Symptoms as a Predictor of the Placebo-Controlled Efficacy of PCI in Stable Coronary Artery Disease.

BACKGROUND: Placebo-controlled evidence from ORBITA-2 found that percutaneous cutaneous intervention (PCI) in stable coronary artery disease with little or no antianginal medication relieved angina, but residual symptoms persisted in many. The reason for this was unclear. OBJECTIVES: ; This ORBITA-2 secondary analysis investigates the relationship between presenting symptoms and disease severity (anatomic, non-invasive, and invasive ischemia) and the ability of symptoms to predict the placebo-controlled efficacy of PCI. METHODS: Pre-randomization symptom severity and nature were assessed using the ORBITA smartphone application and symptom and quality of life questionnaires including the Rose angina questionnaire. Disease severity was assessed using quantitative coronary angiography (QCA), stress echocardiography, fractional flow reserve (FFR), and instantaneous wave-free ratio (iFR). Bayesian ordinal regression was used. RESULTS: At pre-randomization, the median number of daily angina episodes was 0.8 (0.4-1.6), 64% had Rose angina, QCA diameter stenosis 61 (49-74), stress echocardiography score 1.0 (0.0-2.7), FFR 0.63 (0.49-0.75), and iFR 0.78 (0.55-0.87). There was little relationship between symptom severity and nature and disease severity: angina symptom score with QCA ordinal correlation coefficient 0.06 (95% CrI 0.00 to 0.08); stress echocardiography 0.09 (95% CrI 0.02 to 0.10); FFR 0.04 (95% CrI -0.03 to 0.07); and iFR 0.04 (95% CrI -0.01 to 0.07). However, Rose angina and guideline-based typical angina were strong predictors of placebo-controlled PCI efficacy (angina symptom score: OR 1.9, 95% CrI 1.6 to 2.1, Pr(Interaction)=99.9% and OR 1.8, 95% CrI 1.6 to 2.1, Pr(Interaction)=99.9%, respectively). CONCLUSIONS: Although symptom severity and nature were poorly associated with disease severity, the nature of symptoms powerfully predicted the placebo-controlled efficacy of PCI.

Clinical and procedural outcomes of percutaneous coronary intervention for de novo lesions involving the ostial left circumflex coronary artery.

BACKGROUND: Percutaneous treatment for ostial left circumflex artery (LCx) lesions is known to be associated with suboptimal results. AIMS: The present study aims to assess the procedural and long-term clinical outcomes of percutaneous coronary intervention (PCI) for de novo ostial LCx lesions overall and according to the coronary revascularization strategy. METHODS: Consecutive patients undergoing PCI with second generation drug eluting stents or drug coated balloons for de novo ostial LCx lesions in three high-volume Italian centers between 2012 and 2021 were retrospectively evaluated. The primary endpoint was target-vessel revascularization (TVR) at 2 years. Secondary endpoints included major adverse cardiovascular and cerebrovascular events (MACCE), target lesion revascularization, myocardial infarction, stroke, all-cause death, and repeat revascularization. RESULTS: A total of 366 patients were included in the analysis with a median follow-up of 901 (IQR: 450-1728) days. 79.5% of the patients were male, 33.6% were diabetic, 49.7% had a previous PCI, and 23.1% a prior surgical revascularization. Very ostial LCx stenting was performed in 34.1%, crossover from left main to LCx in 17.3%, and a two-stent strategy in 48.6% of cases, respectively. In the overall population, the incidence of TVR at 2 years was 19.0% while MACCE rate was 25.7%. No major differences in clinical outcomes were found according to the stenting strategy. Use of intracoronary imaging was associated with fewer MACCE (HR: 0.47, 95% CI: 0.25-1.13, p = 0.01), while the diameter of the stent implanted in the ostial LCx was associated with less TVR (HR: 0.43, 95% CI: 0.25-0.75, p = 0.002). CONCLUSIONS: Percutaneous revascularization of the ostial LCx is associated with a high rate of TVR, regardless of the stenting strategy. Intracoronary imaging and proper stent sizing may reduce the failure rates.

Safety and efficacy of an ultra low dose fluoroscopic protocol for chronic total occlusion recanalization.

BACKGROUND: Chronic total occlusion (CTO) revascularization is a major source of radiation for both patients and physicians. Therefore, efforts to minimize radiation during CTO percutaneous coronary intervention (PCI) are highly encouraged. AIMS: To evaluate the impact of an Ultra Low fluoroscopic Dose Protocol (ULDP), based on 3.75 frames per second for the fluoroscopy and 7.5 frames per second for the cine acquisition, during CTO PCI. METHODS: One hundred fifty consecutive patients who underwent CTO PCI were retrospectively enrolled. Eighty-five underwent standard dose protocol (SDP) and 65 ULDP. Radiation exposure and acute clinical outcomes were compared between groups. Results were stratified according to lesion complexity. RESULTS: Patients undergoing ULDP, as compared to those undergoing SDP, showed a significant reduction of kerma area product, both for simple lesions (6861.0 vs. 13236.0 mGy × cm2 ; p = 0.014) and complex lesions (CL) (8865.0 vs. 16618.0 mGy × cm2 ; p < 0.001). Similarly, Air Kerma (AK) was lower when ULDP was used (1222.5 vs. 2015.0 cGy in SL, p = 0.134; 1499.0 vs. 2794.0 cGy in CL, p < 0.001). No significant differences were reported regarding procedural success and in-hospital major adverse cardiovascular events between groups. Notably, there was not any crossover from ULDO to SDP due to poor quality images. Interestingly, fluoroscopy time, procedural time and contrast volume was significantly lower in patients undergoing ULDP only for CLs. CONCLUSIONS: ULDP significantly reduces radiation exposure in the setting of high complexity procedures such as CTO PCI. This reduction seemed to be greater with increased procedural complexity and did not impact acute success or adverse clinical events.

Clinical outcomes in women and men with small aortic annuli undergoing transcatheter aortic valve implantation: A multicenter, retrospective, propensity score-matched comparison.

BACKGROUND: Sex-specific characteristics in patients with aortic stenosis and small annuli undergoing transcatheter aortic valve implantation (TAVI) might affect clinical outcomes and hemodynamics. METHODS: TAVI-SMALL 2 international retrospective registry included 1378 patients with severe aortic stenosis and small annuli (annular perimeter <72 mm or area < 400 mm2) treated with transfemoral TAVI at 16 high-volume centers between 2011 and 2020. Women (n = 1233) were compared with men (n = 145). One-to-one propensity score (PS) matching resulted in 99 pairs. Primary endpoint was incidence of all-cause mortality. Incidence of pre-discharge severe prosthesis-patient mismatch (PPM) and its association with all-cause mortality were investigated. Binary logistic and Cox regression were performed to adjust the treatment effect for PS quintiles. RESULTS: Incidence of all-cause mortality at a median follow-up of 377 days did not differ between sex in the overall (10.3 vs. 9.8%, p = 0.842) and PS-matched (8.5 vs. 10.9%, p = 0.586) populations. After PS matching, pre-discharge severe PPM was numerically higher in women vs. men (10.2 vs. 4.3%), even though no evidence of a difference was found (p = 0.275). Within the overall population, women with severe PPM suffered a higher incidence of all-cause mortality when compared to those with less than moderate PPM (log-rank p = 0.024) and less than severe PPM (p = 0.027). CONCLUSIONS: No difference in all-cause mortality at medium-term follow-up was observed between women and men with aortic stenosis and small annuli undergoing TAVI. Incidence of pre-discharge severe PPM was numerically higher in women than men, and it was associated with increased all-cause mortality in women.

Radial Artery Pseudoaneurysm Complicating Distal Transradial Access for Chronic Total Occlusion Recanalization.

We report a case of a distal radial access (dRA) pseudoaneurysm complicating a chronic total occlusion (CTO) percutaneous coronary intervention (PCI). After hospital discharge, the patient developed progressive pain and swelling at the access site and ultrasound revealed a distal radial artery pseudoaneurysm. This completely resolved conservatively with manual compression. This case highlights a potential vascular complication of the recently introduced dRA with its conservative management.

Heart failure with preserved, mid-range, and reduced ejection fraction across health care settings: an observational study.

AIMS: This study aimed to assess the sex-specific distribution of heart failure (HF) with preserved, mid-range, and reduced ejection fraction across three health care settings. METHODS AND RESULTS: In this descriptive observational study, we retrieved the distribution of HF types [with reduced ejection fraction (HFrEF), mid-range ejection fraction (HFmrEF), and preserved ejection fraction (HFpEF)] for men and women between 65 and 79 years of age in three health care settings from a single country: (i) patients with screening-detected HF in the high-risk community (i.e. those with shortness of breath, frailty, diabetes mellitus, and chronic obstructive pulmonary disease) from four screening studies, (ii) patients with confirmed HF from primary care derived from a single observational study, and (iii) patients with confirmed HF from outpatient cardiology clinics participating in a registry. Among 1407 patients from the high-risk community, 288 had screen-detected HF (15% HFrEF, 12% HFmrEF, 74% HFpEF), and 51% of the screen-detected HF patients were women. In both women (82%) and men (65%), HFpEF was the most prevalent HF type. In the routine general practice population (30 practices, 70 000 individuals), among the 160 confirmed HF cases, 35% had HFrEF, 23% HFmrEF, and 43% HFpEF, and in total, 43% were women. In women, HFpEF was the most prevalent HF type (52%), while in men, this was HFrEF (41%). In outpatient cardiology clinics (n = 34), of the 4742 HF patients (66% HFrEF, 15% HFmrEF, 20% HFpEF), 36% were women. In both women (56%) and men (71%), HFrEF was the most prevalent HF type. CONCLUSIONS: Both HF types and sex distribution vary considerably in HF patients of 65-79 years of age among health care settings. From the high-risk community through to general practice to the cardiology outpatient setting, there is a shift in HF type from HFpEF to HFrEF and a decrease in the proportion of HF patients that are women.

Clinical research study implementation of case-finding strategies for heart failure and chronic obstructive pulmonary disease in the elderly with reduced exercise tolerance or dyspnea: A cluster randomized trial.

BACKGROUND: Heart failure (HF) and chronic obstructive pulmonary disease (COPD) often remain undiagnosed in older individuals, although both disorders inhibit functionality and impair health. The aim of the study was to assess the effectiveness of a case-finding strategy of these disorders. METHODS: This is a clustered randomized trial; 18 general practices from the vicinity of Utrecht, the Netherlands, were randomly allocated to a case-finding strategy or usual care. Multimorbid community subjects (≥65 years) with dyspnea or reduced exercise tolerance were eligible for inclusion. The case-finding strategy consisted of history taking, physical examination, blood tests, electrocardiography, spirometry, and echocardiography. Subsequent treatment decisions were at the discretion of the general practitioner. Questionnaires regarding health status and functionality were filled out at baseline and after 6 months of follow-up. Information regarding changes in medication and health care use during the 6 months follow-up was extracted. RESULTS: A total of 829 participants were randomized: 389 in the case-finding strategy group and 440 in the usual care group. More patients in the case-finding group received a new diagnosis of HF or COPD than the usual care group (cumulative incidence 34% vs 2% and 17% vs. 2%, respectively). Scores for health status, functionality, and health care use were similar between the 2 strategies after 6 months of follow-up. CONCLUSIONS: A case-finding strategy applied in primary care to multimorbid older people with dyspnea or reduced exercise tolerance resulted in a number of new diagnoses of HF and COPD but did not result in short-term improvement of health status compared to usual care.

Discovery of biomarkers for the presence and progression of left ventricular diastolic dysfunction and HEart faiLure with Preserved ejection Fraction in patients at risk for cardiovascular disease: rationale and design of the HELPFul case-cohort study in a Dutch cardiology outpatient clinic.

INTRODUCTION: Left ventricular diastolic dysfunction (LVDD) is a common condition in both sexes that may deteriorate into heart failure (HF) with preserved ejection fraction (pEF), although this seems to happen more often in women than in men. Both LVDD and HFpEF often go unrecognised, necessitating the discovery of biomarkers that aid both the identification of individuals with LVDD at risk of developing HF and identification of individuals most likely to benefit from treatment. METHODS AND ANALYSIS: HELPFul is an ongoing case-cohort study at a Dutch cardiology outpatient clinic enrolling patients aged 45 years and older without history of cardiovascular disease, who were referred by the general practitioner for cardiac evaluation. We included a random sample of patients and enriched the cohort with cases (defined as an E/e' ≥8 measured with echocardiography). Information about medical history, cardiovascular risk factors, electrocardiography, echocardiography, exercise test performance, common carotid intima-media thickness measurement and standard cardiovascular biomarkers was obtained from the routine care data collected by the cardiology outpatient clinic. Study procedure consists of extensive venous blood collection for biobanking and additional standardised questionnaires. Follow-up will consist of standardised questionnaires by mail and linkage to regional and national registries. We will perform cardiac magnetic resonance imaging and coronary CT angiography in a subgroup of patients to investigate the extent of macrovascular and microvascular coronary disease. ETHICS AND DISSEMINATION: The study protocol was approved by the Institutional Review Board of the University Medical Center Utrecht. Results will be disseminated through national and international conferences and in peer-reviewed journals in cardiovascular disease. TRIAL REGISTRATION: NTR6016;Pre-results.

Mid-regional pro-atrial natriuretic peptide for the early detection of non-acute heart failure.

BACKGROUND: Diagnosing non-acute heart failure (HF) remains challenging, notably in the early stages of the syndrome. The diagnostic value of mid-regional pro-atrial natriuretic peptide (MR-proANP) has been proven in acute onset HF, but its role in early non-acute HF is unknown. We aimed to determine the diagnostic value of MR-proANP in suspected non-acute HF. METHODS AND RESULTS: In total, 721 people suspected of non-acute HF in primary care underwent standardised diagnostic work-up including chest X-ray, electrocardiogram, N-terminal pro-B-type natriuretic peptide (NT-proBNP) measurement and echocardiography. Of these, 245 people underwent additional MR-proANP measurements. The outcome of HF was assessed by an expert panel comprised of two cardiologists and one expert physician, who used all available diagnostic information including echocardiography, but were blinded to biomarker results. Of the 245 people (mean age 71.0 years, 62.9% female), 72 (29.4%) were diagnosed with HF. The c-statistics of MR-proANP and NT-proBNP as single diagnostic test were 0.77 [95% confidence interval (CI) 0.70-0.84] and 0.79 (95% CI 0.73-0.86), respectively. The cut-point with the highest accuracy for MR-proANP was 120 pmol/L [sensitivity/specificity/positive predictive value (PPV)/negative predictive value (NPV) 0.72, 0.69, 0.46, and 0.86, respectively], and the best exclusionary cut-point was 40 pmol/L (sensitivity/specificity/PPV/NPV 0.99, 0.06, 0.30, and 0.92, respectively). After addition of MR-proANP on top of a previously validated clinical model, the c-statistic rose from 0.82 (95% CI 0.76-0.88) to 0.86 (95% CI 0.80-0.92), and with the addition of NT-proBNP to 0.87 (95% CI 0.81-0.92). No sex interactions between the biomarkers and HF were found in the multivariable models. CONCLUSION: MR-proANP provides added diagnostic value in suspected non-acute HF, similar to NT-proBNP.

Opportunistic screening models for high-risk men and women to detect diastolic dysfunction and heart failure with preserved ejection fraction in the community.

BACKGROUND: The prevalence of undetected left ventricular diastolic dysfunction is high, especially in the elderly with comorbidities. Left ventricular diastolic dysfunction is a prognostic indicator of heart failure, in particularly of heart failure with preserved ejection fraction and of future cardiovascular and all-cause mortality. Therefore we aimed to develop sex-specific diagnostic models to enable the early identification of men and women at high-risk of left ventricular diastolic dysfunction with or without symptoms of heart failure who require more aggressive preventative strategies. DESIGN: Individual patient data from four primary care heart failure-screening studies were analysed (1371 participants, excluding patients classified as heart failure and left ventricular ejection fraction <50%). METHODS: Eleven candidate predictors were entered into logistic regression models to be associated with the presence of left ventricular diastolic dysfunction/heart failure with preserved ejection fraction in men and women separately. Internal-external cross-validation was performed to develop and validate the models. RESULTS: Increased age and ß-blocker therapy remained as predictors in both the models for men and women. The model for men additionally consisted of increased body mass index, moderate to severe shortness of breath, increased pulse pressure and history of ischaemic heart disease. The models performed moderately and similarly well in men (c-statistics range 0.60-0.75) and women (c-statistics range 0.51-0.76) and the performance improved significantly following the addition of N-terminal pro b-type natriuretic peptide (c-statistics range 0.61-0.80 in women and 0.68-0.80 in men). CONCLUSIONS: We provide an easy-to-use screening tool for use in the community, which can improve the early detection of left ventricular diastolic dysfunction/heart failure with preserved ejection fraction in high-risk men and women and optimise tailoring of preventive interventions.

Circulating levels of P-selectin and E-selectin relate to cardiovascular magnetic resonance-derived aortic characteristics in young adults from the general population, a cross-sectional study.

BACKGROUND: Although endothelial cell adhesion molecules (CAMs) are postulated to play a key role in early atherosclerosis, studies on endothelial CAMs are mainly pertained to middle-aged populations and populations with an unfavourable cardiovascular risk burden. Therefore, this study evaluated whether circulating endothelial CAMs are related to cardiovascular magnetic resonance imaging (CMR) derived indicators of arterial wall alterations in a random sample of young adults from the general population. METHODS: This cross-sectional study is part of the general-population-based Atherosclerosis-Monitoring-and-Biomarker-measurements-In-The-YOuNg (AMBITYON) cohort study. In 131 adults (age: 25-35 years), demography, anthropometry and a lipid spectrum was acquired. Thoracic aortic wall area, wall thickness and pulse wave velocity (PWV) were measured using a 3 T CMR-system. From stored blood samples, four CAMs (E-selectin, P-selectin, vascular CAM-1 and intercellular CAM-1) were measured using dedicated methods. Linear mixed-effects regression analysis was used to evaluate the relation of these CAMs with the selected aortic characteristics. RESULTS: Of the studied endothelial CAMs, P-selectin related to natural logarithm transformed aortic wall thickness (ß = 0.18 mm/(µg/ml), [95% confidence interval: 0.04, 0.31], p = 0.01) whereas E-selectin related to natural logarithm transformed aortic PWV (ß = 3.01 (m/s)/(µg/ml), [95% confidence interval: 0.08, 5.95], p = 0.04). Of note, VCAM-1 and ICAM-1 did not relate to the selected aortic characteristics. CONCLUSIONS: In young adults from the general population, circulating P-selectin and E-selectin levels appear positively related to CMR-derived aortic wall thickness and PWV, possibly pointing towards atherogenic inflammatory arterial wall alterations inflicted by these CAMs already in young adulthood. TRIAL REGISTRATION: Netherlands National Trial Register (NTR): NTR4742 , Registered 18 August 2014, retrospectively registered.

The prevalence of left ventricular diastolic dysfunction and heart failure with preserved ejection fraction in men and women with type 2 diabetes: A systematic review and meta-analysis.

OBJECTIVE: Type 2 diabetes is a risk factor for the development of left ventricular diastolic dysfunction and heart failure with preserved ejection fraction. Our aim was to provide a summary estimate of the prevalence of left ventricular diastolic dysfunction and heart failure with preserved ejection fraction in type 2 diabetes patients and to investigate sex disparities. METHODS AND RESULTS: A systematic search of the databases Medline and Embase was conducted for studies reporting the prevalence of left ventricular diastolic dysfunction or heart failure with preserved ejection fraction among type 2 diabetes patients. Studies were only included if echocardiography was performed. Prevalence estimates were pooled using random-effects meta-analysis. A total of 28 studies were included. Data on the prevalence of left ventricular diastolic dysfunction were available in 27 studies. The pooled prevalence for left ventricular diastolic dysfunction in the hospital population (2959 type 2 diabetes participants) and in the general population (2813 type 2 diabetes participants) was 48% [95% confidence interval: 38%-59%] and 35% (95% confidence interval: 24%-46%), respectively. Heterogeneity was high in both populations, with estimates ranging from 19% to 81% in the hospital population and from 23% to 54% in the general population. For women and men, the pooled prevalence estimates of left ventricular diastolic dysfunction were 47% (95% confidence interval: 37%-58%) and 46% (95% confidence interval: 37%-55%), respectively. Only two studies presented the prevalence of heart failure with preserved ejection fraction; 8% (95% confidence interval: 5%-14%) in a hospital population and 25% (95% confidence interval: 21%-28%) in the general population [18% in men (mean age: 73.8; standard deviation: 8.6) and 28% in women (mean age: 74.9; standard deviation: 6.9)]. CONCLUSION: The prevalence of left ventricular diastolic dysfunction among type 2 diabetes patients is similarly high in men and women, while heart failure with preserved ejection fraction seems to be more common in women than men, at least in community people with type 2 diabetes.

Vascular extracellular vesicles in comorbidities of heart failure with preserved ejection fraction in men and women: The hidden players. A mini review.

Left ventricular diastolic dysfunction, the main feature of heart failure with preserved ejection fraction (HFpEF), is thought to be primarily caused by comorbidities affecting the endothelial function of the coronary microvasculature. Circulating extracellular vesicles, released by the endothelium have been postulated to reflect endothelial damage. Therefore, we reviewed the role of extracellular vesicles, in particularly endothelium microparticles, in these comorbidities, including obesity and hypertension, to identify if they may be potential markers of the endothelial dysfunction underlying left ventricular diastolic dysfunction and HFpEF.

Prevalence of left ventricular systolic dysfunction and heart failure with reduced ejection fraction in men and women with type 2 diabetes mellitus: a systematic review and meta-analysis.

BACKGROUND: Type 2 diabetes mellitus (T2D) is associated with the development of left ventricular systolic dysfunction (LVSD) and heart failure with reduced ejection fraction (HFrEF). T2D patients with LVSD are at higher risk of mortality and morbidity than patients without LVSD, while progression of LVSD can be delayed or halted by the use of proven therapies. As estimates of the prevalence are scarce and vary considerably, the aim of this study was to retrieve summary estimates of the prevalence of LVSD/HFrEF in T2D and to see if there were any sex differences. METHODS: A systematic search of Medline and Embase was performed to extract the prevalence of LVSD/HFrEF in T2D (17 studies, mean age 50.1 ± 6.3 to 71.5 ± 7.5), which were pooled using random-effects meta-analysis. RESULTS: The pooled prevalence of LVSD was higher in hospital populations (13 studies, n = 5835, 18% [95% CI 17-19%]), than in the general population (4 studies, n = 1707, 2% [95% CI 2-3%]). Seven studies in total reported sex-stratified prevalence estimates (men: 7% [95% CI 5-8%] vs. women: 1.3% [95% CI 0.0.2.2%]). The prevalence of HFrEF was available in one general population study (5.8% [95% CI 3.7.6%], men: 6.8% vs. women: 3.0%). CONCLUSIONS: The summary prevalence of LVSD is higher among T2D patients from a hospital setting compared with from the general population, with a higher prevalence in men than in women in both settings. The prevalence of HFrEF among T2D in the population was only assessed in a single study and again was higher among men than women.

Efficient selective screening for heart failure in elderly men and women from the community: A diagnostic individual participant data meta-analysis.

Background Prevalence of undetected heart failure in older individuals is high in the community, with patients being at increased risk of morbidity and mortality due to the chronic and progressive nature of this complex syndrome. An essential, yet currently unavailable, strategy to pre-select candidates eligible for echocardiography to confirm or exclude heart failure would identify patients earlier, enable targeted interventions and prevent disease progression. The aim of this study was therefore to develop and validate such a model that can be implemented clinically. Methods and results Individual patient data from four primary care screening studies were analysed. From 1941 participants >60 years old, 462 were diagnosed with heart failure, according to criteria of the European Society of Cardiology heart failure guidelines. Prediction models were developed in each cohort followed by cross-validation, omitting each of the four cohorts in turn. The model consisted of five independent predictors; age, history of ischaemic heart disease, exercise-related shortness of breath, body mass index and a laterally displaced/broadened apex beat, with no significant interaction with sex. The c-statistic ranged from 0.70 (95% confidence interval (CI) 0.64-0.76) to 0.82 (95% CI 0.78-0.87) at cross-validation and the calibration was reasonable with Observed/Expected ratios ranging from 0.86 to 1.15. The clinical model improved with the addition of N-terminal pro B-type natriuretic peptide with the c-statistic increasing from 0.76 (95% CI 0.70-0.81) to 0.89 (95% CI 0.86-0.92) at cross-validation. Conclusion Easily obtainable patient characteristics can select older men and women from the community who are candidates for echocardiography to confirm or refute heart failure.

Women in Translational Medicine: Tools to Break the Glass Ceiling.

Despite the recent movements for female equality and empowerment, few women occupy top positions in scientific decision-making. The challenges women face during their career may arise from societal biases and the current scientific culture. We discuss the effect of such biases at three different levels of the career and provide suggestions to tackle them. At the societal level, gender roles can create a negative feedback loop in which women are discouraged from attaining top positions and men are discouraged from choosing a home-centred lifestyle. This loop can be broken early in life by providing children with female role models that have a work-centred life and opening up the discussion about gender roles at a young age. At the level of hiring, unconscious biases can lead to a preference for male candidates. The introduction of (unbiased) artificial intelligence algorithms and gender champions in the hiring process may restore the balance and give men and women an equal chance. At the level of coaching and evaluation, barriers that women face should be addressed on a personal level through the introduction of coaching and mentoring programmes. In addition, women may play a pivotal role in shifting the perception of scientific success away from bibliometric outcomes only towards a more diverse assessment of quality and societal relevance. Taken together, these suggestions may break the glass ceiling in the scientific world for women; create more gender diversity at the top and improve translational science in medicine.

High Levels of (Un)Switched Memory B Cells Are Associated With Better Outcome in Patients With Advanced Atherosclerotic Disease.

BACKGROUND: Atherosclerosis is an inflammatory lipid disorder and the main underlying pathology of acute ischemic events. Despite a vast amount of data from murine atherosclerosis models, evidence of B-cell involvement in human atherosclerotic disease is limited. We therefore investigated the association of circulating B-cell subtypes with the occurrence of secondary cardiovascular events in advanced atherosclerotic disease. METHODS AND RESULTS: This cohort study consists of 168 patients who were included in the Athero-Express biobank between 2009 and 2011. Before surgery, peripheral blood mononuclear cells were isolated and stored in liquid nitrogen. After gentle thawing of the peripheral blood mononuclear cells, different B-cell subtypes including naïve, (un)switched memory, and CD27+CD43+ B1-like B cells, were analyzed by flow cytometry. Univariable and multivariable Cox proportional hazard models were used to analyze associations between B-cell subtypes, circulating antibodies and secondary cardiovascular manifestations during the 3-year follow-up period. Mean age was 70.1±9.6 years, males represented 62.8% of the population, and 54 patients had secondary manifestations during follow-up. High numbers of unswitched memory cells were protective against secondary outcome (hazard ratio, 0.30 [95% CI, 0.13-0.69]; P<0.01). Similar results were obtained for the switched memory cells that also showed to be protective against secondary outcome (hazard ratio, 0.33 [95% CI, 0.14-0.77]; P=0.01). CONCLUSIONS: A high number of (un)switched memory B cells is associated with better outcome following carotid artery endarterectomy. These findings suggest a potential role for B-cell subsets in prediction and prevention of secondary cardiovascular events in patients with atherosclerosis.