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      Sex Differences in Comorbidity, Therapy, and Health Services’ Use of Heart Failure in Spain: Evidence from Real-World Data

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          Abstract

          Heart failure (HF) is becoming increasingly prevalent and affects both men and women. However, women have traditionally been underrepresented in HF clinical trials. In this study, we aimed to analyze sex differences in the comorbidity, therapy, and health services’ use of HF patients. We conducted a cross-sectional study in Aragón (Spain) and described the characteristics of 17,516 patients with HF. Women were more frequent (57.4 vs. 42.6%, p < 0.001) and older (83 vs. 80 years, p < 0.001) than men, and presented a 33% lower risk of 1-year mortality ( p < 0.001). Both sexes showed similar disease burdens, and 80% suffered six or more diseases. Some comorbidities were clearly sex-specific, such as arthritis, depression, and hypothyroidism in women, and arrhythmias, ischemic heart disease, and COPD in men. Men were more frequently anti-aggregated and anti-coagulated and received more angiotensin-converting-enzyme (ACE) inhibitors and beta-blockers, whereas women had more angiotensin II antagonists, antiinflammatories, antidepressants, and thyroid hormones dispensed. Men were admitted to specialists (79.0 vs. 70.6%, p < 0.001), hospital (47.0 vs. 38.1%, p < 0.001), and emergency services (57.6 vs. 52.7%, p < 0.001) more frequently than women. Our results highlight the need to conduct future studies to confirm the existence of these differences and of developing separate HF management guidelines for men and women that take into account their sex-specific comorbidity.

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          Most cited references41

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          Heart failure: preventing disease and death worldwide

          Heart failure is a life-threatening disease and addressing it should be considered a global health priority. At present, approximately 26 million people worldwide are living with heart failure. The outlook for such patients is poor, with survival rates worse than those for bowel, breast or prostate cancer. Furthermore, heart failure places great stresses on patients, caregivers and healthcare systems. Demands on healthcare services, in particular, are predicted to increase dramatically over the next decade as patient numbers rise owing to ageing populations, detrimental lifestyle changes and improved survival of those who go on to develop heart failure as the final stage of another disease. It is time to ease the strain on healthcare systems through clear policy initiatives that prioritize heart failure prevention and champion equity of care for all. Despite the burdens that heart failure imposes on society, awareness of the disease is poor. As a result, many premature deaths occur. This is in spite of the fact that most types of heart failure are preventable and that a healthy lifestyle can reduce risk. Even after heart failure has developed, premature deaths could be prevented if people were taught to recognize the symptoms and seek immediate medical attention. Public awareness campaigns focusing on these messages have great potential to improve outcomes for patients with heart failure and ultimately to save lives. Compliance with clinical practice guidelines is also associated with improved outcomes for patients with heart failure. However, in many countries, there is considerable variation in how closely physicians follow guideline recommendations. To promote equity of care, improvements should be encouraged through the use of hospital performance measures and incentives appropriate to the locality. To this end, policies should promote the research required to establish an evidence base for performance measures that reflect improved outcomes for patients. Continuing research is essential if we are to address unmet needs in caring for patients with heart failure. New therapies are required for patients with types of heart failure for which current treatments relieve symptoms but do not address the disease. More affordable therapies are desperately needed in the economically developing world. International collaborative research focusing on the causes and treatment of heart failure worldwide has the potential to benefit tens of millions of people. Change at the policy level has the power to drive improvements in prevention and care that will save lives. It is time to make a difference across the globe by confronting the problem of heart failure.
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            Noncardiac comorbidity increases preventable hospitalizations and mortality among Medicare beneficiaries with chronic heart failure.

            We studied the impact of noncardiac comorbidity on potentially preventable hospitalizations and mortality in elderly patients with chronic heart failure (CHF). Chronic HF disproportionately affects older individuals, who typically have extensive comorbidity. However, little is known about how noncardiac comorbidity complicates care in these patients. This was a cross-sectional study of 122,630 individuals age >/=65 years with CHF identified through a 5% random sample of all U.S. Medicare beneficiaries. We assessed the relationship of the 20 most common noncardiac comorbidities to one-year potentially preventable hospitalizations and total mortality. Preventable hospitalizations were determined by admissions for ambulatory care sensitive conditions using predefined criteria. Sixty-five percent of the sample had at least one hospitalization, of which 50% were potentially preventable. Exacerbations of CHF accounted for 55% of potentially preventable hospitalizations. Nearly 40% of patients with CHF had >/=5 noncardiac comorbidities, and this group accounted for 81% of the total inpatient hospital days experienced by all CHF patients. The risk of hospitalization and potentially preventable hospitalization strongly increased with the number of chronic conditions (both p < 0.0001). After controlling for demographic factors and other diagnoses, comorbidities that were associated consistently with notably higher risks for CHF-preventable and all-cause preventable hospitalizations, and mortality, included chronic obstructive pulmonary disease/bronchiectasis, renal failure, diabetes, depression, and other lower respiratory diseases (all p < 0.01). Noncardiac comorbidities are highly prevalent in older patients with CHF and strongly associate with adverse clinical outcomes. Cardiologists and other providers routinely caring for older patients with CHF may improve outcomes in this high-risk population by better recognizing non-CHF conditions, which may complicate traditional CHF management strategies.
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              Sex-based differences in the effect of digoxin for the treatment of heart failure.

              The Digitalis Investigation Group trial reported that treatment with digoxin did not decrease overall mortality among patients with heart failure and depressed left ventricular systolic function, although it did reduce hospitalizations slightly. Even though the epidemiologic features, causes, and prognosis of heart failure vary between men and women, sex-based differences in the effect of digoxin were not evaluated. We conducted a post hoc subgroup analysis to assess whether there were sex-based differences in the effect of digoxin therapy among the 6800 patients in the Digitalis Investigation Group study. The presence of an interaction between sex and digoxin therapy with respect to the primary end point of death from any cause was evaluated with the use of Mantel-Haenszel tests of heterogeneity and a multivariable Cox proportional-hazards model, adjusted for demographic and clinical variables. There was an absolute difference of 5.8 percent (95 percent confidence interval, 0.5 to 11.1) between men and women in the effect of digoxin on the rate of death from any cause (P=0.034 for the interaction). Specifically, women who were randomly assigned to digoxin had a higher rate of death than women who were randomly assigned to placebo (33.1 percent vs. 28.9 percent; absolute difference, 4.2 percent, 95 percent confidence interval, -0.5 to 8.8). In contrast, the rate of death was similar among men randomly assigned to digoxin and men randomly assigned to placebo (35.2 percent vs. 36.9 percent; absolute difference, -1.6 percent; 95 percent confidence interval, -4.2 to 1.0). In the multivariable analysis, digoxin was associated with a significantly higher risk of death among women (adjusted hazard ratio for the comparison with placebo, 1.23; 95 percent confidence interval, 1.02 to 1.47), but it had no significant effect among men (adjusted hazard ratio, 0.93; 95 percent confidence interval, 0.85 to 1.02; P=0.014 for the interaction). The effect of digoxin therapy differs between men and women. Digoxin therapy is associated with an increased risk of death from any cause among women, but not men, with heart failure and depressed left ventricular systolic function. Copyright 2002 Massachusetts Medical Society
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                Author and article information

                Journal
                Int J Environ Res Public Health
                Int J Environ Res Public Health
                ijerph
                International Journal of Environmental Research and Public Health
                MDPI
                1661-7827
                1660-4601
                23 March 2020
                March 2020
                : 17
                : 6
                : 2136
                Affiliations
                [1 ]Research Group on Heart Failure, IIS Aragón, Internal Medicine Service, Hospital General de la Defensa, 50009 Zaragoza, Spain; agraciagut@ 123456gmail.com
                [2 ]EpiChron Research Group, Aragon Health Sciences Institute (IACS), IIS Aragón, REDISSEC, Miguel Servet University Hospital, 50009 Zaragoza, Spain; bpoblador.iacs@ 123456aragon.es (B.P.-P.); sprados.iacs@ 123456aragon.es (A.P.-T.)
                [3 ]Research Group on Heart Failure, Faculty of Medicine, Internal Medicine Service, Lozano Blesa University Hospital, 50009 Zaragoza, Spain; fruizl@ 123456unizar.es
                Author notes
                [* ]Correspondence: agimenomi.iacs@ 123456aragon.es ; Tel.: +34-976-765-500 (ext. 5375)
                [†]

                These authors contributed equally to this work and served as senior co-authors.

                Author information
                https://orcid.org/0000-0002-5704-6056
                https://orcid.org/0000-0003-0438-8834
                https://orcid.org/0000-0002-5440-1710
                Article
                ijerph-17-02136
                10.3390/ijerph17062136
                7143043
                32210137
                b17bbaf2-f1bb-4a75-9ed9-4fdf1fde7a81
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 29 February 2020
                : 20 March 2020
                Categories
                Article

                Public health
                heart failure,epidemiology,comorbidity,medication,health services use,sex,gender
                Public health
                heart failure, epidemiology, comorbidity, medication, health services use, sex, gender

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