Psychological distress as a crucial determinant for quality of life in patients with noncardiac chest pain in Central China: A cross-sectional study.

Increased psychiatric comorbidity, predominantly anxiety and depressive symptoms, and lower quality of life (QoL) are associated with noncardiac chest pain (NCCP). We aimed to investigate the roles of anxiety and depression in the impaired QoL of NCCP patients in Central China.In this hospital-based cross-sectional study, 200 consecutive patients who complained of chest pain with normal coronary angiography were enrolled in the Department of Cardiology and Gastroenterology, Union Hospital, Wuhan, China. Meanwhile, 100 healthy controls, with age and sex-matched, were recruited. Upper gastrointestinal endoscopy was undergone and a standardized symptom questionnaire was completed in NCCP patients. Levels of anxiety and depression and QoL were assessed using locally translated and validated versions of the Hospital Anxiety and Depression Scale (HADS) and the 36-item Short Form Health Survey (SF-36), respectively.The NCCP patients had poorer physical and mental QoL compared with the controls, and nearly half of them had anxiety (49.7%) and depression (40.1%). Those with anxiety and/or depression had lower physical (PCS) and mental (MCS) component summary score compared with those without anxiety and depression. Increased levels of anxiety and depression were associated with lower PCS (r = -0.469 and -0.523 respectively, P < 0.001) and MCS (r = -0.474 and -0.440, respectively, P < 0.001). The chest pain, heartburn, and anxiety were independent factors influence on both PCS and MCS. Moreover, psychological distress, besides directly acting on the QoL, may also mediate indirectly effects of physical symptoms on both the physical and mental QoL.We demonstrated that anxiety and depression are important determinants for the QoL of NCCP patients. Therefore, interventions should emphasize on identifying and treating the psychological impact in NCCP.

Introduction

Noncardiac chest pain (NCCP) is a common problem with the annual prevalence at approximately 23% in the western population and 13% to 15% in Chinese subjects,[ which can be defined as the experience of recurrent substernal or angina-like chest pain in the absence of coronary artery disease or other apparent cardiac abnormalities evaluated by reasonable cardiac examination.[

NCCP is a benign condition with the estimated 10-year mortality of less than 1%,[ however, it is one of the most frightening pains which may be a warning sign of coronary artery disease or myocardial infarction.[ It leads to impaired quality of life (QoL) with daily disability and emotional distress, and increased health care costs due to repeat hospitalizations, emergency department visits and cardiac examinations.[ Although gastroesophageal reflux disease (GERD), esophageal dysmotilities such as achalasia, diffuse esophageal spasm and nutcracker esophagus, and musculoskeletal disorders explain most cases of this disorder,[ it is still inadequate to be responsible for the exaggerated symptoms of pain and obviously decreased health-related QoL. Recently, increased psychological morbidity, such as panic disorders, unique perceptual, and coping style, have been reported in patients with NCCP.[ Psychiatric symptoms may cause the chest pain alone, or along with the organic disorders, which may be the reason why the pain is difficult to cure or usually recurrent.

Anxiety and depression are major comorbid psychological factors of NCCP.[ It is understandable that patients coexisting with anxiety or depression may more concern about having a serious heart disease, and more likely to possess higher rate of seeking medical consultation and lower QoL.[ However, much is still to be learned about the role of psychological impact on the health-related QoL in patients with NCCP, particularly in Chinese subjects. Furthermore, in many cases, more emphasis has been given on the treatment of really physical symptoms, but ignored the adjustment to the invisible psychological disorders in these subjects. This issue may provide a good starting point for interventions of NCCP, since psychiatric symptoms may relate to persistent chest pain and continuing physical and mental incapacity.

In this study, a standardized questionnaire contained items to assess the main physical symptoms, mental disorders (anxiety and depression) and health-related QoL was designed and conducted in NCCP patients in Central China. We aimed to identify the interactions among physical symptoms, psychological disorders, and the QoL in NCCP subjects, in particular, the roles of anxiety and depression in the impaired QoL in these subjects. This may be meaningful for the treatment of those with NCCP, while an individualized biopsychosocial model has been proposed.[

Methods

Subjects

In this cross-sectional study, consecutive patients were invited from those who seeking care for a chief complaint of chest pain and undergoing coronary angiography at the Division of Cardiology and Gastroenterology, Union Hospital, Wuhan, China. And the patients with normal or near normal electrocardiogram and coronary angiography, defined as epicardial coronary artery stenoses <30%,[ were enrolled. A final sample of 200 NCCP patients was received in this study. Meanwhile, 100 healthy controls, with age and sex-matched with the total NCCP patients, were recruited. Patients were invited for upper gastrointestinal endoscopy and a standardized questionnaire (as detailed below) was conducted. This study was approved by the Institutional Ethical Review Committee of Huazhong University of Science and Technology, China ([2011] No.025).

The questionnaire

Demographic characteristics

Demographic information was collected using a self-report questionnaire, including age, sex, height, weight, education and occupation, as well as living habits (smoking, alcohol, tea and coffee).

The Rose angina questionnaire

The frequency, severity, duration, and other characteristics of the chest pain were recorded using a Chinese version of the translated Rose angina questionnaire, which has a intraclass correlation coefficient at 0.91, and a sensitivity and specificity of 68% and 95% for the diagnosis of ischemic heart disease, respectively.[ NCCP was defined as nonexertional chest pain according to the Rose angina questionnaire and had not been diagnosed as ischemic heart diseases by coronary angiography.[ Musculoskeletal-like chest pain referred to chest pain worse on movement, breathing, or pressing on the chest wall.[

The gastrointestinal symptom questionnaire

Gastrointestinal symptoms were assessed, including esophageal symptoms (heartburn, acid regurgitation, dysphagia, regurgitation, odynophagia, and sense of obstruction when swallowing) and extraesophageal symptoms (chronic cough, hoarseness of voice, asthma, pneumonia, and oral discomfort) related to GERD, as well as symptoms associated with functional dyspepsia (FD). The severity and frequency gastrointestinal symptoms were graded on a 5-point Likert scale (1–5) as previously described.[ GERD was defined as acid regurgitation and/or heartburn occurring at least weekly.[ In addition, the history of esophageal, gastric, cardiac or pulmonary disease, and the medication were recorded.

The hospital anxiety and depression scale

The Hospital Anxiety and Depression Scale (HADS) is widely used scale for detecting depression and anxiety in the clinic setting, which comprises of 14 items with a scale of 0 to 3 for each items. There is a total score of 21 for anxiety (7 items) and depression (7 items), respectively. A cut-off point of 8 is deemed to have anxiety or depression, and it has an optimal balance between sensitivity and specificity, and 8 to 10 points is mildly abnormal, 11 to 14 points is moderately abnormal, 15 to 21 points is severe abnormal.[

The 36-item Short Form Health Survey

The health-related QoL was assessed using the 36-item Short Form Health Survey (SF-36), which consists of 8 dimensions and divides into two aspects, the physical component score (PCS, including physical function, role-physical, bodily pain, and general health) and the mental component score (MCS, including vitality, social functioning, role-emotional, and mental health).[ It is well-documented according to validity and reliability in available language versions.[ The scores range from 0 to 100, and higher scores indicating a better health-related QoL.[

Data collection and statistical analysis

Data of questionnaires were cleaned, coded, and double-entered using EpiData software 3.1. Statistical results were presented as the mean ± SD or number of patients (%). SPSS 18.0 and AMOS 18.0 (SPSS, Inc., Chicago, IL) were used for data analysis. Two-sided P < 0.05 was considered statistically significant.

Sample size was calculated with 95% confidence level and 85% power with a P-value of 0.05. Continuous variables were analyzed by means of 1-way ANOVA or nonparametric Kruskal–Wallis test, followed by the least significant difference (LSD) test or Dunnett T3 test for multiple comparisons when required. Categorical variables were compared via Chi-square test or Fisher exact test as appropriate. Spearman correlation analysis was used to identify the correlations among somatic symptoms, psychological status, and the QoL. Multiple regression analysis was then performed to determine the independent factors effect on the QoL. The missing data were excluded. To find the best model, a stepwise procedure was carried out with the entry P < 0.05 and removal  > 0.10, and collinearity diagnostics indicated no marked multicollinearity with tolerance >0.1 and variance inflation factor (VIF) <5.

In order to test the multiple interactions between somatic symptoms and psychological disorders, and their direct and indirect effects on the QoL, a path analysis with a covariance matrix as input and full information maximum likelihood estimation was conducted. Model modification was guided by the Wald statistics and modification indices. The goodness-of-fit indices, including comparative fit index (CFI) and nonnormed fit index (NNFI), as well as the root mean square error of approximation (RMSEA) and standardized root mean square residual (SRMR) were calculated to evaluate the model fit. A model with CFI > 0.95, RMSEA < 0.10, SRMR < 0.08 is indicative of good model fit.[

Results

Demographic characteristics of NCCP patients

Totally 200 NCCP patients (mean age, 58 years; range, 21–82 years; 113 male and 87 female) included in this study. The NCCP patients were divided into 4 subgroups according to the HADS-scores, that is, NCCP without anxiety or depression (contained patients without anxiety or depression, N = 88), NCCP with anxiety (contained patients with anxiety only and with both anxiety and depression N = 98), NCCP with depression (contained patients with depression only and with both depression and anxiety, N = 79), NCCP with anxiety and depression (contained patients with both anxiety and depression, N = 68). Subjects of NCCP with anxiety and/or depression were a little younger than those without anxiety or depression (52.9 ± 10.4 vs 48.9 ± 11.2, P = 0.040). However, there was no significant difference in gender, body mass index (BMI), education, occupation and living habits for smoking, alcohol, tea and coffee between subjects of NCCP with and without anxiety or depression (Table 1). Besides, the healthy controls were matched with the total NCCP group (age: 51.06 ± 10.22; female/male: 1/1.14; BMI: 22.87 ± 3.04; all P > 0.05).

Table 1

Characteristics of NCCP patients.

Upper gastrointestinal endoscopy findings in NCCP patients

A total of 88 (44.0%) patients with NCCP completed the upper gastrointestinal endoscopy. In these patients, 33 (37.5%) cases were normal, 3 (3.4%) cases were Barrett esophagus, 5 (5.7%) cases were esophagitis, 46 (52.3%) cases were mild gastritis, and only 1 (1.1%) case was gastric ulcer. In patients with typical reflux symptoms, about 61.2% (60/98) completed the endoscopy and most of them were normal or just mild gastritis (88.3% (53/60)). About 42.7% (32/75) of NCCP patients with dyspepsia symptoms underwent endoscopy and 96.9% (31/32) of them were normal or mild gastritis.

Chest pain and other symptoms in NCCP patients

The proportions of patients with chest pain < once per month, ≥ once per month, and ≥ once per week were 29.0%, 31.5%, and 39.5%, respectively. And most of these patients had a moderate to severe chest pain (44.5% and 37.5%, respectively). 12.5% of NCCP subjects with a muscular chest pain. Nearly half (44.0%) of NCCP patients were diagnosed with GERD. Heartburn (43.5%) and acid regurgitation (44.5%) were chief esophageal symptoms, and 36.5% of subjects had extraesophageal symptoms. Moreover, a significant number (37.5%) of patients suffered symptoms associated with FD (Table 2).

Table 2

Physical symptoms in NCCP patients (N = 200).

Anxiety and depression in NCCP patients

Nearly half of the NCCP patients had anxiety (49.7%) and obviously higher than the controls (11.0%), the odds ratio (OR) was 5.197 (95% confidence interval (CI), 2.843–9.501, P < 0.001). The NCCP patients diagnosed as depression also more than the controls (40.1% vs 16.0%), the OR was 5.417 (95% CI, 2.721–10.78, P < 0.001). Moreover, most of the NCCP patients diagnosed as anxiety or depression were mild to moderate (Table 3).

Table 3

Psychological state in NCCP patients and healthy controls.

Health-related QoL in NCCP patients

The NCCP patients had a poorer QoL compared with the controls, with a lower PCS (59.89 ± 20.86 vs 79.78 ± 15.96, P < 0.05), MCS (63.51 ± 23.61 vs 79.90 ± 18.87, P < 0.05), and total score (60.77 ± 2.10 vs 79.84 ± 15.20, P < 0.05) (Fig. 1). Compared with those without anxiety or depression, the PCS and MCS as well as total QoL score were much lower (all P < 0.01) in NCCP subjects with anxiety, with depression, and with both anxiety and depression (Table 4).

Figure 1

Health-related QoL in NCCP patients. The NCCP patients had a poorer quality of life compared with the healthy controls, with a lower physical component summary score (PCS), mental component summary score (MCS), and total scores. ∗P < 0.05, NCCP patients versus healthy controls.

Table 4

Quality of life in NCCP patients.

Effects of physical symptoms, anxiety and depression on the QoL in NCCP patients

The correlation analysis suggested that severity (CPS) and frequency (CPF) of chest pain, esophageal symptoms (heartburn, acid regurgitation, dysphagia) were positive related to levels of anxiety and depression, while negative correlated with the PCS and MCS of NCCP patients. In addition, FD symptoms and extraesophageal symptoms also had significant positive correlations with both anxiety and depression, but only negative correlated to the MCS. Other symptoms, such as muscular chest pain, odynophagia, sense of obstruction when swallowing had no significant correlation to levels of anxiety and depression and health-related QoL (Table 5). Increased levels of anxiety and depression were associated with lower PCS (r = −0.469 and −0.523, respectively, P < 0.001) and MCS (r = −0.474 and −0.440, respectively, P < 0.001) (Table 5). Furthermore, the results of multiple regression analysis showed that CPF, CPS, heartburn, and anxiety were the independent factors effects on both the physical and mental QoL of NCCP patients (Table 6).

Table 5

Correlations analyses among physical symptoms, psychological state, and quality of life in NCCP patients (N = 197).

Table 6

Multiple linear regression analyses of the influence of physical symptoms and psychological state on quality of life in NCCP patients.

Direct and indirect effects of symptoms, anxiety and depression on the QoL in NCCP patients in a path model

A path model was established among symptoms, anxiety and depression and the QoL in NCCP patients as it is shown in Fig. 2. The final path model had a good fitness with χ2(6) = 14.846, P = 0.021; CFI = 0.979, NNFI = 0.907, SRMR = 0.030, RMSEA = 0.087 with 90% CI [0.031, 0.144]. It suggested that psychological impact could direct effects on the QoL, as well as the chest pain. Moreover, anxiety and depression may mediate the indirect effects of chest pain on the QoL (Fig. 2). CPS and CPF had indirect effects on PCS (−0.135, P = 0.010 and −0.114, P = 0.022, respectively) and MCS (−0.103, P = 0.014 and −0.87, P = 0.027, respectively) (Table 7). Relatively, the effects of esophageal and extraesophageal symptoms and FD symptoms seemed to be less direct but an indirect effects on the physical and mental QoL (Fig. 2).

Figure 2

Path model of physical symptoms, psychological distress, and quality of life in patients with NCCP. Model fit statistics: χ2(6) = 14.846, P = 0.021; CFI = 0.979, NNFI = 0.907, SRMR = 0.030, RMSEA = 0.087 with 90% CI [0.031, 0.144]. Solid lines represent statistically significant standardized path coefficients (∗P < 0.05, ∗∗P < 0.01); dashed lines represent nonsignificant standardized path coefficients. CPF = chest pain frequency, CPS = chest pain severity, e = error variances, Eso. = esophageal symptoms, Extra-Eso. = extraesophageal symptoms, FD = functional dyspepsia, MCS = mental component summary score, PCS = physical component summary score, Psy. = psychological disorder.

Table 7

Direct and anxiety/depression-mediated indirect effects of chest pain on quality of life in NCCP patients.

Discussion

Chest pain is a common and alarm symptom that leads to serious psychological distress and decreasing in the QoL in western society, even though more than half of these patients are noncardiac origin.[ It may also be true in Chinese populations. In this study, particularly, role of psychological distress in impaired health-related QoL of NCCP patients in Central China were assessed. The results revealed that high ratio of anxiety and depression, and poorer physical and mental QoL existed in NCCP subjects, moreover, anxiety and depression were closely associated with lower QoL. Psychological distress, besides directly acting on the QoL, may also mediate indirectly effects of physical symptoms on both the physical and mental QoL.

Impairment of QoL, both the physical and mental aspects, was evident in NCCP patients compared with the healthy subjects as we demonstrated. Moreover, it has been reported that NCCP patients were generally accompanied by poorer QoL and more frequent of work absenteeism, similarly as it was in cardiac chest pain (CCP) patients.[ We further confirmed that chest pain, heartburn, and anxiety are major independent influencing factors on the QoL of NCCP patients. It suggested that the symptoms of illness and the psychological distress may be main factors to be responsible for the poor QoL.

In our patients, the chest pain had a strong negative correlation with both the mental and physical QoL. It was no doubt that physical illness play an important role in the determination of physical and mental well-being. Esophageal and gastric abnormalities are main symptoms overlapped with NCCP, especially the GERD-related symptoms. About 44.0% of NCCP patients were diagnosed with GERD according to the GERD questionnaire with typical symptoms, based on our results. It was consistent with the report that GERD is the most common cause of NCCP.[ A range of 22% to 80% of those with NCCP had pathological acid reflux on 24-hour esophageal pH monitoring.[ The major reflux symptoms, including heartburn, acid regurgitation, and dysphagia, were negatively related to the mental and physical QoL. Besides, extraesophageal symptoms and FD were also an important factors influence on the mental aspect of QoL in NCCP patients, which frequently overlapped with GERD[ and existed in 36.5% and 37.5% of NCCP subjects, respectively.

Psychological disorders, predominantly the anxiety and depressive symptoms, have been shown to be associated with NCCP in a population based study in China.[ We demonstrated that approximately 49.7% and 40.1% of the NCCP patients had various degrees of anxiety and depression, respectively. Moreover, many patients with NCCP who do not meet criteria for psychiatric disorders still experience significant psychological distress and dysfunction.[ We speculated that psychological impact plays an important role in the determination of QoL levels. The reasons were as follows: NCCP patients with anxiety and/or depression had much lower physical and mental QoL compared with those without anxiety and depression; anxiety and depression were significantly and negatively correlated to the MCS and PCS; anxiety was an independent factor influence on the QoL of NCCP, which was in agreement with the anxiety-based theories of NCCP.[ Those with anxiety had more affective distress related to pain and exaggerated functional disability, such as panic, catastrophizing, and somatization.[

Physical symptoms, such as chest pain, heartburn, acid regurgitation, and dysphagia, were closely related to the psychologic state in patients with NCCP as we shown. However, the causality between each other is complicated and inconclusive. NCCP patients with psychological distress experienced more severe and frequent chest pain and more concerned about pain.[ On the contrary, patients with nonlethal chest pain may experience more disease conviction, higher levels of depression and anxiety, more cardioprotective behavior, such as avoiding activities that they thought might be harmful to their heart.[ This may be especially true in the patients with Type D personality which is the independent factor affected on the presence of psychopathology in NCCP patients.[ Our further study exhibited that the chest pain could indirectly effects on both physical and mental QoL in NCCP patients through increasing the anxiety and depression. In this sense, psychological burden, such as anxiety and depression, may be an important determinant of QoL in patients with NCCP. Therefore, identification of psychological disorders seems especially important, since higher levels of depression and anxiety lead NCCP patients to repeatedly seek for medical consultation and intervention, accompanied by reductions in QoL.[

This study also had several limitations. First, although the path model suggested that physical symptoms could act on psychological states, through which indirectly influence on the QoL, the prospective studies are still required to examine and confirm the cause–effect relationships among each other. Second, although the HADS and SF-36 questionnaire were widely used in clinics for assessment of anxiety/depression and health-related QoL, it need further evaluating the applicability of translated version of these self-reported questionnaires on Chinese NCCP subjects. Third, we did not follow-up with our NCCP patients, thus, it should be our subsequent works to follow-up the patients and verify our conclusions.

In summary, high proportion of anxiety and depression were closely associated with the poor QoL in NCCP patients. Besides the directly effects on the QoL, anxiety and depression may also mediate the indirect effects of chest pain on the physical and mental QoL in NCCP patients, which indicated that psychological distress was the crucial determinants of QoL in patients with NCCP. Therefore, we suggested that, in addition to therapies targeting the physical illness, interventions to identify and treat the psychological impact may be of great benefit to NCCP patients.