Sex-Based Differences in Heart Failure Frailty Explored

MODEL RELEASED. Senior woman holding chest.
This study sought to characterize sex differences in heart failure physical frailty phenotypes.

Women with heart failure (HF) are significantly more likely to be physically frail compared with men with HF, according to research results published in Circulation: Heart Failure.

Because 1 of every 2 patients with HF is considered frail, and because there is a strong association between frailty and poor clinical outcomes, researchers sought to both characterize sex differences in physical frailty phenotypes in HF and identify distinguishing characteristics of physical frailty in HF.

Adult patients 21 years or older with New York Heart Association (NYHA) functional classification I-IV were included in the current study. Participants were recruited through both HF and general cardiology clinics at a single center in the Pacific Northwest between 2018 and 2020. Researchers collected sociodemographic data through a questionnaire, while pertinent clinical data were collected through a medical record review.

Physical frailty was measured via the frailty phenotype criteria adapted and used specifically for those with HF. These included unintentional weight loss, weakness, physical exhaustion, slowness, and low physical activity.

A total of 115 patients (56 women) were included in the cohort, most of whom had nonischemic HF. Just under half of patients—43%—had physical frailty, including more women than men (odds ratio [OR], 3.86). Other significant factors associated with frailty were a higher comorbidity burden, higher left ventricular ejection fraction (LVEF), HF with preserved ejection phenotype, lower hemoglobin, and not undergoing angiotensin-converting enzyme inhibitor (ACEi) or angiotensin II receptor blocker (ARB) therapy.

Results of a backward stepwise regression model showed that women had a 4.6 times greater odds of being physical frail vs men. Both type 2 diabetes and a lack of ACEi or ARB use were significant predictors of physical frailty. Women were more likely to meet criteria for weakness, slowness, physical exhaustion, and low physical activity (ORs, 2.43, 4.69, 5.46, and 2.34, respectively).

After stratifying for sex, investigators found that physical frail women had a higher overall burden of comorbidity, as well as more type 2 diabetes vs those who were not physically frail. Women who were physically frail also had significantly worse symptoms of dyspnea and sleep-related impairment and pain intensity. No significant differences in terms of body composition characteristics were noted.

Men who were physically frail had a higher overall comorbidity burden and were more likely to have type 2 diabetes and stage 3 chronic kidney disease vs men who were not physically frail. These men also had lower hemoglobin, worse dyspnea, and worse depressive symptoms. Physically frail men also had a significantly lower appendicular muscle mass index and a higher percent of body and trunk fat.

Study limitations include the racially homogenous cohort, the inclusion of primarily patients with HF with reduced ejection fraction and a nonischemic HF etiology, as well as a lack of generalizability to those living outside the study area and the small sample size.

“Physical frailty significantly affects more women compared with men with HF, even after adjusting for covariates,” the researchers concluded. “Future research is needed to further identify distinguishing characteristics of physical frailty from the biological level to the behavioral level among women and men with HF.”


Denfeld QE, Habecker BA, Camacho SA, et al. Characterizing sex differences in physical frailty phenotypes in heart failure. Circ Heart Fail. Published online August 25, 2021. doi:10.1161/circheartfailure.120.008076