A majority of patients with heart failure (HF) experience HF symptoms, such as dyspnea, fatigue, and/or edema, in the United States and in Korea,1–4 which are frequently associated with poor health-related quality of life (HRQOL) and high rates of hospitalization.3,5 More severe HF symptoms were significantly associated with poorer HRQOL, and HF symptoms alone explained 56% of the variance in HRQOL.5 More severe HF symptoms were also significantly associated with shorter event-free survivals (odds ratio, 1.769; P = .014).5 Thus, HF symptoms should be managed appropriately to improve HRQOL and to reduce high rates of hospitalizations.
To prevent or manage HF symptoms appropriately, symptom status (overall presence, frequency, severity, and distress of HF symptoms)5 needs to be explored in detail, and factors associated with HF symptoms need to be determined and managed. Although the most common HF symptoms have been reported frequently,2,3 more detailed information on frequencies, severity, and distress of individual HF symptom status has not been frequently reported, especially in male and female patients separately.4 We developed a theoretical framework from the literature for factors affecting HF symptoms (Figure). In the theoretical framework, 4 categories of multidimensional factors, including sociodemographic, clinical, psychological, and behavioral, are associated with HF symptoms. For example, older age and female sex (sociodemographic)6,7; higher body mass index, more comorbidities, lower levels of left ventricular ejection fraction (LVEF), and treatment with diuretics (clinical)1,5,8; depressive symptoms and lower levels of perceived control (psychological)1,5,6,9; and higher consumption of sodium (behavioral)9 have been associated with more severe HF symptoms.
Some literature suggests sex differences in HF symptoms and also in the factors associated with them based on statistical differences in the variables between male and female patients. In symptom status, female patients show more severe HF symptoms and more improvement in dyspnea than male patients.7,10 There were sex differences in those factors affecting HF symptoms, such as age, comorbidities, medication, and depressive symptoms. Male patients are frequently younger than female patients.10,11 More male patients have higher body mass index and a history of myocardial infarction than female patients, whereas more female patients have diabetes and hypertension than male patients.12,13 A combination of angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers and β-blockers was more frequently prescribed in male than female patients.14 Female patients commonly show a higher prevalence or severity of depressive symptoms than male patients.11 All older age, less frequent prescription of HF medications, and more depressive symptoms might lead to more severe HF symptoms in female patients than male patients.6,11,14 Overall, these findings suggest sex differences in both HF symptoms and factors associated with HF symptoms, which imply the needs for different symptom management strategies for male and female patients. However, few researchers investigated sex differences in HF symptoms and factors associated with them. Therefore, the purpose of this study was to examine both HF symptom status and the possible multidimensional factors associated with HF symptoms in male and female patients with HF, based on our proposed theoretical model (Figure).
Study Design and Setting
This was a secondary analysis of an observational study that was conducted using a convenience sample from 3 medical centers in South Korea to examine multiple domains of cognitive function and the relationships to physical function in patients with HF.15
As information on the sample of the parent study has been presented elsewhere,15 the brief information is presented here. In the parent study, the inclusion criteria were a confirmed diagnosis of HF with reduced systolic function (LVEF: male, ≤52%; female, ≤54%)16 and age of 21 years or older. The exclusion criteria were the presence of severe cognitive or psychiatric issues and fatal comorbidities (eg, cancer). Eligible patients were recruited through referrals from the clinicians at the inpatient and outpatient clinics of the 3 medical centers.
The approval of the parent study was obtained from the relevant institutional review boards. All research participants provided written informed consent. The investigation conforms with the principles outlined in the Declaration of Helsinki.
Data Collection and Measures
The research team collected data on the possible factors associated with HF symptoms, including sociodemographic factors (ie, age and sex), clinical factors (ie, body mass index, comorbidities, medication, and LVEF), psychological factors (ie, depressive symptoms and perceived control), and a behavioral factor (ie, self-care maintenance), and HF symptoms between June 2015 and May 2016. The team also collected data on marital status, education, New York Heart Association functional class, and HF etiology to describe the sample characteristics. Comorbidities were assessed by Charlson Comorbidity Index,17 with a possible score of the weighted values ranging from 0 to 34 with higher scores indicating more comorbid conditions.
With the exception of LVEF, data on all sociodemographic and clinical characteristics were collected using the standardized sociodemographic and clinical questionnaires through patient interviews or medical record reviews. Standard 2-dimensional and Doppler echocardiography were used to determine the LVEF.
Depressive symptoms were measured using the Patient Health Questionnaire-9.18 Possible total scores range from 0 to 27, with higher scores indicating more severe depressive symptoms.18 Reliability and validity have been supported in this population.18 The Cronbach α in the current study was .86.
Perceived control was measured using the Control Attitudes Scale-Revised.19 The possible total scores range from 8 to 40, with higher scores indicating higher levels of perceived control. Reliability and validity have been supported in this population.19 The Cronbach α in the current study was .79.
Self-care maintenance was measured using the Maintenance Subscale of the Self-Care of Heart Failure Index version 6.2.20 Possible total scores range from 0 to 100, with higher scores indicating higher levels of self-care.20 Reliability and validity have been supported.20,21 The Cronbach α in the current study was .67.
Heart failure symptoms were measured by the Korean version of the Symptom Status Questionnaire-Heart Failure.22 This instrument consists of 7 combined items to assess the presence, frequency, severity, and distress associated with the 7 common HF symptoms, such as dyspnea during daytime, dyspnea when lying down, fatigue, chest pain, edema, sleeping difficulties, and dizziness. Possible total scores range from 0 to 84, with higher scores indicating more severe HF symptoms. Reliability and validity have also been supported.22 The Cronbach α in the current study was .76.
Descriptive statistics were used to describe the characteristics of male and female patients. In addition, sample characteristics and presence of each individual symptom in male and female patients were compared using t tests for continuous variables and χ2 tests for categorical variables. The frequency, severity, and distress of each individual symptom in both sexes were compared using Mann-Whitney U tests. Factors associated with HF symptoms in both sexes were examined using multiple regression analyses with the stepwise method (P values for entry and removal were .05 and .10, respectively.). Data from 70 male patients and 49 female patients were included in the analyses. In Fan and Meng's1 study, depressive symptoms and LVEF were significantly associated with HF symptoms and explained 33% of the variance in HF symptoms (effect size, 0.49). Although we included more independent variables, we conservatively used the effect size of 0.49 from the previous study. Considering an effect size of 0.49, a β/α ratio of 1, sample sizes of 70 for male and 49 for female, and 10 independent variables, the estimated power for male and female patients was 97% and 92%, respectively (G*Power 3.1.5).23 Two-tailed tests with a significance level less than .05 were used for all analyses.
The sample characteristics of the 70 male and 49 female patients are presented in Table 1. Male patients had higher levels of education and less severe depressive symptoms than female patients. More male patients were married, had New York Heart Association functional class I or II, and had ischemic HF.
Male patients had less severe HF symptoms than female patients (Table 1). The most common HF symptom in both male and female patients was fatigue (54.3% vs 69.4%), but the frequency, severity, and distress in several individual symptoms differed by sex (Table 2). In male patients, the symptoms most frequently occurring after fatigue were sleeping difficulty, dyspnea during daytime, dizziness, and chest pain; in female patients, these were dyspnea during daytime, sleeping difficulty, edema, and dizziness. In the presence of individual HF symptoms, edema was the only individual HF symptom that more female patients experienced than male patients. In the frequency and severity of the individual HF symptoms, dyspnea during daytime, fatigue, and edema occurred less frequently with a lower severity in male patients than in female patients. In the distress associated with individual HF symptoms, male patients experienced less distress due to fatigue and edema than female patients.
There were similarities and differences in the factors associated with HF symptoms in male and female patients (Table 3). In both sexes, less severe depressive symptoms were associated with less severe HF symptoms. In addition to depressive symptoms, in male patients, fewer comorbidities, prescription of diuretics, and higher levels of perceived control were associated with less severe HF symptoms, and all these factors explained 68.8% of the variance in HF symptoms. In female patients, depressive symptoms alone explained 68.6% of the variance in HF symptoms. The R2 and adjusted R2 in men (0.688 vs 0.669) and women (0.686 vs 0.679) were similar.
The findings of this study demonstrate the sex differences in HF symptoms and factors associated with HF symptoms, which imply that different symptom management strategies may be needed for male and female patients. Male patients had less severe HF symptoms than female patients according to their overall symptom status and also the frequency, severity, and/or distress of several individual symptoms. In female patients, only depressive symptoms explained approximately 69% of the variance in HF symptoms, indicating the considerable role of depressive symptoms in HF symptom status. On the other hand, in male patients, 2 psychological and 2 clinical factors in the model explained also approximately 69% of the variance in HF symptoms.
Those variable(s) in each model considerably explained HF symptoms in both male and female patients with HF. To our knowledge, both this detailed information on individual HF symptom status and factors affecting HF symptoms in each of male and female patients have not been reported in previous studies, and our findings show some important targets for effective interventions in both male and female patients with HF to improve HF symptoms.
Although the most common HF symptoms in both male and female patients with HF were similar, there were some sex differences in individual HF symptom status, including frequency, severity, and distress. In both male and female patients, fatigue and dyspnea during daytime were the most common HF symptoms, which was similar to the findings from previous studies.2,3 However, in the current study, female patients experienced more frequent, severe, and distressful dyspnea during daytime, fatigue, and edema than male patients did. In previous studies, the relationships between sex and HF symptoms were inconsistent. A previous HF study reported that female patients showed more severe HF symptoms than male patients.7 In other studies, there were no sex differences in HF symptoms24 or in baseline dyspnea and edema,10 but female sex was a factor affecting improvement of moderate or severe dyspnea,10 and the relationships between left ventricular size and HF symptoms in male and female patients was opposite.24 Larger left ventricular size was associated with better HF symptoms in female patients but was associated with worse HF symptoms in male patients.24 Thus, further studies are needed to examine sex differences and the mechanisms in individual symptoms. The current study presented sex differences in the frequency, severity, and distress of several individual HF symptoms, which have rarely been reported. Our findings suggest that clinicians need to assess individual HF symptoms more in-depth in both male and female patients, especially dyspnea, fatigue, and edema in female patients.
There were also sex differences in the factors associated with HF symptoms. The only factor that was significantly associated with HF symptoms in both male and female patients was depressive symptoms. The strong association between depressive symptoms and HF symptoms in both sexes was consistent with that in previous studies.1,5,6,9 In female patients, although only depressive symptoms were associated with HF symptoms, depressive symptoms explained almost 69% of the variance in HF symptoms. However, in male patients, 4 factors were significantly associated with HF symptoms and explained the same amount of variance in HF symptoms (69%). Sex differences in factors associated with HF symptoms may be due to sex differences in the HF symptom status and also a very strong association between depressive symptoms and HF symptoms in female patients. Both HF and depressive symptom instruments assessed fatigue, which may have, in part, affected the relationships examined in the current study. However, the HF symptom instrument in the current study assessed the frequency, severity, and distress of fatigue, whereas the depressive symptom instrument assessed only the frequency. Although depressive symptoms are highly prevalent in both male and female patients with HF,11 depressive symptoms in female patients are more severe than those in male patients.11 Thus, clinicians need to assess and manage depressive symptoms in both sexes, especially in female patients, to improve HF symptoms.
In male patients, more factors were significantly associated with HF symptoms. Higher levels of perceived control were associated with less severe HF symptoms. In this sample, the levels of perceived control in male and female patients were similar (28.00 and 27.46, respectively) and comparable with those observed in male and female patients with HF in a previous study (29.4).25 In 1 study,6 perceived control at baseline predicted HF symptoms at 3 months, whereas in another study,9 perceived control was not associated with HF symptoms. Thus, further studies are needed to examine their relationships in both male and female patients. Fewer comorbidities were also associated with less severe HF symptoms in male patients, which is consistent with the significant association between comorbidities and HF symptoms in the total sample of male and female patients in a previous HF study.5 Common comorbidities in patients with HF, such as chronic obstructive lung disease and cancer, can worsen common HF symptoms, including dyspnea and fatigue.26,27 Despite no sex differences in the prescription of medication, prescription of diuretics was associated with less severe HF symptoms only in male patients. No prescription of diuretics and not taking diuretics may lead to fluid retention, which causes development or worsening of HF symptoms, such as dyspnea, fatigue, and edema.28 The reason for no relationship between prescription of diuretics and HF symptoms in female patients may be because they more adhere to a sodium-restricted diet than male patients, which may reduce the effects of diuretics on HF symptoms in female patients,29 and the strong association of depressive symptoms with HF symptoms in female patients. Thus, clinicians should consider perceived control, comorbidities, and medications in patients with HF, especially in male patients, to manage HF symptoms effectively.
The findings of this study suggest that the recognition and management of psychological factors, such as perceived control and/or depressive symptoms, are critical for both male and female patients in improving HF symptoms. Depressive symptoms are the most commonly observed psychological issues in patients with HF, but they are not recognized and managed appropriately. For example, approximately 43% of patients with HF had depressive symptoms, but only 23% had a diagnosis of depression.30 Although almost 50% of patients with HF had depressive symptoms, only 26% took antidepressants.11 More importantly, although 33% of patients with HF took antidepressants, more than 64% still had mild to moderate depressive symptoms.30 These findings and the strong relationship between psychological factors and HF symptoms in the current study suggest that clinicians need to assess and manage depressive symptoms, perceived control, and HF symptoms more comprehensively. Complementary alternative medicine, such as meditation, has been shown to reduce occurrence of depressive symptoms and HF symptoms31,32 and improve perceived control.32
There are some limitations. Self-care was assessed using a subjective self-report instrument with suboptimal level of reliability, which might differ from the actual self-care,33 and both HF symptom and depressive symptom instruments assessed frequency of lack of energy, which might impact the relationships examined. Some variables, such as sodium intake and medication adherence, that can affect HF symptoms could not be included. Causal relationships among all the variables in the theoretical framework could not be tested in this study and can be tested in prospective studies using structural equation modeling. In future studies, sex differences and the mechanisms can be examined more comprehensively using interaction terms.
There were sex differences in HF symptom status and factors associated with HF symptoms. Although fatigue was the most common HF symptom in both sexes, male patients experienced several individual symptoms less frequently with lower levels of severity and distress than female patients did. Depressive symptoms in female patients and 4 psychological and clinical factors in male patients explained considerable amount of the variance in HF symptoms. Clinicians and researchers need to develop effective interventions for each sex to recognize and manage the relevant factor(s) to improve HF symptoms. Further studies are needed to test all the suggested relationships among all the variables in the theoretical framework in prospective studies and also gender differences using interaction terms.
What's New and Important?
- There were sex differences in HF symptom status: Male patients had less severe HF symptoms than female patients according to their overall symptom status and also the frequency, severity, and/or distress of several individual symptoms.
- There were sex differences in factors associated with HF symptoms: Less severe depressive symptoms alone in female patients were associated with HF symptoms, whereas less severe depressive symptoms, higher levels of perceived control, fewer comorbidities, and use of diuretics in male patients were significantly associated with HF symptoms.
- Although the findings only partially supported the associations of some independent variables with the dependent variable in the theoretical framework, those variable(s) in each model approximately explained 69% of the variance in HF symptoms in both male and female patients.
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