Gender and Survival in Patients With Heart Failure
Gender and Survival in Patients With Heart Failure
Aim The aim of this study was to investigate the relationship between gender and survival of patients with heart failure, using data from both randomized trials and observational studies, and the relative contribution of age, left ventricular systolic function, aetiology, and diabetes to differences in prognosis between men and women.
Methods and results Data from 31 studies (41 949 patients; 28 052 men, 13 897 women) from the Meta-Analysis Global Group In Chronic Heart Failure (MAGGIC) individual patient meta-analysis were used. We performed survival analysis to assess the association of gender with mortality, adjusting for predictors of mortality, including age, reduced or preserved ejection fraction (EF), and ischaemic or non-ischaemic aetiology. Women were older [70.5 ( standard deviation 12.1) vs. 65.6 (standard deviation 11.6) years], more likely to have a history of hypertension (49.9% vs. 40.0%), and less likely to have a history of ischaemic heart disease (46.3% vs. 58.7%) and reduced EF (62.6% vs. 81.6%) compared with men. During 3 years follow-up, 3521 (25%) women and 7232 (26%) men died. After adjustment, male gender was an independent predictor of mortality, and the better prognosis associated with female gender was more marked in patients with heart failure of non-ischaemic, compared with ischaemic, aetiology (P-value for interaction = 0.03) and in patients without, compared with those with, diabetes (P-value for interaction <0.0001).
Conclusion This large, individual patient data meta-analysis has demonstrated that survival is better for women with heart failure compared with men, irrespective of EF. This survival benefit is slightly more marked in non-ischaemic heart failure but is attenuated by concomitant diabetes.
While the populations of patients with heart failure (HF) studied in clinical trials are dominated by men, in routine clinical practice half or more of all patients with HF are women. Whether prognosis differs for men and women with HF is controversial. Many studies have associated female sex with better survival, although several failed to identify such an association and one study has reported worse prognosis for women. Moreover, in HF populations, sex is strongly associated with a number of clinical variables that influence prognosis such as age, aetiology, and in particular left ventricular ejection fraction (EF), associations which may confound the independent effect of sex on survival. Assessment of the relationship between sex and prognosis is further complicated by the relatively small numbers of women in randomized, controlled trials involving patients with HF, in large part due to the exclusion from these trials of older patients and patients with HF with preserved EF, both of which are more prevalent among women with HF.
The potential reasons for differences in survival for men and women with HF are uncertain. Differences in survival between men and women with HF fail to show a consistent relationship to either aetiology (ischaemic or non-ischaemic) or to whether patients had reduced or preserved EF. The greater prevalence of diabetes and the relative under-use of evidence-based therapies among women compared with men with HF may theoretically contribute to worse prognosis for women. However, HF with preserved EF is more common among women than men, and this may be expected to lead to better survival for these patients.
The main results from the Meta-Analysis Global Group In Chronic Heart Failure (MAGGIC) meta-analysis demonstrated that HF patients with preserved EF have a lower risk of death than patients with reduced EF, regardless of age, sex, and aetiology of HF. The main analysis also showed that male sex was an independent predictor of mortality [hazard ratio (HR) 1.23, 95% confidence interval (CI) 1.18–1.28]. The aim of the current analysis was to assess comprehensively the relationship between sex and survival in patients with HF, using a large individual patient data set. Our hypothesis was that age, left ventricular EF, aetiology, and diabetes would have a different impact on survival for men and women with HF.
Abstract and Introduction
Abstract
Aim The aim of this study was to investigate the relationship between gender and survival of patients with heart failure, using data from both randomized trials and observational studies, and the relative contribution of age, left ventricular systolic function, aetiology, and diabetes to differences in prognosis between men and women.
Methods and results Data from 31 studies (41 949 patients; 28 052 men, 13 897 women) from the Meta-Analysis Global Group In Chronic Heart Failure (MAGGIC) individual patient meta-analysis were used. We performed survival analysis to assess the association of gender with mortality, adjusting for predictors of mortality, including age, reduced or preserved ejection fraction (EF), and ischaemic or non-ischaemic aetiology. Women were older [70.5 ( standard deviation 12.1) vs. 65.6 (standard deviation 11.6) years], more likely to have a history of hypertension (49.9% vs. 40.0%), and less likely to have a history of ischaemic heart disease (46.3% vs. 58.7%) and reduced EF (62.6% vs. 81.6%) compared with men. During 3 years follow-up, 3521 (25%) women and 7232 (26%) men died. After adjustment, male gender was an independent predictor of mortality, and the better prognosis associated with female gender was more marked in patients with heart failure of non-ischaemic, compared with ischaemic, aetiology (P-value for interaction = 0.03) and in patients without, compared with those with, diabetes (P-value for interaction <0.0001).
Conclusion This large, individual patient data meta-analysis has demonstrated that survival is better for women with heart failure compared with men, irrespective of EF. This survival benefit is slightly more marked in non-ischaemic heart failure but is attenuated by concomitant diabetes.
Introduction
While the populations of patients with heart failure (HF) studied in clinical trials are dominated by men, in routine clinical practice half or more of all patients with HF are women. Whether prognosis differs for men and women with HF is controversial. Many studies have associated female sex with better survival, although several failed to identify such an association and one study has reported worse prognosis for women. Moreover, in HF populations, sex is strongly associated with a number of clinical variables that influence prognosis such as age, aetiology, and in particular left ventricular ejection fraction (EF), associations which may confound the independent effect of sex on survival. Assessment of the relationship between sex and prognosis is further complicated by the relatively small numbers of women in randomized, controlled trials involving patients with HF, in large part due to the exclusion from these trials of older patients and patients with HF with preserved EF, both of which are more prevalent among women with HF.
The potential reasons for differences in survival for men and women with HF are uncertain. Differences in survival between men and women with HF fail to show a consistent relationship to either aetiology (ischaemic or non-ischaemic) or to whether patients had reduced or preserved EF. The greater prevalence of diabetes and the relative under-use of evidence-based therapies among women compared with men with HF may theoretically contribute to worse prognosis for women. However, HF with preserved EF is more common among women than men, and this may be expected to lead to better survival for these patients.
The main results from the Meta-Analysis Global Group In Chronic Heart Failure (MAGGIC) meta-analysis demonstrated that HF patients with preserved EF have a lower risk of death than patients with reduced EF, regardless of age, sex, and aetiology of HF. The main analysis also showed that male sex was an independent predictor of mortality [hazard ratio (HR) 1.23, 95% confidence interval (CI) 1.18–1.28]. The aim of the current analysis was to assess comprehensively the relationship between sex and survival in patients with HF, using a large individual patient data set. Our hypothesis was that age, left ventricular EF, aetiology, and diabetes would have a different impact on survival for men and women with HF.
