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Circulation - recientes

Cardiovascular Disease and Breast Cancer: Where These Entities Intersect: A Scientific Statement From the American Heart Association [AHA Scientific Statements]
19/2/2018
Laxmi S. Mehta, Karol E. Watson, Ana Barac, Theresa M. Beckie, Vera Bittner, Salvador Cruz–Flores, Susan Dent, Lavanya Kondapalli, Bonnie Ky, Tochukwu Okwuosa, Ileana L. Pina, Annabelle Santos Volgman
ver resumen
Cardiovascular disease (CVD) remains the leading cause of mortality in women, yet many people perceive breast cancer to be the number one threat to women’s health. CVD and breast cancer have several overlapping risk factors, such as obesity and smoking. Additionally, current breast cancer treatments can have a negative impact on cardiovascular health (eg, left ventricular dysfunction, accelerated CVD), and for women with pre-existing CVD, this might influence cancer treatment decisions by both the patient and the provider. Improvements in early detection and treatment of breast cancer have led to an increasing number of breast cancer survivors who are at risk of long-term cardiac complications from cancer treatments. For older women, CVD poses a greater mortality threat than breast cancer itself. This is the first scientific statement from the American Heart Association on CVD and breast cancer. This document will provide a comprehensive overview of the prevalence of these diseases, shared risk factors, the cardiotoxic effects of therapy, and the prevention and treatment of CVD in breast cancer patients.

Second Annual Go Red for Women Issue [Editor’s Page]
19/2/2018
Sharon C. Reimold, Joseph A. Hill
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Redressing the Red Dress [On My Mind]
19/2/2018
Donna R. Zwas
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Poorly Understood Maternal Risks of Pregnancy in Women With Heart Disease [On My Mind]
19/2/2018
Karen Florio, Tara Banaszek Daming, Anna Grodzinsky
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Who Resembles a Scientific Leader—Jack or Jill? [Perspective]
19/2/2018
Christine Kolehmainen, Molly Carnes
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Sex Difference in Patients With Ischemic Heart Failure Undergoing Surgical Revascularization [Original Research Article]
19/2/2018
Ileana L. Pina, Qi Zheng, Lilin She, Hanna Szwed, Irene M. Lang, Pedro S. Farsky, Serenella Castelvecchio, Jolanta Biernat, Alexandros Paraforos, Dragana Kosevic, Liliana E. Favaloro, Jose C. Nicolau, Padmini Varadaraȷan, Eric J. Velazquez, Ramdas G. Pai, Nicole Cyrille, Kerry L. Lee, Patrice Desvigne–Nickens
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Background:Female sex is conventionally considered a risk factor for coronary artery bypass grafting (CABG) and has been included as a poor prognostic factor in multiple cardiac operative risk evaluation scores. We aimed to investigate the association of sex and the long-term benefit of CABG in patients with ischemic left ventricular dysfunction enrolled in the prospective STICH trial (Surgical Treatment for Ischemic Heart Failure Study).Methods:The STICH trial randomized 1212 patients (148 [12%] women and 1064 [88%] men) with coronary artery disease and left ventricular ejection fraction ≤35% to CABG+medical therapy (MED) versus MED alone. Long-term (10-year) outcomes with each treatment were compared according to sex.Results:At baseline, women were older (63.4 versus 59.3 years; P=0.016) with higher body mass index (27.9 versus 26.7 kg/m2; P=0.001). Women had more coronary artery disease risk factors (diabetes mellitus, 55.4% versus 37.2%; hypertension, 70.9% versus 58.6%; hyperlipidemia, 70.3% versus 58.9%) except for smoking (13.5% versus 21.8%) and had lower rates of prior CABG (0% versus 3.4%; all P<0.05) than men. Moreover, women had higher New York Heart Association class (class III/IV, 66.2% versus 57.0%), lower 6-minute walk capacity (300 versus 350 m), and lower Kansas City Cardiomyopathy Questionnaire overall summary scores (51 versus 63; all P<0.05). Over 10 years of follow-up, all-cause mortality (49.0% versus 65.8%; adjusted hazard ratio, 0.67; 95% confidence interval, 0.52–0.86; P=0.002) and cardiovascular mortality (34.3% versus 52.3%; adjusted hazard ratio, 0.65; 95% confidence interval, 0.48–0.89; P=0.006) were significantly lower in women compared with men. With randomization to CABG+MED versus MED treatment, there was no significant interaction between sex and treatment group in all-cause mortality, cardiovascular mortality, or the composite of all-cause mortality or cardiovascular hospitalization (all P>0.05). In addition, surgical deaths were not statistically different (1.5% versus 5.1%; P=0.187) between sexes among patients randomized to CABG per protocol as initial treatment.Conclusions:Sex is not associated with the effect of CABG+MED versus MED on all-cause mortality, cardiovascular mortality, the composite of death or cardiovascular hospitalization, or surgical deaths in patients with ischemic left ventricular dysfunction. Thus, sex should not influence treatment decisions about CABG in these patients.Clinical Trial Registration:URL: https://www.clinicaltrials.gov. Unique identifier: NCT00023595.

Sex Differences in the Presentation and Perception of Symptoms Among Young Patients With Myocardial Infarction [Original Research Article]
19/2/2018
Judith H. Lichtman, Erica C. Leifheit, Basmah Safdar, Haikun Bao, Harlan M. Krumholz, Nancy P. Lorenze, Mitra Daneshvar, John A. Spertus, Gail D’Onofrio
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Background:Some studies report that women are less likely to present with chest pain for acute myocardial infarction (AMI). Information on symptom presentation, perception of symptoms, and care-seeking behaviors is limited for young patients with AMI.Methods:We interviewed 2009 women and 976 men aged 18 to 55 years hospitalized for AMI at 103 US hospitals participating in the VIRGO study (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients). Structured patient interviews during the index AMI hospitalization were used to collect information on symptom presentation, perception of symptoms, and care-seeking behaviors. We compared patient characteristics and presentation information by sex. Multivariable hierarchical logistic regression was used to evaluate the association between sex and symptom presentation.Results:The majority of women (87.0%) and men (89.5%) presented with chest pain (defined as pain, pressure, tightness, or discomfort). Women were more likely to present with ≥3 associated symptoms than men (eg, epigastric symptoms, palpitations, and pain or discomfort in the jaw, neck, arms, or between the shoulder blades; 61.9% for women versus 54.8% for men, P<0.001). In adjusted analyses, women with an ST-segment–elevation AMI were more likely than men to present without chest pain (odds ratio, 1.51; 95% confidence interval, 1.03–2.22). In comparison with men, women were more likely to perceive symptoms as stress/anxiety (20.9% versus 11.8%, P<0.001) but less likely to attribute symptoms to muscle pain (15.4% versus 21.2%, P=0.029). Approximately 29.5% of women and 22.1% of men sought medical care for similar symptoms before their hospitalization (P<0.001); however, 53% of women reported that their provider did not think these symptoms were heart-related in comparison with 37% of men (P<0.001).Conclusions:The presentation of AMI symptoms was similar for young women and men, with chest pain as the predominant symptom for both sexes. Women presented with a greater number of additional non–chest pain symptoms regardless of the presence of chest pain, and both women and their healthcare providers were less likely to attribute their prodromal symptoms to heart disease in comparison with men.

Sauce for the Goose Versus Sauce for the Gander [Editorials]
19/2/2018
Nanette K. Wenger
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Mental Stress-Induced-Myocardial Ischemia in Young Patients With Recent Myocardial Infarction [Original Research Article]
19/2/2018
Viola Vaccarino, Samaah Sullivan, Muhammad Hammadah, Kobina Wilmot, Ibhar Al Mheid, Ronnie Ramadan, Lisa Elon, Pratik M. Pimple, Ernest V. Garcia, Jonathon Nye, Amit J. Shah, Ayman Alkhoder, Oleksiy Levantsevych, Hawkins Gay, Malik Obideen, Minxuan Huang, Tene T. Lewis, J. Douglas Bremner, Arshed A. Quyyumi, Paolo Raggi
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Background:Mental stress-induced myocardial ischemia (MSIMI) is frequent in patients with coronary artery disease and is associated with worse prognosis. Young women with a previous myocardial infarction (MI), a group with unexplained higher mortality than men of comparable age, have shown elevated rates of MSIMI, but the mechanisms are unknown.Methods:We studied 306 patients (150 women and 156 men) ≤61 years of age who were hospitalized for MI in the previous 8 months and 112 community controls (58 women and 54 men) frequency matched for sex and age to the patients with MI. Endothelium-dependent flow-mediated dilation and microvascular reactivity (reactive hyperemia index) were measured at rest and 30 minutes after mental stress. The digital vasomotor response to mental stress was assessed using peripheral arterial tonometry. Patients received 99mTc-sestamibi myocardial perfusion imaging at rest, with mental (speech task) and conventional (exercise/pharmacological) stress.Results:The mean age of the sample was 50 years (range, 22–61). In the MI group but not among controls, women had a more adverse socioeconomic and psychosocial profile than men. There were no sex differences in cardiovascular risk factors, and among patients with MI, clinical severity tended to be lower in women. Women in both groups showed a higher peripheral arterial tonometry ratio during mental stress but a lower reactive hyperemia index after mental stress, indicating enhanced microvascular dysfunction after stress. There were no sex differences in flow-mediated dilation changes with mental stress. The rate of MSIMI was twice as high in women as in men (22% versus 11%, P=0.009), and ischemia with conventional stress was similarly elevated (31% versus 16%, P=0.002). Psychosocial and clinical risk factors did not explain sex differences in inducible ischemia. Although vascular responses to mental stress (peripheral arterial tonometry ratio and reactive hyperemia index) also did not explain sex differences in MSIMI, they were predictive of MSIMI in women only.Conclusions:Young women after MI have a 2-fold likelihood of developing MSIMI compared with men and a similar increase in conventional stress ischemia. Microvascular dysfunction and peripheral vasoconstriction with mental stress are implicated in MSIMI among women but not among men, perhaps reflecting women’s proclivity toward ischemia because of microcirculatory abnormalities.

Pregnancy Outcomes in Women With Rheumatic Mitral Valve Disease [Original Research Article]
19/2/2018
Iris M. van Hagen, Sara A. Thorne, Nasser Taha, Ghada Youssef, Amro Elnagar, Harald Gabriel, Yahia ElRakshy, Bernard Iung, Mark R. Johnson, Roger Hall, Jolien W. Roos-Hesselink
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Background:Cardiac disease is 1 of the major causes of maternal mortality. We studied pregnancy outcomes in women with rheumatic mitral valve disease.Methods:The Registry of Pregnancy and Cardiac Disease is an international prospective registry, and consecutive pregnant women with cardiac disease were included. Pregnancy outcomes in all women with rheumatic mitral valve disease and no prepregnancy valve replacement is described in the present study (n=390). A maternal cardiac event was defined as cardiac death, arrhythmia requiring treatment, heart failure, thromboembolic event, aortic dissection, endocarditis, acute coronary syndrome, and hospitalization for other cardiac reasons or cardiac intervention. Associations between patient characteristics and cardiac outcomes were checked in a 3-level model (patient–center–country).Results:Most patients came from emerging countries (75%). Mitral stenosis (MS) with or without mitral regurgitation (MR) was present in 273 women, isolated MR in 117. The degree of MS was mild in 20.9%, moderate in 39.2%, severe in 19.8%, and severity not classified in the remainder. Maternal death during pregnancy occurred in 1 patient with severe MS. Hospital admission occurred in 23.1% of the women with MS, and the main reason was heart failure (mild MS 15.8%, moderate 23.4%, severe 48.1%; P<0.001). Heart failure occurred in 23.1% of patients with moderate or severe MR. An intervention during pregnancy was performed in 16 patients, 14 had percutaneous balloon mitral commissurotomy, and 2 had surgical valve replacement (1 for MS, 1 for MR). In multivariable modeling, prepregnancy New York Heart Association class >1 was an independent predictor of maternal cardiac events. Follow-up at 6 months postpartum was available for 53%, and 3 more patients died (1 with severe MS, 1 with moderate MS, 1 with moderate to severe MR).Conclusions:Although mortality was only 1.9% during pregnancy, ≈50% of the patients with severe rheumatic MS and 23% of those with significant MR developed heart failure during pregnancy. Prepregnancy counseling and considering mitral valve interventions in selected patients are important to prevent these complications.

Rheumatic Heart Disease in Pregnancy [Editorials]
19/2/2018
Katharine A. French, Athena Poppas
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Genetics, Lifestyle, and Low-Density Lipoprotein Cholesterol in Young and Apparently Healthy Women [Original Research Article]
19/2/2018
Jan-Willem Balder, Antoine Rimbert, Xiang Zhang, Martijn Viel, Roan Kanninga, Freerk van Dijk, Peter Lansberg, Richard Sinke, Jan Albert Kuivenhoven
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Background:Atherosclerosis starts in childhood but low-density lipoprotein cholesterol (LDL-C), a causal risk factor, is mostly studied and dealt with when clinical events have occurred. Women are usually affected later in life than men and are underdiagnosed, undertreated, and understudied in cardiovascular trials and research. This study aims at a better understanding of lifestyle and genetic factors that affect LDL-C in young women.Methods:We randomly selected for every year of age 8 women with LDL-C ≤1st percentile (≤50 mg/dL) and 8 women with LDL-C ≥99th percentile (≥186 mg/dL) from 28 000 female participants aged between 25 to 40 years of a population-based cohort study. The resulting groups include 119 and 121 women, respectively, of an average 33 years of age. A gene-sequencing panel was used to assess established monogenic and polygenic origins of these phenotypes. Information on lifestyle was extracted from questionnaires. A healthy lifestyle score was allocated based on a recently developed algorithm.Results:Of the women with LDL-C ≤1st percentile, 19 (15.7%) carried mutations that are causing monogenic hypocholesterolemia and 60 (49.6%) were genetically predisposed to low LDL-C on the basis of an extremely low weighted genetic risk score. In comparison with control groups, a healthier lifestyle was not associated with low LDL-C in women without genetic predispositions. Among women with LDL-C ≥99th percentile, 20 women (16.8%) carried mutations that cause familial hypercholesterolemia, whereas 25 (21%) were predisposed to high LDL-C on the basis of a high-weighted genetic risk score. The women in whom no genetic origin for hypercholesterolemia could be identified were found to exhibit a significantly unfavorable lifestyle in comparison with controls.Conclusions:This study highlights the need for early assessment of the cardiovascular risk profile in apparently healthy young women to identify those with LDL-C ≥99th percentile for their age: first, because, in this study, 17% of the cases were molecularly diagnosed with familial hypercholesterolemia, which needs further attention; second, because our data indicate that an unfavorable lifestyle is significantly associated with severe hypercholesterolemia in genetically unaffected women, which may also need further attention.

Female Sex Is a Risk Modifier Rather Than a Risk Factor for Stroke in Atrial Fibrillation [Original Research Article]
19/2/2018
Peter Bronnum Nielsen, Flemming Skȷoth, Thure Filskov Overvad, Torben Bȷerregaard Larsen, Gregory Y. H. Lip
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Background:Stroke risk in atrial fibrillation is assessed by using the CHA2DS2-VASc score. Sex category (Sc, ie, female sex) confers 1 point on CHA2DS2-VASc. We hypothesized that female sex is a stroke risk modifier, rather than an overall risk factor, when added to a CHA2DS2-VA (sex-independent thromboembolism risk) score scale.Methods:Using 3 nationwide registries, we identified patients with incident nonvalvular atrial fibrillation from January 1, 1997, through December 31, 2015. Patients receiving oral anticoagulant treatment at baseline were excluded, and person-time was censored at the time of treatment initiation (if any). CHA2DS2-VA scores were calculated for men and women, and were followed for up to 1 year in the Danish National Patient Registry. The primary outcome was a primary hospital code for ischemic stroke or systemic embolism (thromboembolism). We calculated crude event rates for risk strata as events per 100 person-years. For quantifying absolute risk of stroke, we calculated risks based on the pseudovalue method. Female sex as a prognostic factor was investigated by inclusion as an interaction term on the CHA2DS2-VA score to calculate the thromboembolic risk ratio for different score points.Results:A total of 239 671 patients with atrial fibrillation (48.7% women) contributed to the analyses. The mean ages for women and men were 76.6 years and 70.3 years, respectively; the mean CHA2DS2-VA scores were 2.7 for women and 2.3 for men. The overall 1-year thromboembolic rate per 100 person-years for women was 7.3 and 5.7 for men. The 1-year absolute risk of thromboembolism was 0.5% among men and women with a CHA2DS2-VA score of 0 and increased up to >7% among very comorbid patients (score >5). The risk ratio (male as reference) across points >1 indicated that women exhibit a higher stroke risk. The interaction was statistically significant (P<0.001).Conclusions:Female sex is a risk modifier for stroke in patients with atrial fibrillation. Initial decisions on oral anticoagulant treatment could be guided by a CHA2DS2-VA score (ie, excluding the sex category criterion), but the Sc risk component modifies and accentuates stroke risk in women who would have been eligible for oral anticoagulant treatment on the basis of ≥2 additional stroke risk factors.

Metabolic Predictors of Incident Coronary Heart Disease in Women [Original Research Article]
19/2/2018
Nina P. Paynter, Raȷi Balasubramanian, Franco Giulianini, Dong D. Wang, Lesley F. Tinker, Shuba Gopal, Amy A. Deik, Kevin Bullock, Kerry A. Pierce, Justin Scott, Miguel A. Martinez–Gonzalez, Ramon Estruch, JoAnn E. Manson, Nancy R. Cook, Christine M. Albert, Clary B. Clish, Kathryn M. Rexrode
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Background:Although metabolomic profiling offers promise for the prediction of coronary heart disease (CHD), and metabolic risk factors are more strongly associated with CHD in women than men, limited data are available for women.Methods:We applied a liquid chromatography–tandem mass spectrometry metabolomics platform to measure 371 metabolites in a discovery set of postmenopausal women (472 incident CHD cases, 472 controls) with validation in an independent set of postmenopausal women (312 incident CHD cases, 315 controls).Results:Eight metabolites, primarily oxidized lipids, were significantly dysregulated in cases after the adjustment for matching and CHD risk factors in both the discovery and validation data sets. One oxidized phospholipid, C34:2 hydroxy-phosphatidylcholine, remained associated with CHD after further adjustment for other validated metabolites. Subjects with C34:2 hydroxy-phosphatidylcholine levels in the highest quartile had a 4.7-fold increase in CHD odds in comparison with the lowest quartile; C34:2 hydroxy-phosphatidylcholine also significantly improved the area under the curve (P<0.01) for CHD. The C34:2 hydroxy-phosphatidylcholine findings were replicated in a third replication data set of 980 men and women (230 cardiovascular events) with a stronger association observed in women.Conclusions:These data replicate known metabolite predictors, identify novel markers, and support the relationship between lipid oxidation and subsequent CHD.

Gender/Sex as a Social Determinant of Cardiovascular Risk [In Depth]
19/2/2018
Adrienne O’Neil, Anna J. Scovelle, Allison J. Milner, Anne Kavanagh
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The social gradient for cardiovascular disease (CVD) onset and outcomes is well established. The American Heart Association’s Social Determinants of Risk and Outcomes of Cardiovascular Disease Scientific Statement advocates looking beyond breakthroughs in biological science toward a social determinants approach that focuses on socioeconomic position, race and ethnicity, social support, culture and access to medical care, and residential environments to curb the burden of CVD going forward. Indeed, the benefits of this approach are likely to be far reaching, enhancing the positive effects of advances in CVD related to prevention and treatment while reducing health inequities that contribute to CVD onset and outcomes. It is disappointing that the role of gender has been largely neglected despite being a critical determinant of cardiovascular health. It is clear that trajectories and outcomes of CVD differ by biological sex, yet the tendency for sex and gender to be conflated has contributed to the idea that both are constant or fixed with little room for intervention. Rather, as distinct from biological sex, gender is socially produced. Overlaid on biological sex, gender is a broad term that shapes and interacts with one’s cognition to guide norms, roles, behaviors, and social relations. It is a fluid construct that varies across time, place, and life stage. Gender can interact with biological sex and, indeed, other social determinants, such as ethnicity and socioeconomic position, to shape cardiovascular health from conception, through early life when health behaviors and risk factors are shaped, into adolescence and adulthood. This article will illustrate how gender shapes the early adoption of health behaviors in childhood, adolescence, and young adulthood by focusing on physical activity, drinking, and smoking behaviors (including the influence of role modeling). We will also discuss the role of gender in psychosocial stress with a focus on trauma from life events (childhood assault and intimate partner violence) and work, home, and financial stresses. We conclude by exploring potential biological pathways, with a focus on autonomic functioning, which may underpin gender as a social determinant of cardiovascular health. Finally, we discuss implications for cardiovascular treatment and awareness campaigns and consider whether gender equality strategies could reduce the burden of CVD for men and women at the population level.

Association of Spontaneous Preterm Delivery and Future Maternal Cardiovascular Disease [Primer]
19/2/2018
Margo B. Minissian, Sarah Kilpatrick, Jo-Ann Eastwood, Wendie A. Robbins, Eynav E. Accortt, Janet Wei, Chrisandra L. Shufelt, Lynn V. Doering, C. Noel Bairey Merz
ver resumen
Cardiovascular disease (CVD) risk factors are well established. However, little is known about a woman’s cardiovascular response to pregnancy, which appears to be an early marker of future maternal CVD risk. Spontaneous preterm delivery (sPTD) has been associated with a ≤3-fold increased risk of maternal CVD death later in life compared with having a term delivery. This review focuses on 3 key areas to critically assess the association of sPTD and future maternal CVD risk: (1) CVD risk factors, (2) inflammatory biomarkers of interest, and (3) specific forms of vascular dysfunction, such as endothelial function and arterial stiffness, and mechanisms by which each may be linked to sPTD. The association of sPTD with subsequent future maternal CVD risk suggests that a woman’s abnormal response to pregnancy may serve as her first physiological stress test. These findings suggest that future research is needed to understand why women with sPTD may be at risk for CVD to implement effective interventions earlier in a woman’s life.

Women Not Receiving Optimal Preventive Medications [Cardiology News]
19/2/2018
Bridget M. Kuehn
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Myocardial Scar Is Prevalent and Associated With Subclinical Myocardial Dysfunction in Women With Suspected Ischemia But No Obstructive Coronary Artery Disease [Research Letter]
19/2/2018
Janet Wei, May Bakir, Navid Darounian, Quanlin Li, Sofy Landes, Puja K. Mehta, Chrisandra L. Shufelt, Eileen M. Handberg, Sheryl F. Kelsey, George Sopko, Carl J. Pepine, John W. Petersen, Daniel S. Berman, Louise E.J. Thomson, C. Noel Bairey Merz
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Prevalence of Subclinical Coronary Artery Disease Assessed by Coronary Computed Tomography Angiography in 45- to 55-Year-Old Women With a History of Preeclampsia [Research Letter]
19/2/2018
Gerbrand A. Zoet, Laura Benschop, Eric Boersma, Ricardo P.J. Budde, Bart C.J.M. Fauser, Yolanda van der Graaf, Christianne J.M. de Groot, Angela H.E.M. Maas, Jeanine E. Roeters van Lennep, Eric A.P. Steegers, Frank L. Visseren, Bas B. van Rijn, Birgitta K. Velthuis, Arie Franx
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Long-Term Analysis of Sex Differences in Prestigious Authorships in Cardiovascular Research Supported by the National Institutes of Health [Research Letter]
19/2/2018
Carolin Lerchenmuller, Marc J. Lerchenmueller, Olav Sorenson
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