World Psychiatric Association-Asian Journal of Psychiatry Commission on Psychiatric Education in the 21st century.

Psychiatric practice faces many challenges in the first quarter of 21st century. Society has transformed, as have training requirements and patient expectations, underlining an urgent need to look at educational programmes. Meanwhile, awareness has grown around psychiatric disorders and there are evolving workforce trends, with more women going to medical school and specialising in psychiatry. Trainee psychiatrists carry different expectations for work-life balance and are increasingly becoming conscious of their own mental health. A tendency to see health as a commodity and the litigious nature of society has elicited additional pressures for healthcare professionals. Cartesian mind-body dualism has created further complexity and this can often be frustrating for patients and care-partners alike. In many cultures across Asia and beyond, patients can present with physical symptoms to express underlying psychological distress with increasing physical investigations. Simultaneously, in various countries, a shift from asylums to community-based interventions and then home treatments have changed psychiatric care in remarkable ways. These changes have added to pressures faced by mental healthcare professionals. However, trainees and other mental healthcare professionals continue to receive similar training as they did a generation ago. The tensions and differences in ideology/orientation between different branches of psychiatry have made responses to patient needs challenging. Recognising that it is difficult to predict the future, this World Psychiatric Association-Asian Journal of Psychiatry Commission makes recommendations that could help institutions and individuals enhance psychiatric education. This Commission draws from existing resources and recent developments to propose a training framework for future psychiatrists.

"What matters to you?": The relevance of patient priorities in dialysis care for assessment and clinical practice.

BACKGROUND: Dialysis patients are confronted with numerous, complex problems, which make it difficult to identify individual patient's most prominent problems. The objectives of this study were to (1) identify dialysis patients' most prominent problems from a patient perspective and (2) to calculate disease-specific norms for questionnaires measuring these problems. METHODS: One hundred seventy-five patients treated with hemodialysis or peritoneal dialysis completed a priority list on several domains of functioning (e.g., physical health, mental health, social functioning, and daily activities) and a set of matching questionnaires assessing patient functioning on these domains. Patient priorities were assessed by calculating the importance ranking of each domain on the priority list. Subsequently, disease-specific norm scores were calculated for all questionnaires, both for the overall sample and stratified by patient characteristics. RESULTS: Fatigue was listed as patients' most prominent problem. Priorities differed between male and female patients, younger and older patients, and home and center dialysis patients, which was also reflected in their scores on the corresponding domains of functioning. Therefore, next to general norm scores, we calculated corrections to the general norms to take account of patient characteristics (i.e., sex, age, and dialysis type). CONCLUSIONS: Results highlight the importance of having attention for the specific priorities and needs of each individual patient. Adequate disease-specific, norm-based assessment is not only necessary for diagnostic procedures but is an essential element of patient-centered care: It will help to better understand and respect individual patient needs and tailor treatment accordingly.

Advanced glycation endproducts and dicarbonyls in end-stage renal disease: associations with uraemia and courses following renal replacement therapy.

BACKGROUND: End-stage renal disease (ESRD) is strongly associated with cardiovascular disease (CVD) risk. Advanced glycation endproducts (AGEs) and dicarbonyls, major precursors of AGEs, may contribute to the pathophysiology of CVD in ESRD. However, detailed data on the courses of AGEs and dicarbonyls during the transition of ESRD patients to renal replacement therapy are lacking. METHODS: We quantified an extensive panel of free and protein-bound serum AGEs [N ∈-(carboxymethyl)lysine (CML), N ∈-(carboxyethyl)lysine (CEL), N δ-(5-hydro-5-methyl-4-imidazolon-2-yl)ornithine (MG-H1)], serum dicarbonyls [glyoxal (GO), methylglyoxal (MGO), 3-deoxyglucosone (3-DG)] and tissue AGE accumulation [estimated by skin autofluorescence (SAF)] in a combined cross-sectional and longitudinal observational study of patients with ESRD transitioning to dialysis or kidney transplantation (KTx), prevalent dialysis patients and healthy controls. Cross-sectional comparisons were performed with linear regression analyses, and courses following renal replacement therapy were analysed with linear mixed models. RESULTS: Free and protein-bound AGEs, dicarbonyls and SAF were higher in chronic kidney disease (CKD) Stage 5 non-dialysis (CKD 5-ND; n = 52) and CKD Stage 5 dialysis (CKD 5-D; n = 35) than in controls (n = 42). In addition, free AGEs, protein-bound CML, GO and SAF were even higher in CKD 5-D than in CKD5-ND. Similarly, following dialysis initiation (n = 43) free and protein-bound AGEs, and GO increased, whereas SAF remained similar. In contrast, following KTx (n = 21), free and protein-bound AGEs and dicarbonyls, but not SAF, markedly declined. CONCLUSIONS: AGEs and dicarbonyls accumulate in uraemia, which is even exaggerated by dialysis initiation. In contrast, KTx markedly reduces AGEs and dicarbonyls. Given their associations with CVD risk in high-risk populations, lowering AGE and dicarbonyl levels may be valuable.

A worldwide survey on training provisions for psychiatric trainees in WPA member associations.

This World Psychiatric Association (WPA) global survey of its WPA member society presidents using an online self-administered 15-item questionnaire successfully recruited 47 WPA member countries or regions (response rate = 39.8%) to provide responses about training provisions of psychiatric education at undergraduate, postgraduate, and post-qualified levels in their respective countries. There were significantly fewer responses from the low and middle income countries (LMIC) than the high income countries (HIC). At undergraduate level, the median duration of psychiatric education during medical school education was 4.0%. However, the current allocated time for psychiatric education was only around one-third to one-half of the time considered as optimal by the member countries or regions (optimal mean = 8.9%; optimal median = 10%). At the postgraduate level, the duration of training varied widely from 12-72 months, with a mean duration of 48 months. In 31% of the respondent countries, psychiatrists only required 36 or fewer months of post-graduate training. The number of months of training required for training a psychiatrist was significantly fewer in the LMIC than HIC. At post-qualified continuing medical education level, all respondents reported providing post-qualified continuing medical education. With the advent of internet technology, many respondents prefer having online training.

Education in psychiatry in Western Europe.

Education in psychiatry and practice varies hugely across Europe. Historical events and cultural differences, different languages and concepts about mental suffering, and mental healthcare organization in European countries have all contributed to the actual status. After presenting the legal framework and the role of major stakeholders, this review discusses failing initiatives, possible obstacles, and solutions to come to a more harmonized training. This review then gives an overview of the actual status of psychiatric training before shortly presenting the Task Force on Education in European Psychiatry. Initiatives to train the trainers, the introductions of newer teaching modalities in postgraduate training, and the role of the European Psychiatric Association in continuous medical education precede the conclusion.

Endothelial dysfunction and low-grade inflammation in the transition to renal replacement therapy.

INTRODUCTION: End-stage renal disease (ESRD) strongly associates with cardiovascular disease (CVD) risk. This risk is not completely mitigated by renal replacement therapy. Endothelial dysfunction (ED) and low-grade inflammation (LGI) may contribute to the increased CVD risk. However, data on serum biomarkers of ED and LGI during the transition to renal replacement therapy (dialysis and kidney transplantation) are scarce. METHODS: We compared serum biomarkers of ED and LGI between 36 controls, 43 participants with chronic kidney disease (CKD) stage 5 non-dialysis (CKD5-ND), 20 participants with CKD stage 5 hemodialysis (CKD5-HD) and 14 participants with CKD stage 5 peritoneal dialysis (CKD5-PD). Further, in 34 and 15 participants repeated measurements were available during the first six months following dialysis initiation and kidney transplantation, respectively. Serum biomarkers of ED (sVCAM-1, E-selectin, P-selectin, thrombomodulin, sICAM-1, sICAM-3) and LGI (hs-CRP, SAA, IL-6, IL-8, TNF-α) were measured with a single- or multiplex array detection system based on electro-chemiluminescence technology. RESULTS: In linear regression analyses adjusted for potential confounders, participants with ESRD had higher levels of most serum biomarkers of ED and LGI than controls. In addition, in CKD5-HD levels of serum biomarkers of ED and LGI were largely similar to those in CKD5-ND. In contrast, in CKD5-PD levels of biomarkers of ED were higher than in CKD5-ND and CKD5-HD. Similarly, in linear mixed model analyses sVCAM-1, thrombomodulin, sICAM-1 and sICAM-3 increased after PD initiation. In contrast, incident HD patients showed an increase in sVCAM-1, P-selectin and TNF-α, but a decline of hs-CRP, SAA and IL-6. Further, following kidney transplantation sVCAM-1, thrombomodulin, sICAM-3 and TNF-α were lower at three months post-transplantation and remained stable in the three months thereafter. CONCLUSIONS: Levels of serum biomarkers of ED and LGI were higher in ESRD as compared with controls. In addition, PD initiation and, less convincingly, HD initiation may increase levels of selected serum biomarkers of ED and LGI on top of uremia per se. In contrast to dialysis, several serum biomarkers of ED and LGI markedly declined following kidney transplantation.

Relations of advanced glycation endproducts and dicarbonyls with endothelial dysfunction and low-grade inflammation in individuals with end-stage renal disease in the transition to renal replacement therapy: A cross-sectional observational study.

BACKGROUND: Cardiovascular disease (CVD) related mortality and morbidity are high in end-stage renal disease (ESRD). The pathophysiology of CVD in ESRD may involve non-traditional CVD risk factors, such as accumulation of advanced glycation endproducts (AGEs), dicarbonyls, endothelial dysfunction (ED) and low-grade inflammation (LGI). However, detailed data on the relation of AGEs and dicarbonyls with ED and LGI in ESRD are limited. METHODS: We examined cross-sectional Spearman's rank correlations of AGEs and dicarbonyls with serum biomarkers of ED and LGI in 43 individuals with chronic kidney disease (CKD) stage 5 not on dialysis (CKD5-ND). Free and protein-bound serum AGEs (N∈-(carboxymethyl)lysine (CML), N∈-(carboxyethyl)lysine (CEL), Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)ornithine (MG-H1)) and serum dicarbonyls (glyoxal, methylglyoxal, 3-deoxyglucosone) were analyzed with tandem mass spectrometry, and tissue AGE accumulation was estimated by skin autofluorescence (SAF). Further, serum biomarkers of ED and LGI included sVCAM-1, sE-selectin, sP-selectin, sThrombomodulin, sICAM-1, sICAM-3, hs-CRP, SAA, IL-6, IL-8 and TNF-α. RESULTS: After adjustment for age, sex and diabetes status, protein-bound CML was positively correlated with sVCAM-1; free CEL with sVCAM-1 and sThrombomodulin; glyoxal with sThrombomodulin; and methylglyoxal with sVCAM-1 (correlation coefficients ranged from 0.36 to 0.44). In addition, free CML was positively correlated with SAA; protein-bound CML with IL-6; free CEL with hs-CRP, SAA and IL-6; free MG-H1 with SAA; protein-bound MG-H1 with IL-6; and MGO with hs-CRP and IL-6 (correlation coefficients ranged from 0.33 to 0.38). Additional adjustment for eGFR attenuated partial correlations of serum AGEs and serum dicarbonyls with biomarkers of ED and LGI. CONCLUSIONS: In individuals with CKD5-ND, higher levels of serum AGEs and serum dicarbonyls were related to biomarkers of ED and LGI after adjustment for age, sex and diabetes mellitus. Correlations were attenuated by eGFR, suggesting that eGFR confounds and/or mediates the relation of serum AGEs and dicarbonyls with ED and LGI.

Health-related quality of life in end-stage renal disease patients: the effects of starting dialysis in the first year after the transition period.

BACKGROUND/AIMS: Prevalent dialysis patients have low scores of health-related quality of life (HRQOL) which are associated with increased risk of hospitalization and mortality. Also in CKD-5 non-dialysis patients, HRQOL scores seem to be lower as compared with the general population. This study firstly aimed to compare HRQOL between CKD-5 non-dialysis and prevalent dialysis patients in a cross-sectional analysis and to assess longitudinal changes over 1 year after the dialysis initiation. Secondly, the correlation between HRQOL and physical activity (PA) was explored. METHODS: Cross-sectional 44 CKD-5 non-dialysis, 29 prevalent dialysis, and 20 healthy controls were included. HRQOL was measured by Short Form-36 questionnaires to measure physical and mental domains of health expressed by the physical component summary (PCS) and mental component summary (MCS) scores. PA was measured by a SenseWear™ pro3. Longitudinally, HRQOL was assessed in 38 CKD-5 non-dialysis patients (who were also part of the cross-sectional analysis), before dialysis initiation until 1 year after dialysis initiation. RESULTS: PCS scores were significantly lower both in CKD-5 non-dialysis patients and in prevalent dialysis patients as compared with healthy controls (p < 0.001). MCS scores were significantly lower in both CKD-5 non-dialysis patients (p = 0.003), and in dialysis patients (p = 0.022), as compared with healthy controls. HRQOL scores did not change significantly from the CKD-5 non-dialysis phase into the first year after dialysis initiation. PA was significantly related to PCS in both CKD-5 non-dialysis patients (r = 0.580; p < 0.001), and dialysis patients (r = 0.476; p = 0.009). CONCLUSIONS: HRQOL is already low in the CKD-5 non-dialysis phase. In the first year after dialysis initiation, HRQOL did not change significantly. Given the correlation between PCS score and PA, physical activity programs may be potential tools to improve HRQOL in both CKD-5 non-dialysis as well as in prevalent dialysis patients.

Physical Activity in End-Stage Renal Disease Patients: The Effects of Starting Dialysis in the First 6 Months after the Transition Period.

OBJECTIVES: Physical inactivity in end-stage renal disease (ESRD) patients is associated with increased mortality, and might be related to abnormalities in body composition (BC) and physical performance. It is uncertain to what extent starting dialysis influences the effects of ESRD on physical activity (PA). This study aimed to compare PA and physical performance between stage 5 chronic kidney disease (CKD-5) non-dialysis and dialysis patients, and healthy controls, to assess alterations in PA during the transition from CKD-5 non-dialysis to dialysis, and to relate PA to BC. METHODS: For the cross-sectional analyses 44 CKD-5 non-dialysis patients, 29 dialysis patients, and 20 healthy controls were included. PA was measured by the SenseWear™ pro3. Also, the walking speed and handgrip strength (HGS) were measured. BC was measured by the Body Composition Monitor©. Longitudinally, these parameters were assessed in 42 CKD-5 non-dialysis patients (who were also part of the cross-sectional analysis), before the start of dialysis and 6 months thereafter. RESULTS: PA was significantly lower in CKD-5 non-dialysis patients as compared to that in healthy controls but not as compared to that in dialysis patients. HGS was significantly lower in dialysis patients as compared to that in healthy controls. Walking speed was significantly lower in CKD-5 non-dialysis patients as compared to that in healthy controls but not as compared to that in dialysis patients. Six months after starting dialysis, activity related energy expenditure (AEE) and walking speed significantly increased. CONCLUSIONS: PA is already lower in CKD-5 non-dialysis patients as compared to that in healthy controls and does not differ from that of dialysis patients. However, the transition phase from CKD-5 non-dialysis to dialysis is associated only with a modest improvement in AEE.

A retrospective multicenter case series evaluating a novel 3.0-mm expanding tapered body implant for the rehabilitation of missing incisors.

OBJECTIVE: Narrow-diameter implants are indicated for narrow sites, small interdental/interimplant spaces, or sites with congenitally missing teeth. They also offer a substitute for invasive augmentation procedures. The authors retrospectively evaluated the performance of a new 3.0-mm diameter implant for rehabilitating small anterior spaces. METHOD AND MATERIALS: This observational multicenter retrospective case series included consecutive patients needing single-unit restoration for mandibular and lateral maxillary incisors. The outcome variables were: implant survival, Plaque Index, pocket probing depth (PPD), Jemt's papilla index, bleeding on probing (BOP), and marginal bone remodeling. RESULTS: In total, 45 patients received 58 3.0-mm implants placed in healed sites (n = 22), extraction sockets (n = 16), or sites with congenitally missing teeth (n = 20). Average follow-up time was 15.1 ± 5.2 months. Prosthetic loading was immediate (n = 23), early (n = 16), or delayed (n = 19). Two implants were lost, and two prosthetic complications occurred. One-year bone remodeling averaged -0.36 ± 0.85 mm (n = 44). PPD averaged 1.75 ± 0.58 mm. Neither BOP nor plaque was detected around implants. CONCLUSIONS: At 1-year follow-up, narrow 3.0-mm diameter implants placed in mandibular and lateral maxillary incisor sites demonstrate a high survival rate and support stable marginal bone levels and healthy soft tissue.

Training in psychiatry throughout Europe.

Psychiatry is the largest medical specialty in Europe. Despite efforts to bring harmonisation, training in psychiatry in Europe continues to be very diverse. The Union Européenne des Médecins Spécialistes (UEMS) has issued as from 2000 a charter of requirements for the training in psychiatry with an additional European Framework for Competencies in Psychiatry in 2009. Yet these have not been implemented throughout Europe. In this paper, the diversity in training throughout Europe is approached from different angles: the cultural differences between countries with regards to how mental health care is considered and founded on, the cultural differences between people throughout Europe in all states. The position of psychotherapy is emphasised. What once was the cornerstone of psychiatry as medical specialty seems to have become a neglected area. Seeing the patient with mental health problems within his cultural context is important, but considering him within his family context. The purpose of any training is enabling the trainee to gain the knowledge and acquire the competencies necessary to become a well-equipped professional is the subject of the last paragraph in which trainees consider their position and early career psychiatrists look back to see whether what they were trained in matches with what they need in the working situation. Common standard for training and certification are a necessity within Europe, for the benefit of the profession of psychiatrist but also for patient safety. UEMS is advised to join forces with the Council of National Psychiatric Associations (NPAs) within the EPA and trainings and early career psychiatrist, to discuss with the users what standards should be implemented in all European countries and how a European board examination could ensure professional quality of psychiatrists throughout the continent.

A Time for Action on Health Inequities: Foundations of the 2014 Geneva Declaration on Person- and People-centered Integrated Health Care for All.

Global inequalities contribute to marked disparities in health and wellness of human populations. Many opportunities now exist to provide health care to all people in a person- and people-centered way that is effective, equitable, and sustainable. We review these opportunities and the scientific, historical, and philosophical considerations that form the basis for the International College of Person-centered Medicine's 2014 Geneva Declaration on Person- and People-centered Integrated Health Care for All. Using consistent time-series data, we critically examine examples of universal healthcare systems in Chile, Spain, and Cuba. In a person-centered approach to public health, people are recognized to have intrinsic dignity and are treated with respect to encourage their developing health and happiness. A person-centered approach supports the freedom and the responsibility to develop one's life in ways that are personally meaningful and that are respectful of others and the environment in which we live together. Evidence suggests that health care organizations function well when they operate in a person-and people-centered way because that stimulates better coordination, cooperation, and social trust. Health care coverage must be integrated at several interconnected levels in order to be effective, efficient, and fair. To reduce the burden of disease, integration is needed between the people seeking and delivering care, within the social network of each person, across the trajectory of each person's life, among primary caregivers and specialists, and across multiple sectors of society. For integration to succeed across all these levels, it must foster common values and a shared vision of the future.

The state of psychiatry in Belgium.

Belgium, at the crossroads of different cultures, developed complex governmental structures hindering the development of comprehensive mental health policies. A total of 10.2% of the gross domestic product is spent on healthcare but only 6.1% of this total expenditure goes to mental health. Although mental healthcare is largely accessible and offers high levels of quality, it is questionable whether this can be maintained, given the economic climate. The collection of epidemiological data is problematic due to the different ways registration takes place within different care systems and the complexity of the state structure and its consecutive constitutional reforms. Coming from a largely hospital-driven psychiatric care, mental healthcare reforms of past decades have created more community-based care and new care pathways, still an on-going process. Psychiatry as a profession is currently challenged. Teaching mental health issues remains extremely limited within medical schools, resources for research are disproportionally limited, and working conditions less favourable, all this compared with other specialisms. Hence few graduates choose a career in psychiatry. Changing the public perception of what psychiatry is about, redefining the identity of psychiatrists as medical specialists, and their work have become important challenges for the next future.

Valsartan improves {beta}-cell function and insulin sensitivity in subjects with impaired glucose metabolism: a randomized controlled trial.

OBJECTIVE: Recently, the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research Trial demonstrated that treatment with the angiotensin receptor blocker (ARB) valsartan for 5 years resulted in a relative reduction of 14% in the incidence of type 2 diabetes in subjects with impaired glucose metabolism (IGM). We investigated whether improvements in ß-cell function and/or insulin sensitivity underlie these preventive effects of the ARB valsartan in the onset of type 2 diabetes. RESEARCH DESIGN AND METHODS: In this randomized controlled, double-blind, two-center study, the effects of 26 weeks of valsartan (320 mg daily; n = 40) or placebo (n = 39) on ß-cell function and insulin sensitivity were assessed in subjects with impaired fasting glucose and/or impaired glucose tolerance, using a combined hyperinsulinemic-euglycemic and hyperglycemic clamp with subsequent arginine stimulation and a 2-h 75-g oral glucose tolerance test (OGTT). Treatment effects were analyzed using ANCOVA, adjusting for center, glucometabolic status, and sex. RESULTS: Valsartan increased first-phase (P = 0.028) and second-phase (P = 0.002) glucose-stimulated insulin secretion compared with placebo, whereas the enhanced arginine-stimulated insulin secretion was comparable between groups (P = 0.25). In addition, valsartan increased the OGTT-derived insulinogenic index (representing first-phase insulin secretion after an oral glucose load; P = 0.027). Clamp-derived insulin sensitivity was significantly increased with valsartan compared with placebo (P = 0.049). Valsartan treatment significantly decreased systolic and diastolic blood pressure compared with placebo (P < 0.001). BMI remained unchanged in both treatment groups (P = 0.89). CONCLUSIONS: Twenty-six weeks of valsartan treatment increased glucose-stimulated insulin release and insulin sensitivity in normotensive subjects with IGM. These findings may partly explain the beneficial effects of valsartan in the reduced incidence of type 2 diabetes.

Progression of aortic calcification is associated with disorders of mineral metabolism and mortality in chronic dialysis patients.

BACKGROUND: Previous studies have shown that simple imaging methods may be useful for detection of vascular calcifications in dialysis patients. Based on annual, plain chest X-rays during follow-up on dialysis, we studied the associations of mineral metabolism with the presence and progression of aortic calcification. In addition, we assessed the impact of aortic calcification on mortality. METHODS: Three hundred and eighty-four patients who started haemodialysis or peritoneal dialysis between 1997 and 2007 were included (age 61 ± 15 years, 64% male, 61% haemodialysis). Annual chest X-rays were screened for calcification in the aortic arch, and patients were categorized as having no, moderate or severe calcification. Progression was defined as an increase in calcification category during follow-up on dialysis. RESULTS: At baseline, 96 (25%) patients had severe, 205 (53%) patients had moderate and 83 (22%) patients had no aortic calcification. For 237 of the 288 patients with no or moderate calcifications at baseline, X-rays were available for follow-up. During follow-up (mean 2.3 years), aortic calcification progressed in 71 patients (30%). We found that baseline plasma calcium > 9.5 mg/dL and iPTH > 300 pg/mL were associated with progression [odds ratios of 3.1, 95% confidence interval (1.2-8.2) and 4.4 (1.4-14.1), respectively]. Progression of aortic calcification was significantly associated with increased risk of all-cause mortality (hazard ratio: 1.9; 95% CI: 1.2-3.1) and cardiovascular mortality (hazard ratio: 2.7; 95% CI: 1.3-5.6). CONCLUSIONS: Aortic calcification progressed in almost a third of the patients during dialysis. Hypercalcaemia and hyperparathyroidism were associated with an increased risk of progression. Progression of aortic calcification was significantly related to an increased mortality risk.

Albuminuria, but not estimated glomerular filtration rate, is associated with maladaptive arterial remodeling: the Hoorn Study.

OBJECTIVE: Arterial remodeling aims to maintain a constant circumferential wall stress (sigmac). A failing remodeling process is associated with stroke. Data on the relationship between chronic kidney disease and arterial remodeling are scarce. METHODS: We investigated the association between a lower glomerular filtration rate (GFR) and microalbuminuria with arterial remodeling of the common carotid artery (CCA) in a population-based study of 806 patients. CCA properties including intima-media thickness and interadventitial diameter (IAD) were assessed. Lumen diameter, circumferential wall tension (CWT), and circumferential wall stress (sigmac) were calculated. GFR was estimated (eGFR) by the Modification of Diet in Renal Disease formula. Albuminuria was expressed as urinary albumin/creatinine ratio. RESULTS: Mean eGFR was 60.3 (+/-10.8) ml/min/1.73 m2; median urinary albumin/creatinine ratio was 0.57 (range 0.10-26.6 mg/mmol). After adjustment for age, sex, glucose tolerance status, and prevalent cardiovascular disease, eGFR was not independently associated with CCA properties. A greater urinary albumin/creatinine ratio (per quartile) was associated with a greater lumen diameter [regression coefficient beta with 95% confidence interval, 0.14 (0.08-0.20; P < 0.01)], IAD [0.15 (0.09-0.21; P < 0.01)], CWT [0.95 (0.52-1.38; P < 0.01)], and sigmac [1.7 (0.5-2.9; P < 0.01)] but not with a greater IMT [0.01 (-0.002-0.02; P = 0.12)]. Additional adjustments for mean arterial pressure, pulse pressure, and eGFR did not change the results. CONCLUSION: Greater albuminuria is independently associated with an increase in lumen diameter and IAD of the CCA. In addition, greater albuminuria is associated with a maladaptive carotid remodeling process as shown by an increase in CWT and sigmac. These findings may explain, why microalbuminuria is associated with a greater risk of cardiovascular disease and especially stroke.

Undercarboxylated matrix GLA protein levels are decreased in dialysis patients and related to parameters of calcium-phosphate metabolism and aortic augmentation index.

BACKGROUND: Vascular calcifications are related to cardiovascular mortality and morbidity in dialysis patients. Limited data exist on the role of calcification inhibitors, such as matrix-carboxyglutamic acid protein (MGP) in dialysis patients. METHODS: In 120 dialysis patients and 41 age-matched healthy controls, circulating undercarboxylated (uc) MGP levels were measured with a novel ELISA-based competitive assay. The association between ucMGP levels and determinants of bone mineral metabolism, including the calcification inhibitor fetuin-A, was studied. Moreover, the relation between ucMGP levels and arterial stiffness was investigated. RESULTS: The ucMGP level was significantly lower in dialysis patients compared to controls (173 +/- 70 vs. 424 +/- 126 nmol/l; p < 0.0001). After adjustment for age, sex and duration of dialysis an independent negative association between time-averaged phosphate levels [regression coefficient beta with 95% confidence interval = -64 (-107 to -21)] and a positive association between serum ucMGP and fetuin-A [131 (55-208)] was observed. Duration of dialysis was inversely correlated with ucMGP (r = -0.24, p = 0.007). ucMGP levels were not related to high-sensitivity C-reactive protein or time-averaged calcium levels. After adjustment for age, sex, cardiovascular disease, diabetes, height and mean arterial pressure, ucMGP level was negatively associated with the aortic augmentation index [-0.036 (-0.061 to -0.010)] but not with pulse wave velocity or pulse pressure. CONCLUSION: Significantly lower serum ucMGP levels were observed in dialysis patients compared to healthy controls. ucMGP levels were inversely associated with phosphate and positively associated with serum fetuin-A levels. Furthermore, ucMGP levels were inversely associated with the aortic augmentation index. These data suggest that low ucMGP levels may be a marker of active calcification.

Estimated glomerular filtration rate and urinary albumin excretion are independently associated with greater arterial stiffness: the Hoorn Study.

Mild renal insufficiency is a risk factor for cardiovascular disease (CVD). Both a decline in GFR and (micro)albuminuria are associated with greater cardiovascular mortality. In ESRD, arterial stiffness, an important cause of CVD, is known to be greater, but few data exist in individuals with mild renal insufficiency or microalbuminuria. This study investigated the association of impaired renal function expressed as lower GFR or greater urinary albumin excretion with arterial stiffness. In a population-based study in 806 individuals (402 men), mean age 68 yr (range 50 to 87), peripheral arterial stiffness (by compliance and distensibility of the carotid, brachial, and femoral arteries and by the carotid elastic modulus [E(inc)]) and central arterial stiffness (by total systemic arterial compliance, carotid-femoral transit time, and aortic augmentation index) were measured ultrasonically. GFR was estimated (eGFR) by the Modification of Diet in Renal Disease (MDRD) formula. Urinary albumin excretion was expressed as urinary albumin/creatinine ratio (UACR). eGFR was 60.6 +/- 11.1 ml/min per 1.73 m(2). Median UACR was 0.57 mg/mmol (range 0.1 to 26.6). After adjustment for age, mean arterial pressure (MAP), gender, and glucose tolerance status (GTS), each 5-ml/min per 1.73 m(2) lower eGFR was associated with a lower distensibility coefficient of the carotid (regression coefficient beta -0.20 10(-3)/kPa; 95% confidence interval [CI] -0.34 to -0.07 10(-3)/kPa) and brachial artery (-0.15 10(-3)/kPa; 95% CI -0.28 to -0.03 10(-3)/kPa) and a greater carotid E(inc) (0.02 kPa; 95% CI 0.0004 to 0.04 kPa). No statistically significant association was found of eGFR with other arterial stiffness indices. After adjustment for age, MAP, gender, and GTS, a greater UACR (per quartile) was associated with a greater E(inc) (0.03 kPa; 95% CI 0.001 to 0.07 kPa) and a trend to a lower distensibility coefficient (-0.24 10(-3)/kPa; 95% CI -0.49 to 0.02 10(-3)/kPa) of the carotid artery. After adjustment for age, MAP, gender, and GTS, a greater UACR (per quartile) was in addition associated with a shorter carotid-femoral transit time (-1.67 ms; 95% CI -3.24 to -0.10 ms). These associations were not substantially changed by mutual adjustment for eGFR and UACR. In individuals with mild renal insufficiency, both a lower eGFR and a greater albumin excretion, even below levels that are considered to reflect microalbuminuria, are independently associated with greater arterial stiffness. Moreover, these associations were mutually independent. These findings may explain, in part, why eGFR and microalbuminuria are associated with greater risk for CVD and suggest that amelioration of arterial stiffness could be a target of intervention.