Effect of Hemodiafiltration or Hemodialysis on Mortality in Kidney Failure.

BACKGROUND: Several studies have suggested that patients with kidney failure may benefit from high-dose hemodiafiltration as compared with standard hemodialysis. However, given the limitations of the various published studies, additional data are needed. METHODS: We conducted a pragmatic, multinational, randomized, controlled trial involving patients with kidney failure who had received high-flux hemodialysis for at least 3 months. All the patients were deemed to be candidates for a convection volume of at least 23 liters per session (as required for high-dose hemodiafiltration) and were able to complete patient-reported outcome assessments. The patients were assigned to receive high-dose hemodiafiltration or continuation of conventional high-flux hemodialysis. The primary outcome was death from any cause. Key secondary outcomes were cause-specific death, a composite of fatal or nonfatal cardiovascular events, kidney transplantation, and recurrent all-cause or infection-related hospitalizations. RESULTS: A total of 1360 patients underwent randomization: 683 to receive high-dose hemodiafiltration and 677 to receive high-flux hemodialysis. The median follow-up was 30 months (interquartile range, 27 to 38). The mean convection volume during the trial in the hemodiafiltration group was 25.3 liters per session. Death from any cause occurred in 118 patients (17.3%) in the hemodiafiltration group and in 148 patients (21.9%) in the hemodialysis group (hazard ratio, 0.77; 95% confidence interval, 0.65 to 0.93). CONCLUSIONS: In patients with kidney failure resulting in kidney-replacement therapy, the use of high-dose hemodiafiltration resulted in a lower risk of death from any cause than conventional high-flux hemodialysis. (Funded by the European Commission Research and Innovation; CONVINCE Dutch Trial Register number, NTR7138.).

Rationale and design for the randomized placebo-controlled double-blind trial studying the effect of single antiplatelet therapy (clopidogrel) versus dual antiplatelet therapy (clopidogrel/acetylsalicylic acid) on the occurrence of atherothrombotic events following lower extremity peripheral transluminal angioplasty (CLEAR-PATH).

RATIONALE: Antiplatelet therapy (APT) is the standard of care after endovascular revascularization (EVR) in patients with peripheral artery disease (PAD). APT aims to prevent both major adverse cardiovascular events (MACE) and major adverse limb events (MALE). Nonetheless, the rates of MACE and MALE after EVR remain high. In coronary artery and cerebrovascular disease, dual APT (DAPT)compared to acetylsalicylic acid alone has been proven to reduce MACE without increasing the risk of major bleeding when applied for a restricted number of weeks. However, within the PAD population, insufficient data are available to understand the potential attributable effect of DAPT over single APT (SAPT). Therefore, prospective randomized studies in targeted study populations are warranted. TRIAL DESIGN: CLEAR-PATH is a Dutch multicenter, double-blind, placebo-controlled, randomized trial comparing SAPT (clopidogrel 75 mg plus placebo) with DAPT (clopidogrel 75 mg plus acetylsalicylic acid 80 mg) in patients with PAD undergoing EVR. CLEAR-PATH includes a time-to-event analysis with a follow-up of one year. The primary composite efficacy endpoint consists of all-cause mortality, nonfatal stroke, nonfatal myocardial infarction, severe limb ischemia, (indication for) re-intervention due to any symptomatic restenosis, re-occlusion, or due to acute limb ischemia, and major amputation. The primary safety endpoint contains major bleeding following the Thrombolysis in Myocardial Infarction classification. The enrolment started in August 2022. In total 450 primary efficacy outcome events are required which expectedly amounts to 1696 subjects. Recruitment will take approximately 36 months. CONCLUSION: CLEAR-PATH will assess the efficacy and safety of DAPT compared to SAPT following EVR in PAD patients. TRIAL REGISTRATION NUMBER: NL80009.041.21.

Dutch cardio-oncology cohort: Incident cardiovascular disease predisposes to a higher cancer mortality rate.

BACKGROUND: Cardiovascular disease (CVD) and cancer are the two leading causes of death worldwide. Given their high prevalence, it is important to understand the disease burden of cancer mortality in CVD patients. OBJECTIVE: We aimed to evaluate whether patients with incident CVD have a higher risk of malignancy-related mortality, compared to the general population without CVD. METHODS: We performed a national population-based cohort study selecting patients with incident CVD in the Netherlands between 01 April 2000 and 31 December 2005. A reference cohort was selected from the Dutch population using age, sex and ethnicity. Mortality follow-up data were evaluated after data linkage of national registries from Statistics Netherlands until 31 December 2020. RESULTS: A total of 2,240,879 individuals were selected with a mean follow-up of 12 years (range 0.4-21.0), of which 738,666 patients with incident CVD with a mean age of 71 ± 15 years. Malignancy mortality per 1000 person years was 84 for the reference group and 118 for patients with CVD, with the highest rate of 258 in patients with heart failure. Patients with CVD had a higher malignancy mortality risk, compared to the reference group: HR 1.35 (95%CI 1.33-1.36). Highest risks were observed in patients with venous diseases (HR 2.27, 95%CI 2.17-2.36) and peripheral artery disease (HR 1.87, 95%CI 1.84-2.01). CONCLUSION: Results show that CVD predisposes to a higher cancer mortality rate. Of all CVD subtypes, HF patients have the highest cancer mortality rate and the hazards were highest in patients with venous diseases and peripheral artery disease.

Prognostic Factors and Models to Predict Mortality Outcomes in Patients with Peripheral Arterial Disease: A Systematic Review.

OBJECTIVE: Predicting adverse outcomes in patients with peripheral arterial disease (PAD) is a complex task owing to the heterogeneity in patient and disease characteristics. This systematic review aimed to identify prognostic factors and prognostic models to predict mortality outcomes in patients with PAD Fontaine stage I - III or Rutherford category 0 - 4. DATA SOURCES: PubMed, Embase, and Cochrane Database of Systematic Reviews were searched to identify studies examining individual prognostic factors or studies aiming to develop or validate a prognostic model for mortality outcomes in patients with PAD. REVIEW METHODS: Information on study design, patient population, prognostic factors, and prognostic model characteristics was extracted, and risk of bias was evaluated. RESULTS: Sixty nine studies investigated prognostic factors for mortality outcomes in PAD. Over 80 single prognostic factors were identified, with age as a predictor of death in most of the studies. Other common factors included sex, diabetes, and smoking status. Six studies had low risk of bias in all domains, and the remainder had an unclear or high risk of bias in at least one domain. Eight studies developed or validated a prognostic model. All models included age in their primary model, but not sex. All studies had similar discrimination levels of > 70%. Five of the studies on prognostic models had an overall high risk of bias, whereas two studies had an overall unclear risk of bias. CONCLUSION: This systematic review shows that a large number of prognostic studies have been published, with heterogeneity in patient populations, outcomes, and risk of bias. Factors such as sex, age, diabetes, hypertension, and smoking are significant in predicting mortality risk among patients with PAD Fontaine stage I - III or Rutherford category 0 - 4.

The Effect of Artificial Intelligence on Patient-Physician Trust: Cross-Sectional Vignette Study.

BACKGROUND: Clinical decision support systems (CDSSs) based on routine care data, using artificial intelligence (AI), are increasingly being developed. Previous studies focused largely on the technical aspects of using AI, but the acceptability of these technologies by patients remains unclear. OBJECTIVE: We aimed to investigate whether patient-physician trust is affected when medical decision-making is supported by a CDSS. METHODS: We conducted a vignette study among the patient panel (N=860) of the University Medical Center Utrecht, the Netherlands. Patients were randomly assigned into 4 groups-either the intervention or control groups of the high-risk or low-risk cases. In both the high-risk and low-risk case groups, a physician made a treatment decision with (intervention groups) or without (control groups) the support of a CDSS. Using a questionnaire with a 7-point Likert scale, with 1 indicating "strongly disagree" and 7 indicating "strongly agree," we collected data on patient-physician trust in 3 dimensions: competence, integrity, and benevolence. We assessed differences in patient-physician trust between the control and intervention groups per case using Mann-Whitney U tests and potential effect modification by the participant's sex, age, education level, general trust in health care, and general trust in technology using multivariate analyses of (co)variance. RESULTS: In total, 398 patients participated. In the high-risk case, median perceived competence and integrity were lower in the intervention group compared to the control group but not statistically significant (5.8 vs 5.6; P=.16 and 6.3 vs 6.0; P=.06, respectively). However, the effect of a CDSS application on the perceived competence of the physician depended on the participant's sex (P=.03). Although no between-group differences were found in men, in women, the perception of the physician's competence and integrity was significantly lower in the intervention compared to the control group (P=.009 and P=.01, respectively). In the low-risk case, no differences in trust between the groups were found. However, increased trust in technology positively influenced the perceived benevolence and integrity in the low-risk case (P=.009 and P=.04, respectively). CONCLUSIONS: We found that, in general, patient-physician trust was high. However, our findings indicate a potentially negative effect of AI applications on the patient-physician relationship, especially among women and in high-risk situations. Trust in technology, in general, might increase the likelihood of embracing the use of CDSSs by treating professionals.

Sex differences in body composition in people with prediabetes and type 2 diabetes as compared with people with normal glucose metabolism: the Maastricht Study.

AIMS/HYPOTHESIS: Obesity is a major risk factor for type 2 diabetes. However, body composition differs between women and men. In this study we investigate the association between diabetes status and body composition and whether this association is moderated by sex. METHODS: In a population-based cohort study (n=7639; age 40-75 years, 50% women, 25% type 2 diabetes), we estimated the sex-specific associations, and differences therein, of prediabetes (i.e. impaired fasting glucose and/or impaired glucose tolerance) and type 2 diabetes (reference: normal glucose metabolism [NGM]) with dual-energy x-ray absorptiometry (DEXA)- and MRI-derived measures of body composition and with hip circumference. Sex differences were analysed using adjusted regression models with interaction terms of sex-by-diabetes status. RESULTS: Compared with their NGM counterparts, both women and men with prediabetes and type 2 diabetes had more fat and lean mass and a greater hip circumference. The differences in subcutaneous adipose tissue, hip circumference and total and peripheral lean mass between type 2 diabetes and NGM were greater in women than men (women minus men [W-M] mean difference [95% CI]: 15.0 cm2 [1.5, 28.5], 3.2 cm [2.2, 4.1], 690 g [8, 1372] and 443 g [142, 744], respectively). The difference in visceral adipose tissue between type 2 diabetes and NGM was greater in men than women (W-M mean difference [95% CI]: -14.8 cm2 [-26.4, -3.1]). There was no sex difference in the percentage of liver fat between type 2 diabetes and NGM. The differences in measures of body composition between prediabetes and NGM were generally in the same direction, but were not significantly different between women and men. CONCLUSIONS/INTERPRETATION: This study indicates that there are sex differences in body composition associated with type 2 diabetes. The pathophysiological significance of these sex-associated differences requires further study.

Temporal Trends and Determinants of Stroke Risk in Patients With Medically Treated Asymptomatic Carotid Stenosis.

BACKGROUND: Effectiveness of carotid procedures (surgery and stenting) in patients with asymptomatic carotid artery stenosis (ACAS) depends on the absolute risk reduction that patients might receive from these procedures. We aimed to quantify the risk of ipsilateral ischemic stroke and examined temporal trends and determinants of these risks in patients with ACAS treated conservatively. METHODS: We conducted a systematic review from inception to March 9, 2023, of peer-reviewed trials and cohort studies describing ipsilateral ischemic stroke risk in medically treated patients with ACAS of ≥50%. Risk of bias was assessed with an adapted version of the Quality in Prognosis Studies tool. We calculated the annual incidence rates of ipsilateral ischemic stroke. We explored temporal trends and associations of sex and degree of stenosis with ipsilateral ischemic stroke using Poisson metaregression analysis and incidence rate ratios, respectively. RESULTS: After screening 5915 reports, 73 studies describing ipsilateral ischemic stroke rates of 28 625 patients with midyear of recruitment ranging from 1976 to 2014 were included. The incidence of ipsilateral ischemic stroke was 0.98 (95% CI, 0.93-1.04) per 100 patient-years (median duration of follow-up, 3.3 years). The incidence decreased 24% with every 5 years more recent midyear of recruitment (rate ratio, 0.76 [95% CI, 0.73-0.78]). Incidence rates of ipsilateral ischemic stroke were lower in female patients (rate ratio, 0.74 [95% CI, 0.63-0.87]) and in patients with moderate versus severe stenosis when assessed in cohort studies, with incidence rate ratios of 0.41 ([95% CI, 0.35-0.49] cutoff, 70%) and 0.42 ([95% CI, 0.30-0.59] cutoff, 80%). CONCLUSIONS: Reported risks of ipsilateral ischemic stroke in patients with ACAS have declined 24% every 5 years from mid-1970s onward, further challenging the routine use of carotid procedures. Risks were lower in female patients and more than twice as high with severe compared with moderate ACAS. Inclusion of these findings in individualized risk assessment can help to determine the benefit of carotid procedures in selected individual patients with ACAS. REGISTRATION: URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42021222940.

Long-term peridialytic blood pressure changes are related to mortality.

BACKGROUND: In chronic haemodialysis (HD) patients, the relationship between long-term peridialytic blood pressure (BP) changes and mortality has not been investigated. METHODS: To evaluate whether long-term changes in peridialytic BP are related to mortality and whether treatment with HD or haemodiafiltration (HDF) differs in this respect, the combined individual participant data of three randomized controlled trials comparing HD with HDF were used. Time-varying Cox regression and joint models were applied. RESULTS: During a median follow-up of 2.94 years, 609 of 2011 patients died. As for pre-dialytic systolic BP (pre-SBP), a severe decline (≥21 mmHg) in the preceding 6 months was independently related to increased mortality [hazard ratio (HR) 1.61, P = .01] when compared with a moderate increase. Likewise, a severe decline in post-dialytic diastolic BP (DBP) was associated with increased mortality (adjusted HR 1.96, P < .0005). In contrast, joint models showed that every 5-mmHg increase in pre-SBP and post-DBP during total follow-up was related to reduced mortality (adjusted HR 0.97, P = .01 and 0.94, P = .03, respectively). No interaction was observed between BP changes and treatment modality. CONCLUSION: Severe declines in pre-SBP and post-DBP in the preceding 6 months were independently related to mortality. Therefore peridialytic BP values should be interpreted in the context of their changes and not solely as an absolute value.

Ethnic Differences in Carotid Intima Media Thickness and Plaque Presence - The HELIUS study.

Introduction In the Netherlands, the prevalence of cardiovascular diseases (CVD) is higher among South-Asian Surinamese and lower among Moroccans compared to the Dutch. Traditional risk factors for atherosclerotic CVD do not fully explain these disparities. We aim to assess ethnic differences in plaque presence and intima media thickness (cIMT) and explore to which extent these differences are explained by traditional risk factors. Methods We used cross-sectional data from a subgroup of participants enrolled in the multi-ethnic population-based HEalthy Life In an Urban Setting (HELIUS) study who underwent carotid ultrasonography. Logistic and linear regression models were built to assess ethnic differences in plaque presence and cIMT with the Dutch population as reference. Additional models were created to adjust for socioeconomic status, body height and cardiovascular risk factors. Results Of the 3022 participants, 1183, 1051 and 790 individuals were of Dutch, South-Asian Surinamese and Moroccan descent. Mean age was 60.9 years (SD 8.0), 52.8% was female. Compared to the Dutch, we found lower odds for plaque presence in Moroccans (0.77, 95% CI 0.62; 0.95) and no significant differences between the South-Asian Surinamese and Dutch population (0.91, 95% CI 0.76; 1.10). After adjustment for CVD risk factors, we found a lower plaque presence in South-Asian Surinamese (0.63, 95% CI 0.48; 0.82). In both Moroccan and South-Asian Surinamese individuals, adjustment for socioeconomic status did not materially change the results. cIMT was lower in South-Asian Surinamese compared to the Dutch (-17.9 µm, 95% CI -27.9; -7.9) and partly explained by ethnic differences in body height as South-Asian Surinamese individuals were, on average, shorter than the Dutch population. No differences in cIMT between Moroccans and Dutch were found. Conclusions cIMT and plaque prevalence differ between ethnic groups independent of CVD risk. Lower plaque prevalence in Moroccans was partly attributable to a lower prevalence of traditional CVD risk factors, while body height was an important contributor to differences in cIMT in South-Asians. This study emphasizes the need for ethnic-specific cut-off values for plaque presence and cIMT.

Asking informed consent may lead to significant participation bias and suboptimal cardiovascular risk management in learning healthcare systems.

BACKGROUND: The Utrecht Cardiovascular Cohort - CardioVascular Risk Management (UCC-CVRM) was set up as a learning healthcare system (LHS), aiming at guideline based cardiovascular risk factor measurement in all patients in routine clinical care. However, not all patients provided informed consent, which may lead to participation bias. We aimed to study participation bias in a LHS by assessing differences in and completeness of cardiovascular risk management (CVRM) indicators in electronic health records (EHRs) of consenting, non-consenting, and non-responding patients, using the UCC-CVRM as an example. METHODS: All patients visiting the University Medical Center Utrecht for first time evaluation of a(n) (a)symptomatic vascular disease or condition were invited to participate. Routine care data was collected in the EHR and an informed consent was asked. Differences in patient characteristics were compared between consent groups. We performed multivariable logistic regression to identify determinants of non-consent. We used multinomial regression for an exploratory analysis for the determinants of non-response. Presence of CVRM indicators were compared between consent groups. A waiver (19/641) was obtained from our ethics committee. RESULTS: Out of 5730 patients invited, 2378 were consenting, 1907 non-consenting, and 1445 non-responding. Non-consent was related to young and old age, lower education level, lower BMI, physical activity and haemoglobin levels, higher heartrate, cardiovascular disease history and absence of proteinuria. Non-response increased with young and old age, higher education level, physical activity, HbA1c and decreased with lower levels of haemoglobin, BMI, and systolic blood pressure. Presence of CVRM indicators was 5-30% lower in non-consenting patients and even lower in non-responding patients, compared to consenting patients. Non-consent and non-response varied across specialisms. CONCLUSIONS: A traditional informed consent procedure in a LHS may lead to participation bias and potentially to suboptimal CVRM, which is detrimental for feedback on findings in a LHS. This underlines the importance of reassessing the informed consent procedure in a LHS.

Antioxidants for adults with chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is a significant risk factor for cardiovascular disease (CVD) and death. Increased oxidative stress in people with CKD has been implicated as a potential causative factor. Antioxidant therapy decreases oxidative stress and may consequently reduce cardiovascular morbidity and death in people with CKD. This is an update of a Cochrane review first published in 2012. OBJECTIVES: To examine the benefits and harms of antioxidant therapy on death and cardiovascular and kidney endpoints in adults with CKD stages 3 to 5, patients undergoing dialysis, and kidney transplant recipients. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies until 15 November 2022 using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov. SELECTION CRITERIA: We included all randomised controlled trials investigating the use of antioxidants, compared with placebo, usual or standard care, no treatment, or other antioxidants, for adults with CKD on cardiovascular and kidney endpoints. DATA COLLECTION AND ANALYSIS: Titles and abstracts were screened independently by two authors who also performed data extraction using standardised forms. Results were pooled using random effects models and expressed as risk ratios (RR) or mean difference (MD) with 95% confidence intervals (CI). Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: We included 95 studies (10,468 randomised patients) that evaluated antioxidant therapy in adults with non-dialysis-dependent CKD (31 studies, 5342 patients), dialysis-dependent CKD (41 studies, 3444 patients) and kidney transplant recipients (21 studies, 1529 patients). Two studies enrolled dialysis and non-dialysis patients (153 patients). Twenty-one studies assessed the effects of vitamin antioxidants, and 74 assessed the effects of non-vitamin antioxidants. Overall, the quality of included studies was moderate to low or very low due to unclear or high risk of bias for randomisation, allocation concealment, blinding, and loss to follow-up. Compared with placebo, usual care, or no treatment, antioxidant therapy may have little or no effect on cardiovascular death (8 studies, 3813 patients: RR 0.94, 95% CI 0.64 to 1.40; I² = 33%; low certainty of evidence) and probably has little to no effect on death (any cause) (45 studies, 7530 patients: RR 0.95, 95% CI 0.82 to 1.11; I² = 0%; moderate certainty of evidence), CVD (16 studies, 4768 patients: RR 0.79, 95% CI 0.63 to 0.99; I² = 23%; moderate certainty of evidence), or loss of kidney transplant (graft loss) (11 studies, 1053 patients: RR 0.88, 95% CI 0.67 to 1.17; I² = 0%; moderate certainty of evidence). Compared with placebo, usual care, or no treatment, antioxidants had little to no effect on the slope of urinary albumin/creatinine ratio (change in UACR) (7 studies, 1286 patients: MD -0.04 mg/mmol, 95% CI -0.55 to 0.47; I² = 37%; very low certainty of evidence) but the evidence is very uncertain. Antioxidants probably reduced the progression to kidney failure (10 studies, 3201 patients: RR 0.65, 95% CI 0.41 to 1.02; I² = 41%; moderate certainty of evidence), may improve the slope of estimated glomerular filtration rate (change in eGFR) (28 studies, 4128 patients: MD 3.65 mL/min/1.73 m², 95% CI 2.81 to 4.50; I² = 99%; low certainty of evidence), but had uncertain effects on the slope of serum creatinine (change in SCr) (16 studies, 3180 patients: MD -13.35 µmol/L, 95% CI -23.49 to -3.23; I² = 98%; very low certainty of evidence). Possible safety concerns are an observed increase in the risk of infection (14 studies, 3697 patients: RR 1.30, 95% CI 1.14 to 1.50; I² = 3%; moderate certainty of evidence) and heart failure (6 studies, 3733 patients: RR 1.40, 95% CI 1.11 to 1.75; I² = 0; moderate certainty of evidence) among antioxidant users. Results of studies with a low risk of bias or longer follow-ups generally were comparable to the main analyses. AUTHORS' CONCLUSIONS: We found no evidence that antioxidants reduced death or improved kidney transplant outcomes or proteinuria in patients with CKD. Antioxidants likely reduce cardiovascular events and progression to kidney failure and may improve kidney function. Possible concerns are an increased risk of infections and heart failure among antioxidant users. However, most studies were of suboptimal quality and had limited follow-up, and few included people undergoing dialysis or kidney transplant recipients. Furthermore, the large heterogeneity in interventions hampers drawing conclusions on the efficacy and safety of individual agents.

Validation of spot urine in estimating 24-h urinary sodium, potassium and sodium-to-potassium ratio during three different sodium diets in healthy adults.

PURPOSE: To evaluate the validity of spot urine assay methods in estimating the 24-h urinary sodium, potassium and sodium-to-potassium ratio during three different sodium diets. MATERIALS AND METHODS: Twelve healthy volunteers were asked to adhere to 3 dietary sodium targets (3.3-5.0g/day,<3.3 g/day and >5.0 g/day) for three consecutive weeks and to measure salt excretion daily in spot urine samples using a self-monitoring device. On day 7 of each week, 24-h urine was collected to compare measured with estimated 24-h salt excretion (by the Kawasaki, Tanaka and INTERSALT equations). RESULTS: Correlation coefficients relating measured and estimated 24-h sodium excretion were low and not significant for Kawasaki and INTERSALT and moderate for the Tanaka equation (τ 0.56-0.64,p<.05). Bland-Altman plots showed considerable differences between estimated and measured sodium excretion across all salt diets. Over 40% of the participants showed an absolute difference between measured and estimated 24-h sodium of more than 1000 mg/day. The correlation coefficients between 24-h and spot Na/K ratio were 0.67, 0.94 and 0.85(p<.05), and mean differences were 0.59, 0.06 and 0.48 for the intermediate, low and high sodium diets, respectively. CONCLUSION: These findings do not support estimation of individual 24-h salt excretion from spot urine by the Kawasaki, Tanaka, or INTERSALT formula. Plain language summaryAccurate monitoring of salt intake is essential to improve BP control. At present, measurement of sodium and potassium excretion in multiple non-consecutive 24-h urinary collections is considered the gold standard for measuring dietary sodium intake. However, this method is burdensome, time-consuming and error prone.Therefore, we assessed and compared the validity of three formula-based approaches to estimate 24-h urinary sodium and potassium excretion and the Na/K ratio from spot urine samples measured by a self-monitoring device under three different sodium diets using 24-h urine collections as the reference.We conclude that use of three commonly used equations that estimate 24-h urinary sodium and potassium excretion result in substantial bias, poor precision and poor accuracy and are therefore not recommended. The Na/K ratio based on multiple casual urine samples may be a useful, low-burden, low-cost alternative method to 24-h urine collection for monitoring daily salt intake.

Rosuvastatin Slows Progression of Carotid Intima-Media Thickness: The METEOR-China Randomized Controlled Study.

BACKGROUND: Atherosclerosis is the leading cause of cardiovascular disease worldwide, including in China. Primary prevention, through lipid-lowering, could avert development of atherosclerosis. Carotid intima-media thickness (CIMT) is a well-validated measure of atherosclerosis used in intervention studies as the primary outcome and alternative end point for cardiovascular disease events. METHODS: This randomized, double-blind, placebo-controlled, multicenter, parallel-group study assessed the effects of rosuvastatin 20 mg/d compared with placebo on progression of CIMT over 104 weeks in Chinese people with subclinical atherosclerosis. The primary end point was the annualized rate of change in mean of the maximum CIMT measurements taken 7× over the study period from each of 12 carotid artery sites (near and far walls of the right and left common carotid artery, carotid bulb, and internal carotid artery). Secondary end points included CIMT changes at different artery sites and lipid-parameter changes. Safety was also assessed. RESULTS: Participants were randomized (1:1) to receive rosuvastatin (n=272) or placebo (n=271). Baseline characteristics were well balanced between groups. The change in mean of the maximum CIMT of the 12 carotid sites was 0.0038 mm/y (95% CI, -0.0023-0.0100) for the rosuvastatin group versus 0.0142 mm/y (95% CI, 0.0080-0.0204) for the placebo group, with a difference of -0.0103 mm/y (95% CI, -0.0191 to -0.0016; P=0.020). For the CIMT secondary end points, the results were generally consistent with the primary end point. There were clinically relevant improvements in lipid parameters with rosuvastatin. We observed an adverse-event profile consistent with the known safety profile of rosuvastatin. CONCLUSIONS: Rosuvastatin 20 mg/d significantly reduced the progression of CIMT over 2 years in Chinese adults with subclinical atherosclerosis and was well tolerated. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02546323.

CONVINCE in the context of existing evidence on haemodiafiltration.

Haemodiafiltration (HDF) provides a greater removal of larger solutes and protein-bound compounds than conventional high-flux haemodialysis (HD). There are indications that the patients receiving the highest convection volumes of HDF result in improved survival compared with HD. However, the comparative efficacy of HDF versus HD remains unproven. Here we provide a comparative account of the methodology and aims of 'the comparison of high-dose HDF with high-flux HD' (CONVINCE) study in the context of the totality of evidence and how this study will contribute to reaching a higher level of certainty regarding the comparative efficacy of HDF versus HD in people with end-stage kidney disease.

Differences in Symptom Presentation in Women and Men with Confirmed Lower Limb Peripheral Artery Disease: A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate the differences in symptoms between men and women that present with lower limb peripheral artery disease (PAD). DATA SOURCES: Systematic review and meta-analysis using PubMed, EMBASE, and the Cochrane Library. REVIEW METHODS: A systematic search of the literature to identify studies that examined PAD and its symptoms using PubMed, EMBASE, and the Cochrane Library, which were screened in duplicate by two reviewers. Information on study design, source of data, population characteristics, and outcomes of interest was extracted and used the Newcastle-Ottawa Scale and Cochrane risk of bias tool. Quality of evidence was rated using the GRADE methodology. Estimates of relative effects were pooled to generate pooled odds ratios (OR) and their 95% confidence interval (CI) using a random effects model. RESULTS: Thirteen cross sectional studies, six cohorts, one case control, and one randomised clinical trial, reporting on 1 929 966 patients with confirmed PAD (established by clinical history, clinical examination, and/or ankle brachial index, or further tests) were included. Women presented less often with intermittent claudication than men (25.9% vs. 30.2%) OR 0.78 (95% CI 0.72 - 0.84, very low quality of evidence), while rest pain and atypical leg symptoms were more prevalent in women (12.8% vs. 9.2%) OR 1.40 (95% CI 1.22 - 1.60, very low quality of evidence) and (22.8% vs. 19.8%) OR 1.18 (95% CI 0.96 - 1.45, very low quality of evidence), respectively. CONCLUSION: Women with PAD more often present with rest pain, while their prevalence of intermittent claudication is lower. They also tend to present more often with atypical leg symptoms. This study underlines that PAD symptom presentation differs between the sexes. Therefore, clinicians and researchers should not consider men and women as a single population and report their data separately.

Number of measurement days needed for obtaining a reliable estimate of home blood pressure and hypertension status.

PURPOSE: Out-of-office blood pressure (BP) measurements are essential for the diagnosis and monitoring of hypertension. Current guidelines vary in their recommendations on the protocol for home blood pressure monitoring (HBPM). We aimed to assess the number of blood pressure (BP) measurement days needed for a reliable estimation of true home BP (the expected BP level over time) and hypertension status, using the European guideline-based 7-day HBPM protocol as a reference. MATERIALS AND METHODS: Data from 567 adults who performed a 7-day HBPM were analysed. Blood pressure was measured twice daily (morning and evening readings) using the Microlife Average Mode (MAM), which takes a weighted average of 3 consecutive BP readings. The variability of average BP for an increasing number of measurements was assessed using a linear mixed model including a random intercept per individual and correlated residuals. The reliability of home hypertension status was assessed by the κ statistic. RESULTS: Mean home BP of the population was 143 ± 16/84 ± 10 mm Hg. On average, the first BP measurements gave the highest values which then decreased over time. Systolic BP in the morning was systematically lower than systolic BP in the evening (142 ± 17mm Hg versus 144 ± 17 mm Hg, p <0.05). The average of 7 twice-daily MAM BP measurements was at most 5.2/3.3 mm Hg higher and 9.5/4.8 mm Hg lower than the true home BP for 95% of the individuals. Reducing this protocol to 3 days increased this variability by 1.5/1.0 mm Hg and 4.8/2.3 mm Hg, respectively. For diagnosing home hypertension, there was good agreement with a minimum of 4.5 days of HBPM (ĸ-statistic 0.88; 95% Confidence Interval: 0.82-0.94). CONCLUSION: Twice-daily MAM BP measurements for 3 consecutive days provide a reliable estimate of home BP. At least 4.5 consecutive days of HBPM are required for a reliable diagnosis of home hypertension.

Clinical characteristics do not reliably identify non-adherence in patients with uncontrolled hypertension.

PURPOSE: Chemical adherence testing is a reliable method to assess adherence to antihypertensive drugs. However, it is expensive and has limited availability in clinical practice. To reduce the number and costs of chemical adherence tests, we aimed to develop and validate a clinical screening tool to identify patients with a low probability of non-adherence in patients with uncontrolled hypertension. MATERIALS AND METHODS: In 495 patients with uncontrolled hypertension referred to the University Medical Centre Utrecht (UMCU), the Netherlands, a penalised logistic regression model including seven pre-specified easy-to-measure clinical variables was derived to estimate the probability of non-adherence. Non-adherence was defined as not detecting at least one of the prescribed antihypertensive drugs in plasma or urine. Model performance and test characteristics were evaluated in 240 patients with uncontrolled hypertension referred to the Heartlands Hospital, United Kingdom. RESULTS: Prevalence of non-adherence to antihypertensive drugs was 19% in the UMCU and 44% in the Heartlands Hospital population. After recalibration of the model's intercept, predicted probabilities agreed well with observed frequencies. The c-statistic of the model was 0.63 (95%CI 0.53-0.72). Predicted probability cut-off values of 15%-22.5% prevented testing in 5%-15% of the patients, carrying sensitivities between 97% (64-100) and 90% (80-95), and negative predictive values between 74% (10-99) and 70% (50-85). CONCLUSION: The combination of seven clinical variables is not sufficient to reliably discriminate adherent from non-adherent individuals to safely reduce the number of chemical adherence tests. This emphasises the complex nature of non-adherence behaviour and thus the need for objective chemical adherence tests in patients with uncontrolled hypertension.

Poor cardiovascular health is associated with subclinical atherosclerosis in apparently healthy sub-Saharan African populations: an H3Africa AWI-Gen study.

BACKGROUND: The cardiovascular health index (CVHI) introduced by the American Heart Association is a valid, accessible, simple, and translatable metric for monitoring cardiovascular health in a population. Components of the CVHI include the following seven cardiovascular risk factors (often captured as life's simple 7): smoking, dietary intake, physical activity, body mass index, blood pressure, glucose, and total cholesterol. We sought to expand the evidence for its utility to under-studied populations in sub-Saharan Africa, by determining its association with common carotid intima-media thickness (CIMT). METHODS: We conducted a cross-sectional study involving 9011 participants drawn from Burkina Faso, Ghana, Kenya, and South Africa. We assessed established classical cardiovascular risk factors and measured carotid intima-media thickness of the left and right common carotid arteries using B-mode ultrasonography. Adjusted multilevel mixed-effect linear regression was used to determine the association of CVHI with common CIMT. In the combined population, an individual participant data meta-analyses random-effects was used to conduct pooled comparative sub-group analyses for differences between countries, sex, and socio-economic status. RESULTS: The mean age of the study population was 51 ± 7 years and 51% were women, with a mean common CIMT of 637 ± 117 µm and CVHI score of 10.3 ± 2.0. Inverse associations were found between CVHI and common CIMT (ß-coefficients [95% confidence interval]: Burkina Faso, - 6.51 [- 9.83, - 3.20] µm; Ghana, - 5.42 [- 8.90, - 1.95]; Kenya, - 6.58 [- 9.05, - 4.10]; and South Africa, - 7.85 [- 9.65, - 6.05]). Inverse relations were observed for women (- 4.44 [- 6.23, - 2.65]) and men (- 6.27 [- 7.91, - 4.64]) in the pooled sample. Smoking (p < 0.001), physical activity (p < 0.001), and hyperglycemia (p < 0.001) were related to CIMT in women only, while blood pressure and obesity were related to CIMT in both women and men (p < 0.001). CONCLUSION: This large pan-African population study demonstrates that CVHI is a strong marker of subclinical atherosclerosis, measured by common CIMT and importantly demonstrates that primary prevention of atherosclerotic cardiovascular disease in this understudied population should target physical activity, smoking, obesity, hypertension, and hyperglycemia.

Sex differences in the association of prediabetes and type 2 diabetes with microvascular complications and function: The Maastricht Study.

BACKGROUND: Women with type 2 diabetes are disproportionally affected by macrovascular complications; we here investigated whether this is also the case for microvascular complications and retinal microvascular measures. METHODS: In a population-based cohort study of individuals aged 40-75 years (n = 3410; 49% women, 29% type 2 diabetes (oversampled by design)), we estimated sex-specific associations, and differences therein, of (pre)diabetes (reference: normal glucose metabolism), and of continuous measures of glycemia with microvascular complications and retinal measures (nephropathy, sensory neuropathy, and retinal arteriolar and venular diameters and dilatation). Sex differences were analyzed using regression models with interaction terms (i.e. sex-by- (pre)diabetes and sex-by-glycemia) and were adjusted for potential confounders. RESULTS: Men with type 2 diabetes (but not those with prediabetes) compared to men with normal glucose metabolism, (and men with higher levels of glycemia), had significantly higher prevalences of nephropathy (odds ratio: 1.58 95% CI (1.01;2.46)) and sensory neuropathy (odds ratio: 2.46 (1.67;3.63)), larger retinal arteriolar diameters (difference: 4.29 µm (1.22;7.36)) and less retinal arteriolar dilatation (difference: - 0.74% (- 1.22; - 0.25)). In women, these associations were numerically in the same direction, but generally not statistically significant (odds ratios: 1.71 (0.90;3.25) and 1.22 (0.75;1.98); differences: 0.29 µm (- 3.50;4.07) and: - 0.52% (- 1.11;0.08), respectively). Interaction analyses revealed no consistent pattern of sex differences in the associations of either prediabetes or type 2 diabetes or glycemia with microvascular complications or retinal measures. The prevalence of advanced-stage complications was too low for evaluation. CONCLUSIONS: Our findings show that women with type 2 diabetes are not disproportionately affected by early microvascular complications.