Article

Sex-specific differences in heart failure

The fundamental differences in heart failure between men and women

At proCardio 2022, the Global Cardiac Biomarker Forum, Prof Emily Lau (Massachusetts General Hospital, Boston, USA) spoke about sex-specific differences in heart failure (HF), highlighting that “heart failure is fundamentally different in men and women” describing several sex-specific differences ranging across pathophysiology, risk factors, diagnosis and outcomes.1,2 

Regarding pathophysiology, Prof Lau noted that the main driving factor of HF development in men is known to be apoptosis or loss of cardiomyocytes. Whereas in women, coronary microvascular dysfunction and accompanying downstream effects seem to be more important.3 With respect to disease manifestation and outcomes, Prof Lau explained that HF seems to have a greater impact on quality of life and exercise intolerance in women, even though their disease prognosis is typically better compared to men.4-9 Interestingly, when it comes to treatment, she noted there may also be sex-specific differences in treatment responses, referring to data suggesting that ARNI may have a beneficial effect in women compared to men with HFpEF.10

Prof Lau also discussed how sex can influence biomarkers, noting that baseline levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) are higher in healthy women compared to men, which is attenuated in people with HF.3,11,12 She also explained how the ability of NT-proBNP to predict outcomes might be greater in men versus women, although data on this is conflicting.11-13 Prof Lau commented how interpretation of biomarker levels in women is further complicated by hormonal and menopause status, for example, NT-proBNP levels are lowest in men and highest in pre-menopausal women on contraceptives.14,15

Finally, Prof Lau highlighted that, despite these fundamental differences in men and women, treatment is currently still the same.16,17 She believes that taking these sex-specific differences into account when adjusting therapy would allow for truly personalised and, more importantly, effective patient care. 

Key facts
  • Several sex-specific differences exist in heart failure influencing pathophysiology, risk factors, diagnosis, and outcomes1,2
  • Biomarkers, such as N-terminal pro-B-type natriuretic peptide (NT-proBNP), differ between men and women in terms of baseline levels as well as prognostic performance3,11,12
  • Sex-specific differences might also influence therapeutic efficacies, as observed for Angiotensin Receptor-Neprilysin Inhibition (ARNI) in patients with HF with preserved ejection fraction (HFpEF)10
  • In the future, truly personalised and more effective patient care may be achieved by taking these fundamental differences into account when making treatment decisions

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References

  1. Bairey Merz, C Noel et al. “Insights from the NHLBI-Sponsored Women's Ischemia Syndrome Evaluation (WISE) Study: Part II: gender differences in presentation, diagnosis, and outcome with regard to gender-based pathophysiology of atherosclerosis and macrovascular and microvascular coronary disease.” Journal of the American College of Cardiology vol. 47,3 Suppl (2006): S21-9. 
  2. Beale, Anna L et al. “Sex Differences in Cardiovascular Pathophysiology: Why Women Are Overrepresented in Heart Failure With Preserved Ejection Fraction.” Circulation vol. 138,2 (2018): 198-205. 
  3. Lau ES, et al. Sexual Dimorphism in Cardiovascular Biomarkers: Clinical and Research Implications. Circ Res. 2022;130(4):578-92.
  4. Stolfo D, et al. Sex-Based Differences in Heart Failure Across the Ejection Fraction Spectrum: Phenotyping, and Prognostic and Therapeutic Implications. JACC Heart Fail. 2019;7(6):505-15.
  5. Dunlay SM, Roger VL. Gender Differences in the Pathophysiology, Clinical Presentation, and Outcomes of Ischemic Heart Failure. Curr Heart Fail Rep. 2012;9, 267-76. 
  6. O'Meara E, et al. 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.
  7. Parashar S, et al. 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.
  8. Martinez-Selles M, et al. 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.
  9. Faxén UL, et al. Patient reported outcome in HFpEF: Sex-specific differences in quality of life and association with outcome. Int J Cardiol. 2018;267: 128-32. 
  10. Solomon SD, et al. Angiotensin-Neprilysin Inhibition in Heart Failure with Preserved Ejection Fraction. N Engl J Med. 2019;381(17):1609-20.
  11. Suthahar N, et al. Sex-Specific Associations of Cardiovascular Risk Factors and Biomarkers With Incident Heart Failure. J Am Coll Cardiol. 2020;76(12):1455-65.
  12. Magnussen C, et al. Sex-Specific Epidemiology of Heart Failure Risk and Mortality in Europe: Results From the BiomarCaRE Consortium. Heart failure. 2019;7(3):204-13.
  13. Kim HL, et al. Gender Difference in the Prognostic Value of N-Terminal Pro-B Type Natriuretic Peptide in Patients With Heart Failure - A Report From the Korean Heart Failure Registry (KorHF). Circ J. 2017;81(9):1329-36.
  14. Lam CS, et al. Influence of sex and hormone status on circulating natriuretic peptides. J Am Coll Cardiol. 2011;58(6):618-26. 
  15. Lau ES, et al. Sex Differences in Circulating Biomarkers of Cardiovascular Disease. J Am Coll Cardiol. 2019;74(12):1543-1553.
  16. McDonagh TA, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021;42(36):3599-3726.
  17. Heidenreich PA,  2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Card Fail. 2022;28(5):e1-e167.