Advertisement

Sex Differences in Heart Failure

  • Gianluigi Savarese
  • Domenico D’Amario
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1065)

Abstract

Heart failure (HF) represents a global pandemic health problem with a high impact on health-care costs, affecting about 26 million adults worldwide. The overall HF prevalence and incidence are ~2% and ~0.2% per year, respectively, in Western countries, with half of the HF population with reduced ejection fraction (HFpEF) and half with preserved (HFpEF) or mid-range ejection fraction (HFmrEF). Sex differences may exist in HF. More males have HFrEF or HFmrEF and an ischemic etiology, whereas more females have HFpEF and hypertension, diastolic dysfunction, and valvular pathologies as HF etiologies. Females are generally older, have a higher EF, higher frequency of HF-related symptoms, and lower NYHA functional status. Generally, it is observed that female HF patients tend to have more comorbidities such as atrial fibrillation, diabetes, hypertension, anemia, iron deficiency, renal disease, arthritis, frailty, depression, and thyroid abnormalities. However, overall, females have better prognosis in terms of mortality and hospitalization risk compared with men, regardless of EF. Potential sex differences in HF characteristics may be underestimated because of the underrepresentation of females in cardiovascular research and, in particular, the sex imbalance in clinical trial enrollment may avoid to identify sex-specific differences in treatments’ benefit.

Keywords

Heart failure Pathophysiology Sex differences Comorbidities Treatments 

References

  1. 1.
    Ponikowski P, Anker SD, AlHabib KF, Cowie MR, Force TL, Hu S, Jaarsma T, Krum H, Rastogi V, Rohde LE, Samal UC, Shimokawa H, Budi Siswanto B, Sliwa K, Filippatos G. Heart failure: preventing disease and death worldwide. ESC Heart Fail. 2014;1(1):4–25.PubMedCrossRefPubMedCentralGoogle Scholar
  2. 2.
    Benjamin EJ, Blaha MJ, Chiuve SE, Cushman M, Das SR, Deo R, de Ferranti SD, Floyd J, Fornage M, Gillespie C, Isasi CR, Jimenez MC, Jordan LC, Judd SE, Lackland D, Lichtman JH, Lisabeth L, Liu S, Longenecker CT, Mackey RH, Matsushita K, Mozaffarian D, Mussolino ME, Nasir K, Neumar RW, Palaniappan L, Pandey DK, Thiagarajan RR, Reeves MJ, Ritchey M, Rodriguez CJ, Roth GA, Rosamond WD, Sasson C, Towfighi A, Tsao CW, Turner MB, Virani SS, Voeks JH, Willey JZ, Wilkins JT, Wu JH, Alger HM, Wong SS, Muntner P, American Heart Association Statistics C, Stroke Statistics S. Heart disease and stroke statistics-2017 update: a report from the American Heart Association. Circulation. 2017;135(10):e146–603.PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JG, Coats AJ, Falk V, Gonzalez-Juanatey JR, Harjola VP, Jankowska EA, Jessup M, Linde C, Nihoyannopoulos P, Parissis JT, Pieske B, Riley JP, Rosano GM, Ruilope LM, Ruschitzka F, Rutten FH, van der Meer P, Authors/Task Force M. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2016;37(27):2129–200.CrossRefGoogle Scholar
  4. 4.
    Zile MR, Baicu CF, Gaasch WH. Diastolic heart failure--abnormalities in active relaxation and passive stiffness of the left ventricle. N Engl J Med. 2004;350(19):1953–9.PubMedCrossRefPubMedCentralGoogle Scholar
  5. 5.
    Baicu CF, Zile MR, Aurigemma GP, Gaasch WH. Left ventricular systolic performance, function, and contractility in patients with diastolic heart failure. Circulation. 2005;111(18):2306–12.PubMedCrossRefPubMedCentralGoogle Scholar
  6. 6.
    Yip G, Wang M, Zhang Y, Fung JW, Ho PY, Sanderson JE. Left ventricular long axis function in diastolic heart failure is reduced in both diastole and systole: time for a redefinition? Heart. 2002;87(2):121–5.PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    McMurray JJ, Adamopoulos S, Anker SD, Auricchio A, Bohm M, Dickstein K, Falk V, Filippatos G, Fonseca C, Gomez-Sanchez MA, Jaarsma T, Kober L, Lip GY, Maggioni AP, Parkhomenko A, Pieske BM, Popescu BA, Ronnevik PK, Rutten FH, Schwitter J, Seferovic P, Stepinska J, Trindade PT, Voors AA, Zannad F, Zeiher A, Guidelines ESCCfP. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: the Task Force for the diagnosis and treatment of acute and chronic heart failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2012;33(14):1787–847.PubMedCrossRefPubMedCentralGoogle Scholar
  8. 8.
    Burnett H, Earley A, Voors AA, Senni M, McMurray JJ, Deschaseaux C, Cope S. Thirty years of evidence on the efficacy of drug treatments for chronic heart failure with reduced ejection fraction: a network meta-analysis. Circ Heart Fail. 2017;10(1). https://doi.org/10.1161/CIRCHEARTFAILURE.116.003529.Google Scholar
  9. 9.
    Massie BM, Carson PE, McMurray JJ, Komajda M, McKelvie R, Zile MR, Anderson S, Donovan M, Iverson E, Staiger C, Ptaszynska A, Investigators IP. Irbesartan in patients with heart failure and preserved ejection fraction. N Engl J Med. 2008;359(23):2456–67.PubMedCrossRefPubMedCentralGoogle Scholar
  10. 10.
    Yusuf S, Pfeffer MA, Swedberg K, Granger CB, Held P, McMurray JJ, Michelson EL, Olofsson B, Ostergren J. Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-Preserved Trial. Lancet. 2003;362(9386):777–81.PubMedCrossRefPubMedCentralGoogle Scholar
  11. 11.
    Pitt B, Pfeffer MA, Assmann SF, Boineau R, Anand IS, Claggett B, Clausell N, Desai AS, Diaz R, Fleg JL, Gordeev I, Harty B, Heitner JF, Kenwood CT, Lewis EF, O’Meara E, Probstfield JL, Shaburishvili T, Shah SJ, Solomon SD, Sweitzer NK, Yang S, McKinlay SM, Investigators T. Spironolactone for heart failure with preserved ejection fraction. N Engl J Med. 2014;370(15):1383–92.PubMedCrossRefPubMedCentralGoogle Scholar
  12. 12.
    Lam CS, Donal E, Kraigher-Krainer E, Vasan RS. Epidemiology and clinical course of heart failure with preserved ejection fraction. Eur J Heart Fail. 2011;13(1):18–28.PubMedCrossRefPubMedCentralGoogle Scholar
  13. 13.
    Lam CS, Solomon SD. The middle child in heart failure: heart failure with mid-range ejection fraction (40–50%). Eur J Heart Fail. 2014;16(10):1049–55.PubMedCrossRefPubMedCentralGoogle Scholar
  14. 14.
    Dunlay SM, Roger VL, Weston SA, Jiang R, Redfield MM. Longitudinal changes in ejection fraction in heart failure patients with preserved and reduced ejection fraction. Circ Heart Fail. 2012;5(6):720–6.PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Koh AS, Tay WT, Teng THK, Vedin O, Benson L, Dahlstrom U, Savarese G, CSP L, Lund LH. A comprehensive population-based characterization of heart failure with mid-range ejection fraction. Eur J Heart Fail. 2017;19:1624–34.PubMedCrossRefPubMedCentralGoogle Scholar
  16. 16.
    Bleumink GS, Knetsch AM, Sturkenboom MC, Straus SM, Hofman A, Deckers JW, Witteman JC, Stricker BH. Quantifying the heart failure epidemic: prevalence, incidence rate, lifetime risk and prognosis of heart failure The Rotterdam Study. Eur Heart J. 2004;25(18):1614–9.PubMedCrossRefPubMedCentralGoogle Scholar
  17. 17.
    Zarrinkoub R, Wettermark B, Wandell P, Mejhert M, Szulkin R, Ljunggren G, Kahan T. The epidemiology of heart failure, based on data for 2.1 million inhabitants in Sweden. Eur J Heart Fail. 2013;15(9):995–1002.PubMedCrossRefPubMedCentralGoogle Scholar
  18. 18.
    Mosterd A, Hoes AW, de Bruyne MC, Deckers JW, Linker DT, Hofman A, Grobbee DE. Prevalence of heart failure and left ventricular dysfunction in the general population; The Rotterdam Study. Eur Heart J. 1999;20(6):447–55.PubMedCrossRefPubMedCentralGoogle Scholar
  19. 19.
    Hogg K, Swedberg K, McMurray J. Heart failure with preserved left ventricular systolic function; epidemiology, clinical characteristics, and prognosis. J Am Coll Cardiol. 2004;43(3):317–27.PubMedCrossRefPubMedCentralGoogle Scholar
  20. 20.
    Savarese G, Lund LH. Global public health burden of heart failure. Card Fail Rev. 2017;3(1):7–11.PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Schocken DD, Arrieta MI, Leaverton PE, Ross EA. Prevalence and mortality rate of congestive heart failure in the United States. J Am Coll Cardiol. 1992;20(2):301–6.PubMedCrossRefPubMedCentralGoogle Scholar
  22. 22.
    Ho KK, Pinsky JL, Kannel WB, Levy D. The epidemiology of heart failure: the Framingham Study. J Am Coll Cardiol. 1993;22(4 Suppl A):6A–13A.PubMedCrossRefPubMedCentralGoogle Scholar
  23. 23.
    Ohlmeier C, Mikolajczyk R, Frick J, Prutz F, Haverkamp W, Garbe E. Incidence, prevalence and 1-year all-cause mortality of heart failure in Germany: a study based on electronic healthcare data of more than six million persons. Clin Res Cardiol. 2015;104(8):688–96.PubMedCrossRefPubMedCentralGoogle Scholar
  24. 24.
    Gomez-Soto FM, Andrey JL, Garcia-Egido AA, Escobar MA, Romero SP, Garcia-Arjona R, Gutierrez J, Gomez F. Incidence and mortality of heart failure: a community-based study. Int J Cardiol. 2011;151(1):40–5.PubMedCrossRefPubMedCentralGoogle Scholar
  25. 25.
    Ni H. Prevalence of self-reported heart failure among US adults: results from the 1999 National Health Interview Survey. Am Heart J. 2003;146(1):121–8.PubMedCrossRefPubMedCentralGoogle Scholar
  26. 26.
    Bursi F, Weston SA, Redfield MM, Jacobsen SJ, Pakhomov S, Nkomo VT, Meverden RA, Roger VL. Systolic and diastolic heart failure in the community. JAMA. 2006;296(18):2209–16.PubMedCrossRefPubMedCentralGoogle Scholar
  27. 27.
    Goyal P, Almarzooq ZI, Horn EM, Karas MG, Sobol I, Swaminathan RV, Feldman DN, Minutello RM, Singh HS, Bergman GW, Wong SC, Kim LK. Characteristics of hospitalizations for heart failure with preserved ejection fraction. Am J Med. 2016;129(6):635 e15–26.CrossRefGoogle Scholar
  28. 28.
    Owan TE, Hodge DO, Herges RM, Jacobsen SJ, Roger VL, Redfield MM. Trends in prevalence and outcome of heart failure with preserved ejection fraction. N Engl J Med. 2006;355(3):251–9.PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Cowie MR, Wood DA, Coats AJ, Thompson SG, Poole-Wilson PA, Suresh V, Sutton GC. Incidence and aetiology of heart failure; a population-based study. Eur Heart J. 1999;20(6):421–8.PubMedCrossRefPubMedCentralGoogle Scholar
  30. 30.
    Kannel WB. Incidence and epidemiology of heart failure. Heart Fail Rev. 2000;5(2):167–73.PubMedCrossRefPubMedCentralGoogle Scholar
  31. 31.
    Meyer S, Brouwers FP, Voors AA, Hillege HL, de Boer RA, Gansevoort RT, van der Harst P, Rienstra M, van Gelder IC, van Veldhuisen DJ, van Gilst WH, van der Meer P. Sex differences in new-onset heart failure. Clin Res Cardiol. 2015;104(4):342–50.PubMedCrossRefPubMedCentralGoogle Scholar
  32. 32.
    Roger VL, Weston SA, Redfield MM, Hellermann-Homan JP, Killian J, Yawn BP, Jacobsen SJ. Trends in heart failure incidence and survival in a community-based population. JAMA. 2004;292(3):344–50.PubMedCrossRefPubMedCentralGoogle Scholar
  33. 33.
    Johansson S, Wallander MA, Ruigomez A, Garcia Rodriguez LA. Incidence of newly diagnosed heart failure in UK general practice. Eur J Heart Fail. 2001;3(2):225–31.PubMedCrossRefPubMedCentralGoogle Scholar
  34. 34.
    Ceia F, Fonseca C, Mota T, Morais H, Matias F, de Sousa A, Oliveira A, Investigators E. Prevalence of chronic heart failure in Southwestern Europe: the EPICA study. Eur J Heart Fail. 2002;4(4):531–9.PubMedCrossRefPubMedCentralGoogle Scholar
  35. 35.
    Lloyd-Jones DM, Larson MG, Leip EP, Beiser A, D’Agostino RB, Kannel WB, Murabito JM, Vasan RS, Benjamin EJ, Levy D. Lifetime risk for developing congestive heart failure: the Framingham Heart Study. Circulation. 2002;106(24):3068–72.PubMedCrossRefPubMedCentralGoogle Scholar
  36. 36.
    Brouwers FP, de Boer RA, van der Harst P, Voors AA, Gansevoort RT, Bakker SJ, Hillege HL, van Veldhuisen DJ, van Gilst WH. Incidence and epidemiology of new onset heart failure with preserved vs. reduced ejection fraction in a community-based cohort: 11-year follow-up of PREVEND. Eur Heart J. 2013;34(19):1424–31.PubMedCrossRefGoogle Scholar
  37. 37.
    Gerber Y, Weston SA, Redfield MM, Chamberlain AM, Manemann SM, Jiang R, Killian JM, Roger VL. A contemporary appraisal of the heart failure epidemic in Olmsted County, Minnesota, 2000 to 2010. JAMA Intern Med. 2015;175(6):996–1004.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Fonarow GC, Stough WG, Abraham WT, Albert NM, Gheorghiade M, Greenberg BH, O’Connor CM, Sun JL, Yancy CW, Young JB, Investigators O-H, Hospitals. Characteristics, treatments, and outcomes of patients with preserved systolic function hospitalized for heart failure: a report from the OPTIMIZE-HF Registry. J Am Coll Cardiol. 2007;50(8):768–77.PubMedCrossRefGoogle Scholar
  39. 39.
    Wenger NK, Speroff L, Packard B. Cardiovascular health and disease in women. N Engl J Med. 1993;329(4):247–56.PubMedCrossRefGoogle Scholar
  40. 40.
    Ho KK, Anderson KM, Kannel WB, Grossman W, Levy D. Survival after the onset of congestive heart failure in Framingham Heart Study subjects. Circulation. 1993;88(1):107–15.PubMedCrossRefPubMedCentralGoogle Scholar
  41. 41.
    Vaartjes I, Hoes AW, Reitsma JB, de Bruin A, Grobbee DE, Mosterd A, Bots MI. Age- and gender-specific risk of death after first hospitalization for heart failure. BMC Public Health. 2010;10:637.PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Martinez-Selles M, Doughty RN, Poppe K, Whalley GA, Earle N, Tribouilloy C, McMurray JJ, Swedberg K, Kober L, Berry C, Squire I, Meta-Analysis Global Group In Chronic Heart F. Gender and survival in patients with heart failure: interactions with diabetes and aetiology. Results from the MAGGIC individual patient meta-analysis. Eur J Heart Fail. 2012;14(5):473–9.PubMedCrossRefPubMedCentralGoogle Scholar
  43. 43.
    O’Meara E, Clayton T, McEntegart MB, McMurray JJ, Pina IL, Granger CB, Ostergren J, Michelson EL, Solomon SD, Pocock S, Yusuf S, Swedberg K, Pfeffer MA, Investigators C. Sex differences in clinical characteristics and prognosis in a broad spectrum of patients with heart failure: results of the Candesartan in Heart failure: assessment of reduction in mortality and morbidity (CHARM) program. Circulation. 2007;115(24):3111–20.PubMedCrossRefPubMedCentralGoogle Scholar
  44. 44.
    Deswal A, Bozkurt B. Comparison of morbidity in women versus men with heart failure and preserved ejection fraction. Am J Cardiol. 2006;97(8):1228–31.PubMedCrossRefPubMedCentralGoogle Scholar
  45. 45.
    Lam CS, Carson PE, Anand IS, Rector TS, Kuskowski M, Komajda M, McKelvie RS, McMurray JJ, Zile MR, Massie BM, Kitzman DW. Sex differences in clinical characteristics and outcomes in elderly patients with heart failure and preserved ejection fraction: the Irbesartan in Heart Failure with Preserved Ejection Fraction (I-PRESERVE) trial. Circ Heart Fail. 2012;5(5):571–8.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Rodriguez F, Wang Y, Johnson CE, Foody JM. National patterns of heart failure hospitalizations and mortality by sex and age. J Card Fail. 2013;19(8):542–9.PubMedCrossRefPubMedCentralGoogle Scholar
  47. 47.
    Parashar S, Katz R, Smith NL, Arnold AM, Vaccarino V, Wenger NK, Gottdiener JS. Race, gender, and mortality in adults > or =65 years of age with incident heart failure (from the Cardiovascular Health Study). Am J Cardiol. 2009;103(8):1120–7.PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Adams KF Jr, Sueta CA, Gheorghiade M, O’Connor CM, Schwartz TA, Koch GG, Uretsky B, Swedberg K, McKenna W, Soler-Soler J, Califf RM. Gender differences in survival in advanced heart failure. Insights from the FIRST study. Circulation. 1999;99(14):1816–21.PubMedCrossRefPubMedCentralGoogle Scholar
  49. 49.
    Martinez-Selles M, Dominguez M, Martinez E, Garcia Fernandez MA, Garcia E. Women with left ventricular ejection fraction < or = 20% have better prognosis than men. Int J Cardiol. 2007;120(2):276–8.PubMedCrossRefPubMedCentralGoogle Scholar
  50. 50.
    Ghali JK, Krause-Steinrauf HJ, Adams KF, Khan SS, Rosenberg YD, Yancy CW, Young JB, Goldman S, Peberdy MA, Lindenfeld J. Gender differences in advanced heart failure: insights from the BEST study. J Am Coll Cardiol. 2003;42(12):2128–34.PubMedCrossRefPubMedCentralGoogle Scholar
  51. 51.
    Hsich EM, Grau-Sepulveda MV, Hernandez AF, Peterson ED, Schwamm LH, Bhatt DL, Fonarow GC. Sex differences in in-hospital mortality in acute decompensated heart failure with reduced and preserved ejection fraction. Am Heart J. 2012;163(3):430-7–437 e1-3.CrossRefGoogle Scholar
  52. 52.
    Nakada Y, Kawakami R, Nakano T, Takitsume A, Nakagawa H, Ueda T, Nishida T, Onoue K, Soeda T, Okayama S, Takeda Y, Watanabe M, Kawata H, Okura H, Saito Y. Sex differences in clinical characteristics and long-term outcome in acute decompensated heart failure patients with preserved and reduced ejection fraction. Am J Physiol Heart Circ Physiol. 2016;310(7):H813–20.PubMedCrossRefPubMedCentralGoogle Scholar
  53. 53.
    Zsilinszka R, Shrader P, DeVore AD, Hardy NC, Mentz RJ, Pang PS, Peacock WF, Fonarow GC, Hernandez AF. Sex differences in the management and outcomes of heart failure with preserved ejection fraction in patients presenting to the emergency department with acute heart failure. J Card Fail. 2016;22(10):781–8.CrossRefPubMedGoogle Scholar
  54. 54.
    Kajimoto K, Minami Y, Sato N, Otsubo S, Kasanuki H, Investigators of the Acute Decompensated Heart Failure Syndromes Registry. Gender differences in left ventricular ejection fraction and outcomes among patients hospitalized for acute decompensated heart failure. Am J Cardiol. 2017;119:1623–30.PubMedCrossRefPubMedCentralGoogle Scholar
  55. 55.
    Hobbs FD, Kenkre JE, Roalfe AK, Davis RC, Hare R, Davies MK. Impact of heart failure and left ventricular systolic dysfunction on quality of life: a cross-sectional study comparing common chronic cardiac and medical disorders and a representative adult population. Eur Heart J. 2002;23(23):1867–76.PubMedCrossRefPubMedCentralGoogle Scholar
  56. 56.
    Chin MH, Goldman L. Gender differences in 1-year survival and quality of life among patients admitted with congestive heart failure. Med Care. 1998;36(7):1033–46.PubMedCrossRefPubMedCentralGoogle Scholar
  57. 57.
    Stewart S, Ekman I, Ekman T, Oden A, Rosengren A. Population impact of heart failure and the most common forms of cancer: a study of 1 162 309 hospital cases in Sweden (1988 to 2004). Circ Cardiovasc Qual Outcomes. 2010;3(6):573–80.PubMedCrossRefPubMedCentralGoogle Scholar
  58. 58.
    Hoekstra T, Jaarsma T, van Veldhuisen DJ, Hillege HL, Sanderman R, Lesman-Leegte I. Quality of life and survival in patients with heart failure. Eur J Heart Fail. 2013;15(1):94–102.PubMedCrossRefPubMedCentralGoogle Scholar
  59. 59.
    Riegel B, Moser DK, Carlson B, Deaton C, Armola R, Sethares K, Shively M, Evangelista L, Albert N. Gender differences in quality of life are minimal in patients with heart failure. J Card Fail. 2003;9(1):42–8.PubMedCrossRefPubMedCentralGoogle Scholar
  60. 60.
    Friedman MM. Gender differences in the health related quality of life of older adults with heart failure. Heart Lung. 2003;32(5):320–7.PubMedCrossRefGoogle Scholar
  61. 61.
    Simon M, Boutouyrie P, Narayanan K, Gaye B, Tafflet M, Thomas F, Guibout C, Perier MC, Pannier B, Jouven X, Empana JP. Sex disparities in ideal cardiovascular health. Heart (British Cardiac Society). 2017;103:1595–601.Google Scholar
  62. 62.
    He J, Ogden LG, Bazzano LA, Vupputuri S, Loria C, Whelton PK. Risk factors for congestive heart failure in US men and women: NHANES I epidemiologic follow-up study. Arch Intern Med. 2001;161(7):996–1002.PubMedCrossRefGoogle Scholar
  63. 63.
    Lee DS, Gona P, Vasan RS, Larson MG, Benjamin EJ, Wang TJ, Tu JV, Levy D. Relation of disease pathogenesis and risk factors to heart failure with preserved or reduced ejection fraction: insights from the framingham heart study of the national heart, lung, and blood institute. Circulation. 2009;119(24):3070–7.PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Dunlay SM, Weston SA, Jacobsen SJ, Roger VL. Risk factors for heart failure: a population-based case-control study. Am J Med. 2009;122(11):1023–8.PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Hsich EM, Pina IL. Heart failure in women: a need for prospective data. J Am Coll Cardiol. 2009;54(6):491–8.PubMedCrossRefGoogle Scholar
  66. 66.
    Taylor AL. Heart failure in women. Curr Heart Fail Rep. 2015;12(2):187–95.PubMedCrossRefGoogle Scholar
  67. 67.
    Dunlay SM, Roger VL. Gender differences in the pathophysiology, clinical presentation, and outcomes of ischemic heart failure. Curr Heart Fail Rep. 2012;9(4):267–76.PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Kishi S, Reis JP, Venkatesh BA, Gidding SS, Armstrong AC, Jacobs DR Jr, Sidney S, Wu CO, Cook NL, Lewis CE, Schreiner PJ, Isogawa A, Liu K, Lima JA. Race-ethnic and sex differences in left ventricular structure and function: the Coronary Artery Risk Development in Young Adults (CARDIA) Study. J Am Heart Assoc. 2015;4(3):e001264.PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Meyer S, van der Meer P, van Deursen VM, Jaarsma T, van Veldhuisen DJ, van der Wal MH, Hillege HL, Voors AA. Neurohormonal and clinical sex differences in heart failure. Eur Heart J. 2013;34(32):2538–47.PubMedCrossRefGoogle Scholar
  70. 70.
    Azad N, Kathiravelu A, Minoosepeher S, Hebert P, Fergusson D. Gender differences in the etiology of heart failure: a systematic review. J Geriatr Cardiol. 2011;8(1):15–23.PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Jacobs AK. Coronary intervention in 2009. Are women no different than men? Circ Cardiovasc Interv. 2009;2(1):69–78.CrossRefPubMedGoogle Scholar
  72. 72.
    Crea F, Battipaglia I, Andreotti F. Sex differences in mechanisms, presentation and management of ischaemic heart disease. Atherosclerosis. 2015;241(1):157–68.PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Mitoff PR, Gam D, Ivanov J, Al-hesayen A, Azevedo ER, Newton GE, Parker JD, Mak S. Cardiac-specific sympathetic activation in men and women with and without heart failure. Heart. 2011;97(5):382–7.PubMedCrossRefGoogle Scholar
  74. 74.
    Galvao M, Kalman J, DeMarco T, Fonarow GC, Galvin C, Ghali JK, Moskowitz RM. Gender differences in in-hospital management and outcomes in patients with decompensated heart failure: analysis from the Acute Decompensated Heart Failure National Registry (ADHERE). J Card Fail. 2006;12(2):100–7.PubMedCrossRefGoogle Scholar
  75. 75.
    Frazier CG, Alexander KP, Newby LK, Anderson S, Iverson E, Packer M, Cohn J, Goldstein S, Douglas PS. Associations of gender and etiology with outcomes in heart failure with systolic dysfunction: a pooled analysis of 5 randomized control trials. J Am Coll Cardiol. 2007;49(13):1450–8.PubMedCrossRefGoogle Scholar
  76. 76.
    Petrie MC, Dawson NF, Murdoch DR, Davie AP, McMurray JJ. Failure of women’s hearts. Circulation. 1999;99(17):2334–41.PubMedCrossRefGoogle Scholar
  77. 77.
    Borlaug BA. Defining HFpEF: where do we draw the line? Eur Heart J. 2016;37(5):463–5.PubMedCrossRefGoogle Scholar
  78. 78.
    Luo T, Kim JK. The role of estrogen and estrogen receptors on cardiomyocytes: an overview. Can J Cardiol. 2016;32(8):1017–25.PubMedCrossRefGoogle Scholar
  79. 79.
    Bouma W, Noma M, Kanemoto S, Matsubara M, Leshnower BG, Hinmon R, Gorman JH 3rd, Gorman RC. Sex-related resistance to myocardial ischemia-reperfusion injury is associated with high constitutive ARC expression. Am J Physiol Heart Circ Physiol. 2010;298(5):H1510–7.PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Harvey RE, Coffman KE, Miller VM. Women-specific factors to consider in risk, diagnosis and treatment of cardiovascular disease. Womens Health (Lond). 2015;11(2):239–57.CrossRefGoogle Scholar
  81. 81.
    Ntusi NB, Mayosi BM. Aetiology and risk factors of peripartum cardiomyopathy: a systematic review. Int J Cardiol. 2009;131(2):168–79.PubMedCrossRefPubMedCentralGoogle Scholar
  82. 82.
    Arany Z, Elkayam U. Peripartum cardiomyopathy. Circulation. 2016;133(14):1397–409.CrossRefPubMedGoogle Scholar
  83. 83.
    Hilfiker-Kleiner D, Sliwa K. Pathophysiology and epidemiology of peripartum cardiomyopathy. Nat Rev Cardiol. 2014;11(6):364–70.PubMedCrossRefPubMedCentralGoogle Scholar
  84. 84.
    Wang F, He Q, Sun Y, Dai X, Yang XP. Female adult mouse cardiomyocytes are protected against oxidative stress. Hypertension. 2010;55(5):1172–8.PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    Franssen C, Chen S, Unger A, Korkmaz HI, De Keulenaer GW, Tschope C, Leite-Moreira AF, Musters R, Niessen HW, Linke WA, Paulus WJ, Hamdani N. Myocardial microvascular inflammatory endothelial activation in heart failure with preserved ejection fraction. JACC Heart Fail. 2016;4(4):312–24.PubMedCrossRefPubMedCentralGoogle Scholar
  86. 86.
    Tasevska-Dinevska G, Kennedy LM, Cline-Iwarson A, Cline C, Erhardt L, Willenheimer R. Gender differences in variables related to B-natriuretic peptide, left ventricular ejection fraction and mass, and peak oxygen consumption, in patients with heart failure. Int J Cardiol. 2011;149(3):364–71.PubMedCrossRefPubMedCentralGoogle Scholar
  87. 87.
    Elmariah S, Goldberg LR, Allen MT, Kao A. Effects of gender on peak oxygen consumption and the timing of cardiac transplantation. J Am Coll Cardiol. 2006;47(11):2237–42.PubMedCrossRefPubMedCentralGoogle Scholar
  88. 88.
    Luchner A, Brockel U, Muscholl M, Hense HW, Doring A, Riegger GA, Schunkert H. Gender-specific differences of cardiac remodeling in subjects with left ventricular dysfunction: a population-based study. Cardiovasc Res. 2002;53(3):720–7.PubMedCrossRefPubMedCentralGoogle Scholar
  89. 89.
    Greiten LE, Holditch SJ, Arunachalam SP, Miller VM. Should there be sex-specific criteria for the diagnosis and treatment of heart failure? J Cardiovasc Transl Res. 2014;7(2):139–55.PubMedPubMedCentralCrossRefGoogle Scholar
  90. 90.
    Salton CJ, Chuang ML, O’Donnell CJ, Kupka MJ, Larson MG, Kissinger KV, Edelman RR, Levy D, Manning WJ. Gender differences and normal left ventricular anatomy in an adult population free of hypertension. A cardiovascular magnetic resonance study of the Framingham Heart Study Offspring Cohort. J Am Coll Cardiol. 2002;39(6):1055–60.PubMedCrossRefPubMedCentralGoogle Scholar
  91. 91.
    Wingate S. Cardiovascular anatomy and physiology in the female. Crit Care Nurs Clin North Am. 1997;9(4):447–52.PubMedCrossRefPubMedCentralGoogle Scholar
  92. 92.
    Chugh SS, Uy-Evanado A, Teodorescu C, Reinier K, Mariani R, Gunson K, Jui J. Women have a lower prevalence of structural heart disease as a precursor to sudden cardiac arrest: The Ore-SUDS (Oregon Sudden Unexpected Death Study). J Am Coll Cardiol. 2009;54(22):2006–11.PubMedPubMedCentralCrossRefGoogle Scholar
  93. 93.
    Jessup M, Pina IL. Is it important to examine gender differences in the epidemiology and outcome of severe heart failure? J Thorac Cardiovasc Surg. 2004;127(5):1247–52.PubMedCrossRefPubMedCentralGoogle Scholar
  94. 94.
    Gori M, Lam CS, Gupta DK, Santos AB, Cheng S, Shah AM, Claggett B, Zile MR, Kraigher-Krainer E, Pieske B, Voors AA, Packer M, Bransford T, Lefkowitz M, McMurray JJ, Solomon SD, Investigators P. Sex-specific cardiovascular structure and function in heart failure with preserved ejection fraction. Eur J Heart Fail. 2014;16(5):535–42.PubMedCrossRefPubMedCentralGoogle Scholar
  95. 95.
    Russo C, Jin Z, Palmieri V, Homma S, Rundek T, Elkind MS, Sacco RL, Di Tullio MR. Arterial stiffness and wave reflection: sex differences and relationship with left ventricular diastolic function. Hypertension. 2012;60(2):362–8.PubMedPubMedCentralCrossRefGoogle Scholar
  96. 96.
    Shim CY, Park S, Choi D, Yang WI, Cho IJ, Choi EY, Chung N, Ha JW. Sex differences in central hemodynamics and their relationship to left ventricular diastolic function. J Am Coll Cardiol. 2011;57(10):1226–33.CrossRefPubMedGoogle Scholar
  97. 97.
    Vinereanu D, Margulescu AD. The fallacy of resting echocardiographic parameters of cardiac function in heart failure with preserved ejection fraction: add global longitudinal strain to the list. Eur J Heart Fail. 2017;19(7):901–3.PubMedCrossRefPubMedCentralGoogle Scholar
  98. 98.
    DeVore AD, McNulty S, Alenezi F, Ersboll M, Vader JM, Oh JK, Lin G, Redfield MM, Lewis G, Semigran MJ, Anstrom KJ, Hernandez AF, Velazquez EJ. Impaired left ventricular global longitudinal strain in patients with heart failure with preserved ejection fraction: insights from the RELAX trial. Eur J Heart Fail. 2017;19(7):893–900.PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Scantlebury DC, Borlaug BA. Why are women more likely than men to develop heart failure with preserved ejection fraction? Curr Opin Cardiol. 2011;26(6):562–8.CrossRefPubMedGoogle Scholar
  100. 100.
    Mehilli J, Ndrepepa G, Kastrati A, Nekolla SG, Markwardt C, Bollwein H, Pache J, Martinoff S, Dirschinger J, Schwaiger M, Schomig A. Gender and myocardial salvage after reperfusion treatment in acute myocardial infarction. J Am Coll Cardiol. 2005;45(6):828–31.PubMedCrossRefPubMedCentralGoogle Scholar
  101. 101.
    Cavasin MA, Tao Z, Menon S, Yang XP. Gender differences in cardiac function during early remodeling after acute myocardial infarction in mice. Life Sci. 2004;75(18):2181–92.PubMedCrossRefPubMedCentralGoogle Scholar
  102. 102.
    Fliegner D, Schubert C, Penkalla A, Witt H, Kararigas G, Dworatzek E, Staub E, Martus P, Ruiz Noppinger P, Kintscher U, Gustafsson JA, Regitz-Zagrosek V. Female sex and estrogen receptor-beta attenuate cardiac remodeling and apoptosis in pressure overload. Am J Physiol Regul Integr Comp Physiol. 2010;298(6):R1597–606.CrossRefPubMedGoogle Scholar
  103. 103.
    Gardner JD, Brower GL, Janicki JS. Gender differences in cardiac remodeling secondary to chronic volume overload. J Card Fail. 2002;8(2):101–7.PubMedPubMedCentralCrossRefGoogle Scholar
  104. 104.
    Guerra S, Leri A, Wang X, Finato N, Di Loreto C, Beltrami CA, Kajstura J, Anversa P. Myocyte death in the failing human heart is gender dependent. Circ Res. 1999;85(9):856–66.PubMedCrossRefPubMedCentralGoogle Scholar
  105. 105.
    Lu H, Melendez GC, Levick SP, Janicki JS. Prevention of adverse cardiac remodeling to volume overload in female rats is the result of an estrogen-altered mast cell phenotype. Am J Physiol Heart Circ Physiol. 2012;302(3):H811–7.PubMedCrossRefPubMedCentralGoogle Scholar
  106. 106.
    Petre RE, Quaile MP, Rossman EI, Ratcliffe SJ, Bailey BA, Houser SR, Margulies KB. Sex-based differences in myocardial contractile reserve. Am J Physiol Regul Integr Comp Physiol. 2007;292(2):R810–8.PubMedCrossRefPubMedCentralGoogle Scholar
  107. 107.
    Johnstone D, Limacher M, Rousseau M, Liang CS, Ekelund L, Herman M, Stewart D, Guillotte M, Bjerken G, Gaasch W, et al. Clinical characteristics of patients in studies of left ventricular dysfunction (SOLVD). Am J Cardiol. 1992;70(9):894–900.PubMedCrossRefPubMedCentralGoogle Scholar
  108. 108.
    Ng AC, Wong HS, Yong AS, Sindone AP. Impact of gender on outcomes in chronic systolic heart failure. Int J Cardiol. 2007;117(2):214–21.PubMedCrossRefPubMedCentralGoogle Scholar
  109. 109.
    Wang TJ, Larson MG, Levy D, Leip EP, Benjamin EJ, Wilson PW, Sutherland P, Omland T, Vasan RS. Impact of age and sex on plasma natriuretic peptide levels in healthy adults. Am J Cardiol. 2002;90(3):254–8.PubMedCrossRefPubMedCentralGoogle Scholar
  110. 110.
    Christ M, Laule-Kilian K, Hochholzer W, Klima T, Breidthardt T, Perruchoud AP, Mueller C. Gender-specific risk stratification with B-type natriuretic peptide levels in patients with acute dyspnea: insights from the B-type natriuretic peptide for acute shortness of breath evaluation study. J Am Coll Cardiol. 2006;48(9):1808–12.PubMedCrossRefGoogle Scholar
  111. 111.
    Meyer S, Teerlink JR, Metra M, Ponikowski P, Cotter G, Davison BA, Felker GM, Filippatos G, Greenberg BH, Hua TA, Severin T, Qian M, Voors AA. Sex differences in early dyspnea relief between men and women hospitalized for acute heart failure: insights from the RELAX-AHF study. Clin Res Cardiol. 2017;106(4):280–92.PubMedCrossRefGoogle Scholar
  112. 112.
    Nieminen MS, Harjola VP, Hochadel M, Drexler H, Komajda M, Brutsaert D, Dickstein K, Ponikowski P, Tavazzi L, Follath F, Lopez-Sendon JL. Gender related differences in patients presenting with acute heart failure. Results from EuroHeart Failure Survey II. Eur J Heart Fail. 2008;10(2):140–8.PubMedCrossRefGoogle Scholar
  113. 113.
    Tsuchihashi-Makaya M, Hamaguchi S, Kinugawa S, Goto K, Goto D, Furumoto T, Yamada S, Yokoshiki H, Takeshita A, Tsutsui H. Sex differences with respect to clinical characteristics, treatment, and long-term outcomes in patients with heart failure. Int J Cardiol. 2011;150(3):338–9.PubMedCrossRefGoogle Scholar
  114. 114.
    Andreotti F, Conti E, Lanza GA, Crea F. Sex, survival bias, and mortality following acute myocardial infarction. Ital Heart J. 2003;4(8):508–10.PubMedGoogle Scholar
  115. 115.
    van Deursen VM, Urso R, Laroche C, Damman K, Dahlstrom U, Tavazzi L, Maggioni AP, Voors AA. Co-morbidities in patients with heart failure: an analysis of the European Heart Failure Pilot Survey. Eur J Heart Fail. 2014;16(1):103–11.PubMedCrossRefPubMedCentralGoogle Scholar
  116. 116.
    Hopper I, Kotecha D, Chin KL, Mentz RJ, von Lueder TG. Comorbidities in heart failure: are there gender differences? Curr Heart Fail Rep. 2016;13(1):1–12.PubMedCrossRefGoogle Scholar
  117. 117.
    Mentz RJ, Kelly JP, von Lueder TG, Voors AA, Lam CS, Cowie MR, Kjeldsen K, Jankowska EA, Atar D, Butler J, Fiuzat M, Zannad F, Pitt B, O’Connor CM. Noncardiac comorbidities in heart failure with reduced versus preserved ejection fraction. J Am Coll Cardiol. 2014;64(21):2281–93.PubMedPubMedCentralCrossRefGoogle Scholar
  118. 118.
    Pitt B. Male gender, diabetes, COPD, anemia, and creatinine clearance < 30 mL/min predicted hospitalization after heart failure diagnosis. Ann Intern Med. 2010;152(8):JC4-2–3.Google Scholar
  119. 119.
    Dunlay SM, Roger VL, Redfield MM. Epidemiology of heart failure with preserved ejection fraction. Nat Rev Cardiol. 2017;14(10):591–602.CrossRefPubMedGoogle Scholar
  120. 120.
    Kenchaiah S, Vasan RS. Heart failure in women – insights from the Framingham Heart Study. Cardiovasc Drugs Ther. 2015;29(4):377–90.PubMedPubMedCentralCrossRefGoogle Scholar
  121. 121.
    Silverberg D, Wexler D, Blum M, Schwartz D, Iaina A. The association between congestive heart failure and chronic renal disease. Curr Opin Nephrol Hypertens. 2004;13(2):163–70.PubMedCrossRefPubMedCentralGoogle Scholar
  122. 122.
    Ronco C, Ronco F. Cardio-renal syndromes: a systematic approach for consensus definition and classification. Heart Fail Rev. 2012;17(2):151–60.PubMedCrossRefPubMedCentralGoogle Scholar
  123. 123.
    Schefold JC, Filippatos G, Hasenfuss G, Anker SD, von Haehling S. Heart failure and kidney dysfunction: epidemiology, mechanisms and management. Nat Rev Nephrol. 2016;12(10):610–23.PubMedCrossRefPubMedCentralGoogle Scholar
  124. 124.
    Vassalotti JA, Centor R, Turner BJ, Greer RC, Choi M, Sequist TD. Practical approach to detection and management of chronic kidney disease for the primary care clinician. Am J Med. 2016;129(2):153–162.e7.PubMedCrossRefPubMedCentralGoogle Scholar
  125. 125.
    Heywood JT, Fonarow GC, Costanzo MR, Mathur VS, Wigneswaran JR, Wynne J, Committee ASA, Investigators. High prevalence of renal dysfunction and its impact on outcome in 118,465 patients hospitalized with acute decompensated heart failure: a report from the ADHERE database. J Card Fail. 2007;13(6):422–30.PubMedCrossRefPubMedCentralGoogle Scholar
  126. 126.
    Conde-Martel A, Arkuch ME, Formiga F, Manzano-Espinosa L, Aramburu-Bodas O, Gonzalez-Franco A, Davila-Ramos MF, Suarez-Pedreira I, Herrero-Domingo A, Montero-Perez-Barquero M. Gender related differences in clinical profile and outcome of patients with heart failure. Results of the RICA Registry. Rev Clin Esp. 2015;215(7):363–70.PubMedCrossRefPubMedCentralGoogle Scholar
  127. 127.
    Kosiborod M, Curtis JP, Wang Y, et al. Anemia and outcomes in patients with heart failure: a study from the national heart care project. Arch Intern Med. 2005;165(19):2237–44.PubMedCrossRefPubMedCentralGoogle Scholar
  128. 128.
    Arora NP, Ghali JK. Iron deficiency anemia in heart failure. Heart Fail Rev. 2013;18(4):485–501.PubMedCrossRefPubMedCentralGoogle Scholar
  129. 129.
    van Veldhuisen DJ, Anker SD, Ponikowski P, Macdougall IC. Anemia and iron deficiency in heart failure: mechanisms and therapeutic approaches. Nat Rev Cardiol. 2011;8(9):485–93.PubMedCrossRefPubMedCentralGoogle Scholar
  130. 130.
    Cleland JG, Zhang J, Pellicori P, Dicken B, Dierckx R, Shoaib A, Wong K, Rigby A, Goode K, Clark AL. Prevalence and outcomes of anemia and hematinic deficiencies in patients with chronic heart failure. JAMA Cardiol. 2016;1(5):539–47.PubMedCrossRefPubMedCentralGoogle Scholar
  131. 131.
    Ebner N, Jankowska EA, Ponikowski P, Lainscak M, Elsner S, Sliziuk V, Steinbeck L, Kube J, Bekfani T, Scherbakov N. The impact of iron deficiency and anaemia on exercise capacity and outcomes in patients with chronic heart failure. Results from the studies investigating co-morbidities aggravating heart failure. Int J Cardiol. 2016;205:6–12.PubMedCrossRefPubMedCentralGoogle Scholar
  132. 132.
    de Silva R, Rigby AS, Witte KK, Nikitin NP, Tin L, Goode K, Bhandari S, Clark AL, Cleland JG. Anemia, renal dysfunction, and their interaction in patients with chronic heart failure. Am J Cardiol. 2006;98(3):391–8.PubMedCrossRefPubMedCentralGoogle Scholar
  133. 133.
    Kajimoto K, Minami Y, Sato N, Otsubo S, Kasanuki H. Gender differences in anemia and survival in patients hospitalized for acute decompensated heart failure with preserved or reduced ejection fraction. Am J Cardiol. 2017;120(3):435–42.CrossRefPubMedGoogle Scholar
  134. 134.
    Ogah OS, Davison BA, Sliwa K, Mayosi BM, Damasceno A, Sani MU, Mondo C, Dzudie A, Ojji DB, Kouam C, Suliman A, Schrueder N, Yonga G, Ba SA, Maru F, Alemayehu B, Edwards C, Cotter G. Gender differences in clinical characteristics and outcome of acute heart failure in sub-Saharan Africa: results of the THESUS-HF study. Clin Res Cardiol. 2015;104(6):481–90.PubMedCrossRefPubMedCentralGoogle Scholar
  135. 135.
    Cohen-Solal A, Damy T, Terbah M, Kerebel S, Baguet J-P, Hanon O, Zannad F, Laperche T, Leclercq C, Concas V, Duvillié L, Darné B, Anker S, Mebazaa A. High prevalence of iron deficiency in patients with acute decompensated heart failure. Eur J Heart Fail. 2014;16(9):984–91.PubMedCrossRefPubMedCentralGoogle Scholar
  136. 136.
    Kajimoto K, Sato N, Takano T. Association between anemia, clinical features and outcome in patients hospitalized for acute heart failure syndromes. Eur Heart J: Acute Card Care. 2014;4(6):568–76.Google Scholar
  137. 137.
    Yamauchi T, Sakata Y, Takada T, Nochioka K, Miura M, Tadaki S, Ushigome R, Sato K, Onose T, Tsuji K. Prognostic impact of anemia in patients with chronic heart failure–with special reference to clinical background: report from the CHART-2 Study. Circ J. 2015;79(9):1984–93.PubMedCrossRefPubMedCentralGoogle Scholar
  138. 138.
    McNallan SM, Chamberlain AM, Gerber Y, Singh M, Kane RL, Weston SA, Dunlay SM, Jiang R, Roger VL. Measuring frailty in heart failure: a community perspective. Am Heart J. 2013;166(4):768–74.PubMedCrossRefPubMedCentralGoogle Scholar
  139. 139.
    Altimir S, Lupon J, Gonzalez B, Prats M, Parajon T, Urrutia A, Coll R, Valle V. Sex and age differences in fragility in a heart failure population. Eur J Heart Fail. 2005;7(5):798–802.PubMedCrossRefPubMedCentralGoogle Scholar
  140. 140.
    Gonzalez-Moneo MJ, Sanchez-Benavides G, Verdu-Rotellar JM, Cladellas M, Bruguera J, Quinones-Ubeda S, Enjuanes C, Pena-Casanova J, Comin-Colet J. Ischemic aetiology, self-reported frailty, and gender with respect to cognitive impairment in chronic heart failure patients. BMC Cardiovasc Disord. 2016;16(1):163.PubMedPubMedCentralCrossRefGoogle Scholar
  141. 141.
    Kaila K, Haykowsky MJ, Thompson RB, Paterson DI. Heart failure with preserved ejection fraction in the elderly: scope of the problem. Heart Fail Rev. 2012;17(4-5):555–62.PubMedPubMedCentralCrossRefGoogle Scholar
  142. 142.
    Gottlieb SS, Khatta M, Friedmann E, Einbinder L, Katzen S, Baker B, Marshall J, Minshall S, Robinson S, Fisher ML, Potenza M, Sigler B, Baldwin C, Thomas SA. The influence of age, gender, and race on the prevalence of depression in heart failure patients. J Am Coll Cardiol. 2004;43(9):1542–9.PubMedPubMedCentralCrossRefGoogle Scholar
  143. 143.
    Jiang W, Alexander J, Christopher E, et al. Relationship of depression to increased risk of mortality and rehospitalization in patients with congestive heart failure. Arch Intern Med. 2001;161(15):1849–56.PubMedCrossRefGoogle Scholar
  144. 144.
    Freedland KE, Hesseler MJ, Carney RM, Steinmeyer BC, Skala JA, Dávila-Román VG, Rich MW. Major depression and long-term survival of patients with heart failure. Psychosom Med. 2016;78(8):896–903.PubMedPubMedCentralCrossRefGoogle Scholar
  145. 145.
    Vaccarino V, Kasl SV, Abramson J, Krumholz HM. Depressive symptoms and risk of functional decline and death in patients with heart failure. J Am Coll Cardiol. 2001;38(1):199–205.PubMedCrossRefGoogle Scholar
  146. 146.
    Ghali JK, Lindenfeld J. Sex differences in response to chronic heart failure therapies. Expert Rev Cardiovasc Ther. 2008;6(4):555–65.PubMedCrossRefGoogle Scholar
  147. 147.
    Gan SC, Beaver SK, Houck PM, MacLehose RF, Lawson HW, Chan L. Treatment of acute myocardial infarction and 30-day mortality among women and men. N Engl J Med. 2000;343(1):8–15.PubMedCrossRefGoogle Scholar
  148. 148.
    Berg J, Bjorck L, Nielsen S, Lappas G, Rosengren A. Sex differences in survival after myocardial infarction in Sweden, 1987–2010. Heart. 2017;103(20):1625–30.PubMedPubMedCentralCrossRefGoogle Scholar
  149. 149.
    Shekelle PG, Rich MW, Morton SC, Atkinson CS, Tu W, Maglione M, Rhodes S, Barrett M, Fonarow GC, Greenberg B, Heidenreich PA, Knabel T, Konstam MA, Steimle A, Warner Stevenson L. Efficacy of angiotensin-converting enzyme inhibitors and beta-blockers in the management of left ventricular systolic dysfunction according to race, gender, and diabetic status: a meta-analysis of major clinical trials. J Am Coll Cardiol. 2003;41(9):1529–38.PubMedCrossRefPubMedCentralGoogle Scholar
  150. 150.
    Garg R, Yusuf S. Overview of randomized trials of angiotensin-converting enzyme-inhibitors on mortality and morbidity in patients with heart-failure (Vol 273, Pg 1450, 1995). Jama-J Am Med Assoc. 1995;274(6):462–2.Google Scholar
  151. 151.
    Keyhan G, Chen SF, Pilote L. Angiotensin-converting enzyme inhibitors and survival in women and men with heart failure. Eur J Heart Fail. 2007;9(6-7):594–601.CrossRefPubMedGoogle Scholar
  152. 152.
    Young JB, Dunlap ME, Pfeffer MA, Probstfield JL, Cohen-Solal A, Dietz R, Granger CB, Hradec J, Kuch J, McKelvie RS, McMurray JJ, Michelson EL, Olofsson B, Ostergren J, Held P, Solomon SD, Yusuf S, Swedberg K, Candesartan in Heart Failure Assessment of Reduction in M, Morbidity I, Committees. Mortality and morbidity reduction with Candesartan in patients with chronic heart failure and left ventricular systolic dysfunction: results of the CHARM low-left ventricular ejection fraction trials. Circulation. 2004;110(17):2618–26.PubMedCrossRefPubMedCentralGoogle Scholar
  153. 153.
    Cohn JN, Tognoni G, Valsartan Heart Failure Trial I. A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N Engl J Med. 2001;345(23):1667–75.PubMedCrossRefPubMedCentralGoogle Scholar
  154. 154.
    McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, Rouleau JL, Shi VC, Solomon SD, Swedberg K, Zile MR, Investigators P-H, Committees. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371(11):993–1004.CrossRefPubMedPubMedCentralGoogle Scholar
  155. 155.
    Hudson M, Rahme E, Behlouli H, Sheppard R, Pilote L. Sex differences in the effectiveness of angiotensin receptor blockers and angiotensin converting enzyme inhibitors in patients with congestive heart failure – a population study. Eur J Heart Fail. 2007;9(6-7):602–9.CrossRefPubMedGoogle Scholar
  156. 156.
    Zannad F, McMurray JJ, Krum H, van Veldhuisen DJ, Swedberg K, Shi H, Vincent J, Pocock SJ, Pitt B, Group E-HS. Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med. 2011;364(1):11–21.PubMedCrossRefPubMedCentralGoogle Scholar
  157. 157.
    Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, Palensky J, Wittes J. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med. 1999;341(10):709–17.PubMedCrossRefPubMedCentralGoogle Scholar
  158. 158.
    Packer M, Bristow MR, Cohn JN, Colucci WS, Fowler MB, Gilbert EM, Shusterman NH. The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. U.S. Carvedilol Heart Failure Study Group. N Engl J Med. 1996;334(21):1349–55.PubMedCrossRefPubMedCentralGoogle Scholar
  159. 159.
    Packer M, Coats AJ, Fowler MB, Katus HA, Krum H, Mohacsi P, Rouleau JL, Tendera M, Castaigne A, Roecker EB, Schultz MK, DeMets DL, Carvedilol Prospective Randomized Cumulative Survival Study G. Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med. 2001;344(22):1651–8.PubMedCrossRefPubMedCentralGoogle Scholar
  160. 160.
    Leizorovicz A, Lechat P, Cucherat M, Bugnard F. Bisoprolol for the treatment of chronic heart failure: a meta-analysis on individual data of two placebo-controlled studies – CIBIS and CIBIS II. Cardiac Insufficiency Bisoprolol Study. Am Heart J. 2002;143(2):301–7.PubMedCrossRefGoogle Scholar
  161. 161.
    Ghali JK, Pina IL, Gottlieb SS, Deedwania PC, Wikstrand JC, Group M-HS. Metoprolol CR/XL in female patients with heart failure: analysis of the experience in Metoprolol Extended-Release Randomized Intervention Trial in Heart Failure (MERIT-HF). Circulation. 2002;105(13):1585–91.PubMedCrossRefGoogle Scholar
  162. 162.
    Rathore SS, Wang Y, Krumholz HM. Sex-based differences in the effect of digoxin for the treatment of heart failure. N Engl J Med. 2002;347(18):1403–11.PubMedCrossRefGoogle Scholar
  163. 163.
    Adams KF Jr, Patterson JH, Gattis WA, O’Connor CM, Lee CR, Schwartz TA, Gheorghiade M. Relationship of serum digoxin concentration to mortality and morbidity in women in the digitalis investigation group trial: a retrospective analysis. J Am Coll Cardiol. 2005;46(3):497–504.PubMedCrossRefGoogle Scholar
  164. 164.
    MacFadden DR, Crystal E, Krahn AD, Mangat I, Healey JS, Dorian P, Birnie D, Simpson CS, Khaykin Y, Pinter A, Nanthakumar K, Calzavara AJ, Austin PC, Tu JV, Lee DS. Sex differences in implantable cardioverter-defibrillator outcomes: findings from a prospective defibrillator database. Ann Intern Med. 2012;156(3):195–203.PubMedCrossRefPubMedCentralGoogle Scholar
  165. 165.
    Curtis LH, Al-Khatib SM, Shea AM, Hammill BG, Hernandez AF, Schulman KA. Sex differences in the use of implantable cardioverter-defibrillators for primary and secondary prevention of sudden cardiac death. JAMA. 2007;298(13):1517–24.PubMedCrossRefPubMedCentralGoogle Scholar
  166. 166.
    Hernandez AF, Fonarow GC, Liang L, Al-Khatib SM, Curtis LH, LaBresh KA, Yancy CW, Albert NM, Peterson ED. Sex and racial differences in the use of implantable cardioverter-defibrillators among patients hospitalized with heart failure. JAMA. 2007;298(13):1525–32.CrossRefPubMedGoogle Scholar
  167. 167.
    Masoudi FA, Go AS, Magid DJ, Cassidy-Bushrow AE, Gurwitz JH, Liu TI, Reynolds K, Smith DH, Reifler LM, Glenn KA, Fiocchi F, Goldberg R, Gupta N, Peterson PN, Schuger C, Vidaillet H, Hammill SC, Greenlee RT. Age and sex differences in long-term outcomes following implantable cardioverter-defibrillator placement in contemporary clinical practice: findings from the Cardiovascular Research Network. J Am Heart Assoc. 2015;4(6):e002005.PubMedPubMedCentralCrossRefGoogle Scholar
  168. 168.
    Tompkins CM, McNitt S, Polonsky B, Daubert JP, Wang PJ, Moss AJ, Zareba W, Kutyifa V. Sex differences in inappropriate ICD device therapies: MADIT-II and MADIT-CRT. J Cardiovasc Electrophysiol. 2017;28(1):94–102.CrossRefPubMedGoogle Scholar
  169. 169.
    Moss AJ, Zareba W, Hall WJ, Klein H, Wilber DJ, Cannom DS, Daubert JP, Higgins SL, Brown MW, Andrews ML, Multicenter Automatic Defibrillator Implantation Trial III. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med. 2002;346(12):877–83.CrossRefPubMedPubMedCentralGoogle Scholar
  170. 170.
    Albert CM, Quigg R, Saba S, Estes NA 3rd, Shaechter A, Subacius H, Howard A, Levine J, Kadish A, Investigators D. Sex differences in outcome after implantable cardioverter defibrillator implantation in nonischemic cardiomyopathy. Am Heart J. 2008;156(2):367–72.PubMedCrossRefPubMedCentralGoogle Scholar
  171. 171.
    Chatterjee NA, Borgquist R, Chang Y, Lewey J, Jackson VA, Singh JP, Metlay JP, Lindvall C. Increasing sex differences in the use of cardiac resynchronization therapy with or without implantable cardioverter-defibrillator. Eur Heart J. 2017;38(19):1485–94.PubMedPubMedCentralGoogle Scholar
  172. 172.
    Cleland JG, Daubert JC, Erdmann E, Freemantle N, Gras D, Kappenberger L, Tavazzi L, Cardiac Resynchronization-Heart Failure Study I. The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med. 2005;352(15):1539–49.PubMedCrossRefPubMedCentralGoogle Scholar
  173. 173.
    Bristow MR, Saxon LA, Boehmer J, Krueger S, Kass DA, De Marco T, Carson P, DiCarlo L, DeMets D, White BG, DeVries DW, Feldman AM, Comparison of Medical Therapy P, Defibrillation in Heart Failure I. Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med. 2004;350(21):2140–50.PubMedCrossRefPubMedCentralGoogle Scholar
  174. 174.
    Hsich EM, Naftel DC, Myers SL, Gorodeski EZ, Grady KL, Schmuhl D, Ulisney KL, Young JB. Should women receive left ventricular assist device support?: findings from INTERMACS. Circ Heart Fail. 2012;5(2):234–40.PubMedPubMedCentralCrossRefGoogle Scholar
  175. 175.
    Sherazi S, Kutyifa V, McNitt S, Papernov A, Hallinan W, Chen L, Storozynsky E, Johnson BA, Strawderman RL, Massey HT, Zareba W, Alexis JD. Effect of gender on the risk of neurologic events and subsequent outcomes in patients with left ventricular assist devices. Am J Cardiol. 2017;119(2):297–301.PubMedCrossRefPubMedCentralGoogle Scholar
  176. 176.
    Meeteren JV, Maltais S, Dunlay SM, Haglund NA, Beth Davis M, Cowger J, Shah P, Aaronson KD, Pagani FD, Stulak JMA. multi-institutional outcome analysis of patients undergoing left ventricular assist device implantation stratified by sex and race. J Heart Lung Transplant. 2017;36(1):64–70.PubMedCrossRefPubMedCentralGoogle Scholar
  177. 177.
    Morris AA, Pekarek A, Wittersheim K, Cole RT, Gupta D, Nguyen D, Laskar SR, Butler J, Smith A, Vega JD. Gender differences in the risk of stroke during support with continuous-flow left ventricular assist device. J Heart Lung Transplant. 2015;34(12):1570–7.PubMedCrossRefPubMedCentralGoogle Scholar
  178. 178.
    Tsao CI, Chen RJ, Chou NK, Ko WJ, Chi NH, Yu HY, Chen YS, Chen SC, Wang SS. The influence of gender on survival after heart transplantation. Transplant Proc. 2008;40(8):2634–5.PubMedCrossRefPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Division of Cardiology, Department of MedicineKarolinska InstitutetStockholmSweden
  2. 2.Polo di Scienze Cardiovascolari e ToracicheUniversità Cattolica del Sacro Cuore, Fondazione Policlinico A. GemelliRomeItaly

Personalised recommendations