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      Sex and gender in cardiovascular medicine: presentation and outcomes of acute coronary syndrome

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          Abstract

          Although health disparities in women presenting with acute coronary syndrome (ACS) have received growing attention in recent years, clinical outcomes from ACS are still worse for women than for men. Women continue to experience higher patient and system delays and receive less aggressive invasive treatment and pharmacotherapies. Gender- and sex-specific variables that contribute to ACS vulnerability remain largely unknown. Notwithstanding the sex differences in baseline coronary anatomy and function, women and men are treated the same based on guidelines that were established from experimental and clinical trial data over-representing the male population. Importantly, younger women have a particularly unfavourable prognosis and a plethora of unanswered questions remains in this younger population. The present review summarizes contemporary evidence for gender and sex differences in vascular biology, clinical presentation, and outcomes of ACS. We further discuss potential mechanisms and non-traditional risk conditions modulating the course of disease in women and men, such as unrecognized psychosocial factors, sex-specific vascular and neural stress responses, and the potential impact of epigenetic modifications.

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          Most cited references127

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          Estrogen receptors and human disease.

          Estrogens influence many physiological processes in mammals, including but not limited to reproduction, cardiovascular health, bone integrity, cognition, and behavior. Given this widespread role for estrogen in human physiology, it is not surprising that estrogen is also implicated in the development or progression of numerous diseases, which include but are not limited to various types of cancer (breast, ovarian, colorectal, prostate, endometrial), osteoporosis, neurodegenerative diseases, cardiovascular disease, insulin resistance, lupus erythematosus, endometriosis, and obesity. In many of these diseases, estrogen mediates its effects through the estrogen receptor (ER), which serves as the basis for many therapeutic interventions. This Review will describe diseases in which estrogen, through the ER, plays a role in the development or severity of disease.
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            Stable angina pectoris with no obstructive coronary artery disease is associated with increased risks of major adverse cardiovascular events.

            Patients with chest pain and no obstructive coronary artery disease (CAD) are considered at low risk for cardiovascular events but evidence supporting this is scarce. We investigated the prognostic implications of stable angina pectoris in relation to the presence and degree of CAD with no obstructive CAD in focus. We identified 11 223 patients referred for coronary angiography (CAG) in 1998-2009 with stable angina pectoris as indication and 5705 participants from the Copenhagen City Heart Study for comparison. Main outcome measures were major adverse cardiovascular events (MACE), defined as cardiovascular death, myocardial infarction, stroke or heart failure, and all-cause mortality. Significantly more women (65%) than men (32%) had no obstructive CAD (P< 0.001). In Cox's models adjusted for age, body mass index, diabetes, smoking, and use of lipid-lowering or antihypertensive medication, hazard ratios (HRs) associated with no obstructive CAD were similar in men and women. In the pooled analysis, the risk of MACE increased with increasing degrees of CAD with multivariable-adjusted HRs of 1.52 (95% confidence interval, 1.27-1.83) for patients with normal coronary arteries and 1.85 (1.51-2.28) for patients with diffuse non-obstructive CAD compared with the reference population. For all-cause mortality, normal coronary arteries and diffuse non-obstructive CAD were associated with HRs of 1.29 (1.07-1.56) and 1.52 (1.24-1.88), respectively. Patients with stable angina and normal coronary arteries or diffuse non-obstructive CAD have elevated risks of MACE and all-cause mortality compared with a reference population without ischaemic heart disease.
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              International standardization of diagnostic criteria for microvascular angina.

              Standardization of diagnostic criteria for ischemic symptoms due to coronary microvascular dysfunction (CMD) is needed for further investigation of patients presenting with anginal chest pain consistent with "microvascular angina" (MVA). At the annual Coronary Vasomotion Disorders International Study Group (COVADIS) Summits held in August 2014 and 2015, the following criteria were agreed upon for the investigative diagnosis of microvascular angina: (1) presence of symptoms suggestive of myocardial ischemia; (2) objective documentation of myocardial ischemia, as assessed by currently available techniques; (3) absence of obstructive CAD ( 0.80) (4) confirmation of a reduced coronary blood flow reserve and/or inducible microvascular spasm. These standardized criteria provide an investigative structure for mechanistic, diagnostic, prognostic and clinical trial studies aimed at developing an evidence base needed for guidelines in this growing patient population. Standardized criteria will facilitate microvascular angina registries and recruitment of suitable patients into clinical trials. Mechanistic research will also benefit from the implementation of standardized diagnostic criteria for MVA.
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                Author and article information

                Journal
                European Heart Journal
                Oxford University Press (OUP)
                0195-668X
                1522-9645
                December 26 2019
                December 26 2019
                Affiliations
                [1 ]Department of Nuclear Medicine, University Hospital Zurich, Raemistrasse 100, 8091 Zurich, Switzerland
                [2 ]Center for Molecular Cardiology, University of Zurich, Wagistrasse 12, 8952 Schlieren, Switzerland
                [3 ]Division of Cardiology, Department of Internal Medicine, University of Manitoba, 820 Sherbrook Street, Winnipeg MB R3A, Manitoba, Canada
                [4 ]Institute of Clinical Chemistry, University of Zurich and University Hospital Zurich, Raemistrasse 100, 8091 Zurich, Switzerland
                [5 ]Cardiology, University Heart Center, University Hospital Zurich, Raemistrasse 100, 8091 Zurich, Switzerland
                [6 ]Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria
                [7 ]Centre for Preclinical Research and Technology, Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Zwirki i Wigury 61, 02-091 Warsaw, Poland
                [8 ]Institute of Social and Preventive Medicine, University of Bern, Mittelstrasse 43, 3012 Bern, Switzerland
                Article
                10.1093/eurheartj/ehz898
                31876924
                44c48609-4767-41ae-8b9c-5b626965d4df
                © 2019

                https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model

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