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      Sex differences in long-term mortality among acute myocardial infarction patients: Results from the ISAR-RISK and ART studies

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          Abstract

          Background

          Mortality rates in females who survived acute myocardial infarction (AMI) exceed those in males. Differences between sexes in age, cardiovascular risk factors and revascularization therapy have been proposed as possible reasons.

          Objective

          To select sets of female and male patients comparable in respect of relevant risk factors in order to compare the sex-specific risk in a systematic manner.

          Methods

          Data of the ISAR-RISK and ART studies were investigated. Patients were enrolled between 1996 and 2005 and suffered from AMI within 4 weeks prior to enrolment. Patients of each sex were selected with 1:1 equivalent age, previous AMI history, sinus-rhythm presence, hypertension, diabetes mellitus, smoking status, left ventricular ejection fraction (LVEF), and revascularization therapy. Survival times were compared between sex groups in the whole study cohort and in the matched cohort.

          Results

          Of 3840 consecutive AMI survivors, 994 (25.9%) were females and 2846 (74.1%) were males. Females were older and suffered more frequently from hypertension and diabetes mellitus. In the whole cohort, females showed an increased mortality with a hazard ratio (HR) of 1.54 compared to males (p<0.0001). The matched cohort comprised 802 patients of each sex and revealed a trend towards poorer survival in females (HR for female sex 1.14; p = 0.359). However, significant mortality differences with a higher risk in matched females was observed during the first year after AMI (HR = 1.61; p = 0.045) but not during the subsequent years.

          Conclusion

          Matched sub-groups of post-AMI patients showed a comparable long-term mortality. However, a female excess mortality remained during first year after AMI and cannot be explained by differences in age, cardiovascular risk factors, and modes of acute treatment. Other causal factors, including clinical as well as psychological and social aspects, need to be considered. Female post-AMI patients should be followed more actively particularly during the first year after AMI.

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          Most cited references48

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          MatchIt: Nonparametric Preprocessing for Parametric Causal Inference

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            Women and ischemic heart disease: evolving knowledge.

            Evolving knowledge regarding sex differences in coronary heart disease is emerging. Given the lower burden of obstructive coronary artery disease (CAD) and preserved systolic function in women, which contrasts with greater rates of myocardial ischemia and near-term mortality compared with men, we propose the term "ischemic heart disease" as appropriate for this discussion specific to women rather than CAD or coronary heart disease (CHD). This paradoxical difference, where women have lower rates of anatomical CAD but more symptoms, ischemia, and adverse outcomes, appears linked to abnormal coronary reactivity that includes microvascular dysfunction. Novel risk factors can improve the Framingham risk score, including inflammatory markers and reproductive hormones, as well as noninvasive imaging and functional capacity measurements. Risk for women with obstructive CAD is increased compared with men, yet women are less likely to receive guideline-indicated therapies. In the setting of non-ST-segment elevation acute myocardial infarction, interventional strategies are equally effective in biomarker-positive women and men, whereas conservative management is indicated for biomarker-negative women. For women with evidence of ischemia but no obstructive CAD, antianginal and anti-ischemic therapies can improve symptoms, endothelial function, and quality of life; however, trials evaluating impact on adverse outcomes are needed. We hypothesize that women experience more adverse outcomes compared with men because obstructive CAD remains the current focus of therapeutic strategies. Continued research is indicated to devise therapeutic regimens to improve symptom burden and reduce risk in women with ischemic heart disease.
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              Gender disparities in the diagnosis and treatment of non-ST-segment elevation acute coronary syndromes: large-scale observations from the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the American College of Cardiology/American Heart Association Guidelines) National Quality Improvement Initiative.

              We hypothesized that significant disparities in gender exist in the management of patients with non-ST-segment elevation (NSTE) acute coronary syndromes (ACS). Gender-related differences in the diagnosis and treatment of ACS have important healthcare implications. No large-scale examination of these disparities has been completed since the publication of the revised American College of Cardiology/American Heart Association guidelines for management of patients with NSTE ACS. Using data from the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the American College of Cardiology/American Heart Association Guidelines) National Quality Improvement Initiative, we examined differences of gender in treatment and outcomes among patients with NSTE ACS. Women (41% of 35,875 patients) were older (median age 73 vs. 65 years) and more often had diabetes and hypertension. Women were less likely to receive acute heparin, angiotensin-converting enzyme inhibitors, and glycoprotein IIb/IIIa inhibitors and less commonly received aspirin, angiotensin-converting enzyme inhibitors, and statins at discharge. The use of cardiac catheterization and revascularization was higher in men, but among patients with significant coronary disease, percutaneous revascularization was performed in a similar proportion of women and men. Women were at higher risk for unadjusted in-hospital death (5.6% vs. 4.3%), reinfarction (4.0% vs. 3.5%), heart failure (12.1% vs. 8.8%), stroke (1.1% vs. 0.8%), and red blood cell transfusion (17.2% vs. 13.2%), but after adjustment, only transfusion was higher in women. Despite presenting with higher risk characteristics and having higher in-hospital risk, women with NSTE ACS are treated less aggressively than men.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: MethodologyRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: ValidationRole: Visualization
                Role: ConceptualizationRole: Formal analysisRole: MethodologyRole: Writing – original draftRole: Writing – review & editing
                Role: Formal analysisRole: Visualization
                Role: Writing – review & editing
                Role: Writing – review & editing
                Role: Data curationRole: Software
                Role: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: MethodologyRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                20 October 2017
                2017
                : 12
                : 10
                : e0186783
                Affiliations
                [1 ] Innere Medizin I, Klinikum rechts der Isar, Technische Universität München, Munich, Germany
                [2 ] Institut für Medizinische Statistik und Epidemiologie, Technische Universität München, Munich, Germany
                [3 ] National Heart and Lung Institute, Imperial College, London, England
                [4 ] DZHK (German Centre for Cardiovascular Research), Partner site Munich Heart Alliance, Munich, Germany
                University of Bologna, ITALY
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                ‡ These authors are senior authors on this work.

                Author information
                http://orcid.org/0000-0003-3692-5243
                Article
                PONE-D-17-20769
                10.1371/journal.pone.0186783
                5650173
                29053758
                412541a2-316d-4147-b2d0-19892cd14ea5
                © 2017 Ubrich et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 31 May 2017
                : 6 October 2017
                Page count
                Figures: 6, Tables: 4, Pages: 17
                Funding
                The authors received no specific funding for this work.
                Categories
                Research Article
                Medicine and Health Sciences
                Vascular Medicine
                Coronary Heart Disease
                Medicine and Health Sciences
                Cardiology
                Coronary Heart Disease
                Medicine and health sciences
                Pharmaceutics
                Drug therapy
                Cardiovascular therapy
                ACE inhibitor therapy
                Biology and Life Sciences
                Population Biology
                Population Metrics
                Death Rates
                Medicine and Health Sciences
                Surgical and Invasive Medical Procedures
                Cardiovascular Procedures
                Coronary Artery Bypass Grafting
                Medicine and Health Sciences
                Vascular Medicine
                Blood Pressure
                Hypertension
                Medicine and Health Sciences
                Endocrinology
                Endocrine Disorders
                Diabetes Mellitus
                Medicine and Health Sciences
                Metabolic Disorders
                Diabetes Mellitus
                Medicine and Health Sciences
                Surgical and Invasive Medical Procedures
                Cardiovascular Procedures
                Angioplasty
                Coronary Angioplasty
                Medicine and Health Sciences
                Cardiology
                Myocardial Infarction
                Custom metadata
                All relevant data are within the paper and its Supporting Information files.

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