA (EESWA) in normometabolic patients after elective bowel resection with laparotomy. Furthermore, postsurgical pain therapy by continuous thoracic epidural anaesthesia (t-PDA) was compared with continuous intravenous pain therapy regarding EESWA in these patients. METHODS: After obtaining approval by the ethics committee and written informed consent 57 patients participated in the study procedures. A total of 50 patients (23 male, 27 female) were finally included in the data analysis because 7 patients did not meet the criterion of > 80% on-body time of the SWA. Additional (a priori) exclusion criteria were metabolic or cardiopulmonary decompensation or postoperative mechanical ventilation. Before induction of general anesthesia 26 patients received a thoracic epidural catheter. Immediately after surgery the SWA was placed on the right upper arm of each patient for 24 h. A continuous pain therapy was started either an epidural application of ropivacain 0.2% and sufentanil or in the other 24 patients an intravenous infusion of metamizol and tramadol. RESULTS AND DISCUSSION: The data showed good agreement between EESWA and EEHBE. The mean on-body time was found to be 22.94±4.77 h. There were no significant differences between EESWA and EEHBE (p>0.05) corresponding to a high Pearson's coefficient of correlation of 0.985. The mean bias (EESWA-EEHBE) was -0.569±0.378 kcal/kgBW/24 h reflecting a minimal systematic underestimation of REE by SWA of -2.9% compared to EEHBE. The Bland-Altman plot shows interchangeability of EESWA and EEHBE. It was noted that 94% of the data points (47 out of 50 patients) were within ±2 SD and the remaining 3 data points were lying close to the 95% interval. The same results (no significant differences between EESWA and EEHBE) were obtained after differentiation of EEHBE into low (<18 kcal/kgBW/24 h, n=9), medium (18-21 kcal/kgBW/24 h, n=30) and high (>21 kcal/kgBW/24 h, n=11) energy ranges. There were no significant differences in EESWA regarding postsurgical pain therapy regimens. CONCLUSIONS: The SWA showed reliable concordance with daily REE estimated by HBE in normometabolic postsurgery patients. This noninvasive, convenient and easy to handle device may be helpful in determining energy requirements as part of metabolic monitoring. Further research is needed to validate the method in patients with severe metabolic disturbances. The energetic requirements of patients with postoperative t-PDA were not different from those with intravenous pain therapy.

Moderate dosage of tranexamic acid during cardiac surgery with cardiopulmonary bypass and convulsive seizures: incidence and clinical outcome.

BACKGROUND: Convulsive seizures (CS) occur in ∼1% of the patients after cardiac surgery with cardiopulmonary bypass. Recent investigations indicate an up to seven-fold increase in CS in cardiac surgical patients receiving high doses (≥60 mg kg(-1) body weight) of tranexamic acid (TA). METHODS: In a retrospective data analysis of 4883 cardiac surgical patients, we investigated the incidence of CS in patients receiving a moderate dose of TA (24 mg kg(-1) body weight) compared with a reference group not receiving TA as a primary endpoint. Secondary endpoints were intensive care unit stay and in-hospital mortality. We performed propensity score (PS)-adjusted logistic regression analysis to test the association between TA use/non-use and clinical outcomes. RESULTS: Compared with the reference group, the PS-adjusted odds ratio (OR) for CS in the TA group was 1.703 [95% confidence interval (CI): 1.01-2.87; P=0.045; incidence 2.5% vs 1.2%]. Log-ICU-stay was significantly longer (P=0.004) and PS-adjusted relative in-hospital mortality risk was significantly higher for the TA group compared with the reference group (OR=1.89; 95% CI: 1.21-2.96; P=0.005). Both the TA-associated CS incidence and the in-hospital mortality risk were only significant in patients undergoing open-heart surgery (OR=2.034, 95% CI: 1.07-3.87; P=0.034 and OR=2.20, 95% CI: 1.32-3.69; P=0.003, respectively) but not in patients undergoing coronary artery bypass grafting (OR=1.21, 95% CI: 0.49-3.03; P=0.678 and OR=1.13, 95% CI: 0.42-3.02; P=0.809, respectively). CONCLUSIONS: In open-heart surgery, even moderate TA doses are associated with a doubled rate of CS and in-hospital mortality. Prospective trials are needed to further evaluate the safety profile of TA in cardiac surgery.

Vitamin D: do we get enough? A discussion between vitamin D experts in order to make a step towards the harmonisation of dietary reference intakes for vitamin D across Europe.

UNLABELLED: On September 29, 2011, acknowledged experts in the field of vitamin D, mainly European, were brought together in order to discuss the recent scientific advances in relation to vitamin D: the current requirements and associations with various health outcomes. In this article, the discussions resulting from the meeting are summarized. INTRODUCTION: Several groups at risk for developing vitamin D insufficiency have been identified. Accordingly, reviews indicate that a significant percentage of the population worldwide have serum 25-hydroxyvitamin D levels below 50 nmol/l. In addition to the role of vitamin D in bone health, recent studies suggest that it may play a pivotal role in other systems, e.g., the cardiovascular system, pancreas, muscle, immune system and brain. Most evidence, however, is obtained from observational studies and yet inconclusive. METHODS: To exchange and broaden knowledge on the requirements for vitamin D and its effect on various health outcomes, a workshop entitled "Vitamin D Expert Meeting: Do we get enough?", was organized. RESULTS: Despite low vitamin D levels worldwide, consensus on the definition of deficiency is not yet reached. In order to define cut-off points for vitamin D whilst taking into account extraskeletal health effects, randomized controlled trials in these fields are warranted. The experts do emphasize that there is evidence to suggest an important role for vitamin D in the maintenance of optimal bone health at all ages and that vitamin D supplementation, in most studies co-administered with calcium, reduces fracture risk in the senior population. CONCLUSION: To reach a serum 25-hydroxyvitamin D level of 50 nmol/l older adults aged ≥65 years are therefore recommended to meet a mean daily vitamin D intake of 20 µg (800 IU), which is best achieved with a supplement.

Future directions in vitamin D and cardiovascular research.

AIMS: Evidence is accumulating that vitamin D status may influence the risk of cardiovascular disease (CVD). Final confirmation for a causal relationship between vitamin D and CVD is however still lacking. The present viewpoint article outlines several future research directions to close this gap. DATA SYNTHESIS: Future directions include the need of performing large randomised controlled supplementation trials with vitamin D in specific risk groups. In addition, large register sets of data on vitamin D supplementation can be used, provided that adequate statistical methods such as propensity score modelled analysis are applied. To better understand vitamin D-mediated effects on CVD risk, the routine measurement of circulating levels of the hormonal vitamin D form, 1,25-dihydroxyvitamin D, is also necessary, in addition to the determination of its precursor 25-hydroxyvitamin D. Further, genetic association studies may help in clarifying the contribution of vitamin D to the development of CVD. Finally, the interrelationship of vitamin D with physical activity should be considered when studying CVD risk. CONCLUSIONS: Overall, it can be expected that the next 10-15 years will provide an increased clarity concerning the role of vitamin D in CVD.