Review ArticleSex-specific differences drive temporal trends and outcomes of patients hospitalized for heart failure in Germany
Introduction
Heart failure (HF) is a pandemic health problem which affects approximately 1–2% of the Europeans1 and >37 million people worldwide.2 Although incidence rates declined significantly in women and remained widely unchanged in men,3 the prevalence of HF is still increasing. This has been mainly attributed to an ageing population and advances in diagnostics and treatments especially concerning its precursors (e.g., myocardial infarction (MI) and coronary artery disease (CAD))4 resulting in an estimated prevalence of >10% in patients aged ≥70 years.5 Due to the high number of comorbidities associated with HF (almost 79% of patients with HF have three or more comorbidities)6 and the diverse and often unspecific symptoms at clinical presentation (e.g. shortness of breath), its diagnosis remains challenging.1
Sex-specific differences in cardiovascular diseases (CVD) are well known.7., 8., 9., 10., 11. Males have an increased risk to develop CVD (in particular CAD7 and stroke8). Although males and females share most CVD risk factors (CVRF), the importance of these CVRF in both genders seems to be different.10 Sex-specific differences in CVD are not well understood, and data on the outcome after therapies are mostly derived from largely male dominated studies.7,10,12 Sex-specific differences and especially the lack of awareness regarding these differences may result in an underuse of live-saving treatments7,12,13 and potentially lead to a less favorable outcome in females.9,12,13
In HF, substantial sex differences in the clinical features have been reported, specifically with regard to clinical characteristics, etiology, treatment, and outcome.14,15 Sex-specific differences have been described with regard to established CVRF contributing to HF burden of the population.16,17 Moreover, evidence suggests that hospitalizations due to HF are more frequent in men18 whereas women are hospitalized in more advanced stages of the disease.19 Female HF patients survive longer than their male counterparts. Males showed a poorer outcome in short-term but also in long-term survival.14,20,21
Despite this increasing body of evidence regarding sex-specific differences in CVD, current available data about sex-specific disparities in HF are controversial and results of very large nationwide real-world study samples are limited. Women are frequently underrepresented in clinical HF trials and data on the effectiveness of HF interventions in women are therefore difficult to interpret. Since life-threatening interventional treatments in CVD are underused in several CVDs,7,12,13 sex-specific data about the use of these treatments in HF patients is of outstanding interest to improve treatment strategies in HF.
With the present study we intended to provide temporal trends of treatments and outcomes of patients hospitalized for HF hospitalization in Germany between 2005 and 2016 specifically accounting for sex differences and analyze real-world data without selection bias regarding an under-representation of female HF patients.
Section snippets
Data source
The German nationwide inpatient sample (diagnosis related groups [DRG] statistic) was used for this study and the analyses (source: Research Data Center (RDC) of the Federal Statistical Office and the Statistical Offices of the federal states, DRG Statistics 2005–2016, and own calculations). For these analyses, all inpatients with a main diagnosis of HF (ICD-code I50) hospitalized in Germany between 2005 and 2016 were included. For further information see the Supplementary material.
Study endpoints and in-hospital adverse events
The primary
Statistical methods
Statistical analyses are described in the Supplementary material.
Results
Overall, 4,538,977 hospitalizations of patients due to HF between 2005 and 2016 in Germany were included in this study and analysed. Among these, 2,362,496 (52.0%) of the hospitalizations were female and 2,176,481 (48.0%) male patients.
The total numbers of hospitalizations due to HF increased significantly over time in males from 144,378 in 2005 to 219,835 in 2016 (β-estimate 7185.71 (95%CI 6502.23 to 7869.18), P < 0.001 increase per year) as well as in females from 169,852 in 2005 to 225,302
Discussion
The present analysis of the nationwide German inpatient sample with included 4,538,977 hospitalizations due to HF outlines sex-specific temporal trends and important differences between male and female HF patients.
The main findings of our study comprise the following:
- I)
We observed a remarkable increase of hospitalizations in both sexes between 2005 and 2016 with a higher absolute number of hospitalizations in women.
- II)
While the number of hospitalizations increased, the LOS and the mortality rates
Limitations
There are some limitations regarding our study that require consideration: First, the study results are based on ICD and OPS discharge codes of hospitalized patients, which might be under-reported/under-coded. Second, data about the administration of HF standard medications are not available in the dataset of the Federal Statistical Office of Germany. Fourth, we could only provide data for the LOS, but not for the later follow-up.
Conclusions
The increasing number of HF hospitalizations in both sexes (2005–2016) and the high mortality rates indicate that HF remains a major challenge for the health care system and health care providers. Although the prevalence of comorbid conditions and CVRF increased over time, in-hospital mortality decreased in both sexes. There are substantial sex-specific differences regarding CVRF profile, etiologies, treatments and outcomes. Men showed substantial higher rate of CAD, were more often treated
Funding
This study was supported by the German Federal Ministry of Education and Research (BMBF 01EO1503); institutional grant for the Center for Thrombosis and Hemostasis. The authors are responsible for the contents of this publication. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Availability of data and material
The German nationwide inpatient sample (diagnosis related groups [DRG] statistic) was used for this study and the analyses. Analyses were performed on our behalf by the Research Data Center of the Federal Statistical Office and the Statistical Offices of the federal states (source: Research Data Center (RDC) of the Federal Statistical Office and the Statistical Offices of the federal states, DRG Statistics 2005–2016, and own calculations), in Wiesbaden (Germany) and the aggregated statistics
Code availability
Diagnoses are coded according to ICD-10-GM (International Classification of Diseases, 10th Revision with German Modification) and diagnostical, surgical and interventional procedures with OPS codes (surgery, diagnostic and procedures codes [Operationen- und Prozedurenschlüssel]). The software SPSS® (version 20.0; SPSS Inc., Chicago, Illinois) was used for computerised analysis. P values of <0.05 (two-sided) were considered to be statistically significant.
Author contributions
All author(s) were involved in the conception and design of the study and analysis and interpretation of the data; all authors contributed in drafting and revising the paper critically for intellectual content and gave final approval of the version to be published and agree to be accountable for all aspects of the work.
Declaration of competing interest
The authors report no proprietary or commercial interest in any product mentioned or concept discussed in this article. SG, MAO, CJL, TM and KK report no conflict of interest. LH reports having received lecture honoraria from MSD. PW reports having received consultancy and lecture honoraria from Abbot Vascular, AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi-Sankyo and Novartis. TG reports having received consultancy and lecture honoraria from Abbott Vascular and Boston Scientific.
Acknowledgements
We thank the Federal Statistical Office of Germany (Statistisches Bundesamt, DEStatis) for providing the data/results and the kind permission to publish these data/results (source: RDC of the Federal Statistical Office and the Statistical Offices of the federal states, DRG Statistics 2005–2016, own calculation.
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