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Women with a history of preeclampsia have a 5- to 12-fold increased risk to develop end-stage kidney disease. Previous observations in small cohorts suggest that former preeclamptic (fPE) women have subtle abnormalities in renal hemodynamics and renal function, which might predispose them to renal failure in later life. In this study, we analyzed renal function in a cross-sectional cohort consisting of former early-onset preeclamptic (fPE, n=339) and former healthy pregnant women (fHP, n=332), overall with a mean age of 39 years at 10 years postpartum. Estimated glomerular filtration rate (eGFR), assessed by the modification of diet in renal disease (MDRD) and chronic kidney disease-epidemiology (CKD-epi) equations, and urinary protein:creatinine ratios were assessed 10 years postpartum. Median MDRD and CKD-epi eGFR did not significantly differ between fHP and fPE groups, whereas a comparison of distribution of eGFR revealed a shift toward a high-normal MDRD eGFR in the fPE group (χ2, P=0.02) with the same trend for CKD-epi eGFR (χ2, P=0.18). The odds ratio for fPE women having MDRD eGFR >110 mL/min per 1.73 m2 was 1.6 (1.1-2.4). In addition, the median urinary protein:creatinine ratio was slightly higher in fPE (8.5 versus 7.1 mg/mmol; P<0.01) and correlated positively with both MDRD and CKD-epi eGFR in fPE women. No increased incidence of CKD in fPE women was observed. In conclusion, we demonstrate subtle changes in renal function in former early-onset preeclamptic women 10 years postpartum, characterized by a high-normal eGFR and a slightly higher protein excretion. Whether these subtle differences predispose to or predict long-term renal function loss in fPE women remains to be investigated.Clinical Trial Registration: URL: http://www.trialregister.nl. Unique identifier: NTR2668. [ABSTRACT FROM AUTHOR]

Background: Risk-reducing salpingo-oophorectomy (RRSO) around the age of 40 is currently recommended to BRCA1/2 mutation carriers. This procedure decreases the elevated ovarian cancer risk by 80-96% but it initiates premature menopause as well. The latter is associated with short-term and long-term morbidity, potentially affecting quality of life (QoL). Based on recent insights into the Fallopian tube as possible site of origin of serous ovarian carcinomas, an alternative preventive strategy has been put forward: early risk-reducing salpingectomy (RRS) and delayed oophorectomy (RRO). However, efficacy and safety of this alternative strategy have to be investigated. Methods: A multicentre non-randomised trial in 11 Dutch centres for hereditary cancer will be conducted. Eligible patients are premenopausal BRCA1/2 mutation carriers after completing childbearing without (a history of) ovarian carcinoma. Participants choose between standard RRSO at age 35-40 (BRCA1) or 40-45 (BRCA2) and the alternative strategy (RRS upon completion of childbearing and RRO at age 40-45 (BRCA1) or 45-50 (BRCA2)). Women who opt for RRS but do not want to postpone RRO beyond the currently recommended age are included as well. Primary outcome measure is menopause-related QoL. Secondary outcome measures are ovarian/breast cancer incidence, surgery-related morbidity, histopathology, cardiovascular risk factors and diseases, and cost-effectiveness. Mixed model data analysis will be performed. Discussion: The exact role of the Fallopian tube in ovarian carcinogenesis is still unclear. It is not expected that further fundamental research will elucidate this role in the near future. Therefore, this clinical trial is essential to investigate RRS with delayed RRO as alternative risk-reducing strategy in order to improve QoL. [ABSTRACT FROM AUTHOR]

Background: Both acute hyperglycemia as diabetes results in an impaired prognosis in ST-elevation myocardial infarction (STEMI) patients. It is unknown whether there is a different prevalence of diabetes and acute hyperglycemia in men and women within age-groups. Methods: Between 2004 and 2010, 4640 consecutive patients (28% women) with STEMI, were referred for primary PCI. Patients were stratified into two age groups, < 65 years (2447 patients) and ⩾65 years (2193 patients). Separate analyses were performed in 3901 patients without diabetes. Diabetes was defined as known diabetes or HbA1c ⩾6.5 mmol/l at admission. Results: The prevalence of diabetes was comparable between women and men in the younger age group (14% vs 12%, p = 0.52), whereas in the older age group diabetes was more prevalent in women (25% vs 17% p < 0.001). In patients without diabetes, admission glucose was comparable between both genders in younger patients (8.1 ± 2.0 mmol/l vs 8.0 ± 2.2 mmol/l p = 0.36), but in older patients admission glucose was higher in women than in men (8.7 ± 2.1 mmol/l vs 8.4 ± 2.1 mmol/l p = 0.028). After multivariable analyses, the occurrence of increased admission glucose was comparable between men and women in the younger age group (OR 1.1, 95%CI 0.9-1.5), but increased in women in the older age group (OR 1.3, 95% CI 1.1-1.7). Both diabetes and hyperglycemia were associated with a higher oneyear mortality in both men and women. Conclusions: The differences between men and women in hyperglycemia and diabetes in patients with STEMI are age dependent and can only be observed in older patients. This may have implications for medical treatment and should be investigated further. [ABSTRACT FROM AUTHOR]

Background: Intracoronary continuous thermodilution is a novel technique to quantify absolute coronary flow (Q) and resistance (R) and has potential advantages over current methods such as coronary flow reserve (CFR) and index of microvascular resistance (IMR). However, no data are available in patients with ischemia and nonobstructive coronary artery disease (INOCA).Objectives: This study aimed to assess the relationship of Q and R with the established CFR/IMR in INOCA patients, to explore the potential of absolute Q, and to predict self-reported angina.Methods: Consecutive INOCA patients (n = 84; 87% women; mean age 56 ± 8 years) underwent coronary function testing, including acetylcholine (ACH) provocation testing, adenosine (ADE) testing (CFR/IMR), and continuous thermodilution (absolute Q and R) with saline-induced hyperemia.Results: ACH testing was abnormal (ACH+) in 87%, and ADE testing (ADE+) in 38%. The median absolute Q was 198 ml/min, and the median absolute R was 416 WU. The absolute R was higher in patients with ADE+ versus ADE- (495 WU vs. 375 WU; p = 0.04) but did not differ between patients with ACH+ versus ACH- (421 WU vs. 409 WU; p = 0.74). Low Q and high R were associated with severe angina (odds ratio: 3.09; 95% confidence interval: 1.16 to 8.28; p = 0.03; and odds ratio: 2.60; 95% confidence interval: 0.99 to 6.81; p = 0.05), respectively.Conclusions: In this study, absolute R was higher in patients with abnormal CFR/IMR, whereas both Q and R were unrelated to coronary vasospasm. Q and R were associated with angina, although their exact predictive value should be determined in larger studies. [ABSTRACT FROM AUTHOR]

Objective: To compare menopause-related quality of life (QoL) after risk-reducing salpingectomy (RRS) versus risk-reducing salpingo-oophorectomy (RRSO) until 3 years of post-surgery., Design: A prospective study (TUBA study) with treatment allocation based on patients' preference. Data were collected pre-surgery and at 3 months, 1 and 3 years of post-surgery., Setting: Multicentre prospective preference trial in thirteen hospitals in the Netherlands., Population: BRCA1/2 pathogenic variant (PV) carriers aged 25-40 (BRCA1) or 25-45 (BRCA2), who were premenopausal, without a future child wish and without current (treatment for) malignancy., Methods: Treatment allocation was based on patients' preference: either RRS from the age of 25 years with delayed oophorectomy at the maximum age of 45 (BRCA1) or 50 (BRCA2), or RRSO between the ages of 35-40 (BRCA1) or 40-45 (BRCA2). After RRSO, hormone replacement therapy (HRT) was recommended, if not contraindicated. Primarily, menopause-related QoL as measured with the Greene Climacteric Scale (GCS) was compared between the RRS and RRSO without HRT group. Secondarily, GSC-scores of the RRS group were compared with the scores of the RRSO with HRT after surgery group. A higher GSC-score reflects more climacteric symptoms., Results: Until April 2023, 410 participants had undergone RRS and 160 RRSO. The BRCA1/BRCA2 proportions were 51.4%/48.6%. The mean age at surgery (SD) was 37.9 (3.5) years. Participants 3 years after RRSO without HRT had a 4.3 (95% CI 2.1-6.5; p < 0.001) point higher increase in GCS-score from baseline compared to those after RRS, while the difference was 7.9 (95% CI 5.9-9.8) and 8.5 (95% CI 6.5-10.5) points at 3 and 12 months, respectively. Among participants with HRT after surgery, the RRSO group had a 2.4 (95% CI 0.8-3.9; p = 0.002) point higher increase in GCS-score from baseline compared to the RRS group., Conclusions: In this multicentre preference trial, menopause-related QoL was better after RRS than after RRSO, even with HRT after RRSO. Differences between arms were most pronounced until one-year post-surgery., (© 2025 The Author(s). BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Background: Premenopausal risk-reducing salpingo-oophorectomy (RRSO) in women at high familial risk of ovarian cancer leads to immediate menopause. Although early natural menopause is associated with increased cardiovascular disease risk, evidence on long-term cardiovascular disease risk after early surgical menopause is scarce., Objectives: We sought to determine the long-term influence of the timing of RRSO on the development of coronary artery calcium (CAC), an established marker for cardiovascular disease risk., Methods: We conducted a cross-sectional study (N = 733) nested in a nationwide cohort of women at high familial risk of ovarian cancer. In women aged 60-70 years (n = 328), we compared CAC scores between women with a premenopausal RRSO (age ≤45 years) and women with a postmenopausal RRSO (age ≥54 years), using multivariable Poisson analyses. Within the premenopausal RRSO group (n = 498), we also examined the effect of age at RRSO. In addition, we compared the premenopausal RRSO group with an external reference cohort (n = 5,226)., Results: Multivariable analyses showed that the prevalence rates of any CAC (CAC >0), at least moderate CAC (CAC >100), and severe CAC (CAC >400) were comparable between the premenopausal and postmenopausal RRSO groups (relative risk [RR]: 0.93; 95% CI: 0.75-1.15 for any CAC; RR: 0.71; 95% CI: 0.43-1.17 for at least moderate CAC; RR: 0.81; 95% CI: 0.30-2.13 for severe CAC). There was no difference in CAC between the premenopausal RRSO group and a similar aged reference cohort. Timing of premenopausal RRSO (early premenopausal RRSO [<41 years] vs late premenopausal RRSO [41-45 years]) did not affect the outcomes., Conclusions: Our results do not show a long-term adverse effect of surgical menopause on the development of CAC., Competing Interests: The Dutch Cancer Society (KWF) and the Maarten van der Weijden foundation funded this project, registered under grant 10164. The funding body had no role in the design of the study, collection, analysis or interpretation of data or in writing the paper. Dr van der Aalst has received an advanced research grant for ROBINSCA by the European Research Council. Dr Budde has received institutional support to the radiology department of the Erasmus Medical Center by Siemens and HeartFlow; payments to the Erasmus MC for lectures by Bayer and Siemens; and serves unpaid as board member of the European Society of Cardiovascular Radiology and the editorial boards of Radiology: Cardiothoracic Imaging, EHJ Digital Health, and Journal of Hybrid Imaging. Dr de Jong has received research support to the department of radiology of UMC Utrecht by Philips Healthcare. Dr Vliegenthart has received institutional research grants by Siemens Healthineers, Dutch Heart Foundation, Dutch Cancer Foundation, and Netherlands organization for Health Research and Development; speaker fees by Siemens Healthineers and Bayer Healthcare; participates in the strategic advisory board of the Institute for Cardiometabolism and Nutrition; and is president of the European Society of Cardiovascular Radiology. Dr Ausems has received institutional payments by AstraZeneca. Dr de Koning has received institutional grants for the 4-in-the-lung-run trial HORIZON 2020. Dr Maas has received speaker fees by Novartis, Organon and Omron. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Purpose: Breast cancer (BC) treatment can induce adverse events, such as cardiovascular disease (CVD). Defective DNA repair, as in carriers of BRCA1/2 pathogenic variants (BRCA1/2pv), may contribute to CVD risk. We aimed to study if female BRCA1/2pv carriers are more sensitive to develop CVD after BC treatment than BC patients without a known BRCA1/2pv., Methods: In a hospital-based cohort of 17,300 female BC patients, we identified 509 BRCA1/2pv carriers. Cardiovascular morbidity and mortality were assessed through hospital charts and general practitioner questionnaires. We performed Cox regression analyses comparing BRCA1/2pv carriers with all other BC patients, adjusting for age, radiotherapy regimen, chemotherapy regimen, and smoking status., Results: Median follow-up time since BC treatment was 14 years. In total, 1108 women experienced ischemic heart disease (IHD), of whom 20 (1.8%) were BRCA1/2pv carriers. Heart failure (HF) was diagnosed in 638 women, of whom 10 (1.6%) were BRCA1/2pv carriers. BRCA1/2pv carriership was associated with a slight not statistically significant increase of IHD (adjHR 1.51, 95%CI 0.93; 2.42), but not with risk of HF (adjHR 0.86, 95%CI 0.44; 1.69). The association between radiotherapy and IHD risk was not significantly different between BRCA1/2pv carriers [HR 2.30 (95%CI 0.79; 6.66)] and other BC patients (HR 1.50, 95%CI 1.30; 1.73). Associations between anthracycline-based chemotherapy and HF risk also did not differ between carriers and other BC patients (HRs of 4.02 (95%CI 1.02; 15.77) and 2.31 (95%CI 1.77; 3.01), respectively)., Conclusions: In BRCA1/2pv BC patients, we found no evidence for a higher risk of BC treatment-related CVD than in other BC patients., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Despite the progress in the care of individuals with heart failure (HF), important sex disparities in knowledge and management remain, covering all the aspects of the syndrome, from aetiology and pathophysiology to treatment. Important distinctions in phenotypic presentation are widely known, but the mechanisms behind these differences are only partially defined. The impact of sex-specific conditions in the predisposition to HF has gained progressive interest in the HF community. Under-recruitment of women in large randomized clinical trials has continued in the more recent studies despite epidemiological data no longer reporting any substantial difference in the lifetime risk and prognosis between sexes. Target dose of medications and criteria for device eligibility are derived from studies with a large predominance of men, whereas specific information in women is lacking. The present scientific statement encompasses the whole scenario of available evidence on sex-disparities in HF and aims to define the most challenging and urgent residual gaps in the evidence for the scientific and clinical HF communities., (© 2024 European Society of Cardiology.)

There is an increasing interest among professionals in cardiovascular medicine in women-specific risk variables related to gynecologic conditions over the life span. Although adverse lifestyle factors, hypertension, dyslipidemia and insulin resistance are recognized as the most important risk factors in older women, there is still uncertainty over how to account for other risk variables. For instance, migraine from puberty onwards, chronic inflammatory conditions and mental stress affect cardiovascular risk in women. As prevention should start as early in life as possible, appropriate risk estimation in women at middle age is crucial. In case of doubt, a coronary artery calcium score with a computed tomography scan at a radiology department can be helpful to discriminate between low and high risk for an individual. This may also pave the way for safe menopausal hormone therapy if needed. In this paper we summarize the current status of women-specific and other relevant risk variables from the perspective of the cardiologist., Competing Interests: Declaration of competing interest The author receives occasional consultancy fees from Organon and Omron., (Copyright © 2024. Published by Elsevier B.V.)

Competing Interests: RB reports participation on the data safety monitoring board of Aptabio Therapeutics. CG reports funding from Horizon 2020, grants or contracts from Alan Turing Institute, British Heart Foundation, National Institute for Health Research, Abbott Diabetes, Bristol Myers Squibb and European Society of Cardiology, consulting fees from AI Nexus, AstraZeneca, Amgen, Bayer, Bristol Myers Squibb, Boehrinher-Ingleheim, CardioMatics, Chiesi, Daiichi Sankyo, GPRI Research B.V., Menarini, Novartis, iRhythm, Organon, The Phoenix Group; fees from AstraZeneca, Boston Scientific, Menarini, Novartis, Raisio Group, Wondr Medical and Zydus; participation on the data safety monitoring board or advisory board of DANBLCOK trial and TARGET CTCA trial; fiduciary role as Deputy Editor: EHJ Quality of Care and Clinical Outcomes, NICE Indicator Advisory Committee, and Chair ESC Quality Indicator Committee: stock or stock options of CardioMatics; and receipt of other services from Kosmos device. MG reports unpaid leadership or fiduciary role as President of The American Society for Preventive Cardiology. SSA reports leadership or fiduciary role as Associate Vice-President of Global Health; McMaster University and Department of Medicine's Associate Chair of Equity and Diversity; McMaster University; Other financial or non-financial interests: Tier 1 Canada Research Chair in Ethnicity and CVD, Chair in Population Health of Heart & Stroke Foundation and Foundational and grant from Canadian Institutes of Health Research. AHEMM decares consulting fees from Philips and Organon. The other authors have no relevant conflicts of interest to declare related to this manuscript.

Objectives: The aim of this study was to evaluate the incidence of transfusions, including red blood cells (RBC), platelets, and fresh frozen plasma (FFP) during and after coronary artery bypass grafting (CABG) in the Netherlands. Furthermore, the authors aimed to identify the impact of sex on blood product transfusion., Design: A retrospective multicenter cohort study. Data were collected from January 2013 to December 2021 from the Netherlands Heart Registration (NHR) database., Setting: The NHR receives its data from 16 heart centers in the Netherlands., Participants: Patients older than 18 years who underwent CABG in the Netherlands., Interventions: Coronary artery bypass grafting with extracorporeal circulation or off-pump coronary artery bypass grafting., Measurements and Main Results: The incidence of blood transfusion, defined as transfusions intraoperatively and during the length of the hospital admission after CABG. In addition, a differentiation was made according to the type of transfusion (packed RBC, platelets, and FFP). In the overall cohort (N = 42,388), the number of patients who received a transfusion of any type was 27.0% (n = 11,428). Women received more often RBC transfusions compared with men (45.4% v 15.6%, respectively, p < 0.001). There was a significant difference between the 2 sexes regarding platelet transfusion (women 10.0% v men 11.1%, p = 0.005) but not in FFP transfusion. Female sex was independently associated with RBC transfusion, using the multivariate logistic regression analysis., Conclusions: The incidence of any blood transfusion was 27.0%, and was higher in women than in men. The female sex was independently associated with receiving RBC during and after CABG., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Thoracic radiotherapy may damage the myocardium and arteries, increasing cardiovascular disease (CVD) risk. Women with a high local breast cancer (BC) recurrence risk may receive an additional radiation boost to the tumor bed., Objective: We aimed to evaluate the CVD risk and specifically ischemic heart disease (IHD) in BC patients treated with a radiation boost, and investigated whether this was modified by age., Methods: We identified 5260 BC patients receiving radiotherapy between 2005 and 2016 without a history of CVD. Boost data were derived from hospital records and the national cancer registry. Follow-up data on CVD events were obtained from Statistics Netherlands until December 31, 2018. The relation between CVD and boost was evaluated with competing risk survival analysis., Results: 1917 (36.4%) received a boost. Mean follow-up was 80.3 months (SD37.1) and the mean age 57.8 years (SD10.7). Interaction between boost and age was observed for IHD: a boost was significantly associated with IHD incidence in patients younger than 40 years but not in patients over 40 years. The subdistribution hazard ratio (sHR) was calculated for ages from 25 to 75 years, showing a sHR range from 5.1 (95%CI 1.2-22.6) for 25-year old patients to sHR 0.5 (95%CI 0.2-1.02) for 75-year old patients., Conclusion: In patients younger than 40, a radiation boost is significantly associated with an increased risk of CVD. In absolute terms, the increased risk was low. In older patients, there was no association between boost and CVD risk, which is likely a reflection of appropriate patient selection., (© 2024. The Author(s).)

Objective: To study the impact of premenopausal risk-reducing salpingo-oophorectomy (RRSO), compared with postmenopausal RRSO, on urinary incontinence (UI) ≥10 years later., Design: Cross-sectional study, nested in a nationwide cohort., Setting: Multicentre in the Netherlands., Population: 750 women (68% BRCA1/2 pathogenic variant carriers) who underwent either premenopausal RRSO (≤45 years, n = 496) or postmenopausal RRSO (≥54 years, n = 254). All participants were ≥55 years at the time of the study., Methods: Urinary incontinence was assessed by the urinary distress inventory-6 (UDI-6); a score ≥33.3 indicated symptomatic UI. The incontinence impact questionnaire short form (IIQ-SF) was used to assess the impact on women's health-related quality of life (HR-QoL). Differences between groups were analysed using regression analyses adjusting for current age and other confounders., Main Outcome Measures: Differences in UDI-6 scores and IIQ-SF scores between women with a premenopausal and a postmenopausal RRSO., Results: Women in the premenopausal RRSO group had slightly higher UDI-6 scores compared with women in the postmenopausal RRSO group (P = 0.053), and their risk of symptomatic UI was non-significantly increased (odds ratio [OR] 2.1, 95% confidence interval [95% CI] 0.93-4.78). A premenopausal RRSO was associated with a higher risk of stress UI (OR 3.5, 95% CI 1.2-10.0) but not with urge UI. The proportions of women with a significant impact of UI on HR-QoL were similar in the premenopausal and postmenopausal RRSO groups (10.4% and 13.0%, respectively; P = 0.46)., Conclusions: More than 15 years after premenopausal RRSO, there were no significant differences in overall symptomatic UI between women with a premenopausal and those with a postmenopausal RRSO., (© 2023 John Wiley & Sons Ltd.)

Background Coronary flow reserve (CFR) and microvascular resistance reserve (MRR) are physiological parameters to assess coronary microvascular dysfunction. CFR and MRR can be assessed using bolus or continuous thermodilution, and the correlation between these methods has not been clarified. Furthermore, their association with angina and quality of life is unknown. Methods and Results In total, 246 consecutive patients with angina and nonobstructive coronary arteries from the multicenter Netherlands Registry of Invasive Coronary Vasomotor Function Testing (NL-CFT) were investigated. The 36-item Short Form Health Survey Quality of Life and Seattle Angina questionnaires were completed by 153 patients before the invasive measurements. CFR and MRR were measured consecutively with bolus and continuous thermodilution. Mean continuous thermodilution-derived coronary flow reserve (CFR abs ) was significantly lower than mean bolus thermodilution-derived coronary flow reserve (CFR bolus ) (2.6±1.0 versus 3.5±1.8; P <0.001), with a modest correlation ( ρ =0.305; P <0.001). Mean continuous thermodilution-derived microvascular resistance reserve (MRR abs ) was also significantly lower than mean bolus thermodilution-derived MRR (MRR bolus ) (3.1±1.1 versus 4.2±2.5; P <0.001), with a weak correlation ( ρ =0.280; P <0.001). CFR bolus and MRR bolus showed no correlation with any of the angina and quality of life domains, whereas CFR abs and MRR abs showed a significant correlation with physical limitation ( P =0.005, P =0.009, respectively) and health ( P =0.026, P =0.012). In a subanalysis in patients in whom spasm was excluded, the correlation further improved (MRR abs versus physical limitation: ρ =0.363; P =0.041, MRR abs versus physical health: ρ =0.482; P =0.004). No association with angina frequency and stability was found. Conclusions Absolute flow measurements using continuous thermodilution to calculate CFR abs and MRR abs weakly correlate with, and are lower than, the surrogates CFR bolus and MRR bolus . Absolute flow parameters showed a relationship with physical complaints. No relationship with angina frequency and stability was found.

Background: Childhood cancer survivors (CCS) are at risk for cardiotoxicity., Objectives: We sought to assess how cardiac dysfunction measurements in CCS overlap and are differentially influenced by risk factors., Methods: This cross-sectional Dutch Childhood Cancer Survivor Study evaluated echocardiograms of 1,397 ≥5-year CCS and 277 siblings. Of CCS, n = 1,254 received cardiotoxic (anthracyclines/mitoxantrone/radiotherapy involving the heart region [RT heart ]) and n = 143 received potentially cardiotoxic (cyclophosphamide, ifosfamide, or vincristine) therapy. We assessed demographic, treatment-related, and traditional cardiovascular risk factors for cardiac dysfunction using multivariable logistic regression., Results: CCS were a median of 26.7 years after diagnosis; 49% were women. Abnormal left ventricular ejection fraction (LVEF) (defined as <52% in men, <54% in women) occurred most commonly in CCS treated with anthracyclines and RT heart combined (38%). Age/sex-specific abnormal global longitudinal strain (GLS) occurred most commonly in CCS treated with RT heart , either with (41%) or without (38%) anthracyclines. Of CCS with normal LVEF, 20.2% showed abnormal GLS. Diastolic dysfunction grade ≥II was rare. Abnormal LVEF was mainly associated with female sex, anthracycline dose, and only in women, RT heart dose. Abnormal GLS was associated with female sex, RT heart dose, diastolic blood pressure, and only in women, anthracycline dose. Cyclophosphamide, ifosfamide, and vincristine were not associated with LVEF or GLS. Compared with siblings, CCS showed higher risk of abnormal LVEF (OR: 2.9; 95% CI: 1.4-6.6) and GLS (OR: 2.1; 95% CI: 1.2-3.7), independent of (potentially) cardiotoxic treatment-related and cardiovascular risk factors., Conclusions: Abnormal LVEF and GLS constitute complementary measures of systolic dysfunction among long-term CCS. Their diagnostic value may differ according to cardiotoxic exposures. Also, CCS have residual, unexplained risk of cardiac dysfunction. (Early Detection of Cardiac Dysfunction in Childhood Cancer Survivors, a DCOG LATER study; NTR7481)., Competing Interests: This work was supported by grant CVON 2015-021 of the Dutch Heart Foundation and grant 171 DCOG LATER program of KiKa and ODAS. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2023 The Authors.)

Background: The awareness of cancer therapy-related adverse cardiac effects is fueled by recent literature on cardiotoxicity incidence and detection strategies. Although this influences the sense of urgency, in current practice, cardiotoxicity monitoring and treatment is not structurally performed. With this study, we aimed to evaluate current perspectives on cardio-oncology and to assess needs, ultimately to determine an agenda for improvements in current practice., Material and Methods: A national multidisciplinary 36-question survey was conducted. The survey was developed by a multidisciplinary team, theoretically based on an implementation checklist and distributed by email, through cardiology and oncology societies as well as social media., Results: One hundred ninety professionals completed the survey, of which 66 were cardiologists, 66 radiation oncologists, and 58 medical oncologists and hematologists. Many professionals were unaware of their specialisms' cardio-oncology guidelines: 62.1% of cardiologists and 29.3% of the hematologists and medical oncologists respectively. Many cardiologists (N = 46; 69.7%), radiation oncologists (N = 45; 68.2%), and hematologists and medical oncologists (N = 38; 65.5%) expressed that they did not have sufficient knowledge to treat cardio-oncology patients and would either refer a patient or aspire to gain more knowledge on the topic., Conclusion: The field of cardio-oncology is advancing rapidly, with progress in stratification and detection strategies leading to the development of new guidelines and consensus statements. However, the application of these guidelines in current practice appears to be lagging. Professionals express a need for additional training and a practical guideline including risk stratification, monitoring, and treatment strategies. Multidisciplinary discussion and consensus on cardio-oncology care is vital to improve implementation of cardio-oncology guidelines, ultimately to improve cardiac care for oncology patients., (© 2022. The Author(s).)

Objective: To examine the effect of a premenopausal risk-reducing salpingo-oophorectomy (RRSO) in women at increased risk of ovarian cancer on objective and subjective cognition at least 10 years after RRSO., Design: A cross-sectional study with prospective follow-up, nested in a nationwide cohort., Setting: Multicentre in the Netherlands., Population or Sample: 641 women (66% BRCA1/2 pathogenic variant carriers) who underwent either a premenopausal RRSO ≤ age 45 (n = 436) or a postmenopausal RRSO ≥ age 54 (n = 205). All participants were older than 55 years at recruitment., Methods: Participants completed an online cognitive test battery and a questionnaire on subjective cognition. We used multivariable regression analyses, adjusting for age, education, breast cancer, hormone replacement therapy, cardiovascular risk factors and depression., Main Outcome Measures: The influence of RRSO on objective and subjective cognition of women with a premenopausal RRSO compared with women with a postmenopausal RRSO., Results: After adjustment, women with a premenopausal RRSO (mean time since RRSO 18.2 years) performed similarly on objective cognitive tests compared with women with a postmenopausal RRSO (mean time since RRSO 11.9 years). However, they more frequently reported problems with reasoning (odds ratio [OR] 1.8, 95% confidence interval [95% CI] 1.1-3.1) and multitasking (OR 1.9, 95% CI 1.1-3.4) than women with a postmenopausal RRSO. This difference between groups disappeared in an analysis restricted to women of comparable ages (60-70 years)., Conclusions: Reassuringly, approximately 18 years after RRSO, we found no association between premenopausal RRSO and objective cognition., (© 2023 John Wiley & Sons Ltd.)

Background: Women with a BRCA1/2 pathogenic variant are advised to undergo premenopausal risk-reducing salpingo-oophorectomy after completion of childbearing, to reduce their risk of ovarian cancer. Several studies reported less sexual pleasure 1 to 3 years after a premenopausal oophorectomy. However, the long-term effects of premenopausal oophorectomy on sexual functioning are unknown., Objective: This study aimed to study long-term sexual functioning in women at increased familial risk of breast or ovarian cancer who underwent a risk-reducing salpingo-oophorectomy either before the age of 46 years (premenopausal group) or after the age of 54 years (postmenopausal group). Subgroup analyses were performed in the premenopausal group, comparing early (before the age of 41 years) and later (at ages 41-45 years) premenopausal risk-reducing salpingo-oophorectomy., Study Design: Between 2018 and 2021, 817 women with a high familial risk of breast or ovarian cancer from an ongoing cohort study were invited to participate in our study. Because of a large difference in age in the study between the premenopausal and postmenopausal salpingo-oophorectomy groups, we restricted the comparison of sexual functioning between the groups to 368 women who were 60 to 70 years old at completion of the questionnaire (226 in the premenopausal group and 142 in the postmenopausal group). In 496 women with a premenopausal risk-reducing salpingo-oophorectomy, we compared the sexual functioning between women in the early premenopausal group (n=151) and women in the later premenopausal group (n=345). Differences between groups were analyzed using multiple regression analyses, adjusting for current age, breast cancer history, use of hormone replacement therapy, body mass index, chronic medication use (yes or no), and body image., Results: Mean times since risk-reducing salpingo-oophorectomy were 20.6 years in the premenopausal group and 10.6 years in the postmenopausal group (P<.001). The mean age at questionnaire completion was 62.7 years in the premenopausal group, compared with 67.0 years in the postmenopausal group (P<.001). Compared with 48.9% of women in the postmenopausal group, 47.4% of women in the premenopausal group were still sexually active (P=.80). Current sexual pleasure scores were the same for women in the premenopausal group and women in the postmenopausal group (mean pleasure score, 8.6; P=.99). However, women in the premenopausal group more often reported substantial discomfort than women in the postmenopausal group (35.6% vs 20.9%; P=.04). After adjusting for confounders, premenopausal risk-reducing salpingo-oophorectomy was associated with substantially more discomfort during sexual intercourse than postmenopausal risk-reducing salpingo-oophorectomy (odds ratio, 3.1; 95% confidence interval, 1.04-9.4). Moreover, after premenopausal risk-reducing salpingo-oophorectomy, more severe complaints of vaginal dryness were observed (odds ratio, 2.6; 95% confidence interval, 1.4-4.7). Women with a risk-reducing salpingo-oophorectomy before the age of 41 years reported similar pleasure and discomfort scores as women with a risk-reducing salpingo-oophorectomy between ages 41 and 45 years., Conclusion: More than 15 years after premenopausal risk-reducing salpingo-oophorectomy, the proportion of sexually active women was comparable with the proportion of sexually active women with a postmenopausal risk-reducing salpingo-oophorectomy. However, after a premenopausal risk-reducing salpingo-oophorectomy, women experienced more vaginal dryness and more often had substantial sexual discomfort during sexual intercourse. This did not lead to less pleasure with sexual activity., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: The risk of cardiovascular disease more than doubles after hypertensive disorders of pregnancy. As early onset chronic hypertension contributes to cardiovascular risk, implementation of screening strategies, using home blood pressure monitoring (HBPM), may help to improve long-term cardiovascular health.We evaluated whether HBPM among women with a history of preeclampsia/HELLP syndrome is feasible for early detection and management of hypertension., Methods: The BP-PRESELF study is a multicenter randomized controlled trial. Participants were randomized to intervention group with HBPM for the duration of 1 year or the control group with 'usual care'. The primary outcome was feasibility of HBPM during 1 year of follow-up, defined as protocol adherence, protocol persistence and patient acceptance. Secondary outcomes were blood pressure levels and prevalence of hypertension., Results: We recruited 198 women with a mean age of 45 years. Protocol adherence decreased during the first 6 months, after which it stabilized. Protocol persistence remained high throughout follow-up. During the study period, 33 women (34%) in the intervention group were diagnosed with hypertension versus only 10 women (11%) in the control group, P <0.001. At 1-year follow-up, mean systolic blood pressure (SD) was 120.4 (11.6) mmHg in the intervention group versus 126.1 (14.3) mmHg in the control group, P =0.003. Mean diastolic blood pressure (SD) values were 77.1 (8.0) mmHg versus 81.7 (9.4) mmHg, P <0.001, respectively. Adjusted systolic and diastolic differences (95% confidence interval) were -6.81 (-10.17, -3.45) and -4.93 (-7.26, -2.61) mm Hg, with 80% less hypertension at 1-year follow-up in the intervention group., Conclusions: HBPM appears to be feasible for follow-up of blood pressure in women after preeclampsia/HELLP syndrome, while it detected hypertension and blood pressure levels reduced in one-third of women in this group., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors. Published by Elsevier B.V.)

Background: Diltiazem is recommended and frequently prescribed in patients with angina and nonobstructive coronary artery disease (ANOCA), suspected of coronary vasomotor dysfunction (CVDys). However, studies substantiating its effect is this patient group are lacking., Objectives: The randomized, placebo-controlled EDIT-CMD (Efficacy of Diltiazem to Improve Coronary Microvascular Dysfunction: A Randomized Clinical Trial) evaluated the effect of diltiazem on CVDys, as assessed by repeated coronary function testing (CFT), angina, and quality of life., Methods: A total of 126 patients with ANOCA were included and underwent CFT. CVDys, defined as the presence of vasospasm (after intracoronary acetylcholine provocation) and/or microvascular dysfunction (coronary flow reserve: <2.0, index of microvascular resistance: ≥25), was confirmed in 99 patients, of whom 85 were randomized to receive either oral diltiazem or placebo up to 360 mg/d. After 6 weeks, a second CFT was performed. The primary end point was the proportion of patients having a successful treatment, defined as normalization of 1 abnormal parameter of CVDys and no normal parameter becoming abnormal. Secondary end points were changes from baseline to 6-week follow-up in vasospasm, index of microvascular resistance, coronary flow reserve, symptoms (Seattle Angina Questionnaire), or quality of life (Research and Development Questionnaire 36)., Results: In total, 73 patients (38 diltiazem vs 35 placebo) underwent the second CFT. Improvement of the CFT did not differ between the groups (diltiazem vs placebo: 21% vs 29%; P = 0.46). However, more patients on diltiazem treatment progressed from epicardial spasm to microvascular or no spasm (47% vs 6%; P = 0.006). No significant differences were observed between the diltiazem and placebo group in microvascular dysfunction, Seattle Angina Questionnaire, or Research and Development Questionnaire 36., Conclusions: This first performed randomized, placebo-controlled trial in patients with ANOCA showed that 6 weeks of therapy with diltiazem, when compared with placebo, did not substantially improve CVDys, symptoms, or quality of life, but diltiazem therapy did reduce prevalence of epicardial spasm. (Efficacy of Diltiazem to Improve Coronary Microvascular Dysfunction: A Randomized Clinical Trial [EDIT-CMD]; NCT04777045)., Competing Interests: Funding Support and Author Disclosures The trial was funded with a research grant from Abbott (to Drs van Royen and Elias-Smale). The sponsor had no involvement in the design of the study, data collection or analysis, or the writing of the manuscript. Dr Smits has received consultancy fees and institutional research grants from Abbott. Dr Damman has received consultancy fees from Philips and Abbott; and research grants from Philips. Dr van Royen has received consultancy fees from Abbott; and research grants from Philips and Abbott. Drs Damman and van Royen are part of the larger Dutch Cardiovascular Alliance consortium IMPRESS (2020B004). Dr Elias-Smale has received a research grant from Abbott. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Menopause transition marks an important phase in life when cardiovascular risk in women gradually takes an adverse turn. Although menopausal hormone therapy has gained a negative appreciation over the last decades, its value in the treatment of disabling vasomotor symptoms is still undisputed. Cardiovascular risk assessment has become a matter of precision medicine, which is helpful for safe menopausal hormone therapy prescription. With a multidisciplinary approach the current available hormone regimens can be even given to women at intermediate cardiovascular risk, when risk factors such as hypertension and dyslipidemia are adequately monitored and treated., (Copyright © 2021 The Author. Published by Elsevier Ltd.. All rights reserved.)

Objective: To assess the temporal trends, characteristics and comorbidities, and in-hospital cardiovascular and obstetric complications and outcomes of pregnant women with current or historical cancer diagnosis at the time of admission for delivery., Methods: We analyzed delivery hospitalizations with or without current or historical cancer between January 1, 2004, and December 31, 2014, from the US National Inpatient Sample database., Results: We included 43,132,097 delivery hospitalizations with no cancer, 39,118 with current cancer, and 67,336 with historical diagnosis of cancer. The 5 most common types of current cancer were hematologic, thyroid, cervical, skin, and breast cancer. Women with current and historical cancer were older (29 years and 32 years vs 27 years) and incurred higher hospital costs ($4131 and $4078 vs $3521) compared with women without cancer. Most of the cancer types were associated with preterm birth (hematologic: adjusted odds ratio [aOR], 1.48 [95% CI, 1.35 to 1.62]; cervical: aOR, 1.47 [95% CI, 1.32 to 1.63]; breast: aOR, 1.93 [95% CI, 1.72 to 2.16]). Current hematologic cancer was associated with the highest risk of peripartum cardiomyopathy (aOR, 12.19 [95% CI, 7.75 to 19.19]), all-cause mortality (aOR, 6.50 [95% CI, 2.22 to 19.07]), arrhythmia (aOR, 3.82 [95% CI, 2.04 to 7.15]), and postpartum hemorrhage (aOR, 1.31 [95% CI, 1.11 to 1.54]). Having a current or historical cancer diagnosis did not confer additional risk for stillbirth; however, metastases increased the risk of maternal mortality and preterm birth., Conclusion: Women with a current or historical diagnosis of cancer at delivery have more comorbidities compared with women without cancer. Clinicians should communicate the risks of multisystem complications to these complex patients., (Copyright © 2021 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Cardiovascular disease is the leading cause of death in women. Decades of grassroots campaigns have helped to raise awareness about the impact of cardiovascular disease in women, and positive changes affecting women and their health have gained momentum. Despite these efforts, there has been stagnation in the overall reduction of cardiovascular disease burden for women in the past decade. Cardiovascular disease in women remains understudied, under-recognised, underdiagnosed, and undertreated. This Commission summarises existing evidence and identifies knowledge gaps in research, prevention, treatment, and access to care for women. Recommendations from an international team of experts and leaders in the field have been generated with a clear focus to reduce the global burden of cardiovascular disease in women by 2030. This Commission represents the first effort of its kind to connect stakeholders, to ignite global awareness of sex-related and gender-related disparities in cardiovascular disease, and to provide a springboard for future research., Competing Interests: Declaration of interests MA reports personal fees from Bayer, Boehringer, Tecnofarma, and Axon, and non-financial support from Boehringer, outside the submitted work. YA reports grants from the Dutch Heart Foundation and has a patent image guided plaque ablation (USP 945593 licenced). CNBM reports grants from US National Institutes of Health (NIH) Study Section, Peer Review Medical Research Program Cardiovascular Health for the Department of Defense Congressionally Directed Medical Research Program, US National Heart, Lung, and Blood Institute (NHLBI) subcontract to Research Triangle Institute International, NHLBI R01, US National Institute on Aging U54, and Women's Ischemia Syndrome Evaluation HFpEF; consulting fees from the US Food and Drug Administration Renal Advisory Panel; and consulting fees or honoraria from iRhythm, Abbott Diagnostics, and Sanofi Vascular. AC reports personal fees from Abbott Vascular, Magenta, Biosensor, Abiomed, and Cardional Health. GAF reports grants from the Australian National Health and Medical Research Council and Abbott Diagnostics; and personal fees from CSL Behring and Janssen. VK reports personal fees from honoraria and for speaking from Bayer, Daichii Sankyo, Amgen, AstraZeneca, and Abbott, outside the submitted work. CSPL reports grants from Boston Scientific, Bayer, Roche Diagnostics, AstraZeneca, Medtronic, and Vifor Pharma; personal fees from Abbott Diagnostics, Amgen, Applied Therapeutics, AstraZeneca, Bayer, Biofourmis, Boehringer Ingelheim, Boston Scientific, Corvia Medical, Cytokinetics, Darma, Us2.ai, JanaCare, Janssen Research & Development, Medtronic, Menarini Group, Merck, MyoKardia, Novartis, Novo Nordisk, Radcliffe Group, Roche Diagnostics, Sanofi, Stealth BioTherapeutics, The Corpus, Vifor Pharma, and WebMD Global; and has a patent pending (PCT/SG2016/050217), and a patent issued (16/216,929). JEP reports grants from BIOTRONIK and AtriCure. JS reports grants from the Canadian Institutes of Health Research, Heart & Stroke Foundation of Canada, Michael Smith Foundation of Health Research, and NIH; and consulting fees from Abbott Vascular, Boston Scientific, Gore, Baylis, and Abiomed. RM reports grants from Abbott Laboratories, Abiomed, Applied Therapeutics, AstraZeneca, Bayer, Beth Israel Deaconess, Bristol-Myers Squibb, Cerecor, Chiesi, Concept Medical, CSL Behring, DSI, Medtronic, Novartis Pharmaceuticals, OrbusNeich, and Zoll; personal fees from Boston Scientific, Cine-Med Research, Janssen Scientific Affairs, Medscape/WebMD, American College of Cardiology, and American Medical Association; non-financial support from Regeneron Pharmaceuticals; consultancy or advisory board fees paid to her institution from Abbott Laboratories, Beth Israel Deaconess, Bristol Myers Squibb, Chiesi, Concept Medical, Daiichi Sankyo, Medtronic, Novartis, CardiaWave, Duke University, Idorsia, Spectranetics/Philips/Volcano Corp; consultant fees paid to the institution of her spouse from Abiomed, Bayer; <1% equity in Applied Therapeutics, Elixir Medical, and STEL; and spouse's <1% equity in ControlRad. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Coronary vasomotor dysfunction, comprising endotypes of coronary spasm and/or impaired microvascular dilatation (IMD), is common in patients with angina and no obstructive coronary arteries (ANOCA). However, there are discrepant reports regarding the prevalence of these endotypes. The objective of this study was to determine the prevalence of coronary vasomotor dysfunction in patients with ANOCA, underlying endotypes, and differences in clinical characteristics., Methods: Prospective registry of patients with ANOCA that underwent clinically indicated invasive coronary function testing (CFT), including acetylcholine spasm testing (2-200 μg) to diagnose coronary spasm, and adenosine testing (140 μg/kg/min) to diagnose IMD, defined as an index of microvascular resistance ≥25 and/or coronary flow reserve <2.0., Results: Of the 111 patients that completed CFT (88% female, mean age 54 years), 96 (86%) showed vasomotor dysfunction. The majority 93 (97%) had coronary spasm, 63% isolated and 34% combined with IMD. Isolated IMD was rare, occurring in only 3 patients (3%). Hypertension was more prevalent in patients with vasomotor dysfunction compared to those without (39% vs. 7%, p = 0.02). Obesity and a higher severity of angiographic atherosclerotic disease were more prevalent in patients with coronary spasm compared to those without (61% vs. 28%; 40% vs. 0%, respectively, both p < 0.01). No differences in angina characteristics were observed between patients with and without vasomotor dysfunction or between endotypes., Conclusions: Coronary vasomotor dysfunction is highly prevalent in patients with ANOCA, especially epicardial or microvascular vasospasm, whereas isolated IMD was rare. Performing a CFT without acetylcholine testing should be strongly discouraged., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Cardiotoxicity is a well-known side effect after anthracyclines and chest radiotherapy in childhood cancer survivors (CCS). The DCCSS LATER 2 CARD (cardiology) study includes evaluation of echocardiographic measurements for early identification of CCS at highest risk of developing heart failure. This paper describes the design, feasibility, and reproducibility of the echocardiography protocol., Methods: Echocardiograms from CCS and sibling controls were prospectively obtained at the participating centers and centrally analyzed. We describe the image acquisition, measurement protocol, and software-specific considerations for myocardial strain analyses. We report the feasibility of the primary outcomes of systolic and diastolic function, as well as reproducibility analyses in 30 subjects., Results: We obtained 1,679 echocardiograms. Biplane ejection fraction (LVEF) measurement was feasible in 91% and 96% of CCS and siblings, respectively, global longitudinal strain (GLS) in 80% and 91%, global circumferential strain (GCS) in 86% and 89%, and ≥2 diastolic function parameters in 99% and 100%, right ventricle free wall strain (RVFWS) in 57% and 65%, and left atrial reservoir strain (LASr) in 72% and 79%. Intra-class correlation coefficients for inter-observer variability were 0.85 for LVEF, 0.76 for GLS, 0.70 for GCS, 0.89 for RVFWS and 0.89 for LASr. Intra-class correlation coefficients for intra-observer variability were 0.87 for LVEF, 0.82 for GLS, 0.82 for GCS, 0.85 for RVFWS and 0.79 for LASr., Conclusion: The DCCSS LATER 2 CARD study includes a protocolized echocardiogram, with feasible and reproducible primary outcome measurements. This ensures high-quality outcome data for prevalence estimates and for reliable comparison of cardiac function parameters., (© 2021 The Authors. Echocardiography published by Wiley Periodicals LLC.)

Background: BRCA1/2 mutation carriers are generally exposed to early menopause due to risk-reducing salpingo-oophorectomy (RRSO) around the age of 40 years. This risk-reducing intervention is based on a 10-40% life-time risk of ovarian cancer in this population. Although effective, premature and acute menopause induces non-cancer related morbidity in both the short and long term. Little is known about the impact of RRSO on the cardiovascular system., Methods: This cross-sectional study explored the relationship between time since RRSO and signs of subclinical atherosclerosis, as measured by carotid intima-media thickness (CIMT) and pulse wave velocity (PWV), in 165 BRCA1/2 mutation carriers. All participants, aged 40 to 63 years, underwent RRSO before the age of 45 years, and at least 5 years ago. Cardiovascular risk factors were assessed by questionnaires and a single screening visit. Data were analyzed using linear regression models., Results: Mean CIMT was 692.7 μm (SD 87.0), and mean central PWV 6.40 m/s (SD 1.42). After adjustment for age and several relevant cardiovascular risk factors, time since RRSO was not associated with CIMT (β=0.68 μm; 95% CI -4.02, 5.38) and PWV (β=44 mm/s; 95% CI -32, 120). Compared to women of a reference group from the general population, lower systolic blood pressure [mean difference 12 mmHg; 95% confidence interval (CI) 10, 14] was found in BRCA1/2 mutation carriers., Conclusions: We found that, in BRCA1/2 mutation carriers, at 5 to 24 years follow-up, time since RRSO is not related to development of subclinical atherosclerosis. However, the follow-up period in these relatively young women might have been too short., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: BRCA1/2 mutation carriers are recommended to undergo risk-reducing salpingo-oophorectomy (RRSO) at 35 to 45 years of age. RRSO substantially decreases ovarian cancer risk, but at the cost of immediate menopause. Knowledge about the potential adverse effects of premenopausal RRSO, such as increased risk of cardiovascular disease, osteoporosis, cognitive dysfunction, and reduced health-related quality of life (HRQoL), is limited., Objective: The aim of this study is to assess the long-term health effects of premenopausal RRSO on cardiovascular disease, bone health, cognitive functioning, urological complaints, sexual functioning, and HRQoL in women with high familial risk of breast or ovarian cancer., Methods: We will conduct a multicenter cross-sectional study with prospective follow-up, nested in a nationwide cohort of women at high familial risk of breast or ovarian cancer. A total of 500 women who have undergone RRSO before 45 years of age, with a follow-up period of at least 10 years, will be compared with 250 women (frequency matched on current age) who have not undergone RRSO or who have undergone RRSO at over 55 years of age. Participants will complete an online questionnaire on lifestyle, medical history, cardiovascular risk factors, osteoporosis, cognitive function, urological complaints, and HRQoL. A full cardiovascular assessment and assessment of bone mineral density will be performed. Blood samples will be obtained for marker analysis. Cognitive functioning will be assessed objectively with an online neuropsychological test battery., Results: This study was approved by the institutional review board in July 2018. In February 2019, we included our first participant. As of November 2020, we had enrolled 364 participants in our study., Conclusions: Knowledge from this study will contribute to counseling women with a high familial risk of breast/ovarian cancer about the long-term health effects of premenopausal RRSO. The results can also be used to offer health recommendations after RRSO., Trial Registration: ClinicalTrials.gov NCT03835793; https://clinicaltrials.gov/ct2/show/NCT03835793., International Registered Report Identifier (irrid): DERR1-10.2196/24414., (©Lara Terra, Maartje J Hooning, Bernadette A M Heemskerk-Gerritsen, Marc van Beurden, Jeanine E Roeters van Lennep, Helena C van Doorn, Joanne A de Hullu, Constantijne Mom, Eleonora B L van Dorst, Marian J E Mourits, Brigitte F M Slangen, Katja N Gaarenstroom, M Carola Zillikens, Tim Leiner, Lizet van der Kolk, Margriet Collee, Marijke Wevers, Margreet G E M Ausems, Klaartje van Engelen, Lieke PV Berger, Christi J van Asperen, Encarna B Gomez-Garcia, Irma van de Beek, Matti A Rookus, Michael Hauptmann, Eveline M Bleiker, Sanne B Schagen, Neil K Aaronson, Angela H E M Maas, Flora E van Leeuwen. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 22.01.2021.)

This consensus document, a summary of the views of an expert panel organized by the European Association of Percutaneous Cardiovascular Interventions (EAPCI), appraises the importance of ischaemia with non-obstructive coronary arteries (INOCA). Angina pectoris affects approximately 112 million people globally. Up to 70% of patients undergoing invasive angiography do not have obstructive coronary artery disease, more common in women than in men, and a large proportion have INOCA as a cause of their symptoms. INOCA patients present with a wide spectrum of symptoms and signs that are often misdiagnosed as non-cardiac leading to under-diagnosis/investigation and under-treatment. INOCA can result from heterogeneous mechanism including coronary vasospasm and microvascular dysfunction and is not a benign condition. Compared to asymptomatic individuals, INOCA is associated with increased incidence of cardiovascular events, repeated hospital admissions, as well as impaired quality of life and associated increased health care costs. This consensus document provides a definition of INOCA and guidance to the community on the diagnostic approach and management of INOCA based on existing evidence from research and best available clinical practice; noting gaps in knowledge and potential areas for further investigation.

Background: The relative frequency of psychological factors in patients with spontaneous coronary artery dissection (SCAD) compared to patients with traditional atherosclerosis-related type 1 acute coronary syndrome (ACS) is unknown. This study examines whether psychological factors and emotional or physical precipitants are more common in SCAD patients versus atherosclerosis-related ACS patients., Methods: Participants with SCAD were recruited from a Dutch SCAD database. Given the predominance of SCAD in women (>90%), only female patients were included. The age- and sex-matched atherosclerosis-related ACS group was identified from a registry database. Online questionnaires and medical records were used to investigate psychological factors and clinical information. Univariate and multivariate logistic regression models were used to examine differences between 172 SCAD patients and 76 ACS patients on emotional and physical precipitants prior to the event and psychological factors after the event., Results: Patients with SCAD were more likely to experience an emotional precipitant in the 24 h prior to the event (56%), compared with the ACS group (39%) (OR = 1.98, 95%CI 1.14-3.44). Multivariate analyses showed that this association remained significant after adjustment for covariates (OR = 2.17, 95%CI 1.08-4.36). At an average of 3.2 years post-hospitalization for the SCAD or atherosclerosis-related ACS event, both patient groups had similar high levels of perceived stress (50% vs. 45%, p = .471) and fatigue (56% vs. 53%, p = .643)., Conclusions: This study shows that risk profiles for SCAD differ from traditional atherosclerosis-related ACS. Our findings may help health professionals to recognize SCAD and offer tailored rehabilitation and prevention programs., Competing Interests: Declaration of Competing Interest RvG has received grants and personal fees from AstraZeneca, Amgen, and Boston Scientific, and personal fees from Abbott vascular, and Sanofi, outside the submitted work., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)