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Be part of the knowledge.™Women more likely to develop acute HF with higher mortality risk after STEMI than men
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Introduction and methods
Previous studies have shown that acute heart failure (HF) after myocardial infarction (MI) leads to an elevated risk of 30-day mortality. These studies also demonstrated that women are more likely to develop symptoms of acute HF after MI [1-3]. There are many factors that can contribute to higher prevalence of acute HF in women compared to men, including higher rates of hypertension and diabetes, and lower rates of evidence-based therapies and less frequent referral for coronary revascularization [4-6]. Data is limited on sex-related differences in acute HF in patients with ST-Segment Elevation Myocardial Infarction (STEMI).
This study assessed the relationships between sex, acute HF and mortality in 10443 STEMI patients (3112 women, 7331 men) enrolled in the large observational and multinational ISACS-TC registry (International Survey of Acute Coronary Syndromes in Transitional Countries; NCT01218776). Patients with a pre-existing diagnosis of HF were excluded.
The primary outcome was 30-day all-cause mortality. Key secondary outcome was incidence of de novo HF (defined as Killip class ≥ II) at hospital presentation.
Main results
- Women were older and more likely to have a family history of CAD, angina, diabetes and hypertension, while men were more likely to be smokers and have a prior history of MI and coronary artery bypass graft. - After the distribution of covariates was balanced, women had an increased risk of the primary outcome of 30-day mortality compared to men (OR: 1.68, 95% CI: 1.44 to 1.96).
- Women had an increased risk for de novo HF compared to men (OR: 1.34; 95% CI: 1.21 to 1.48, P=0.0003).
- Women with de novo HF had a higher mortality compared to men with de novo HF (OR: 1.29; 95% CI: 1.05 to 1.58, P=0.0135).
- Women with de novo HF who underwent primary PCI had an increased risk of 30-day mortality compared to men (OR: 1.45, 95% CI: 1.07 to 1.96 P=0.0151).
- Prolonged time from symptom onset to hospital presentation (≥ 120 min) was associated with higher incidence of de novo heart failure at time of index admission compared early presentations (<120 min) in both sexes. However, the sex-dependent difference in study outcomes was not significantly different for early and late presentations.
Conclusion
This study showed that women had a higher risk of developing de novo acute HF after STEMI. In patients with de novo HF, women had higher mortality rates compared to men. These findings accentuate the need for more research into prevention of sex-specific risks in development of acute HF after MI.
Editorial comment
In her editorial comment [7], Briller places the novel findings of the current study into context with results from previous studies and searches for an explanation for the sex-related differences in clinical outcomes in patients with STEMI. While other studies suggested that women are less likely to receive guideline-directed medical therapy, women in the ISACS-TC registry were surprisingly more likely to take aspirin, ACE inhibitors, beta-blockers or statins before admission. Multivessel disease was present in the majority of both sexes and can thus not explain the elevated mortality in women. The anterior ST-segment elevation was used as a surrogate for infarct size in this study and this also did not explain the different outcomes in men and women. This study did not address racial or ethnic gender differences.
Briller points out that prolonged time from symptoms onset to hospital presentation are well recognized to contribute to adverse outcomes. Women are more likely to have atypical symptoms instead of the classic substernal chest discomfort and are more likely to present >6 h from symptom onset. Etiologies more common in women include plaque erosion, spontaneous coronary dissection, spasm, and Takotsubo syndrome. Briller acknowledges the investigators’ suggestion to focus future research on microvascular dysfunction as another pathologic mechanism.
Briller concludes with the notion that this study underscores the need to develop strategies for improved recognition of ischemic syndromes in women. Further investigations towards the pathophysiology of atherosclerotic disease in women and development of effective interventions for these distinctions are necessary.
References
1. Weaver WD, White HD, Wilcox RG, et al., for the GUSTO-I Investigators. Comparisons of characteristics and outcomes among women and men with acute myocardial infarction treated with thrombolytic therapy. JAMA 1996;275:777–82.
2. Wu AH, Parsons L, Every NR, et al., for the Second National Registry of Myocardial Infarction. Hospital outcomes in patients presenting with congestive heart failure complicating acute myocardial infarction: a report from the Second National Registry of Myocardial Infarction (NRMI-2). J Am Coll Cardiol 2002;40:1389–94.
3. Kashani A, Giugliano RP, Antman EM, et al. Severity of heart failure, treatments, and outcomes after fibrinolysis in patients with STelevation myocardial infarction. Eur Heart J 2004;25:1702–10.
4. Otten AM, Maas AH, Ottervanger JP, et al., for the Zwolle Myocardial Infarction Study Group. Is the difference in outcome between men and women treated by primary percutaneous coronary intervention age dependent? Gender difference in STEMI stratified on age. Eur Heart J Acute Cardiovasc Care 2013;2:334–41.
5. Akhter N, Milford-Beland S, Roe MT, Piana RN, Kao J, Shroff A. Gender differences among patients with acute coronary syndromes undergoing percutaneous coronary intervention in the American College of Cardiology–National Cardiovascular Data Registry (ACC-NCDR). Am Heart J 2009;157:141–8.
6. Hess CN, McCoy LA, Duggirala HJ, et al. Sexbased differences in outcomes after percutaneous coronary intervention for acute myocardial infarction: a report from TRANSLATE-ACS. J Am Heart Assoc 2014;3:e000523.
7. Briller J, The Feminine Mystique in Myocardial Infarction Associated Mortality J Am Coll Cardiol. 2019 Nov, 74 (19) 2390-2391.
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