The use of imputation in clinical decision support systems: a cardiovascular risk management pilot vignette study among clinicians.

Aims: A major challenge of the use of prediction models in clinical care is missing data. Real-time imputation may alleviate this. However, to what extent clinicians accept this solution remains unknown. We aimed to assess acceptance of real-time imputation for missing patient data in a clinical decision support system (CDSS) including 10-year cardiovascular absolute risk for the individual patient. Methods and results: We performed a vignette study extending an existing CDSS with the real-time imputation method joint modelling imputation (JMI). We included 17 clinicians to use the CDSS with three different vignettes, describing potential use cases (missing data, no risk estimate; imputed values, risk estimate based on imputed data; complete information). In each vignette, missing data were introduced to mimic a situation as could occur in clinical practice. Acceptance of end-users was assessed on three different axes: clinical realism, comfortableness, and added clinical value. Overall, the imputed predictor values were found to be clinically reasonable and according to the expectations. However, for binary variables, use of a probability scale to express uncertainty was deemed inconvenient. The perceived comfortableness with imputed risk prediction was low, and confidence intervals were deemed too wide for reliable decision-making. The clinicians acknowledged added value for using JMI in clinical practice when used for educational, research, or informative purposes. Conclusion: Handling missing data in CDSS via JMI is useful, but more accurate imputations are needed to generate comfort in clinicians for use in routine care. Only then can CDSS create clinical value by improving decision-making.

Prediction of Severe Baseline Asymptomatic Carotid Stenosis and Subsequent Risk of Stroke and Cardiovascular Disease.

BACKGROUND: Risk models to identify patients at high risk of asymptomatic carotid artery stenosis (ACAS) can help in selecting patients for screening, but long-term outcomes in these patients are unknown. We assessed the diagnostic and prognostic value of the previously published Prevalence of ACAS (PACAS) risk model to detect ACAS at baseline and to predict subsequent risk of stroke and cardiovascular disease (CVD) during follow-up. METHODS: We validated the discrimination and calibration of the PACAS risk model to detect severe (≥70% narrowing) ACAS with patients from the Reduction of Atherothrombosis for Continued Health registry. We subsequently calculated the incidence rates of stroke and CVD (fatal and nonfatal stroke or myocardial infarction or vascular death) during follow-up in 4 risk groups (low, medium, high, and very high, corresponding to sum scores of ≤9, 10-13, 14-17, and ≥18, respectively). RESULTS: Among 26 384 patients, aged between 45 and 80 years, without prior carotid procedures, 1662 (6.3%) had severe baseline ACAS. During ≈70 000 patient-years of follow-up, 1124 strokes and 2484 CVD events occurred. Discrimination of the PACAS model was 0.67 (95% CI, 0.65-0.68), and calibration showed adequate concordance between predicted and observed risks of severe baseline ACAS after recalibration. Significantly higher incidence rates of stroke (Ptrend<0.011) and CVD (Ptrend<0.0001) during follow-up were found with increasing PACAS risk groups. Among patients with high PACAS sum score of ≥14 (corresponding to 27.7% of all patients), severe baseline ACAS prevalence was 11.4%. In addition, 56.6% of incident strokes and 64.9% of incident CVD events occurred in this group. CONCLUSIONS: The PACAS risk model can reliably identify patients at high risk of severe baseline ACAS. Incidence rates of stroke and CVD during follow-up were significantly higher in patients with high PACAS sum scores. Selective screening of patients with high PACAS sum scores may help to prevent future stroke or CVD.

Left Ventricular Diastolic Dysfunction across Levels of Kidney Function: A Cross-Sectional Study Based on Routine Clinical Practice Data.

Left ventricular diastolic dysfunction (LVDD) commonly coexists with kidney dysfunction. In this study, we investigated the presence of abnormalities in echocardiography parameters indicative of LVDD across stages of kidney function. Methods: We selected patients who visited a university hospital and had a serum creatinine and echocardiography reported in their medical records. Participants were categorized based on their kidney function: normal (estimated glomerular filtration rate [eGFR] ≥ 90 mL/min/1.73 m2), mildly decreased (eGFR: 60-90), moderately decreased (eGFR: 30-60), and severely decreased (eGFR < 30). The relationship between kidney function and echocardiography parameters was examined using logistic and linear regressions. Results: Among 4022 patients (age: 66.5 years [SD: 12.1], 41% women), 26%, 50%, 20%, and 4% had a normal, mildly, moderately, and severely decreased kidney function, respectively. Compared to patients with normal kidney function, patients with mildly decreased kidney function had higher odds for an abnormal E/e' ratio (OR: 1.51 [95% CI: 1.13, 2.02]). Patients with moderately decreased kidney function presented a higher risk of abnormal E/e' (OR: 2.90 [95% CI: 2.08, 4.04]), LAVI (OR: 1.62 [95% CI: 1.13, 2.33]), TR velocity (OR: 2.31 [95% CI: 1.49, 3.57]), and LVMI (OR: 1.70 [95% CI: 1.31, 2.20]), while patients with severely decreased kidney function had higher odds for abnormal E/e' (OR: 2.95 [95% CI: 1.68, 5.17]) and LVMI > 95 g/m2 in women or >115 g/m2 in men (OR: 2.07 [95% CI: 1.27, 3.38]). The linear regression showed a significant inverse association between eGFR and echocardiography parameters, meaning that with worse kidney function, the parameters for LVDD worsened as well. Conclusions: Abnormal echocardiography parameters of LVDD were present even in patients with mildly decreased kidney function. As the kidney function worsened, there was a gradual increase in the risk of abnormal parameters of LVDD.

Frequent hemodialysis versus standard hemodialysis for people with kidney failure: Systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Frequent hemodialysis provided more than three times per week may lower mortality and improve health-related quality of life. Yet, the evidence is inconclusive. We evaluated the benefits and harms of frequent hemodialysis in people with kidney failure compared with standard hemodialysis. METHODS: We performed a systematic review of randomized controlled trials including adults on hemodialysis with highly sensitive searching in MEDLINE, Embase, CENTRAL, and Google Scholar on 3 January 2024. Data were pooled using random-effects meta-analysis. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool. We adjudicated evidence certainty using GRADE. RESULTS: From 11,142 unique citations, only seven studies involving 518 participants proved eligible. The effects of frequent hemodialysis on physical and mental health were imprecise due to few data. Frequent hemodialysis probably had uncertain effect on death from all cause compared with standard hemodialysis (relative risk 0.79, 95% confidence interval 0.33-1.91, low certainty evidence). Data were not reported for death from cardiovascular causes, major cardiovascular events, fatigue or vascular access. CONCLUSION: The evidentiary basis for frequent hemodialysis is incomplete due to clinical trials with few or no events reported for mortality and cardiovascular outcome measures and few participants in which patient-reported outcomes including health-related quality of life and symptoms were reported.

Using a measurement type-independent metric to compare patterns of determinants between patient-reported versus performance-based physical function in hemodialysis patients.

PURPOSE: We applied a previously established common T-score metric for patient-reported and performance-based physical function (PF), offering the unique opportunity to directly compare measurement type-specific patterns of associations with potential laboratory-based, psychosocial, sociodemographic, and health-related determinants in hemodialysis patients. METHODS: We analyzed baseline data from the CONVINCE trial (N = 1,360), a multinational randomized controlled trial comparing high-flux hemodialysis with high-dose hemodiafiltration. To explore the associations of potential determinants with performance-based versus patient-reported PF, we conducted multiple linear regression (backward elimination with cross-validation and Lasso regression). We used standardized T-scores as estimated from the PROMIS PF short-form 4a (patient-reported PF) and the Physical Performance Test (performance-based PF) as dependent variables. RESULTS: Performance-based and patient-reported PF were both significantly associated with a laboratory marker-based indicator of muscle mass (simplified creatinine index), although the effects were relatively small (partial f2 = 0.04). Age was negatively associated with PF; the effect size was larger for performance-based (partial f2 = 0.12) than for patient-reported PF (partial f2 = 0.08). Compared to performance-based PF, patient-reported PF showed a stronger association with self-reported health domains, particularly pain interference and fatigue. When using the individual difference between patient-reported and performance-based T-scores as outcome, we found that younger age and more fatigue were associated with lower patient-reported PF compared to performance-based PF (small effect size). CONCLUSION: Patient-reported and performance-based assessments were similarly associated with an objective marker of physical impairment in hemodialysis patients. Age and fatigue may result in discrepancies when comparing performance-based and patient-reported scores on the common PF scale. Trial Registration CONVINCE is registered in the Dutch Trial Register (Register ID: NL64750.041.18). The registration can be accessed at: https://onderzoekmetmensen.nl/en/trial/52958 .

Sex differences and trends in managing cardiovascular risk factors in primary care: a dynamic cohort study.

BACKGROUND: Treatment targets for cardiovascular risk management make no distinction between women and men. AIM: To explore sex differences in achieving treatment targets in patients that participated in a nurse-led, integrated CVRM care programme in primary care between 2013 and 2019. DESIGN & SETTING: We conducted a dynamic cohort study in the Eindhoven region, south-east of The Netherlands METHOD: We assessed outcomes of three biological risk factors (systolic blood pressure, low density lipoprotein-cholesterol and estimated glomerular filtration rate) and four lifestyle factors (smoking, physical activity, alcohol intake and body mass index). Points (1=on target; 0=not on target) were assigned for biological risk factors, lifestyle factors and an overall score. Using the annual results, we applied, multivariable regression models to study trends over time and differences in trends between women and men. RESULTS: The number of participants increased from 24 889 to 38,067, mean age increased from 67.3 to 71.5 years, with around 52% women each year. The average of seven risk factors on target increased significantly from 4.6 to 4.9 in women, and from 4.7 to 5.0 in men, with no statistical difference between women and men. Differences between women and men in 2013 in the number of both biological and lifestyle factors on target did not materially change over time. CONCLUSION: Integrated cardiovascular management care led to improvements in cardiovascular risk factors on target, equally well in women than in men. Differences in risk factors on target between women and men in 2013 were still present in 2019.

The CONVINCE randomized trial found positive effects on quality of life for patients with chronic kidney disease treated with hemodiafiltration.

In the CONVINCE trial, the primary analysis demonstrated a survival benefit for patients receiving high-dose hemodiafiltration (HDF) as compared with high-flux hemodialysis (HD). A secondary objective was to evaluate effects on health-related quality of life (HRQoL); assessed in eight domains (physical function, cognitive function, fatigue, sleep disturbance, anxiety, depression, pain interference, social participation) applying instruments from the Patient-Reported Outcome Measurement Information System (PROMIS) before randomization and every three months thereafter. In total 1360 adults with dialysis-dependent chronic kidney disease, eligible to receive high-flux HDF (23 liters or more), were randomized (1:1); 84% response rate to all questionnaires. Both groups reported a continuous deterioration in all HRQoL domains. Overall, raw score changes from baseline were more favorable in the HDF group, resulting in a significant omnibus test after a median observation period of 30 months. Most relevant single raw score differences were reported for cognitive function. Patients receiving HDF reported a decline of -0.95 units (95% confidence interval - 2.23 to +0.34) whereas HD treated patients declined by -3.90 units (-5.28 to - 2.52). A joint model, adjusted for mortality differences, utilizing all quarterly assessments, identified a significantly slower HRQoL decline in physical function, cognitive function, pain interference, and social participation for the HDF group. Their physical health summary score declined -0.46 units/year slower compared to the HD group. Thus, the CONVINCE trial showed a beneficial effect of high-dose hemodiafiltration for survival as well as a moderate positive effect on patients' quality of life, most pronounced with respect to their cognitive function. REGISTRATION: NTR7138 on the International Clinical Trials Registry Platform.

Comparison of the Response to an Electronic Versus a Traditional Informed Consent Procedure in Terms of Clinical Patient Characteristics: Observational Study.

BACKGROUND: Electronic informed consent (eIC) is increasingly used in clinical research due to several benefits including increased enrollment and improved efficiency. Within a learning health care system, a pilot was conducted with an eIC for linking data from electronic health records with national registries, general practitioners, and other hospitals. OBJECTIVE: We evaluated the eIC pilot by comparing the response to the eIC with the former traditional paper-based informed consent (IC). We assessed whether the use of eIC resulted in a different study population by comparing the clinical patient characteristics between the response categories of the eIC and former face-to-face IC procedure. METHODS: All patients with increased cardiovascular risk visiting the University Medical Center Utrecht, the Netherlands, were eligible for the learning health care system. From November 2021 to August 2022, an eIC was piloted at the cardiology outpatient clinic. Prior to the pilot, a traditional face-to-face paper-based IC approach was used. Responses (ie, consent, no consent, or nonresponse) were assessed and compared between the eIC and face-to-face IC cohorts. Clinical characteristics of consenting and nonresponding patients were compared between and within the eIC and the face-to-face cohorts using multivariable regression analyses. RESULTS: A total of 2254 patients were included in the face-to-face IC cohort and 885 patients in the eIC cohort. Full consent was more often obtained in the eIC than in the face-to-face cohort (415/885, 46.9% vs 876/2254, 38.9%, respectively). Apart from lower mean hemoglobin in the full consent group of the eIC cohort (8.5 vs 8.8; P=.0021), the characteristics of the full consenting patients did not differ between the eIC and face-to-face IC cohorts. In the eIC cohort, only age differed between the full consent and the nonresponse group (median 60 vs 56; P=.0002, respectively), whereas in the face-to-face IC cohort, the full consent group seemed healthier (ie, higher hemoglobin, lower glycated hemoglobin [HbA1c], lower C-reactive protein levels) than the nonresponse group. CONCLUSIONS: More patients provided full consent using an eIC. In addition, the study population remained broadly similar. The face-to-face IC approach seemed to result in a healthier study population (ie, full consenting patients) than the patients without IC, while in the eIC cohort, the characteristics between consent groups were comparable. Thus, an eIC may lead to a better representation of the target population, increasing the generalizability of results.

Editor's Choice - 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.

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.

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.

Representation of Patients With Chronic Kidney Disease in Clinical Trials of Cardiovascular Disease Medications: A Systematic Review.

Importance: Patients with chronic kidney disease (CKD) are at high risk for cardiovascular disease, but their systematic underrepresentation in cardiovascular randomized clinical trials (RCTs) limits the generation of appropriate evidence to guide cardiovascular risk management (CVRM). Objective: To evaluate the underrepresentation of patients with CKD in cardiovascular RCTs, and to highlight evidence gaps in CVRM medications in this population. Evidence Review: A systematic search was conducted in ClinicalTrials.gov from February 2000 through October 2021 for RCTs with full-text publications. If no full-text publications were found in ClinicalTrials.gov, MEDLINE, Embase, and Google Scholar were also searched. Eligible RCTs were those evaluating the effectiveness of antiplatelets, anticoagulants, blood pressure-lowering drugs, glucose-lowering drugs, or cholesterol-lowering drugs in adults with cardiovascular disease or cardiovascular risk factors. Trials with a sample size of fewer than 100 patients were excluded. Findings: In total, 1194 RCTs involving 2 207 677 participants (mean [SD] age, 63 [6] years; 1 343 970 males [64%]) were included. Since 2000, the percentage of cardiovascular RCTs excluding patients with CKD has increased from 66% to 79% (74% overall [884 RCTs]). In 864 RCTs (72%), more patients were excluded than anticipated on safety grounds (63% [306] of trials required no dose adjustment, and 79% [561] required dose adjustment). In total, 158 RCTs (13%) reported results for patients with CKD separately (eg, in subgroup analyses). Significant evidence gaps exist in most CVRM interventions for patients with CKD, particularly for those with CKD stages 4 to 5. Twenty-three RCTs (2%) reported results for patients with an estimated glomerular filtration rate less than 30 mL/min/1.73 m2, 15 RCTs (1%) reported for patients receiving dialysis, and 1 RCT (0.1%) reported for recipients of kidney transplant. Conclusions and Relevance: Results of this systematic review suggest that representation of patients with CKD in cardiovascular RCTs has not improved in the past 2 decades and that these RCTs excluded more patients with CKD than expected on safety grounds. Lack of reporting or underreporting of results for this patient population is associated with evidence gaps in the effectiveness of most CVRM medications in patients with all stages of CKD, particularly CKD stages 4 to 5.

Practice visitations in primary care to improve performance of cardiovascular risk management: an observational study.

BACKGROUND: Despite programmatic protocolised care and structured support, considerable variation is observed in completeness of registration and achieving targets of cardiovascular risk management (CVRM) between individual GPs in the Netherlands. AIM: To determine whether completeness of registration and achieved targets of cardiovascular risk factors improves with practice visitation. DESIGN & SETTING: Observational study utilising the care group's database (2016-2019), comparing changes in registration and achieved targets in non-visited practices and visited practices. METHOD: We compared completeness scores of registration and scores of targets achieved before visitation and 1 year after visitation. Data were analysed on patient level and GP level. Separate analyses were performed among GPs who were ranked in the lower 25% of score distributions. RESULTS: We observed no clinically relevant improvements in completeness of registration and targets achieved in 2017, 2018, and 2019 that could be attributed to visitations in the previous year, both on individual patient level and on aggregated level per general practice. In practices ranked in the lower 25% of the distribution, improvements over time were clinically relevant and larger than the overall changes. Yet, these findings were irrespective of the number of practice visitations. CONCLUSION: Practice visitations in our setting did not seem to lead to improvements in practice performance, nor in completeness of registration of risk factors or in reaching predefined target goals for cardiovascular risk factors.

Patient characteristics and reasons for discontinuation in a cardiovascular risk management programme in The Netherlands.

BACKGROUND: Since 2010, an increasing number of patients have participated in a nurse-led integrated cardiovascular risk management programme in the Netherlands. Because it is important to understand which patients discontinue and why, when evaluating the effectiveness of the care programme, the aim was to identify the reasons for discontinuation. METHODS: Electronic health records of 3997 patients enrolled in a nurse-led integrated cardiovascular risk management programme that started on April 1st, 2010, were manually scrutinized for reasons for discontinuation between April 1st, 2010, and April 1st, 2018. In addition to death and moving to a diabetes care programme, we describe 7 different reasons why patients discontinued the programme and compared the patient characteristics of those who discontinued the programme without specific reasons with those who remained in the care programme for 8 years. RESULTS: Between April 1st, 2010, and April 1st, 2018, 1,190 participants (29.8%) discontinued the CVRM care programme, of whom 271 participants died (6.8%) and 195 were transferred to a diabetes care programme (4.9%). The remaining 724 patients (18.1%) participated 5 years before discontinuation. Of these, 67 (9.3%) had a previous cardiovascular event at the start of the programme. In 355 patients, a specific reason for discontinuation was not found. At baseline, these patients less frequently had a history of CVD than those who continued the programme for 8 years (1.7 vs. 22.6%), were younger (62 vs. 67 years), had less registered cardiovascular comorbidity (atrial fibrillation: 1.1 vs. 7.2%; congestive heart failure 0.3 vs. 1.2%; chronic kidney disease 0.0 vs. 4.5%), were more often smokers (13.0% vs. 4.3%) and took blood pressure- and lipid-lowering drugs twice as often. CONCLUSIONS: In our study we observed that participants who discontinued the nurse-led integrated CVRM care programme between 2010 and 2018 without specific reason or on request were younger, without previous CVD, had less cardiovascular comorbidity and were better adjusted to medication. Exploring the patients' reasons for discontinuation can contribute to an individualized approach to prevent or reduce discontinuation.

Determination of the clinical relevance of donor epitope-specific HLA-antibodies in kidney transplantation.

In kidney transplantation, survival rates are still partly impaired due to the deleterious effects of donor specific HLA antibodies (DSA). However, not all luminex-defined DSA appear to be clinically relevant. Further analysis of DSA recognizing polymorphic amino acid configurations, called eplets or functional epitopes, might improve the discrimination between clinically relevant vs. irrelevant HLA antibodies. To evaluate which donor epitope-specific HLA antibodies (DESAs) are clinically important in kidney graft survival, relevant and irrelevant DESAs were discerned in a Dutch cohort of 4690 patients using Kaplan-Meier analysis and tested in a cox proportional hazard (CPH) model including nonimmunological variables. Pre-transplant DESAs were detected in 439 patients (9.4%). The presence of certain clinically relevant DESAs was significantly associated with increased risk on graft loss in deceased donor transplantations (p < 0.0001). The antibodies recognized six epitopes of HLA Class I, 3 of HLA-DR, and 1 of HLA-DQ, and most antibodies were directed to HLA-B (47%). Fifty-three patients (69.7%) had DESA against one donor epitope (range 1-5). Long-term graft survival rate in patients with clinically relevant DESA was 32%, rendering DESA a superior parameter to classical DSA (60%). In the CPH model, the hazard ratio (95% CI) of clinically relevant DESAs was 2.45 (1.84-3.25) in deceased donation, and 2.22 (1.25-3.95) in living donation. In conclusion, the developed model shows the deleterious effect of clinically relevant DESAs on graft outcome which outperformed traditional DSA-based risk analysis on antigen level.

Association of mild kidney dysfunction with diastolic dysfunction and heart failure with preserved ejection fraction.

AIMS: We aim to investigate the association between kidney dysfunction and left ventricular diastolic dysfunction parameters and heart failure with preserved ejection fraction (HFpEF) and whether this is sex-specific. METHODS AND RESULTS: We included participants from the HELPFul observational study. Outpatient clinical care data, including echocardiography, and an expert panel judgement on HFpEF was collected. Estimated glomerular filtration rate (eGFR) was calculated by creatinine and cystatin C without race. The association between eGFR with E/e', left ventricular mass index, relative wall thickness, and stage C/D heart failure was tested by multivariable adjusted regression models, stratified by sex, reporting odds ratios and 95% confidence intervals (95% confidence interval). We analysed 880 participants, mean age 62.9 (standard deviation: 9.3) years, 69% female. Four hundred six participants had mild (37.6%) kidney dysfunction (eGFR: 60-89 mL/min/1.73 m2 ) or moderate (8.5%) kidney dysfunction (eGFR: 30-59 mL/min/1.73 m2 ). HFpEF was significantly more prevalent in participants with mild and moderate kidney dysfunction (10.3% and 16.0%, respectively) than participants with normal kidney function (3.4%). A lower kidney function was associated with higher E/e' and higher relative wall thickness values. Participants with moderate kidney dysfunction had a higher likelihood of American College of Cardiology/American Heart Association stage C/D HF (odds ratio: 2.07, 95% confidence interval: 1.23, 3.49) than participants with normal kidney functions. CONCLUSIONS: Both mild and moderate kidney dysfunction are independently associated with left ventricular diastolic dysfunction parameters and HFpEF. This association is independent of sex and strongest for moderate kidney dysfunction. Considering mild-to-moderate kidney dysfunction as risk factor for HFpEF may help identify high-risk groups benefiting most from early intervention.

Ideal cardiovascular health and cardiovascular-related events: a systematic review and meta-analysis.

AIMS: The aim of this study was to systematically review and quantitatively summarize the evidence on the association between Life Simple's 7 (LS7) and multiple cardiovascular diseases (CVDs) and cardiometabolic diseases (CMDs). METHODS AND RESULTS: EMBASE and PubMed were searched from January 2010 to March 2022 for observational studies that investigated the association between ideal cardiovascular health (CVH) with CVD or CMD outcomes in an adult population. Two reviewers independently selected studies according to the eligibility criteria, extracted data, and evaluated risk of bias. Data were analysed with a random-effects meta-analysis. This meta-analysis included 59 studies (1 881 382 participants). Participants with ideal CVH had a considerably lower risk of a variety of CVDs and CMDs as compared with those with poor CVH, varying from 40% lower risk for atrial fibrillation (AF) {hazard ratio [HR] = 0.60 [95% confidence interval (CI) 0.44-0.83]} to 82% lower risk for myocardial infarction [HR = 0.18 (95% CI 0.12-0.28)]. Intermediate CVH was associated with 27-57% lower risk in CVDs and CMDs compared with poor CVH, with the highest hazard for AF [HR = 0.73 (95% CI 0.59-0.91)] and the lowest hazard for peripheral arterial disease [HR = 0.43 (95% CI 0.30-0.60)]. CONCLUSION: Ideal and moderate CVH were associated with a lower incidence of CVDs and CMDs than poor CVH. Life Simple's 7 holds significant potential for promoting overall CVH and thereby contributing to the prevention of CVDs.

KEY FINDINGS: Higher Life's Simple 7 (LS7) score, meaning a healthier lifestyle score, was related to lower risks of cardiovascular diseases (CVDs). Promoting healthy lifestyle (higher LS7 score) could possibly lead to prevention of CVDs.

Healthy lifestyle is very important to prevent cardiovascular diseases (CVDs) and cardiometabolic diseases (CMDs), such as diabetes and kidney diseases. Therefore, in 2010, the American Heart Association introduced Life's Simple 7 (LS7), a scoring system using seven lifestyle factors to measure cardiovascular health in populations, and these factors are diet, physical activity, smoking, blood pressure, blood lipids, blood sugar, and weight. In this review, we investigated the relationship between LS7 score and CVDs or CMDs.

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.