Letter by Martin and Ahmad Regarding Article, “Characterizing Sex Differences in Physical Frailty Phenotypes in Heart Failure”

Background: Although women with heart failure (HF) are potentially more likely to be physically frail compared with men with HF, the underlying contributors to this sex difference are poorly understood. The purpose of this study was to characterize sex differences in physical frailty phenotypes in HF. Methods: We prospectively enrolled adults with class I–IV HF. Physical frailty was measured with the frailty phenotype criteria. Symptoms of dyspnea, sleep-related impairment, pain interference, depression, and anxiety were assessed. Body composition was measured using dual-energy x-ray absorptiometry. Simple comparative statistics and stepwise regression modeling were used. Results: The average age of the sample (n=115) was 63.6±15.7 years, 49% were women, and 73% had nonischemic cause. Forty-three percent of the sample was physically frail. Women had a 4.6 times greater odds of being physically frail compared with men, adjusting for covariates (odds ratio=4.63 [95% CI, 1.81–11.84], P =0.001). Both physically frail men and women were characterized by more type 2 diabetes, higher comorbidity burden, and worse dyspnea symptoms. Physically frail women had significantly worse symptoms compared with non–physically frail women but no difference in body composition characteristics. Physically frail men had significantly lower appendicular muscle mass, higher percent fat, lower hemoglobin, and more depressive symptoms compared with non–physically frail men. Conclusions: Women are significantly more likely to be physically frail compared with men in HF. Physical frailty in both women and men is characterized by comorbidities and worse symptoms; physical frailty in men is characterized by worse physiological characteristics.

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Sex differences in heart failure medications targeting the renin-angiotensin-aldosterone system

European Journal of Pharmacology ◽

10.1016/j.ejphar.2021.173961 ◽

2021 ◽

Vol 897 ◽

pp. 173961

Author(s):

Persoulla A. Nicolaou

Keyword(s):

Heart Failure ◽

Sex Differences ◽

Renin Angiotensin Aldosterone System ◽

Renin Angiotensin

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Sex differences in decompensated heart failure

Annals of Emergency Medicine ◽

10.1016/j.annemergmed.2004.07.326 ◽

2004 ◽

Vol 44 (4) ◽

pp. S100

Author(s):

H.M. Prendergast ◽

M. Latayan ◽

K. Reddy ◽

B. Bunney

Keyword(s):

Heart Failure ◽

Sex Differences ◽

Decompensated Heart Failure

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Despite Elderly Patient with Refractory Heart Failure, Her Physical Frailty was Dramatically Overcome by DOPPO Rehabilitation Program

Journal of Cardiac Failure ◽

10.1016/j.cardfail.2014.07.293 ◽

2014 ◽

Vol 20 (10) ◽

pp. S184

Author(s):

Akifumi Uehara ◽

Akihiro Yokoyama ◽

Kanako Oishi ◽

Yuki Izumi ◽

Satoru Abe ◽

...

Keyword(s):

Heart Failure ◽

Elderly Patient ◽

Rehabilitation Program ◽

Physical Frailty ◽

Refractory Heart Failure

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Sex Differences in the Association between Atrial Fibrillation and 90-Day Adverse Outcomes among Older Adults with Heart Failure: A Retrospective Cohort Study

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18052237 ◽

2021 ◽

Vol 18 (5) ◽

pp. 2237

Author(s):

Youn-Jung Son ◽

Da-Young Kim ◽

Mi Hwa Won

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

Older Adults ◽

Sex Differences ◽

Older Adult ◽

Hospital Readmission ◽

Older Patients ◽

Adverse Outcomes ◽

Prognostic Impact ◽

Male And Female

Sex differences in the prognostic impact of coexisting atrial fibrillation (AF) in older patients with heart failure (HF) have not been well-studied. This study, therefore, compared sex differences in the association between AF and its 90-day adverse outcomes (hospital readmissions and emergency room (ER) visits) among older adults with HF. Of the 250 older adult patients, the prevalence rates of coexisting AF between male and female HF patients were 46.0% and 31.0%, respectively. In both male and female older patients, patients with AF have a significantly higher readmission rate (male 46.0%, and female 34.3%) than those without AF (male 6.8%, and female 12.8%). However, there are no significant differences in the association between AF and ER visits in both male and female older HF patients. The multivariate logistic analysis showed that coexisting AF significantly increased the risk of 90-day hospital readmission in both male and female older patients. In addition, older age in males and longer periods of time after an HF diagnosis in females were associated with an increased risk of hospital readmission. Consequently, prospective cohort studies are needed to identify the impact of coexisting AF on short- and long-term outcomes in older adult HF patients by sex.

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Abstract 302: Sex Differences In Nonlinear Dynamics And Their Circadian Variation In Control Dogs And In A New Arrhythmogenic Canine Model Of Heart Failure

Circulation Research ◽

10.1161/res.115.suppl_1.302 ◽

2014 ◽

Vol 115 (suppl_1) ◽

Author(s):

Yujie Zhu ◽

Steven M Pogwizd

Keyword(s):

Nonlinear Dynamics ◽

Heart Failure ◽

Sex Differences ◽

Sex Difference ◽

Circadian Variation ◽

Holter Monitoring ◽

Canine Model ◽

Nonlinear Parameters ◽

Arrhythmogenic Substrate ◽

Males And Females

Introduction: Females can be more arrhythmogenic than males, and this sex difference can persist with development of chronic heart failure (CHF). The aim of this study was to investigate sex differences in the arrhythmogenic substrate in control dogs and in a new arrhythmogenic canine model of CHF. Methods: CHF was induced in 30 dogs by aortic insufficiency and aortic constriction. Holter monitoring assessed VT and PVCs from 30 dogs, as well as traditional HRV measures and nonlinear dynamics (including correlation dimension (CD), detrended fluctuations analysis α1 (DFAα1), and Shannon entropy (SE)) at baseline, 240 days (240d) and 720 days (720d) after CHF induction. Results: At baseline, females had lower LF/HF (0.27±0.03 vs 0.33±0.02, p=0.04), CD (1.60±0.17 vs 2.21±0.15, p=0.01), DFAα1 (0.62±0.03 vs 0.72±0.03, p=0.03), and SE (2.99±0.02 vs 3.10±0.03, p=0.03 vs males). Females lacked circadian variation in LF/HF, DFAα1, and SE while males had circadian variation in all of these. Of 11 dogs with frequent runs of VT and PVCs, 95% and 91% of total VT runs and total PVCs, respectively, were in females. With CHF, all these linear and nonlinear parameters progressively declined in males and females. CHF females had less decline in LF/HF than males so that by 720 days there was no more sex difference (0.24±0.06, 0.17±0.03 in females vs 0.22±0.05, 0.18±0.01 in males at 240d, 720d). However, for nonlinear parameters of CD, DFAα1, and SE, CHF females had lower values than males (CD: 1.56±0.21, 0.99±0.32 vs 1.87±0.24, 1.50±0.34; DFAα1: 0.51±0.05, 0.43±0.04 vs 0.54±0.07, 0.48±0.04; and SE 2.93±0.08, 2.76±0.08 vs 3.01±0.11, 2.91±0.04 in females vs males at 240d, 720d). With CHF, circadian variation in CD, DFAα1, and SE were lost in both males and females. Conclusions: There are sex differences in the arrhythmogenic substrate in control dogs and in this new arrhythmogenic canine model of moderate CHF. At baseline, females have lower sympathetic stimulation, reduced cardiac chaos, and loss of circadian variation in nonlinear dynamics. With CHF, sex differences in nonlinear dynamics persist; this reflects a loss of complexity and fractal properties that could contribute to increased arrhythmias in female CHF dogs.

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Mineralocorticoid receptors and the heart, multiple cell types and multiple mechanisms: a focus on the cardiomyocyte

Clinical Science ◽

10.1042/cs20130050 ◽

2013 ◽

Vol 125 (9) ◽

pp. 409-421 ◽

Cited By ~ 14

Author(s):

Laura A. Bienvenu ◽

Melissa E. Reichelt ◽

Lea M. D. Delbridge ◽

Morag J. Young

Keyword(s):

Heart Failure ◽

Cardiovascular Disease ◽

Sex Differences ◽

Side Effects ◽

Therapeutic Option ◽

Cell Types ◽

Receptor Activation ◽

Cardiac Events ◽

Cardiac Tissues ◽

Targeted Interventions

MR (mineralocorticoid receptor) activation in the heart plays a central role in the development of cardiovascular disease, including heart failure. The MR is present in many cell types within the myocardium, including cardiomyocytes, macrophages and the coronary vasculature. The specific role of the MR in each of these cell types in the initiation and progression of cardiac pathophysiology is not fully understood. Cardiomyocyte MRs are increasingly recognized to play a role in regulating cardiac function, electrical conduction and fibrosis, through direct signal mediation and through paracrine MR-dependent activity. Although MR blockade in the heart is an attractive therapeutic option for the treatment of heart failure and other forms of heart disease, current antagonists are limited by side effects owing to MR inactivation in other tissues (including renal targets). This has led to increased efforts to develop therapeutics that are more selective for cardiac MRs and which may have reduced the occurrence of side effects in non-cardiac tissues. A major clinical consideration in the treatment of cardiovascular disease is of the differences between males and females in the incidence and outcomes of cardiac events. There is clinical evidence that female sensitivity to endogenous MRs is more pronounced, and experimentally that MR-targeted interventions may be more efficacious in females. Given that sex differences have been described in MR signalling in a range of experimental settings and that the MR and oestrogen receptor pathways share some common signalling intermediates, it is becoming increasingly apparent that the mechanisms of MRs need to be evaluated in a sex-selective manner. Further research targeted to identify sex differences in cardiomyocyte MR activation and signalling processes has the potential to provide the basis for the development of cardiac-specific MR therapies that may also be sex-specific.

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