Author + information
- Received February 12, 2019
- Revision received March 13, 2019
- Accepted March 21, 2019
- Published online May 27, 2019.
- Davide Stolfo, MDa,b,∗ (, )
- Alicia Uijl, MSca,c,
- Ola Vedin, MD, PhDd,
- Anna Strömberg, PhDe,
- Ulrika Ljung Faxén, MD, PhDa,f,
- Giuseppe M.C. Rosano, MD, PhDg,
- Gianfranco Sinagra, MDb,
- Ulf Dahlström, MD, PhDe and
- Gianluigi Savarese, MD, PhDa,∗∗ ()
- aDivision of Cardiology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden
- bDivision of Cardiology, Cardiovascular Department, Azienda Sanitaria Universitaria Integrata di Trieste, Trieste, Italy
- cJulius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
- dDepartment of Medical Sciences, Uppsala University, Uppsala, Sweden. Clinical Development, Boehringer Ingelheim, Stockholm, Sweden
- eDepartment of Medical and Health Sciences and Department of Cardiology, Linköping University, Linköping, Sweden
- fPerioperative Medicine and Intensive Care, Karolinska University Hospital, Stockholm, Sweden
- gCentre for Clinical and Basic Research, Department of Medical Sciences, IRCCS San Raffaele Pisana Rome, Italy
Objectives This study assessed sex-related differences in a large cohort of unselected patients with heart failure (HF) across the ejection fraction (EF) spectrum.
Background Females are under-represented in randomized clinical trials. Potential sex-related differences in HF may question the generalizability of trials.
Methods In the Swedish Heart Failure Registry population multivariate Cox and logistic regression models were fitted to investigate differences in prognosis, prognostic predictors, and treatments across males and females.
Results Of 42,987 patients, 37% were females (55% with HF with preserved EF [HFpEF], 39% with HF with mid-range EF [HFmrEF], and 29% with HF with reduced EF [HFrEF]). Females were older and more symptomatic and more likely to have hypertension and kidney disease but less likely to have diabetes and ischemic heart disease. After adjustments, females were more likely to use beta-blockers and digoxin but less likely to receive HF device therapy. Crude mortality/HF hospitalization rates for HFpEF (hazard ratio [HR]: 1.16) and HFmrEF (HR: 1.14) were significantly higher in females but lower in females with HFrEF (HR: 0.95). After adjustments, the risk was significantly lower in females regardless of EF (HR: 0.80 in HFrEF, HR: 0.91 in HFmrEF, and HR: 0.93 in HFpEF). The main sex-related differences in prognostic predictors concerned diabetes in HFrEF and anemia in HFmrEF.
Conclusions Males and females with HF showed different characteristics across the EF spectrum. Males reported a lower crude risk of mortality/morbidity in HFpEF and HFmrEF but higher risk of HFrEF, although after adjustments, prognosis was better in females regardless of EF. The observed sex-related differences highlight the need for an adequate representation of females in HF randomized controlled trials to improve generalizability.
- heart failure with mid-range ejection fraction
- heart failure with preserved ejection fraction
- heart failure with reduced ejection fraction
- heart failure
Dr. Vedin is an employee of Boehringer Ingelheim AB, Sweden; and has received consulting and lecture fees from Alnylam, Boehringer Ingelheim, Fresenius Medicare, Merck Sharpe and Dohme, Novartis, Orion Pharma, Servier, and Vifor Pharma. Dr. Dahlström has received grants from AstraZeneca; and has received consulting and lecture fees from AstraZeneca and Novartis. Dr. Savarese has received research grants from Boehringer Ingelheim, Merck Sharp and Dohme, and AstraZeneca; and has received honoraria from Vifor, Servier, AstraZeneca, and Roche. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received February 12, 2019.
- Revision received March 13, 2019.
- Accepted March 21, 2019.
- 2019 American College of Cardiology Foundation
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