Sex-specific differences drive temporal trends and outcomes of patients hospitalized for heart failure in Germany

Abstract

Background

Despite remarkable improvements in treatment of cardiovascular disease, heart failure (HF) is still characterized by high mortality rate. Sex-specific differences in HF have been described, but underlying reasons are widely unexplored.

Methods

The nationwide German inpatient sample (2005–2016) was used for this sex-specific analyses. Temporal trends on hospitalizations, mortality, and treatments were analysed and independent predictors of adverse outcomes identified.

Results

The analysis comprises 4,538,977 hospitalizations due to HF (52.0%women) in Germany (2005–2016). Although women were older (median 82(IQR75–87) vs.76(69–82),P < 0.001), coronary artery disease (CAD, 50.3% vs. 30.7%,P < 0.001) was more prevalent in men, who were more often treated with percutaneous intervention (PCI;3.4% vs. 1.4%,P < 0.001) and implantable cardioverter-defibrillator (2.2% vs. 0.5%,P < 0.001). In-hospital mortality was significantly lower in men than in women (8.9% vs.10.2%,P = 0.001) and was reduced in patients who received PCI or implantation of an implantable cardioverter-defibrillator.

While total numbers of hospitalizations between 2005 and 2016 increased in both men (β-estimate 7185.71 (95%CI 6502.23 to 7869.18),P < 0.001) and women (β-estimate 5297.60 (95%CI 4557.37 to 6037.83),P < 0.001) as well as almost all comorbid co-conditions, in-hospital mortality rate decreased more distinctly in women (β-estimate −0.41 (95%CI −0.42 to −0.39),P < 0.001) compared to men (β-estimate −0.29 (95%CI −0.30 to −0.27),P < 0.001).

Conclusions

Interventional treatments of HF were associated with improved outcomes and equally beneficial for both sexes. However, they were more often used in male HF patients, in which CAD is significantly more frequent than in female HF patients. This may explain the higher case fatality rate of HF in females.

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 treatments^7,12,13 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.