Reiner Koerfer

Vitamin D supplementation enhances the beneficial effects of weight loss on cardiovascular disease risk markers

BACKGROUND High blood concentrations of parathyroid hormone and low concentrations of the vitamin D metabolites 25-hydroxyvitamin D [25(OH)D] and calcitriol are considered new cardiovascular disease risk markers. However, there is also evidence that calcitriol increases lipogenesis and decreases lipolysis. OBJECTIVE We investigated the effect of vitamin D on weight loss and traditional and nontraditional cardiovascular disease risk markers in overweight subjects. DESIGN Healthy overweight subjects (n = 200) with mean 25(OH)D concentrations of 30 nmol/L (12 ng/mL) received vitamin D (83 microg/d) or placebo in a double-blind manner for 12 mo while participating in a weight-reduction program. RESULTS Weight loss was not affected significantly by vitamin D supplementation (-5.7 +/- 5.8 kg) or placebo (-6.4 +/- 5.6 kg). However, mean 25(OH)D and calcitriol concentrations increased by 55.5 nmol/L and 40.0 pmol/L, respectively, in the vitamin D group but by only 11.8 nmol/L and 9.3 pmol/L, respectively, in the placebo group (P < 0.001), whereas a more pronounced decrease occurred in the vitamin D group than in the placebo group in blood concentrations of parathyroid hormone (-26.5% compared with -18.7%; P = 0.014), triglycerides (-13.5% compared with +3.0%; P < 0.001), and the inflammation marker tumor necrosis factor-alpha (-10.2% compared with -3.2%; P = 0.049). The beneficial biochemical effects were independent of the loss in body weight, fat mass, and sex. However, compared with placebo, vitamin D supplementation also increased LDL-cholesterol concentrations (+5.4% compared with -2.5%; P < 0.001). CONCLUSIONS The results indicate that a vitamin D supplement of 83 microg/d does not adversely affect weight loss and is able to significantly improve several cardiovascular disease risk markers in overweight subjects with inadequate vitamin D status participating in a weight-reduction program. This trial was registered at clinicaltrials.gov as NCT00493012.

Putting cardiovascular disease and vitamin D insufficiency into perspective.

The aetiology of CVD is still not completely understood. The present review article summarises data supporting the hypothesis that an insufficient vitamin D status may contribute to the worldwide high prevalence of CVD. Human vitamin D status primarily depends on skin exposure to the UVB spectrum of the sunlight. Epidemiological data indicate that geographic latitude, altitude, season, and the place of residence (urban or rural) are associated with CVD mortality. Interestingly, all these factors also have an influence on human UVB exposure and thus on vitamin D status. Several mechanisms might be responsible for a protective role of vitamin D in CVD. These mechanisms include the inhibition of vascular smooth muscle proliferation, the suppression of vascular calcification, the down regulation of pro-inflammatory cytokines, the up regulation of anti-inflammatory cytokines, and the action of vitamin D as a negative endocrine regulator of the renin-angiotensin system. The first intervention trials indicate that vitamin D may suppress cardiovascular risk markers. However, more controlled clinical trials are needed to investigate whether optimal oral vitamin D supplementation is able to reduce CVD morbidity and mortality.

Vitamin D and vascular calcification

Purpose of review Vascular calcification is frequently found in patients with osteoporosis, atherosclerosis and chronic kidney disease, leading to high morbidity and mortality rates. The effects of vitamin D excess and deficiency on vascular calcification are reviewed in this article. Recent findings There is evidence from experimental studies that mediacalcinosis induced by vitamin D excess is an active and reversible process. Vitamin D excess, however, is rarely seen in the general human population. Experimental data also demonstrate that physiologic vitamin D actions include the inhibition of processes that are important for intimal and medial artery calcification such as pro-inflammatory cytokine release, adhesion molecule release, and proliferation and migration of vascular smooth muscle cells. In uremic rats, low levels of the vitamin D hormone calcitriol are associated with massive vascular and soft tissue calcifications. Whereas retrospective studies already indicate a beneficial effect of active vitamin D on mortality rates in chronic kidney disease, little is yet known about the effect of vitamin D deficiency on cardiovascular morbidity and mortality in the general population. Summary Available data indicate that vitamin D exerts a biphasic ‘dose response’ curve on vascular calcification with deleterious consequences not only of vitamin D excess but also of vitamin D deficiency.

Poor outcome in end‐stage heart failure patients with low circulating calcitriol levels

Vitamin D receptor knockout mice develop typical signs of congestive heart failure (CHF). In approximately 20% of stable CHF patients, frankly low concentrations of the vitamin D hormone calcitriol are found.

Vitamin D insufficiency in congestive heart failure: why and what to do about it?

This article gives an overview of the current knowledge on vitamin D status in patients with congestive heart failure (CHF). A serum 25-hydroxyvitamin D level below 50 nmol/l (20 ng/ml) is generally regarded as insufficient. Available data indicate that the majority of CHF patients have 25-hydroxyvitamin D levels in the insufficiency range. Skin synthesis of vitamin D after solar ultraviolet B exposure is the most important vitamin D source for humans. However, CHF patients have relatively low outdoor activities. Consequently, a disease-related sedentary lifestyle is an important cause for the insufficient vitamin D status in CHF patients. There is also evidence from a recently performed case-controlled study that indicators of ultraviolet B exposure are already reduced in CHF patients during childhood, adolescence, and early adulthood compared to healthy controls. We present results indicating that an insufficient vitamin D status may contribute to the etiology/pathogenesis of CHF. Data include a vitamin D-mediated reduction of elevated blood pressure as well as a vitamin D-mediated prevention of enhanced parathyroid hormone levels, a pathophysiological state that contributes to cardiovascular disease. Based on population attributable risks, hypertension and cardiovascular disease have a high impact, accounting for the majority of CHF events.Theoretically, vitamin D status can be improved by adequate skin synthesis of vitamin D and/or adequate oral vitamin D intake. At present, daily oral intake of 50–100μ g vitamin D seems to be the most effective way to improve vitamin D status in CHF patients.

Bovine valved venous xenografts for RVOT reconstruction: results after 71 implantations

BACKGROUND Pediatric right ventricular outflow tract (RVOT) reconstruction with homo- or porcine xenografts is problematic because of limited availability, lack of material for reconstruction, early degeneration, and tissue ingrowth. Contegra, a bovine jugular vein graft, might be an interesting alternative to overcome these problems. PATIENTS AND METHODS Within a Federal Drug Administration controlled study, we implanted 71 Contegra pulmonary valved conduits from May 1999 to September 2001 in 71 patients (male/female 33/38) in the age range 2 days-17.4 years, median 1.2 years. Twenty five were primary repairs, 22 had previous graft implantations, and 24 had other repairs/palliations. Preoperative diagnoses: truncus arteriosus communis (19 patients), tetralogy of Fallot (32), double outlet right ventricle (13), transposition of the great arteries (5), and two rare complex malformations. The size of implanted Contegra conduits ranged from 12 to 22 mm. Echocardiography was performed at 1 and 3 months, and then every 3 months postoperatively. Follow-up time was 27 months (maximal), 80 years in total. Results were compared with our 52 homograft- and 30 Tissuemed porcine xenograft recipients. RESULTS Contegra enables the surgeon to perform all anastomoses without additional material. Its tissue is very apt for suturing and its insufficiencies are common, but without clinical significance or tendency to increase. We saw no sign of conduit or valve degeneration during the whole follow-up up to 27 months. There were no device related adverse events. Redos: five for peripheral pulmonary arteries, two residual ventricular septum defect (VSD) closures. There were six deaths (five early, one late). The maximal transvalvular gradients of 25-42 mmHg were measured in seven patients; these gradients did not increase further during the follow-up. Six patients with completely intact Contegra conduits developed pressure gradients of more than 70 mmHg immediately distal from the conduit. At 27 months, Contegra grafts were advantageous compared to homografts with respect to survival and freedom from explantation. Right ventricle to left ventricle (RV/LV) ratio development and freedom from explantation/redo were equal for Contegra conduits and homografts. Porcine Tissuemed xenografts were significantly inferior. CONCLUSION The Contegra conduit offers unique tailoring and suturing options for primary and redo RVOT reconstruction. At 27 months, its durability seems at least equivalent to homografts and is superior to porcine Tissuemed xenografts.

European experience of DuraHeart™ magnetically levitated centrifugal left ventricular assist system

OBJECTIVE The DuraHeart (Terumo Heart, Inc., Ann Arbor, Michigan, USA) is the worlds first approved magnetically levitated centrifugal left ventricular assist system designed for long-term circulatory support. We report the clinical outcomes of 68 patients implanted with the DuraHeart as a bridge to cardiac transplantation in Europe. METHODS Sixty-eight patients with advanced heart failure (six females), who were eligible for cardiac transplantation were implanted with the DuraHeart between January 2004 and July 2008. Median age was 58 (range: 29-74) years with 31% over 65 years. Thirty-three of these patients received the device as a part of the European multi-center clinical trial. Survival analyses were conducted for 68 patients and other safety and performance data were analyzed based on 33 trial patients. RESULTS Mean support duration was 242+/-243 days (range: 19-1148, median: 161) with a cumulative duration of 45 years. Thirty-five patients (51%) remain ongoing, 18 transplanted, 1 explanted, and 14 died during support with a median time to death of 62 days. The Kaplan-Meier survival rate during support was 81% at 6 months and 77% at 1 year. Of the 13 patients (21%) supported for >1 year, 4 supported for >2 years, 1 supported >3 years, 2 transplanted, 2 died, and 9 ongoing with a mean duration of 744+/-216 days (range: 537-1148, median: 651). Major adverse events included driveline/pocket infection, stroke, bleeding, and right heart failure. There was no incidence of pump mechanical failure, pump thrombosis, or hemolysis. CONCLUSIONS The DuraHeart was able to provide safe and reliable long-term circulatory support with an improved survival and an acceptable adverse event rate in advanced heart failure patients who were eligible for transplantation.

Vitamin D in the prevention and treatment of coronary heart disease

Purpose of reviewThe pathogenesis of coronary heart disease is of multifactorial origin. Probably, not all risk factors are satisfactorily understood. This article outlines beneficial vitamin D effects on cardiac function and the vasculature. In addition, human data associating serum vitamin D metabolite levels or oral vitamin D dosages or both with coronary heart disease outcome parameters are reviewed. Recent findingsThere is accumulating evidence that the vitamin D hormone calcitriol exerts important physiological effects in cardiomyocytes, vascular smooth muscle cells, and the vascular endothelium. Low levels of the calcitriol precursor 25-hydoxyvitamin D are associated with myocardial infarction, congestive heart failure, and calcific aortic stenosis. Deficient calcitriol concentrations probably contribute to the massive vascular calcification seen in chronic kidney disease. In patients with end-stage renal disease and end-stage heart failure, very low-circulating calcitriol levels or nonuse of active vitamin D or both are independently associated with high mortality rates. SummaryDespite these exciting data, it is still too early to recommend exact dosages for the prevention or therapy of coronary heart disease. Prospective, randomized controlled trials with different amounts of vitamin D and probably with its active form calcitriol are needed to determine whether vitamin D can prevent coronary heart disease events and mortality.

Protective and toxic effects of vitamin D on vascular calcification: clinical implications.

The presence of vascular calcification (VC) is a predictor of poor survival in the general population. The development of VC is an active process that requires a pre-existing injury as an inducer and promoting factors such as hyperphosphatemia and hypercalcemia, as well as a deficiency in calcification repressor factors. Vascular smooth muscle cells possess an endogenous enzyme system for the biosynthesis of the vitamin D hormone calcitriol from its precursor 25-hydroxyvitamin D and also a cytosolic calcitriol receptor, indicating that the vasculature is an important target tissue for vitamin D. The toxic effects of supra-physiological vitamin D dosages on the vasculature have been known for several decades. Recent experimental data also demonstrate important physiological effects of vitamin D on factors that are protective for vascular health. This review article summarises the molecular basis of protective and toxic vitamin D actions on the vasculature. Chronic kidney disease can be considered as a human model of severe VC and poor survival. The disease is associated with calcitriol deficiency, hyperparathyroidism, and hyperphosphatemia. Evidence is increasing that phosphate overload plays a key role in the process of VC in chronic kidney disease. The first clinical studies indicate that vitamin D receptor activation can improve survival in these patients. Although less severe than in chronic kidney disease, vitamin D deficiency and secondary hyperparathyroidism are also frequent in the general population, especially in elderly and obese subjects. Future studies should focus on the impact of vitamin D deficiency on VC and clinical outcome in these groups.

First use of the Molecular Adsorbent Recirculating System technique on patients with hypoxic liver failure after cardiogenic shock.

The Molecular Adsorbent Recirculating System (MARS) has been proven to prolong survival in patients with hepatorenal syndrome. MARS is a modified dialysis that uses an albumin containing dialysate, which is recirculated and perfused online through charcoal and anion exchanger columns. It allows the selective removal of albumin bound substances.Despite advances in medical therapy and technology, the prognosis of patients with cardiogenic shock remains poor. Mortality rates are as high as 80%, often because of persistent multiple organ failure. To determine whether patients with hypoxic liver failure after cardiogenic shock after cardiac surgery might benefit from MARS, we performed a prospective, randomized, controlled, single center study. The primary objective was to prove that MARS improves survival.This article is a report on the interim analysis of the first 27 patients included between August 2000 and December 2001; 14 patients were in the MARS group, and 13 patients were in the non-MARS group. All had bilirubin levels greater than 8 mg/ml. Both groups had a similar risk profile. The MARS group received MARS for 3 consecutive days—if bilirubin was still greater than 6 mg/dl afterward, MARS was continued. The non-MARS group received conventional therapy.We had seven survivors in the MARS group (50%) compared with four (32%; p = ns) in the non-MARS group. We conclude that despite the limited number of patients included in this analysis, MARS can be recommended for patients with acute, hypoxic liver failure because it might prolong survival. Further studies in similar patient cohorts are needed to verify our results.