Development of an online patient decision aid for kidney failure treatment modality decisions.

BACKGROUND: Patient decision aids (PtDAs) support patients and clinicians in shared decision-making (SDM). Real-world outcome information may improve patients' risk perception, and help patients make decisions congruent with their expectations and values. Our aim was to develop an online PtDA to support kidney failure treatment modality decision-making, that: 1) provides patients with real-world outcome information, and 2) facilitates SDM in clinical practice. METHODS: The International Patient Decision Aids Standards (IPDAS) development process model was complemented with a user-centred and convergent mixed-methods approach. Rapid prototyping was used to develop the PtDA with a multidisciplinary steering group in an iterative process of co-creation. The results of an exploratory evidence review and a needs-assessment among patients, caregivers, and clinicians were used to develop the PtDA. Seven Dutch teaching hospitals and two national Dutch outcome registries provided real-world data on selected outcomes for all kidney failure treatment modalities. Alpha and beta testing were performed to assess the prototype and finalise development. An implementation strategy was developed to guide implementation of the PtDA in clinical practice. RESULTS: The 'Kidney Failure Decision Aid' consists of three components designed to help patients and clinicians engage in SDM: 1) a paper hand-out sheet, 2) an interactive website, and 3) a personal summary sheet. A 'patients-like-me' infographic was developed to visualise survival probabilities for each treatment modality on the website. Other treatment outcomes were incorporated as event rates (e.g. hospitalisation rates) or explained in text (e.g. the flexibility of each treatment modality). No major revisions were needed after alpha and beta testing. During beta testing, some patients ignored the survival probabilities because they considered these too confronting. Nonetheless, patients agreed that every patient has the right to choose whether they want to view this information. Patients and clinicians believed that the PtDA would help patients make informed decisions, and that it would support values- and preferences-based decision-making. Implementation of the PtDA has started in October 2020. CONCLUSIONS: The 'Kidney Failure Decision Aid' was designed to facilitate SDM in clinical practice and contains real-world outcome information on all kidney failure treatment modalities. It is currently being investigated for its effects on SDM in a clinical trial.

Association of Traditional Cardiovascular Risk Factors With Venous Thromboembolism: An Individual Participant Data Meta-Analysis of Prospective Studies.

BACKGROUND: Much controversy surrounds the association of traditional cardiovascular disease risk factors with venous thromboembolism (VTE). METHODS: We performed an individual level random-effect meta-analysis including 9 prospective studies with measured baseline cardiovascular disease risk factors and validated VTE events. Definitions were harmonized across studies. Traditional cardiovascular disease risk factors were modeled categorically and continuously using restricted cubic splines. Estimates were obtained for overall VTE, provoked VTE (ie, VTE occurring in the presence of 1 or more established VTE risk factors), and unprovoked VTE, pulmonary embolism, and deep-vein thrombosis. RESULTS: The studies included 244 865 participants with 4910 VTE events occurring during a mean follow-up of 4.7 to 19.7 years per study. Age, sex, and body mass index-adjusted hazard ratios for overall VTE were 0.98 (95% confidence interval [CI]: 0.89-1.07) for hypertension, 0.97 (95% CI: 0.88-1.08) for hyperlipidemia, 1.01 (95% CI: 0.89-1.15) for diabetes mellitus, and 1.19 (95% CI: 1.08-1.32) for current smoking. After full adjustment, these estimates were numerically similar. When modeled continuously, an inverse association was observed for systolic blood pressure (hazard ratio=0.79 [95% CI: 0.68-0.92] at systolic blood pressure 160 vs 110 mm Hg) but not for diastolic blood pressure or lipid measures with VTE. An important finding from VTE subtype analyses was that cigarette smoking was associated with provoked but not unprovoked VTE. Fully adjusted hazard ratios for the associations of current smoking with provoked and unprovoked VTE were 1.36 (95% CI: 1.22-1.52) and 1.08 (95% CI: 0.90-1.29), respectively. CONCLUSIONS: Except for the association between cigarette smoking and provoked VTE, which is potentially mediated through comorbid conditions such as cancer, the modifiable traditional cardiovascular disease risk factors are not associated with increased VTE risk. Higher systolic blood pressure showed an inverse association with VTE.

A Policy Call to Address Rare Kidney Disease in Health Care Plans.

Despite a large number of people globally being affected by rare kidney diseases, research support and health care policy programs usually focus on the management of the broad spectrum of CKD without particular attention to rare causes that would require a targeted approach for proper cure. Hence, specific curative approaches for rare kidney diseases are scarce, and these diseases are not treated optimally, with implications on the patients' health and quality of life, on the cost for the health care system, and society. There is therefore a need for rare kidney diseases and their mechanisms to receive the appropriate scientific, political, and policy attention to develop specific corrective approaches. A wide range of policies are required to address the various challenges that target care for rare kidney diseases, including the need to increase awareness, improve and accelerate diagnosis, support and implement therapeutic advances, and inform the management of the diseases. In this article, we provide specific policy recommendations to address the challenges hindering the provision of targeted care for rare kidney diseases, focusing on awareness and prioritization, diagnosis, management, and therapeutic innovation. In combination, the recommendations provide a holistic approach aiming for all aspects of rare kidney disease care to improve health outcomes, reduce the economic effect, and deliver benefits to society. Greater commitment from all the key stakeholders is now needed, and a central role should be assigned to patients with rare kidney disease to partner in the design and implementation of potential solutions.

Cardiovascular and health cost impacts of cuff blood pressure underestimation and overestimation of invasive aortic systolic blood pressure.

OBJECTIVE: Hypertension management is directed by cuff blood pressure (BP), but this may be inaccurate, potentially influencing cardiovascular disease (CVD) events and health costs. This study aimed to determine the impact on CVD events and related costs of the differences between cuff and invasive SBP. METHODS: Microsimulations based on Markov modelling over one year were used to determine the differences in the number of CVD events (myocardial infarction or coronary death, stroke, atrial fibrillation or heart failure) predicted by Framingham risk and total CVD health costs based on cuff SBP compared with invasive (aortic) SBP. Modelling was based on international consortium data from 1678 participants undergoing cardiac catheterization and 30 separate studies. Cuff underestimation and overestimation were defined as cuff SBP less than invasive SBP and cuff SBP greater than invasive SBP, respectively. RESULTS: The proportion of people with cuff SBP underestimation versus overestimation progressively increased as SBP increased. This reached a maximum ratio of 16 : 1 in people with hypertension grades II and III. Both the number of CVD events missed (predominantly stroke, coronary death and myocardial infarction) and associated health costs increased stepwise across levels of SBP control, as cuff SBP underestimation increased. The maximum number of CVD events potentially missed (11.8/1000 patients) and highest costs ($241 300 USD/1000 patients) were seen in people with hypertension grades II and III and with at least 15 mmHg of cuff SBP underestimation. CONCLUSION: Cuff SBP underestimation can result in potentially preventable CVD events being missed and major increases in health costs. These issues could be remedied with improved cuff SBP accuracy.

Internet-based treatment for depressive symptoms in hemodialysis patients: A cluster randomized controlled trial.

OBJECTIVE: To investigate the effectiveness of a guided internet-based self-help intervention for hemodialysis patients with depressive symptoms. METHOD: Chronic hemodialysis patients from nine Dutch hospitals with a depression score on the Beck Depression Inventory - second edition (BDI-II) of ≥10, were cluster-randomized into a five modules guided internet-based self-help problem solving therapy intervention or a parallel care-as-usual control group. Clusters were based on hemodialysis shift. The primary outcome depression was measured with the BDI-II. Analysis was performed with linear mixed models. RESULTS: A total of 190 hemodialysis patients were cluster-randomized to the intervention (n = 89) or control group (n = 101). Post-intervention measurement was completed by 127 patients (67%) and more than half of the patients (54%) completed the intervention. No significant differences were found on the BDI-II score between the groups (mean difference - 0.1, 95%CI -3.0; 2.7, p = 0.94). Per protocol sensitivity analysis showed comparable results. No significant differences in secondary outcomes were observed between groups. CONCLUSIONS: Guided internet-based self-help problem solving therapy for hemodialysis patients with depressive symptoms does not seem to be effective in reducing these symptoms as compared to usual care. Future research should examine how to best design content and accessibility of an intervention for depressive symptoms in hemodialysis patients. TRIAL REGISTRATION: Dutch Trial Register: Trial NL6648 (NTR6834) (prospectively registered 13th November 2017).

Depression, anxiety and quality of life of hemodialysis patients before and during the COVID-19 pandemic.

OBJECTIVE: To investigate the impact of the coronavirus pandemic on mental health in hemodialysis patients, we assessed depression, anxiety and quality of life with valid mental health measures before and after the start of the pandemic. METHODS: Data were used from 121 hemodialysis patients from the ongoing prospective multicenter DIVERS-II study. COVID-19 related stress was measured with the Perceived Stress Scale - 10, depression with the Beck Depression Inventory - second edition (BDI-II)), anxiety with the Beck Anxiety Inventory (BAI) and quality of life with the Short Form - 12 (SF-12). Scores during the first and second COVID-19 wave in the Netherlands were compared to data prior to the pandemic with linear mixed models. RESULTS: No significant differences were found in BDI-II, BAI and SF-12 scores between before and during the pandemic. During the first wave, 33% of participants reported COVID-19 related stress and in the second wave 37%. These patients had higher stress levels (mean difference (MD) 4.7 (95%CI 1.5; 8.0), p = 0.005) and BDI-II scores (MD 4.9 (95%CI 0.7; 9.0), p = 0.021) and lower SF-12 mental component summary scores (MD -5.3 (95%CI -9.0, -1.6), p = 0.006) than patients who did not experienced COVID-19 stress. These differences were already present before the pandemic. CONCLUSION: The COVID-19 pandemic does not seem to influence mental health in hemodialysis patients. However, a substantial subgroup of patients with pre-existent mental health problems may be more susceptible to experience COVID-19 related stress.

Metabolomic profiling of microbial disease etiology in community-acquired pneumonia.

Diagnosis of microbial disease etiology in community-acquired pneumonia (CAP) remains challenging. We undertook a large-scale metabolomics study of serum samples in hospitalized CAP patients to determine if host-response associated metabolites can enable diagnosis of microbial etiology, with a specific focus on discrimination between the major CAP pathogen groups S. pneumoniae, atypical bacteria, and respiratory viruses. Targeted metabolomic profiling of serum samples was performed for three groups of hospitalized CAP patients with confirmed microbial etiologies: S. pneumoniae (n = 48), atypical bacteria (n = 47), or viral infections (n = 30). A wide range of 347 metabolites was targeted, including amines, acylcarnitines, organic acids, and lipids. Single discriminating metabolites were selected using Student's T-test and their predictive performance was analyzed using logistic regression. Elastic net regression models were employed to discover metabolite signatures with predictive value for discrimination between pathogen groups. Metabolites to discriminate S. pneumoniae or viral pathogens from the other groups showed poor predictive capability, whereas discrimination of atypical pathogens from the other groups was found to be possible. Classification of atypical pathogens using elastic net regression models was associated with a predictive performance of 61% sensitivity, 86% specificity, and an AUC of 0.81. Targeted profiling of the host metabolic response revealed metabolites that can support diagnosis of microbial etiology in CAP patients with atypical bacterial pathogens compared to patients with S. pneumoniae or viral infections.

Expression and production of the SERPING1-encoded endogenous complement regulator C1-inhibitor in multiple cohorts of tuberculosis patients.

BACKGROUND: To facilitate better discrimination between patients with active tuberculosis (TB) and latent TB infection (LTBI), whole blood transcriptomic studies have been performed to identify novel candidate host biomarkers. SERPING1, which encodes C1-inhibitor (C1-INH), the natural inhibitor of the C1-complex has emerged as candidate biomarker. Here we collated and analysed SERPING1 expression data and subsequently determined C1-INH protein levels in four cohorts of patients with TB. METHODS: SERPING1 expression data were extracted from online deposited datasets. C1-INH protein levels were determined by ELISA in sera from individuals with active TB, LTBI as well as other disease controls in geographically diverse cohorts. FINDINGS: SERPING1 expression was increased in patients with active TB compared to healthy controls (8/11 cohorts), LTBI (13/14 cohorts) and patients with other (non-TB) lung-diseases (7/7 cohorts). Serum levels of C1-INH were significantly increased in The Gambia and Italy in patients with active TB relative to the endemic controls but not in South Africa or Korea. In the largest cohort (n = 50), with samples collected longitudinally, normalization of C1-INH levels following successful TB treatment was observed. This cohort, also showed the most abundant increase in C1-INH, and a positive correlation between C1q and C1-INH levels. Combined presence of increased levels of both C1q and C1-INH had high specificity for active TB (96 %) but only very modest sensitivity 38 % compared to the endemic controls. INTERPRETATION: SERPING1 transcript expression is increased in TB patients, while serum protein levels of C1-INH were increased in half of the cohorts analysed.

Influence of Age on Upper Arm Cuff Blood Pressure Measurement.

Blood pressure (BP) is a leading global risk factor. Increasing age is related to changes in cardiovascular physiology that could influence cuff BP measurement, but this has never been examined systematically and was the aim of this study. Cuff BP was compared with invasive aortic BP across decades of age (from 40 to 89 years) using individual-level data from 31 studies (1674 patients undergoing coronary angiography) and 22 different cuff BP devices (19 oscillometric, 1 automated auscultation, 2 mercury sphygmomanometry) from the Invasive Blood Pressure Consortium. Subjects were aged 64±11 years, and 32% female. Cuff systolic BP overestimated invasive aortic systolic BP in those aged 40 to 49 years, but with each older decade of age, there was a progressive shift toward increasing underestimation of aortic systolic BP (P<0.0001). Conversely, cuff diastolic BP overestimated invasive aortic diastolic BP, and this progressively increased with increasing age (P<0.0001). Thus, there was a progressive increase in cuff pulse pressure underestimation of invasive aortic PP with increasing decades of age (P<0.0001). These age-related trends were observed across all categories of BP control. We conclude that cuff BP as an estimate of aortic BP was substantially influenced by increasing age, thus potentially exposing older people to greater chance for misdiagnosis of the true risk related to BP.

Disordered mineral metabolism is not a risk factor for loss of residual renal function in dialysis patients.

BACKGROUND: Recent studies showed that mineral metabolism disorders are associated with renal function loss in pre-dialysis patients, but their effects in dialysis patients are less well established. We examined associations between parameters of mineral metabolism and loss of residual renal function (RRF) in dialysis patients. METHODS: We included 1468 incident haemodialysis (HD) and peritoneal dialysis (PD) patients who were not anuric at dialysis initiation from NECOSAD, a prospective multicentre cohort study. We studied the effects of plasma calcium, phosphorus, calcium-phosphorus product and intact PTH concentrations on loss of RRF. Cox regression models were applied to calculate relative risks of total loss of RRF, defined as anuria during the first 3 years of dialysis. The rate of decline of RRF over time was calculated using general linear mixed models. RESULTS: The mean (SD) age was 59 (15), 62% were men and 59% were treated with HD. We found that both HD and PD patients with the highest phosphorus (P < 0.0001) and calcium-phosphorus product (P < 0.0001) levels had the lowest baseline residual glomerular filtration rate (rGFR) values. During follow-up, 136 HD (15%) and 67 PD patients (12%) became anuric. After adjustment for baseline rGFR, there were no significant associations between parameters of mineral metabolism and the risk of becoming anuric. There were also no differences in the rate of decline in RRF between categories of plasma concentrations. CONCLUSION: Disordered mineral metabolism was neither associated with the risk of becoming anuric, nor with the rate of decline in RRF in dialysis patients. Differences in decline were mainly attributable to the baseline rGFR value.

Pulse pressure amplification and risk of cardiovascular disease.

BACKGROUND: Whether pulse pressure amplification (PPA) relates to established markers of cardiovascular risk is unknown. The purpose of this study was to investigate the relationship between PPA and cardiovascular risk factors and cardiovascular risk in a population-based sample of 40- to 80-year old men. METHODS: A cross-sectional, single-center study was performed in 400 men aged 40-80 years. PPA was calculated as a ratio (brachial pulse pressure/central pulse pressure). Detailed information on vascular risk factors was obtained. Aortic pulse wave velocity (PWV) and common carotid intima-media thickness (CIMT), as markers of vascular risk, were measured. We calculated the absolute 10-year risk of coronary heart disease using the Framingham risk score. Regression analysis was used to evaluate the relations under study. RESULTS: In models adjusted for age, mean arterial pressure (MAP), heart rate, and height, significant inverse relations with PPA were found for waist-to-hip ratio, triglycerides, smoking, pack-years, and hypertension. Furthermore, an increased PPA was significantly inversely related to aortic PWV, common CIMT, and history of symptomatic vascular disease. Finally, the Framingham risk score decreased with increasing PPA. CONCLUSION: Our study shows that a higher PPA reflects a lower vascular risk in men between 40 and 80 years of age, as shown by a better cardiovascular risk profile, a reduced PWV, common CIMT, and a lower Framingham risk of coronary heart disease.

Mineral metabolism and mortality in dialysis patients: a reassessment of the K/DOQI guideline.

BACKGROUND: Several studies found associations between higher plasma calcium and phosphorus and mortality in dialysis patients. However, different predefined categories and reference values were applied and the precise shape of these relationships remains unclear. METHODS: We evaluated 1,621 patients from NECOSAD, a prospective multicenter cohort study of incident dialysis patients (60 +/- 15 years, 61% male, 64% hemodialysis). We used multivariate Cox regression and restricted cubic spline regression to study the effects of time-updated plasma concentrations on mortality in a flexible manner. RESULTS: 486 patients (30%) died during follow-up. Elevated phosphorus concentration was associated with higher mortality (p = 0.0009). The association of high calcium with mortality was borderline significant (p = 0.07). Within the studied ranges, we could not identify a threshold where an appreciable change in mortality risk occurred. CONCLUSIONS: Mortality risk started to increase at a relatively low phosphorus concentration (4.5 mg/dl). Low-normal calcium combined with low-normal phosphorus concentration was associated with the lowest mortality.

Complement Component C1q as Serum Biomarker to Detect Active Tuberculosis.

Background: Tuberculosis (TB) remains a major threat to global health. Currently, diagnosis of active TB is hampered by the lack of specific biomarkers that discriminate active TB disease from other (lung) diseases or latent TB infection (LTBI). Integrated human gene expression results have shown that genes encoding complement components, in particular different C1q chains, were expressed at higher levels in active TB compared to LTBI. Methods: C1q protein levels were determined using ELISA in sera from patients, from geographically distinct populations, with active TB, LTBI as well as disease controls. Results: Serum levels of C1q were increased in active TB compared to LTBI in four independent cohorts with an AUC of 0.77 [0.70; 0.83]. After 6 months of TB treatment, levels of C1q were similar to those of endemic controls, indicating an association with disease rather than individual genetic predisposition. Importantly, C1q levels in sera of TB patients were significantly higher as compared to patients with sarcoidosis or pneumonia, clinically important differential diagnoses. Moreover, exposure to other mycobacteria, such as Mycobacterium leprae (leprosy patients) or BCG (vaccinees) did not result in elevated levels of serum C1q. In agreement with the human data, in non-human primates challenged with Mycobacterium tuberculosis, increased serum C1q levels were detected in animals that developed progressive disease, not in those that controlled the infection. Conclusions: In summary, C1q levels are elevated in patients with active TB compared to LTBI in four independent cohorts. Furthermore, C1q levels from patients with TB were also elevated compared to patients with sarcoidosis, leprosy and pneumonia. Additionally, also in NHP we observed increased C1q levels in animals with active progressive TB, both in serum and in broncho-alveolar lavage. Therefore, we propose that the addition of C1q to current biomarker panels may provide added value in the diagnosis of active TB.

How to assess mean blood pressure properly at the brachial artery level.

OBJECTIVES: Mean arterial pressure at the upper arm is traditionally calculated by adding one-third of the pulse pressure to the diastolic pressure. We questioned the general validity of this formula. METHODS: We used previously recorded resting intrabrachial pressure and Riva-Rocci Korotkoff blood pressure measurements in 57 subjects (study A) and 24-h intra-arterial recordings obtained in 22 ambulant subjects (study B). RESULTS: In study A the intra-arterially measured 'real' mean pressure was found at 39.5 +/- 2.5% of pulse pressure above diastolic pressure, namely at a level higher than the expected 33.3% of pulse pressure, in all individuals. Results were not related to age, blood pressure, pulse pressure or heart rate levels. Mean pressure calculated with the traditional one-third rule therefore underestimated 'real' mean pressure by 5.0 +/- 2.3 mmHg (P < 0.01) when calculated from intra-arterial pressure readings, and by 4.9 +/- 5.3 mmHg (P < 0.01) when calculated from Riva-Rocci Korotkoff readings. In study B we showed activity-related variations in the relative level of the 'real' mean pressure, which increased by 1.8 +/- 1.4% (P < 0.01) during sleep, and decreased by 0.5 +/- 0.9% during walking (P < 0.05) and by 0.8 +/- 1.3% during cycling (P < 0.01). CONCLUSION: The mean pressure at the upper arm is underestimated when calculated using the traditional formula of adding one-third of the pulse pressure to the diastolic pressure. This underestimation can be avoided by adding 40% of pulse pressure to the diastolic pressure. The proposed approach needs to be validated through larger scale studies.

Accuracy of Cuff-Measured Blood Pressure: Systematic Reviews and Meta-Analyses.

BACKGROUND: Hypertension (HTN) is the single greatest cardiovascular risk factor worldwide. HTN management is usually guided by brachial cuff blood pressure (BP), but questions have been raised regarding accuracy. OBJECTIVES: This comprehensive analysis determined the accuracy of cuff BP and the consequent effect on BP classification compared with intra-arterial BP reference standards. METHODS: Three individual participant data meta-analyses were conducted among studies (from the 1950s to 2016) that measured intra-arterial aortic BP, intra-arterial brachial BP, and cuff BP. RESULTS: A total of 74 studies with 3,073 participants were included. Intra-arterial brachial systolic blood pressure (SBP) was higher than aortic values (8.0 mm Hg; 95% confidence interval [CI]: 5.9 to 10.1 mm Hg; p < 0.0001) and intra-arterial brachial diastolic BP was lower than aortic values (-1.0 mm Hg; 95% CI: -2.0 to -0.1 mm Hg; p = 0.038). Cuff BP underestimated intra-arterial brachial SBP (-5.7 mm Hg; 95% CI: -8.0 to -3.5 mm Hg; p < 0.0001) but overestimated intra-arterial diastolic BP (5.5 mm Hg; 95% CI: 3.5 to 7.5 mm Hg; p < 0.0001). Cuff and intra-arterial aortic SBP showed a small mean difference (0.3 mm Hg; 95% CI: -1.5 to 2.1 mm Hg; p = 0.77) but poor agreement (mean absolute difference 8.0 mm Hg; 95% CI: 7.1 to 8.9 mm Hg). Concordance between BP classification using the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure cuff BP (normal, pre-HTN, and HTN stages 1 and 2) compared with intra-arterial brachial BP was 60%, 50%, 53%, and 80%, and using intra-arterial aortic BP was 79%, 57%, 52%, and 76%, respectively. Using revised intra-arterial thresholds based on cuff BP percentile rank, concordance between BP classification using cuff BP compared with intra-arterial brachial BP was 71%, 66%, 52%, and 76%, and using intra-arterial aortic BP was 74%, 61%, 56%, and 65%, respectively. CONCLUSIONS: Cuff BP has variable accuracy for measuring either brachial or aortic intra-arterial BP, and this adversely influences correct BP classification. These findings indicate that stronger accuracy standards for BP devices may improve cardiovascular risk management.

Non-invasively measured structural and functional arterial characteristics and coronary heart disease risk in middle aged and elderly men.

BACKGROUND: In cardiovascular (CV) epidemiology, interest increases in studying etiologic and prognostic implications of early structural or functional changes of the large arteries. Examples of such measurements are pulse wave velocity (PWV), carotid intima-media thickness (CIMT) and augmentation index (AIx). PWV and CIMT are established markers of CV risk whereas the role of AIx as indicator of risk has not fully been established. Therefore, our aim was to relate AIx to CV risk and to compare the magnitude of relations of PWV, CIMT and AIx to CV risk. METHODS: Two hundred and ninty-nine men free from cardiovascular disease (mean age 59.2 years), participated in this cross-sectional study. Cardiovascular risk profile was determined and 10-year coronary heart disease risk was estimated using the Framingham risk score (FRS). PWV, CIMT and AIx were measured and data were analyzed using linear regression models. RESULTS: PWV and CIMT were strongest related to FRS whereas AIx showed the weakest relation. Ten-year coronary heart disease risk increased 6.24%, 95% confidence interval (CI) [5.11;7.37] per standard deviation (S.D.) increase in PWV, 6.39% [5.24;7.54] per S.D. increase in CIMT and 2.50% [1.19;3.80] per S.D. increase in AIx. CONCLUSION: In middle aged and elderly men AIx is related to CV risk. However, compared with AIx, PWV and CIMT seem better markers of cardiovascular risk.

Noninvasive arterial measurements of vascular damage in healthy young adults: relation to coronary heart disease risk.

PURPOSE: There is an increasing interest in noninvasive measurements of early structural or functional changes in large arteries such as pulse wave velocity (PWV), carotid intima-media thickness (CIMT), and augmentation index (AIx). These measurements may be applied in etiologic or prognostic research. The role of the AIx as a marker of cardiovascular risk has not fully been established. Our aim was to study whether AIx is related to coronary heart disease (CHD) risk and to compare the strength of the relations of AIx, PWV, and CIMT with cardiovascular risk in healthy young adults. METHODS: Our study included 224 men and 273 women (mean age 28 years, range 27-30 years) from the Atherosclerosis Risk in Young Adults (ARYA) study. Cardiovascular risk profile was determined and CHD risk was estimated using the Framingham risk score. AIx, PWV and CIMT were measured using standard methods. Data were analyzed in strata of gender using linear regression models. RESULTS: In men, PWV and CIMT were most strongly related to CHD risk. The increase in CHD risk per standard deviation increase in measurement was 0.24%/m/s, 95% CI (0.01;0.33) and 0.32%/mm, 95% CI (0.08;0.55), whereas the AIx was not significantly related to CHD risk (0.09 %/% 95% CI [-0.15;0.33]). In women, AIx, PWV, and CIMT were weakly but significantly related to CHD risk; there was no clear difference between the measurements. CONCLUSION: In young men, PWV and CIMT are better measures of CHD risk than AIx. In women, AIx, PWV and CIMT estimate CHD risk equally well.

The Kidney Disease Outcomes Quality Initiative (K/DOQI) Guideline for Bone Metabolism and Disease in CKD: association with mortality in dialysis patients.

BACKGROUND: In 2003, the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (K/DOQI) published a guideline recommending tight control of serum calcium, phosphorus, calcium-phosphorus product (Ca x P), and intact parathyroid hormone levels in patients with chronic kidney disease. Within the context of this guideline, we explored associations of these plasma concentrations with all-cause mortality risk in incident dialysis patients in The Netherlands. METHODS: In a large, prospective, multicenter, cohort study (Netherlands Cooperative Study on the Adequacy of Dialysis), we included 1,629 patients new on hemodialysis or peritoneal dialysis therapy between 1997 and 2004. Multivariate Cox regression models containing calcium level, phosphorus level, intact parathyroid hormone level, age, comorbidity, primary kidney disease, nutritional status, albumin level, dialysis dose, and hemoglobin level were used to examine mortality risks. RESULTS: Mean age was 60 +/- 15 (SD) years, 61% were men, and 64% were treated with hemodialysis. In adjusted time-dependent survival analysis, all-cause mortality risk increased in hemodialysis patients by 40% (hazard ratio [HR], 1.4; 95% confidence interval [CI], 1.1 to 1.7) and in peritoneal dialysis patients by 60% (HR, 1.6; 95% CI, 1.1 to 2.4) for plasma phosphorus levels greater than the target. In addition, having elevated plasma Ca x P product levels increased mortality risk by 40% (HR, 1.4; 95% CI, 1.1 to 1.8) in hemodialysis patients and 50% in peritoneal dialysis patients (HR, 1.5; 95% CI, 1.0 to 2.2). In both patient groups, no significant effects were observed for plasma levels less than the targets. CONCLUSION: In time-dependent survival analysis, the presence of plasma phosphorus and Ca x P product concentrations greater than K/DOQI targets increased all-cause mortality risk in hemodialysis and peritoneal dialysis patients.

Alcohol consumption and augmentation index in healthy young men: the ARYA study.

BACKGROUND: Light-to-moderate alcohol consumption is associated with a decreased risk of ischemic cardiovascular disease, whereas increased alcohol intake is related to hypertension and intracerebral hemorrhage. We studied the effect of alcohol consumption on the augmentation index (AIx), a measure of arterial wave reflection in a population of healthy young men. METHODS: Three hundred twenty-nine men (mean age 28 years) from the Atherosclerosis Risk in Young Adults study (ARYA-study) were studied. The level of alcohol consumption and risk factors for cardiovascular disease were determined. The AIx was estimated by radial applanation tonometry using a Sphygmocor device. The relation between alcohol intake level and AIx was determined using linear regression models. RESULTS: There was a positive graded relation between alcohol intake and AIx. Subjects who did not drink, who drank 1 to 2 glasses/d, or who drank > or =3 glasses of alcohol/d had, respectively, a -0.6% (95% confidence interval [CI] -4.2, 3.0), 0.2% (95% CI -2.6, 2.9), and 3.4% (95% CI 0.2, 6.7) difference in AIx compared with very light drinkers (<1 glass/d). After adjustment for current smoking, body mass index and HDL-cholesterol, those consuming >3 glasses/d had a 3.29% (95% confidence interval CI 0.01, 6.7) higher AIx compared with those consuming <1 glass/d. CONCLUSIONS: In a population of healthy young men, the heaviest drinkers had a significantly higher AIx. This finding supports the evidence that increased alcohol consumption is related to vascular damage at young age.